Infectious Diseases

Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term lung function better predicts mortality risk in SSc

To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019

2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis

To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019

3. Three commonly used quick cognitive assessments often yield flawed results

To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019

4. Missed HIV screening opportunities found among subsequently infected youth

To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019

5. Aspirin appears underused to prevent preeclampsia in SLE patients

To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019

Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term lung function better predicts mortality risk in SSc

To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019

2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis

To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019

3. Three commonly used quick cognitive assessments often yield flawed results

To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019

4. Missed HIV screening opportunities found among subsequently infected youth

To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019

5. Aspirin appears underused to prevent preeclampsia in SLE patients

To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019

Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term lung function better predicts mortality risk in SSc

To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019

2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis

To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019

3. Three commonly used quick cognitive assessments often yield flawed results

To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019

4. Missed HIV screening opportunities found among subsequently infected youth

To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019

5. Aspirin appears underused to prevent preeclampsia in SLE patients

To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019

Influenza activity increased for a second straight week after a 2-week drop and by one measure has topped the high reached in late December, according to the Centers for Disease Control and Prevention.

For the week ending Jan. 26, 2019, there were 16 states at level 10 on the CDC’s 1-10 scale of influenza-like illness (ILI) activity, compared with 12 states during the week ending Dec. 29. With another seven states at levels 8 and 9, that makes 23 in the high range for the week ending Jan. 26, again putting it above the 19 reported for Dec. 29, the CDC’s influenza division reported Feb. 1.

[email protected]

Influenza activity increased for a second straight week after a 2-week drop and by one measure has topped the high reached in late December, according to the Centers for Disease Control and Prevention.

For the week ending Jan. 26, 2019, there were 16 states at level 10 on the CDC’s 1-10 scale of influenza-like illness (ILI) activity, compared with 12 states during the week ending Dec. 29. With another seven states at levels 8 and 9, that makes 23 in the high range for the week ending Jan. 26, again putting it above the 19 reported for Dec. 29, the CDC’s influenza division reported Feb. 1.

[email protected]

Influenza activity increased for a second straight week after a 2-week drop and by one measure has topped the high reached in late December, according to the Centers for Disease Control and Prevention.

For the week ending Jan. 26, 2019, there were 16 states at level 10 on the CDC’s 1-10 scale of influenza-like illness (ILI) activity, compared with 12 states during the week ending Dec. 29. With another seven states at levels 8 and 9, that makes 23 in the high range for the week ending Jan. 26, again putting it above the 19 reported for Dec. 29, the CDC’s influenza division reported Feb. 1.

[email protected]

A 75-year-old man presents with fever, chills, and facial pain. He had an upper respiratory infection 3 weeks ago and has had persistent sinus drainage since. He has tried nasal irrigation and nasal steroids without improvement.

Over the past 5 days, he has had thicker postnasal drip, the development of facial pain, and today fevers as high as 102 degrees. He has a history of giant cell arteritis, for which he takes 30 mg of prednisone daily; coronary artery disease; and hypertension. He has a penicillin allergy (rash on chest, back, and arms 25 years ago). Exam reveals temperature of 101.5 and tenderness over left maxillary sinus.

What treatment do you recommend?

A. Amoxicillin/clavulanate.

B. Cefpodoxime.

C. Levofloxacin.

D. Trimethoprim/sulfamethoxazole.

I think cefpodoxime is probably the best of these choices to treat sinusitis in this patient. Choosing amoxicillin /clavulanate is an option only if you could give the patient a test dose in a controlled setting. I think giving this patient levofloxacin poses greater risk than a penicillin rechallenge. This patient is elderly and on prednisone, both of which increase his risk of tendon rupture if given a quinolone. Also, the Food and Drug Administration released a warning recently regarding increased risk of aortic disease in patients with cardiovascular risk factors who receive fluoroquinolones.¹

Merin Kuruvilla, MD, and colleagues described oral amoxicillin challenge for patients with a history of low-risk penicillin allergy (described as benign rash, benign somatic symptoms, or unknown history with penicillin exposure more than 12 months prior).² The study was done in a single allergy practice where 38 of 50 patients with penicillin allergy histories qualified for the study. Of the 38 eligible patients, 20 consented to oral rechallenge in clinic, and none of them developed immediate or delayed hypersensitivity reactions.

Melissa Iammatteo, MD, et al. studied 155 patients with a history of non–life-threatening penicillin reactions.³ Study participants received placebo followed by a two-step graded challenge to amoxicillin. No reaction occurred in 77% of patients, while 20% of patients had nonallergic reactions, which were equal between placebo and amoxicillin. Only 2.6 % had allergic reactions, all of which were classified as mild.

Reported penicillin allergy occurs in about 10% of community patients, but 90% of these patients can tolerate penicillins.⁴ Patients reporting a penicillin allergy have increased risk for drug resistance and prolonged hospital stays.⁵

The American Academy of Allergy, Asthma & Immunology recommended more widespread and routine performance of penicillin allergy testing in patients with a history of allergy to penicillin or other beta-lactam antibiotics.⁶ Patients who have penicillin allergy histories are more likely to receive drugs, such as clindamycin or a fluoroquinolone, that may carry much greater risks than a beta-lactam antibiotic. It also leads to more vancomycin use, which increases risk of vancomycin resistance.

Allergic reactions to cephalosporins are very infrequent in patients with a penicillin allergy. Eric Macy, MD, and colleagues studied all members of Kaiser Permanente Southern California health plan who had received cephalosporins over a 2-year period.⁷ More than 275,000 courses were given to patients with penicillin allergy, with only about 1% having an allergic reaction and only three cases of anaphylaxis.
 

Pearl: Most patients with a history of penicillin allergy will tolerate penicillins and cephalosporins. Penicillin allergy testing should be done to assess if they have a penicillin allergy, and in low-risk patients (patients who do not recall the allergy or had a maculopapular rash), consideration for oral rechallenge in a controlled setting may be an option. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
 

References

1. Food and Drug Administration. “FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients,” 2018 Dec 20.

2. Ann Allergy Asthma Immunol. 2018 Nov;121(5):627-8.

3. J Allergy Clin Immunol Pract. 2019 Jan;7(1):236-43.

4. Immunol Allergy Clin North Am. 2017 Nov;37(4):643-62.

5. J Allergy Clin Immunol. 2014 Mar;133(3):790-6.

6. J Allergy Clin Immunol Pract. 2017 Mar - Apr;5(2):333-4.

7. J Allergy Clin Immunol. 2015 Mar;135(3):745-52.e5.

A 75-year-old man presents with fever, chills, and facial pain. He had an upper respiratory infection 3 weeks ago and has had persistent sinus drainage since. He has tried nasal irrigation and nasal steroids without improvement.

Over the past 5 days, he has had thicker postnasal drip, the development of facial pain, and today fevers as high as 102 degrees. He has a history of giant cell arteritis, for which he takes 30 mg of prednisone daily; coronary artery disease; and hypertension. He has a penicillin allergy (rash on chest, back, and arms 25 years ago). Exam reveals temperature of 101.5 and tenderness over left maxillary sinus.

What treatment do you recommend?

A. Amoxicillin/clavulanate.

B. Cefpodoxime.

C. Levofloxacin.

D. Trimethoprim/sulfamethoxazole.

I think cefpodoxime is probably the best of these choices to treat sinusitis in this patient. Choosing amoxicillin /clavulanate is an option only if you could give the patient a test dose in a controlled setting. I think giving this patient levofloxacin poses greater risk than a penicillin rechallenge. This patient is elderly and on prednisone, both of which increase his risk of tendon rupture if given a quinolone. Also, the Food and Drug Administration released a warning recently regarding increased risk of aortic disease in patients with cardiovascular risk factors who receive fluoroquinolones.¹

Merin Kuruvilla, MD, and colleagues described oral amoxicillin challenge for patients with a history of low-risk penicillin allergy (described as benign rash, benign somatic symptoms, or unknown history with penicillin exposure more than 12 months prior).² The study was done in a single allergy practice where 38 of 50 patients with penicillin allergy histories qualified for the study. Of the 38 eligible patients, 20 consented to oral rechallenge in clinic, and none of them developed immediate or delayed hypersensitivity reactions.

Melissa Iammatteo, MD, et al. studied 155 patients with a history of non–life-threatening penicillin reactions.³ Study participants received placebo followed by a two-step graded challenge to amoxicillin. No reaction occurred in 77% of patients, while 20% of patients had nonallergic reactions, which were equal between placebo and amoxicillin. Only 2.6 % had allergic reactions, all of which were classified as mild.

Reported penicillin allergy occurs in about 10% of community patients, but 90% of these patients can tolerate penicillins.⁴ Patients reporting a penicillin allergy have increased risk for drug resistance and prolonged hospital stays.⁵

The American Academy of Allergy, Asthma & Immunology recommended more widespread and routine performance of penicillin allergy testing in patients with a history of allergy to penicillin or other beta-lactam antibiotics.⁶ Patients who have penicillin allergy histories are more likely to receive drugs, such as clindamycin or a fluoroquinolone, that may carry much greater risks than a beta-lactam antibiotic. It also leads to more vancomycin use, which increases risk of vancomycin resistance.

Allergic reactions to cephalosporins are very infrequent in patients with a penicillin allergy. Eric Macy, MD, and colleagues studied all members of Kaiser Permanente Southern California health plan who had received cephalosporins over a 2-year period.⁷ More than 275,000 courses were given to patients with penicillin allergy, with only about 1% having an allergic reaction and only three cases of anaphylaxis.
 

Pearl: Most patients with a history of penicillin allergy will tolerate penicillins and cephalosporins. Penicillin allergy testing should be done to assess if they have a penicillin allergy, and in low-risk patients (patients who do not recall the allergy or had a maculopapular rash), consideration for oral rechallenge in a controlled setting may be an option. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
 

References

1. Food and Drug Administration. “FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients,” 2018 Dec 20.

2. Ann Allergy Asthma Immunol. 2018 Nov;121(5):627-8.

3. J Allergy Clin Immunol Pract. 2019 Jan;7(1):236-43.

4. Immunol Allergy Clin North Am. 2017 Nov;37(4):643-62.

5. J Allergy Clin Immunol. 2014 Mar;133(3):790-6.

6. J Allergy Clin Immunol Pract. 2017 Mar - Apr;5(2):333-4.

7. J Allergy Clin Immunol. 2015 Mar;135(3):745-52.e5.

A 75-year-old man presents with fever, chills, and facial pain. He had an upper respiratory infection 3 weeks ago and has had persistent sinus drainage since. He has tried nasal irrigation and nasal steroids without improvement.

Over the past 5 days, he has had thicker postnasal drip, the development of facial pain, and today fevers as high as 102 degrees. He has a history of giant cell arteritis, for which he takes 30 mg of prednisone daily; coronary artery disease; and hypertension. He has a penicillin allergy (rash on chest, back, and arms 25 years ago). Exam reveals temperature of 101.5 and tenderness over left maxillary sinus.

What treatment do you recommend?

A. Amoxicillin/clavulanate.

B. Cefpodoxime.

C. Levofloxacin.

D. Trimethoprim/sulfamethoxazole.

I think cefpodoxime is probably the best of these choices to treat sinusitis in this patient. Choosing amoxicillin /clavulanate is an option only if you could give the patient a test dose in a controlled setting. I think giving this patient levofloxacin poses greater risk than a penicillin rechallenge. This patient is elderly and on prednisone, both of which increase his risk of tendon rupture if given a quinolone. Also, the Food and Drug Administration released a warning recently regarding increased risk of aortic disease in patients with cardiovascular risk factors who receive fluoroquinolones.¹

Merin Kuruvilla, MD, and colleagues described oral amoxicillin challenge for patients with a history of low-risk penicillin allergy (described as benign rash, benign somatic symptoms, or unknown history with penicillin exposure more than 12 months prior).² The study was done in a single allergy practice where 38 of 50 patients with penicillin allergy histories qualified for the study. Of the 38 eligible patients, 20 consented to oral rechallenge in clinic, and none of them developed immediate or delayed hypersensitivity reactions.

Melissa Iammatteo, MD, et al. studied 155 patients with a history of non–life-threatening penicillin reactions.³ Study participants received placebo followed by a two-step graded challenge to amoxicillin. No reaction occurred in 77% of patients, while 20% of patients had nonallergic reactions, which were equal between placebo and amoxicillin. Only 2.6 % had allergic reactions, all of which were classified as mild.

Reported penicillin allergy occurs in about 10% of community patients, but 90% of these patients can tolerate penicillins.⁴ Patients reporting a penicillin allergy have increased risk for drug resistance and prolonged hospital stays.⁵

The American Academy of Allergy, Asthma & Immunology recommended more widespread and routine performance of penicillin allergy testing in patients with a history of allergy to penicillin or other beta-lactam antibiotics.⁶ Patients who have penicillin allergy histories are more likely to receive drugs, such as clindamycin or a fluoroquinolone, that may carry much greater risks than a beta-lactam antibiotic. It also leads to more vancomycin use, which increases risk of vancomycin resistance.

Allergic reactions to cephalosporins are very infrequent in patients with a penicillin allergy. Eric Macy, MD, and colleagues studied all members of Kaiser Permanente Southern California health plan who had received cephalosporins over a 2-year period.⁷ More than 275,000 courses were given to patients with penicillin allergy, with only about 1% having an allergic reaction and only three cases of anaphylaxis.
 

Pearl: Most patients with a history of penicillin allergy will tolerate penicillins and cephalosporins. Penicillin allergy testing should be done to assess if they have a penicillin allergy, and in low-risk patients (patients who do not recall the allergy or had a maculopapular rash), consideration for oral rechallenge in a controlled setting may be an option. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
 

References

1. Food and Drug Administration. “FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients,” 2018 Dec 20.

2. Ann Allergy Asthma Immunol. 2018 Nov;121(5):627-8.

3. J Allergy Clin Immunol Pract. 2019 Jan;7(1):236-43.

4. Immunol Allergy Clin North Am. 2017 Nov;37(4):643-62.

5. J Allergy Clin Immunol. 2014 Mar;133(3):790-6.

6. J Allergy Clin Immunol Pract. 2017 Mar - Apr;5(2):333-4.

7. J Allergy Clin Immunol. 2015 Mar;135(3):745-52.e5.

At present, 300,000 US women undergo breast augmentation surgery each year,¹ making this the second most common aesthetic procedure in women (after liposuction),^2–4 and making it extremely likely that clinicians will encounter women who have breast implants. In addition, approximately 110,000 women undergo breast reconstructive surgery after mastectomy, of whom more than 88,000 (81%) receive implants (2016 data).⁵

This review discusses the evolution of breast implants, their complications, and key considerations with regard to aesthetic and reconstructive breast surgery, as the principles are similar.

EVOLUTION OF IMPLANTS

Reports of breast augmentation surgery, also known as augmentation mammoplasty, date back to 1895, when a fatty tumor (lipoma) was successfully transplanted from a patient’s back to a breast defect in a mastectomy patient.^2,3,6,7 In the 1930s, implantation of a glass ball into a patient’s breast marked the first implant-based breast augmentation.⁶ By 1954, attempts at breast augmentation using local dermal-fat flaps, adipose tissue, and even omentum were described.

Alloplastic materials gained popularity throughout the 1950s and 1960s and included polyurethane, polytetrafluoroethylene (Teflon), and other synthetics. Adverse reactions associated with alloplastic materials were plentiful: local tissue reactions, distortion of the breast mound, increased firmness, and discomfort all contributed to the eventual discontinuation of their use. The history of alloplastic breast augmentation also included epoxy resin, shellac, beeswax, paraffin, rubber, petroleum jelly, and liquefied silicone. Outcomes were not good, and many patients ultimately needed mastectomy.⁷

The first modern breast prosthesis was developed in 1961, and since then, implant composition and design have evolved significantly.⁸

From silicone to saline, and back again

The first silicone gel implants, introduced in the early 1960s,^8–19 had high complication rates—some centers reported an incidence of capsular contracture of up to 70%.^8,11 This is a foreign body reaction in which pathologic scar tissue encases the implant, causing it to distort, appear misshapen, harden, and even become painful.¹¹ Attempts to minimize this reaction led to later generations of silicone implants with polyurethane shells.¹²

Inflatable implants filled with sterile saline solution were originally developed in France in 1965. Unlike silicone implants, saline implants have undergone minimal changes since their inception, and grew in popularity during the 1970s in view of the high rates of capsular contracture with silicone implants.⁸ However, saline implants have their own problems, and as they became increasingly popular, deflation and the unnatural feel of saline sparked a renewed interest in silicone gel.

By the late 1980s, the thinner-shelled generation of silicone implants displayed its own frustrating complications including implant rupture, capsular contracture, infection, and possible systemic and disseminated granulomatous disease. From 1992 to 2006, the US Food and Drug Administration (FDA) placed a moratorium on silicone implants due to concerns about a possible link with autoimmune and connective tissue diseases and the possible carcinogenic nature of silicone.

While silicone implants were prohibited in the United States, development continued abroad, and eventually the moratorium was lifted after several meta-analyses failed to reveal any link regarding the aforementioned concerns.¹³

Today, silicone gel implants dominate the world market.¹⁴ In the United States, approximately 60% of implants contain silicone gel filler, and trends are similar in Europe.⁷

Table 1 summarizes the evolution of silicone breast implants over the last 50 years.^2,6,11,12Table 2 lists the advantages and disadvantages of silicone and saline breast implants.^2,6,8,15

CURRENT IMPLANT OPTIONS

Currently, 3 companies (Allergan, Mentor, Sientra) manufacture and distribute breast implants and implant-associated products such as tissue expanders and sizers in the US market.⁶

Another company, Motiva, makes an implant that is available in Europe, Asia, and Australia, and the device is currently undergoing a 10-year clinical trial in the United States that began recruiting patients in 16 centers in April 2018.¹⁶ Pending final approval, the Cleveland Clinic Department of Plastic Surgery may be among the centers involved in the clinical trial of the Motiva implant. Innovations in the Motiva implant include a high-performance shell that maintains consistent strength and includes a proprietary barrier layer, improved silicone gel filler, 3-D imprinted surface texturing, and an implant shape that adapts with vertical and horizontal movement. It also contains radio-frequency identification transponders that can transmit data about the implant wirelessly.^17–19

Developed in the 1980s, texturing of the implant surface disrupts capsule formation around the prosthesis. Additionally, texturing stabilizes an anatomically shaped (teardrop) implant within the breast pocket, reducing malrotation.^20,21

The first textured implants were covered with polyurethane foam, but they were ultimately withdrawn from the US market because of concern for in vivo degradation to carcinogenic compounds. The focus subsequently turned to texturing implant shells by mechanically creating pores of different sizes. Smooth implants, by contrast, are manufactured by repeatedly dipping the implant shell into liquid silicone.²

The capsular contraction rate has been shown to be lower with textured silicone than with smooth silicone (number needed to treat = 7–9), and evidence suggests a lower risk of needing a secondary procedure.²¹

Form-stable vs fluid-form

Silicone is a polymer. The physical properties of polymers vary greatly and depend on the length of the individual chains and the degree to which those chains are cross-linked. Liquid silicone contains short chains and sparse cross-linking, resulting in an oily compound well suited for lubrication. Silicone gel contains longer chains and more cross-linking and is therefore more viscous.

In “form-stable” implants, the silicone interior has sufficient chain length and cross-linking to retain the designed shape even at rest,² but they require slightly larger incisions.⁷ “Fluid-form” refers to an implant with silicone filler with shorter chain length, less cross-linking, and more fluidity.⁶

Shell

As with silicone fillers, the properties of silicone implant shells also depend on chain length and cross-linking within the polymer. Silicone elastomer shells (Table 1) contain extensively cross-linked chains that impart a flexible yet rubbery character. Silicone elastomers can also be found in facial implants and tissue expanders.²

Implant shape (round vs anatomic)

The shape of an implant is determined by the gel distribution inside of it. To understand gel distribution and implant shape, one must understand the gel-shell ratio. This ratio increases as cohesivity of the filler increases, and it represents increased bonding of the gel filler to the shell and a preserved implant shape at rest.

The gel-shell ratio varies among manufacturers, and a less-viscous filler may be more prone to rippling or loss of upper pole fullness in some patients. For this reason, careful analysis, patient and implant selection, and discussion of complications remain paramount.²

No anatomically shaped implant is manufactured with a smooth shell, but rather with a textured shell that resists malrotation.^6,15 However, in the United States, 95% of patients receive round implants.¹⁶

PATIENT ASSESSMENT

Before breast augmentation surgery, the surgeon assesses a number of factors—physical and psychosocial—and helps the patient choose a type and size of implant. The surgeon and patient also plan where the implants will be placed—ie, above or beneath the chest wall muscle—and where the incisions will be made. Every decision is made in close consultation with the patient, taking into account the patient’s desires and expectations, as well as what the patient’s anatomy allows. An integral component of this shared decision-making process is a discussion of the possible complications, and often photographs to better illustrate what to expect postoperatively. 

Psychosocial factors

One must consider the patient’s psychology, motivations for surgery, and emotional stability. Here, we look for underlying body dysmorphic disorder; excessive or unusual encouragement to undergo the procedure by a spouse, friends, or others; a history of other aesthetic procedures; unrealistic expectations; and other factors influencing the desire to undergo this surgery.

Choosing an implant

Implant selection must take into account the patient’s height, weight,⁷ and overall body morphology: taller patients and those with wider hips or shoulders usually require larger implants. A reliable method for determining the appropriate implant must include the current breast shape, dimensions, volume, skin elasticity, soft-tissue thickness, and overall body habitus. Ultimately, the most important considerations include breast base diameter, implant volume,²⁰ and soft-tissue envelope.

Preoperative sizing can involve placing sample implants within a brassiere so that the patient can preview possible outcomes. This method is particularly effective in minimizing dissatisfaction because it shares ownership of the decision-making process.¹⁵

A computerized implant selection program available in Europe suggests a “best-fit” implant based on a clinician’s measurements.⁷

Traditionally, plastic surgeons place breast implants either beneath the pectoralis major muscle (submuscular placement) or over the pectoralis⁸ but beneath the glandular breast parenchyma (subglandular placement) (Figure 2).⁷

Advantages of submuscular placement are a smoother transition of the upper breast pole from the chest wall and less rippling visible through the skin, due to the additional muscular coverage of the implant. Another advantage is that capsular contraction rates are lower with submuscular placement, likely due to possible contamination of implants by lactiferous ductal microbes when accessing the subglandular plane.^14,20 Disadvantages are pronounced discomfort after surgery and animation deformities with muscle contraction, particularly in young, highly active patients.

A popular modification of submuscular placement involves creating a surgical dissection plane between the subglandular tissue and the pectoralis major fascia. This “dual­­plane” approach allows the parenchyma to retract superiorly and reduce breast ptosis.⁷

Incisions

Table 3 highlights important considerations with regard to incision location.^15,20,21

ANTIBIOTICS

Many surgeons give a single prophylactic dose of antibiotic before surgery, a practice that some studies have shown to be effective in reducing the risk of infection.¹⁵ However, the benefit of routine postoperative use of antibiotics remains unsubstantiated¹⁵: postoperative antibiotic use does not appear to protect against infection, capsular contracture, or overall complications in primary or secondary breast augmentation surgery.²⁰

PERIOPERATIVE PERIOD

At our institution, breast augmentation surgery is an ambulatory procedure—the patient goes home the same day unless circumstances such as pain control warrant admission. This is, however, according to surgeon preference, and differs on a case-by-case basis. General anesthesia is the standard of care.¹⁵

POSTOPERATIVE PERIOD

In the immediate postoperative period, patients are instructed to wear a surgical bra for up to 6 weeks to allow stable scarring. Early mobilization is encouraged.^7,15 Depending on the patient’s situation, recovery, and healing, she may be out of work for about 1 week, sometimes more, sometimes less. 

Additional instructions are surgeon-specific. However, the patient is instructed to avoid bathing, swimming, immersion in water, and wearing underwire brassieres that could impair healing of an inferior incision; instead, patients are often instructed to wear a surgical bra provided on the day of surgery until cleared in the clinic.

Showering is allowed the next day or the second day after surgery, and of course there is no driving while on narcotics. Additionally, patients are counseled extensively regarding hematoma formation and the signs and symptoms of infection.

Patients are typically seen in clinic 1 week after surgery.

The cost of surgery may be $5,000 to $6,000 but can vary significantly from center to center depending on who the patient sees and where, and whether the patient presents for breast reconstruction after cancer or repair of congenital anomalies, or in certain cases of transgender surgery. The patient is typically responsible for the fee, but again this depends on the patient, indications, and particular insurance concerns.

IMPLANT LONGEVITY AND RUPTURE

In the United States, implant rupture rates range from 1.1% to 17.7% at 6 to 10 years after primary augmentation, 2.9% to 14.7% after revision augmentation, 1.5% to 35.4% after primary breast reconstruction, and 0% to 19.6% after revision reconstruction.¹¹

Unfortunately, the existence of multiple implant manufacturers, numerous implant generations, and poorly standardized screening protocols and reporting systems make the true rate of implant rupture difficult to assess without definitive imaging or implant retrieval.¹¹

Damage from surgical instrumentation during implantation is the most common cause of silicone breast implant rupture (50% to 64% of cases).²² Other causes include underfilling and fold flaw from capsular contracture.

Leakage of silicone gel filler may be confined to the periprosthetic capsule (intracapsular rupture) or extend beyond and into the breast parenchyma (extracapsular rupture). One study reported that only 10% of intracapsular ruptures progressed extracapsularly, while 84% of patients with extracapsular involvement remained stable for up to 2 years,²³ indicating that intracapsular rupture may not portend worsening disease.¹¹

Implant rupture occurs silently in most cases, with no clinically detectable signs or symptoms. In other cases, patients may present with alterations in breast shape and size, sudden asymmetry, firmness, pronounced capsular contracture, contour irregularity, or pain.

Aside from physical examination, comprehensive diagnostic testing includes imaging—ultrasonography, mammography, computed tomography, and magnetic resonance imaging (MRI). Of these, MRI is the method of choice, with sensitivity and specificity exceeding 90% for detecting implant rupture.¹¹ Classic findings on MRI include the “linguine” sign from a deflating implant shell, or the teardrop sign from implant sagging. Classic findings on ultrasonography include the “snowstorm” sign of extracapsular rupture and the “stepladder” sign of intracapsular rupture.

Mammography effectively detects free silicone in breast tissue with extracapsular rupture (25% of ruptures according to some studies)²³; however, it cannot detect rupture within the implant capsule. As an aside, submuscular implant placement may interfere less with screening mammography than subglandular implants do.^14,24

Current FDA recommendations to detect implant rupture encourage women with silicone breast implants to undergo screening 3 years after implantation and then every 2 years thereafter; no long-term monitoring is suggested for saline implants.¹⁵ Many plastic surgeons evaluate silicone breast implant patients every 1 to 2 years for contracture and rupture.⁸ Of note, capsular contracture impairs the effectiveness of ultrasonography and may require MRI confirmation.¹¹

If implant rupture is confirmed, the current recommendation is to remove the implant and the capsule. Another implant may be placed depending on the patient’s preference. Rigorous washout remains a key feature of any surgical intervention for ruptured breast implants; however, in the event of extracapsular rupture, resection of silicone granulomas may also be required.¹¹

Reoperation rates for primary breast augmentation surgery approach 20% and are even higher for secondary augmentation over a patient’s lifetime—the highest rate of all aesthetic procedures.^7,14

Capsular contracture is the most common complication of breast augmentation,²⁵ typically presenting within the first postoperative year,^26,27 and the risk increases over time.²⁸ It occurs with both silicone and saline breast implants.

In some studies, the incidence exceeded 4% in the first 2 years after surgery,²⁹ and nearly 50% by 10 years.³⁰ Other studies found rates of 0% to 20% over 13 years.²⁰

The etiology is not well understood and is presumed to be multifactorial, with proposed mechanisms and factors that include bacterial contamination, surface texturing, the implant pocket selected, the incision type, drain placement, antibiotic use, and smoking.²⁵

A meta-analysis from 17,000 implants found that the risk of capsular contracture was significantly higher when an implant was placed in a subglandular pocket than in a submuscular pocket,^22,26 and that although texturing decreased capsular contracture compared with smooth implants, the effect was modest when a textured or smooth implant was placed in a submuscular location.²⁸ With regard to incision location, studies have reported that the incidence of capsular contracture is highest with transaxillary and periareolar incisions, and lowest with inframammary incisions.^20,21

The leading theory is that contamination of the implant (primarily from the mammary ducts) results in biofilm formation. Subclinical hematoma surrounding the implant may also provide key bacterial nutrients.²⁰

Textured implants induce a greater inflammatory response in the capsular tissue, resulting in a thicker capsule; however, contracture rates remain lower with textured than with smooth implants.^14,31 Interestingly, lower rates of capsular contracture have been observed with later-generation, cohesive-gel, form-stable implants than with those of earlier generations.¹²

Although more research is needed, silicone implants appear to confer a higher risk of capsular contracture than saline implants.^14,20

Irrigating the breast pocket intraoperatively with triple antibiotic solution (bacitracin, cefazolin, and gentamicin) before placing the implant may decrease the capsular contracture rate.^15,20

Treatments for capsular contracture include pocket modifications such as capsulotomy (making releasing, relaxing incisions in the scar capsule encasing the implant), capsulectomy (removing portions of or the entire capsule), and replacing the implant in the other pocket (ie, if the original implant was subglandular, the replacement is placed in the submuscular pocket). Patients who have contractures that fail to respond to these treatments may ultimately benefit from implant removal and autologous reconstruction (autoaugmentation) rather than implant replacement.^32,33

ADDITIONAL COMPLICATIONS

Other complications include infection, malposition, rippling, seroma, hematoma, and sensory alterations.

Irrigation during the implantation procedure with a triple antibiotic solution consisting of bacitracin, gentamycin, and cephalexin in normal saline decreases infection and seroma rates.^15,20,34

Some surgeons also choose to irrigate the pocket with a betadine solution, or to cleanse the skin with betadine and place sterile towels and redrape before inserting the implant. Additionally, many prefer using a sterile device much like a pastry funnel called a Keller funnel to insert the implant into the breast pocket.³⁵

Infection is less common with cosmetic augmentations than with implant-based breast reconstruction, likely because of healthier, well-vascularized tissue in patients undergoing cosmetic surgery than in those undergoing mastectomy.¹⁴

Seroma is thought to be a consequence of texturing, and more so with macro- vs microtexturing. Though poorly understood, an association between texturing and double capsules has also been reported.^12,20

After primary breast augmentation, 10-year follow-up rates of capsular contracture, seroma, rippling, and malposition vary across the 3 major silicone implant manufacturers.¹² Hematoma and infection occur in less than 1% of primary augmentation patients.¹⁵

Malposition of the implant over time is less frequent with textured implants because of the higher coefficient of friction compared with smooth implants^.6,8,15

Visible skin rippling may be a consequence of texturing and also of thin body habitus, eg, in patients with a body mass index less than 18.5 kg/m². If the soft-tissue layer of the breast is thin, the natural rippling of smooth saline implant shells are more likely to show when placed in the subglandular pocket. Form-stable implants, by contrast, resist rippling.^12,15

Large implants and extensive lateral dissection can cause alterations in nipple sensation and sensory loss within lower breast pole skin. Axillary incisions may traumatize or damage the intercostobrachial nerve, resulting in upper inner arm sensory aberrations.

Ultimately, the 10-year incidence of secondary surgery ranges from 0% to 36% and the 10-year incidence of capsular contracture ranges from 11% to 19%.¹⁵ Additional cosmetic complaints after augmentation with implants include enlargement of the areola and engorgement of breast veins.¹⁴

BREAST CANCER AND DETECTION

Patients with or without implants do not seem to differ with regard to breast cancer stage upon detection, tumor burden, recurrence, or survival. However, more patients with implants may present with palpable masses, invasive tumors, axillary metastasis, and falsely negative mammograms.

Breast implants may actually facilitate cancer detection on physical examination by providing a more dense or stable surface upon which to palpate the breast tissue. Although they do not necessarily impair mastectomy or breast reconstruction, they may result in an increased rate of revision surgery after breast conservation therapy.^24,36 Mammography remains the standard of care for radiologic diagnosis but can be further supported by MRI and ultrasonography if necessary in patients with implants.

Although concerns persist, multiple studies have demonstrated the safety of fourth- and fifth-generation silicone breast implants with regard to autoimmune disease.⁷

In various clinical studies in mastectomy patients who underwent breast reconstruction with either silicone implants or autologous tissue, no difference was found with regard to the incidence of autoimmune diseases.² Additionally, in meta-analyses of data from more than 87,000 women, no association was found between connective tissue disease and silicone breast implants.^2,11 One study^11,23 noted no increase in autoantibodies in patients with undamaged silicone implants vs patients who experienced rupture.

Studies have also demonstrated that in children born to mothers with breast implants, the risk of rheumatic disease, esophageal disorders, congenital malformations, and death during the perinatal period is comparable with that in controls.³⁷ Another study, examining breastfeeding in women with silicone breast implants, showed no significant difference in silicon levels (used as a proxy for silicone) in breast milk compared with controls without implants; silicon levels were found to be significantly higher in cow’s milk and store-bought formulas.³⁸

BREAST IMPLANT-ASSOCIATED ANAPLASTIC LARGE-CELL LYMPHOMA

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma that develops in tissue adjacent to breast implants. It typically presents as breast swelling 2 to 38 years (mean of 8 years) after implant insertion.^39,40 The swelling may be secondary to periprosthetic seroma formation or, more rarely, palpable disease in the axilla. Patients occasionally complain of pain and, rarely, constitutional symptoms.²⁰ BIA-ALCL is not a disease of the surrounding breast tissue, but rather of the fibrous periprosthetic capsule.²¹

Of note, there is no documented case involving smooth implants,^41–43 but it may be related to fifth-generation textured implants.⁶ At present, it is not possible to definitively state which implant is associated with this condition; hence, more data are needed, and this association is currently under study.

The absolute risk of BIA-ALCL was reported in a Dutch study³⁹ as 1 in 35,000 by age 50, 1 in 12,000 by age 70, and 1 in 7,000 by age 75, with a number needed to harm of 6,920. Overall lifetime risk was estimated at 1 in 30,000 for women with textured implants in a 2015 US study.⁴⁰ In comparison, breast cancer risk is about 1 in 8 women. There is no apparent predilection for patients who underwent cosmetic augmentation vs reconstruction, or who received silicone vs saline implants.

The diagnosis is confirmed by ultrasonographically guided fine-needle aspiration of seroma fluid and subsequent immunohistochemical testing for CD30-positive and ALK-negative T lymphocytes. Other than positron-emission tomography for staging after diagnosis confirmation, imaging is ineffective. Expert opinion does not recommend routine screening unless the aforementioned symptoms arise.

Treatment involves implant removal and total capsulectomy, with samples sent for pathology study with cytokeratin staining.¹² Of note, in all cases of BIA-ALCL in which the disease was limited to the circumscribed scar tissue of the breast capsule, complete surgical excision has proved curative, whereas incomplete capsulectomy portends a greater risk of recurrence and decreased survival.⁴⁴

In cases of advanced or recurrent ALCL, diagnosed late or inappropriately, the National Comprehensive Cancer Network recommends a multidisciplinary approach involving adjuvant chemotherapy and radiation.⁴⁴ Anecdotally, at our institution, we have recently treated several cases of advanced ALCL presenting with invasive chest wall masses with extirpative surgery and subsequent reconstruction with the assistance of our thoracic surgery colleagues, as well as the aforementioned multidisciplinary approach using adjuvant therapy.

The mechanism of this malignancy is currently under investigation, but the current theory implicates an exaggerated lymphoproliferative response to bacterial contamination of the capsule superimposed upon genetic factors in susceptible patients.^42,43

National societies advise plastic surgeons to discuss the risk of BIA-ALCL with all patients at the time of breast augmentation consultation and to report all confirmed cases to the PROFILE registry (Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology).⁴⁵

ARE PATIENTS HAPPIER AFTERWARD?

Studies have shown that after undergoing breast augmentation surgery, patients note improvement in body image, and satisfaction rates range from 85% to 95% with respect to self-confidence and body image.⁴⁶ An evaluation of patient responses on the validated BREAST-Q Augmentation Questionnaire showed the following satisfaction rates: breasts 83%, psychosocial well-being 88%, and sexual functioning 81%.¹⁵

Although epidemiologic studies have reported higher suicide rates in women with cosmetic breast implants, this likely stems from preoperative psychological factors and underscores the role of psychiatric referral in patients with a mental health history or in those whom the surgeon deems it necessary.⁴⁶

Several high-quality studies have demonstrated that quality of life and psychosocial functioning (including depression) markedly improve after breast augmentation surgery.⁴⁷ Among a cohort of Norwegian patients, breast implant surgery resulted in improved motivation to perform daily activities, as well as improved quality of life from both a psychosocial and aesthetic perspective.⁴⁸ Interestingly, a recent study reported that patients who underwent breast implant surgery alone reported greater satisfaction and psychosocial quality of life than patients who underwent combination breast augmentation and mastopexy (breast-lifting) surgery.⁴⁹

Additional data are needed to refine our understanding of the complex interplay between psychosocial factors before and after surgery in patients seeking and undergoing breast augmentation procedures.

At present, 300,000 US women undergo breast augmentation surgery each year,¹ making this the second most common aesthetic procedure in women (after liposuction),^2–4 and making it extremely likely that clinicians will encounter women who have breast implants. In addition, approximately 110,000 women undergo breast reconstructive surgery after mastectomy, of whom more than 88,000 (81%) receive implants (2016 data).⁵

This review discusses the evolution of breast implants, their complications, and key considerations with regard to aesthetic and reconstructive breast surgery, as the principles are similar.

EVOLUTION OF IMPLANTS

Reports of breast augmentation surgery, also known as augmentation mammoplasty, date back to 1895, when a fatty tumor (lipoma) was successfully transplanted from a patient’s back to a breast defect in a mastectomy patient.^2,3,6,7 In the 1930s, implantation of a glass ball into a patient’s breast marked the first implant-based breast augmentation.⁶ By 1954, attempts at breast augmentation using local dermal-fat flaps, adipose tissue, and even omentum were described.

Alloplastic materials gained popularity throughout the 1950s and 1960s and included polyurethane, polytetrafluoroethylene (Teflon), and other synthetics. Adverse reactions associated with alloplastic materials were plentiful: local tissue reactions, distortion of the breast mound, increased firmness, and discomfort all contributed to the eventual discontinuation of their use. The history of alloplastic breast augmentation also included epoxy resin, shellac, beeswax, paraffin, rubber, petroleum jelly, and liquefied silicone. Outcomes were not good, and many patients ultimately needed mastectomy.⁷

The first modern breast prosthesis was developed in 1961, and since then, implant composition and design have evolved significantly.⁸

From silicone to saline, and back again

The first silicone gel implants, introduced in the early 1960s,^8–19 had high complication rates—some centers reported an incidence of capsular contracture of up to 70%.^8,11 This is a foreign body reaction in which pathologic scar tissue encases the implant, causing it to distort, appear misshapen, harden, and even become painful.¹¹ Attempts to minimize this reaction led to later generations of silicone implants with polyurethane shells.¹²

Inflatable implants filled with sterile saline solution were originally developed in France in 1965. Unlike silicone implants, saline implants have undergone minimal changes since their inception, and grew in popularity during the 1970s in view of the high rates of capsular contracture with silicone implants.⁸ However, saline implants have their own problems, and as they became increasingly popular, deflation and the unnatural feel of saline sparked a renewed interest in silicone gel.

By the late 1980s, the thinner-shelled generation of silicone implants displayed its own frustrating complications including implant rupture, capsular contracture, infection, and possible systemic and disseminated granulomatous disease. From 1992 to 2006, the US Food and Drug Administration (FDA) placed a moratorium on silicone implants due to concerns about a possible link with autoimmune and connective tissue diseases and the possible carcinogenic nature of silicone.

While silicone implants were prohibited in the United States, development continued abroad, and eventually the moratorium was lifted after several meta-analyses failed to reveal any link regarding the aforementioned concerns.¹³

Today, silicone gel implants dominate the world market.¹⁴ In the United States, approximately 60% of implants contain silicone gel filler, and trends are similar in Europe.⁷

Table 1 summarizes the evolution of silicone breast implants over the last 50 years.^2,6,11,12Table 2 lists the advantages and disadvantages of silicone and saline breast implants.^2,6,8,15

CURRENT IMPLANT OPTIONS

Currently, 3 companies (Allergan, Mentor, Sientra) manufacture and distribute breast implants and implant-associated products such as tissue expanders and sizers in the US market.⁶

Another company, Motiva, makes an implant that is available in Europe, Asia, and Australia, and the device is currently undergoing a 10-year clinical trial in the United States that began recruiting patients in 16 centers in April 2018.¹⁶ Pending final approval, the Cleveland Clinic Department of Plastic Surgery may be among the centers involved in the clinical trial of the Motiva implant. Innovations in the Motiva implant include a high-performance shell that maintains consistent strength and includes a proprietary barrier layer, improved silicone gel filler, 3-D imprinted surface texturing, and an implant shape that adapts with vertical and horizontal movement. It also contains radio-frequency identification transponders that can transmit data about the implant wirelessly.^17–19

Developed in the 1980s, texturing of the implant surface disrupts capsule formation around the prosthesis. Additionally, texturing stabilizes an anatomically shaped (teardrop) implant within the breast pocket, reducing malrotation.^20,21

The first textured implants were covered with polyurethane foam, but they were ultimately withdrawn from the US market because of concern for in vivo degradation to carcinogenic compounds. The focus subsequently turned to texturing implant shells by mechanically creating pores of different sizes. Smooth implants, by contrast, are manufactured by repeatedly dipping the implant shell into liquid silicone.²

The capsular contraction rate has been shown to be lower with textured silicone than with smooth silicone (number needed to treat = 7–9), and evidence suggests a lower risk of needing a secondary procedure.²¹

Form-stable vs fluid-form

Silicone is a polymer. The physical properties of polymers vary greatly and depend on the length of the individual chains and the degree to which those chains are cross-linked. Liquid silicone contains short chains and sparse cross-linking, resulting in an oily compound well suited for lubrication. Silicone gel contains longer chains and more cross-linking and is therefore more viscous.

In “form-stable” implants, the silicone interior has sufficient chain length and cross-linking to retain the designed shape even at rest,² but they require slightly larger incisions.⁷ “Fluid-form” refers to an implant with silicone filler with shorter chain length, less cross-linking, and more fluidity.⁶

Shell

As with silicone fillers, the properties of silicone implant shells also depend on chain length and cross-linking within the polymer. Silicone elastomer shells (Table 1) contain extensively cross-linked chains that impart a flexible yet rubbery character. Silicone elastomers can also be found in facial implants and tissue expanders.²

Implant shape (round vs anatomic)

The shape of an implant is determined by the gel distribution inside of it. To understand gel distribution and implant shape, one must understand the gel-shell ratio. This ratio increases as cohesivity of the filler increases, and it represents increased bonding of the gel filler to the shell and a preserved implant shape at rest.

The gel-shell ratio varies among manufacturers, and a less-viscous filler may be more prone to rippling or loss of upper pole fullness in some patients. For this reason, careful analysis, patient and implant selection, and discussion of complications remain paramount.²

No anatomically shaped implant is manufactured with a smooth shell, but rather with a textured shell that resists malrotation.^6,15 However, in the United States, 95% of patients receive round implants.¹⁶

PATIENT ASSESSMENT

Before breast augmentation surgery, the surgeon assesses a number of factors—physical and psychosocial—and helps the patient choose a type and size of implant. The surgeon and patient also plan where the implants will be placed—ie, above or beneath the chest wall muscle—and where the incisions will be made. Every decision is made in close consultation with the patient, taking into account the patient’s desires and expectations, as well as what the patient’s anatomy allows. An integral component of this shared decision-making process is a discussion of the possible complications, and often photographs to better illustrate what to expect postoperatively. 

Psychosocial factors

One must consider the patient’s psychology, motivations for surgery, and emotional stability. Here, we look for underlying body dysmorphic disorder; excessive or unusual encouragement to undergo the procedure by a spouse, friends, or others; a history of other aesthetic procedures; unrealistic expectations; and other factors influencing the desire to undergo this surgery.

Choosing an implant

Implant selection must take into account the patient’s height, weight,⁷ and overall body morphology: taller patients and those with wider hips or shoulders usually require larger implants. A reliable method for determining the appropriate implant must include the current breast shape, dimensions, volume, skin elasticity, soft-tissue thickness, and overall body habitus. Ultimately, the most important considerations include breast base diameter, implant volume,²⁰ and soft-tissue envelope.

Preoperative sizing can involve placing sample implants within a brassiere so that the patient can preview possible outcomes. This method is particularly effective in minimizing dissatisfaction because it shares ownership of the decision-making process.¹⁵

A computerized implant selection program available in Europe suggests a “best-fit” implant based on a clinician’s measurements.⁷

Traditionally, plastic surgeons place breast implants either beneath the pectoralis major muscle (submuscular placement) or over the pectoralis⁸ but beneath the glandular breast parenchyma (subglandular placement) (Figure 2).⁷

Advantages of submuscular placement are a smoother transition of the upper breast pole from the chest wall and less rippling visible through the skin, due to the additional muscular coverage of the implant. Another advantage is that capsular contraction rates are lower with submuscular placement, likely due to possible contamination of implants by lactiferous ductal microbes when accessing the subglandular plane.^14,20 Disadvantages are pronounced discomfort after surgery and animation deformities with muscle contraction, particularly in young, highly active patients.

A popular modification of submuscular placement involves creating a surgical dissection plane between the subglandular tissue and the pectoralis major fascia. This “dual­­plane” approach allows the parenchyma to retract superiorly and reduce breast ptosis.⁷

Incisions

Table 3 highlights important considerations with regard to incision location.^15,20,21

ANTIBIOTICS

Many surgeons give a single prophylactic dose of antibiotic before surgery, a practice that some studies have shown to be effective in reducing the risk of infection.¹⁵ However, the benefit of routine postoperative use of antibiotics remains unsubstantiated¹⁵: postoperative antibiotic use does not appear to protect against infection, capsular contracture, or overall complications in primary or secondary breast augmentation surgery.²⁰

PERIOPERATIVE PERIOD

At our institution, breast augmentation surgery is an ambulatory procedure—the patient goes home the same day unless circumstances such as pain control warrant admission. This is, however, according to surgeon preference, and differs on a case-by-case basis. General anesthesia is the standard of care.¹⁵

POSTOPERATIVE PERIOD

In the immediate postoperative period, patients are instructed to wear a surgical bra for up to 6 weeks to allow stable scarring. Early mobilization is encouraged.^7,15 Depending on the patient’s situation, recovery, and healing, she may be out of work for about 1 week, sometimes more, sometimes less. 

Additional instructions are surgeon-specific. However, the patient is instructed to avoid bathing, swimming, immersion in water, and wearing underwire brassieres that could impair healing of an inferior incision; instead, patients are often instructed to wear a surgical bra provided on the day of surgery until cleared in the clinic.

Showering is allowed the next day or the second day after surgery, and of course there is no driving while on narcotics. Additionally, patients are counseled extensively regarding hematoma formation and the signs and symptoms of infection.

Patients are typically seen in clinic 1 week after surgery.

The cost of surgery may be $5,000 to $6,000 but can vary significantly from center to center depending on who the patient sees and where, and whether the patient presents for breast reconstruction after cancer or repair of congenital anomalies, or in certain cases of transgender surgery. The patient is typically responsible for the fee, but again this depends on the patient, indications, and particular insurance concerns.

IMPLANT LONGEVITY AND RUPTURE

In the United States, implant rupture rates range from 1.1% to 17.7% at 6 to 10 years after primary augmentation, 2.9% to 14.7% after revision augmentation, 1.5% to 35.4% after primary breast reconstruction, and 0% to 19.6% after revision reconstruction.¹¹

Unfortunately, the existence of multiple implant manufacturers, numerous implant generations, and poorly standardized screening protocols and reporting systems make the true rate of implant rupture difficult to assess without definitive imaging or implant retrieval.¹¹

Damage from surgical instrumentation during implantation is the most common cause of silicone breast implant rupture (50% to 64% of cases).²² Other causes include underfilling and fold flaw from capsular contracture.

Leakage of silicone gel filler may be confined to the periprosthetic capsule (intracapsular rupture) or extend beyond and into the breast parenchyma (extracapsular rupture). One study reported that only 10% of intracapsular ruptures progressed extracapsularly, while 84% of patients with extracapsular involvement remained stable for up to 2 years,²³ indicating that intracapsular rupture may not portend worsening disease.¹¹

Implant rupture occurs silently in most cases, with no clinically detectable signs or symptoms. In other cases, patients may present with alterations in breast shape and size, sudden asymmetry, firmness, pronounced capsular contracture, contour irregularity, or pain.

Aside from physical examination, comprehensive diagnostic testing includes imaging—ultrasonography, mammography, computed tomography, and magnetic resonance imaging (MRI). Of these, MRI is the method of choice, with sensitivity and specificity exceeding 90% for detecting implant rupture.¹¹ Classic findings on MRI include the “linguine” sign from a deflating implant shell, or the teardrop sign from implant sagging. Classic findings on ultrasonography include the “snowstorm” sign of extracapsular rupture and the “stepladder” sign of intracapsular rupture.

Mammography effectively detects free silicone in breast tissue with extracapsular rupture (25% of ruptures according to some studies)²³; however, it cannot detect rupture within the implant capsule. As an aside, submuscular implant placement may interfere less with screening mammography than subglandular implants do.^14,24

Current FDA recommendations to detect implant rupture encourage women with silicone breast implants to undergo screening 3 years after implantation and then every 2 years thereafter; no long-term monitoring is suggested for saline implants.¹⁵ Many plastic surgeons evaluate silicone breast implant patients every 1 to 2 years for contracture and rupture.⁸ Of note, capsular contracture impairs the effectiveness of ultrasonography and may require MRI confirmation.¹¹

If implant rupture is confirmed, the current recommendation is to remove the implant and the capsule. Another implant may be placed depending on the patient’s preference. Rigorous washout remains a key feature of any surgical intervention for ruptured breast implants; however, in the event of extracapsular rupture, resection of silicone granulomas may also be required.¹¹

Reoperation rates for primary breast augmentation surgery approach 20% and are even higher for secondary augmentation over a patient’s lifetime—the highest rate of all aesthetic procedures.^7,14

Capsular contracture is the most common complication of breast augmentation,²⁵ typically presenting within the first postoperative year,^26,27 and the risk increases over time.²⁸ It occurs with both silicone and saline breast implants.

In some studies, the incidence exceeded 4% in the first 2 years after surgery,²⁹ and nearly 50% by 10 years.³⁰ Other studies found rates of 0% to 20% over 13 years.²⁰

The etiology is not well understood and is presumed to be multifactorial, with proposed mechanisms and factors that include bacterial contamination, surface texturing, the implant pocket selected, the incision type, drain placement, antibiotic use, and smoking.²⁵

A meta-analysis from 17,000 implants found that the risk of capsular contracture was significantly higher when an implant was placed in a subglandular pocket than in a submuscular pocket,^22,26 and that although texturing decreased capsular contracture compared with smooth implants, the effect was modest when a textured or smooth implant was placed in a submuscular location.²⁸ With regard to incision location, studies have reported that the incidence of capsular contracture is highest with transaxillary and periareolar incisions, and lowest with inframammary incisions.^20,21

The leading theory is that contamination of the implant (primarily from the mammary ducts) results in biofilm formation. Subclinical hematoma surrounding the implant may also provide key bacterial nutrients.²⁰

Textured implants induce a greater inflammatory response in the capsular tissue, resulting in a thicker capsule; however, contracture rates remain lower with textured than with smooth implants.^14,31 Interestingly, lower rates of capsular contracture have been observed with later-generation, cohesive-gel, form-stable implants than with those of earlier generations.¹²

Although more research is needed, silicone implants appear to confer a higher risk of capsular contracture than saline implants.^14,20

Irrigating the breast pocket intraoperatively with triple antibiotic solution (bacitracin, cefazolin, and gentamicin) before placing the implant may decrease the capsular contracture rate.^15,20

Treatments for capsular contracture include pocket modifications such as capsulotomy (making releasing, relaxing incisions in the scar capsule encasing the implant), capsulectomy (removing portions of or the entire capsule), and replacing the implant in the other pocket (ie, if the original implant was subglandular, the replacement is placed in the submuscular pocket). Patients who have contractures that fail to respond to these treatments may ultimately benefit from implant removal and autologous reconstruction (autoaugmentation) rather than implant replacement.^32,33

ADDITIONAL COMPLICATIONS

Other complications include infection, malposition, rippling, seroma, hematoma, and sensory alterations.

Irrigation during the implantation procedure with a triple antibiotic solution consisting of bacitracin, gentamycin, and cephalexin in normal saline decreases infection and seroma rates.^15,20,34

Some surgeons also choose to irrigate the pocket with a betadine solution, or to cleanse the skin with betadine and place sterile towels and redrape before inserting the implant. Additionally, many prefer using a sterile device much like a pastry funnel called a Keller funnel to insert the implant into the breast pocket.³⁵

Infection is less common with cosmetic augmentations than with implant-based breast reconstruction, likely because of healthier, well-vascularized tissue in patients undergoing cosmetic surgery than in those undergoing mastectomy.¹⁴

Seroma is thought to be a consequence of texturing, and more so with macro- vs microtexturing. Though poorly understood, an association between texturing and double capsules has also been reported.^12,20

After primary breast augmentation, 10-year follow-up rates of capsular contracture, seroma, rippling, and malposition vary across the 3 major silicone implant manufacturers.¹² Hematoma and infection occur in less than 1% of primary augmentation patients.¹⁵

Malposition of the implant over time is less frequent with textured implants because of the higher coefficient of friction compared with smooth implants^.6,8,15

Visible skin rippling may be a consequence of texturing and also of thin body habitus, eg, in patients with a body mass index less than 18.5 kg/m². If the soft-tissue layer of the breast is thin, the natural rippling of smooth saline implant shells are more likely to show when placed in the subglandular pocket. Form-stable implants, by contrast, resist rippling.^12,15

Large implants and extensive lateral dissection can cause alterations in nipple sensation and sensory loss within lower breast pole skin. Axillary incisions may traumatize or damage the intercostobrachial nerve, resulting in upper inner arm sensory aberrations.

Ultimately, the 10-year incidence of secondary surgery ranges from 0% to 36% and the 10-year incidence of capsular contracture ranges from 11% to 19%.¹⁵ Additional cosmetic complaints after augmentation with implants include enlargement of the areola and engorgement of breast veins.¹⁴

BREAST CANCER AND DETECTION

Patients with or without implants do not seem to differ with regard to breast cancer stage upon detection, tumor burden, recurrence, or survival. However, more patients with implants may present with palpable masses, invasive tumors, axillary metastasis, and falsely negative mammograms.

Breast implants may actually facilitate cancer detection on physical examination by providing a more dense or stable surface upon which to palpate the breast tissue. Although they do not necessarily impair mastectomy or breast reconstruction, they may result in an increased rate of revision surgery after breast conservation therapy.^24,36 Mammography remains the standard of care for radiologic diagnosis but can be further supported by MRI and ultrasonography if necessary in patients with implants.

Although concerns persist, multiple studies have demonstrated the safety of fourth- and fifth-generation silicone breast implants with regard to autoimmune disease.⁷

In various clinical studies in mastectomy patients who underwent breast reconstruction with either silicone implants or autologous tissue, no difference was found with regard to the incidence of autoimmune diseases.² Additionally, in meta-analyses of data from more than 87,000 women, no association was found between connective tissue disease and silicone breast implants.^2,11 One study^11,23 noted no increase in autoantibodies in patients with undamaged silicone implants vs patients who experienced rupture.

Studies have also demonstrated that in children born to mothers with breast implants, the risk of rheumatic disease, esophageal disorders, congenital malformations, and death during the perinatal period is comparable with that in controls.³⁷ Another study, examining breastfeeding in women with silicone breast implants, showed no significant difference in silicon levels (used as a proxy for silicone) in breast milk compared with controls without implants; silicon levels were found to be significantly higher in cow’s milk and store-bought formulas.³⁸

BREAST IMPLANT-ASSOCIATED ANAPLASTIC LARGE-CELL LYMPHOMA

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma that develops in tissue adjacent to breast implants. It typically presents as breast swelling 2 to 38 years (mean of 8 years) after implant insertion.^39,40 The swelling may be secondary to periprosthetic seroma formation or, more rarely, palpable disease in the axilla. Patients occasionally complain of pain and, rarely, constitutional symptoms.²⁰ BIA-ALCL is not a disease of the surrounding breast tissue, but rather of the fibrous periprosthetic capsule.²¹

Of note, there is no documented case involving smooth implants,^41–43 but it may be related to fifth-generation textured implants.⁶ At present, it is not possible to definitively state which implant is associated with this condition; hence, more data are needed, and this association is currently under study.

The absolute risk of BIA-ALCL was reported in a Dutch study³⁹ as 1 in 35,000 by age 50, 1 in 12,000 by age 70, and 1 in 7,000 by age 75, with a number needed to harm of 6,920. Overall lifetime risk was estimated at 1 in 30,000 for women with textured implants in a 2015 US study.⁴⁰ In comparison, breast cancer risk is about 1 in 8 women. There is no apparent predilection for patients who underwent cosmetic augmentation vs reconstruction, or who received silicone vs saline implants.

The diagnosis is confirmed by ultrasonographically guided fine-needle aspiration of seroma fluid and subsequent immunohistochemical testing for CD30-positive and ALK-negative T lymphocytes. Other than positron-emission tomography for staging after diagnosis confirmation, imaging is ineffective. Expert opinion does not recommend routine screening unless the aforementioned symptoms arise.

Treatment involves implant removal and total capsulectomy, with samples sent for pathology study with cytokeratin staining.¹² Of note, in all cases of BIA-ALCL in which the disease was limited to the circumscribed scar tissue of the breast capsule, complete surgical excision has proved curative, whereas incomplete capsulectomy portends a greater risk of recurrence and decreased survival.⁴⁴

In cases of advanced or recurrent ALCL, diagnosed late or inappropriately, the National Comprehensive Cancer Network recommends a multidisciplinary approach involving adjuvant chemotherapy and radiation.⁴⁴ Anecdotally, at our institution, we have recently treated several cases of advanced ALCL presenting with invasive chest wall masses with extirpative surgery and subsequent reconstruction with the assistance of our thoracic surgery colleagues, as well as the aforementioned multidisciplinary approach using adjuvant therapy.

The mechanism of this malignancy is currently under investigation, but the current theory implicates an exaggerated lymphoproliferative response to bacterial contamination of the capsule superimposed upon genetic factors in susceptible patients.^42,43

National societies advise plastic surgeons to discuss the risk of BIA-ALCL with all patients at the time of breast augmentation consultation and to report all confirmed cases to the PROFILE registry (Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology).⁴⁵

ARE PATIENTS HAPPIER AFTERWARD?

Studies have shown that after undergoing breast augmentation surgery, patients note improvement in body image, and satisfaction rates range from 85% to 95% with respect to self-confidence and body image.⁴⁶ An evaluation of patient responses on the validated BREAST-Q Augmentation Questionnaire showed the following satisfaction rates: breasts 83%, psychosocial well-being 88%, and sexual functioning 81%.¹⁵

Although epidemiologic studies have reported higher suicide rates in women with cosmetic breast implants, this likely stems from preoperative psychological factors and underscores the role of psychiatric referral in patients with a mental health history or in those whom the surgeon deems it necessary.⁴⁶

Several high-quality studies have demonstrated that quality of life and psychosocial functioning (including depression) markedly improve after breast augmentation surgery.⁴⁷ Among a cohort of Norwegian patients, breast implant surgery resulted in improved motivation to perform daily activities, as well as improved quality of life from both a psychosocial and aesthetic perspective.⁴⁸ Interestingly, a recent study reported that patients who underwent breast implant surgery alone reported greater satisfaction and psychosocial quality of life than patients who underwent combination breast augmentation and mastopexy (breast-lifting) surgery.⁴⁹

Additional data are needed to refine our understanding of the complex interplay between psychosocial factors before and after surgery in patients seeking and undergoing breast augmentation procedures.

At present, 300,000 US women undergo breast augmentation surgery each year,¹ making this the second most common aesthetic procedure in women (after liposuction),^2–4 and making it extremely likely that clinicians will encounter women who have breast implants. In addition, approximately 110,000 women undergo breast reconstructive surgery after mastectomy, of whom more than 88,000 (81%) receive implants (2016 data).⁵

This review discusses the evolution of breast implants, their complications, and key considerations with regard to aesthetic and reconstructive breast surgery, as the principles are similar.

EVOLUTION OF IMPLANTS

Reports of breast augmentation surgery, also known as augmentation mammoplasty, date back to 1895, when a fatty tumor (lipoma) was successfully transplanted from a patient’s back to a breast defect in a mastectomy patient.^2,3,6,7 In the 1930s, implantation of a glass ball into a patient’s breast marked the first implant-based breast augmentation.⁶ By 1954, attempts at breast augmentation using local dermal-fat flaps, adipose tissue, and even omentum were described.

Alloplastic materials gained popularity throughout the 1950s and 1960s and included polyurethane, polytetrafluoroethylene (Teflon), and other synthetics. Adverse reactions associated with alloplastic materials were plentiful: local tissue reactions, distortion of the breast mound, increased firmness, and discomfort all contributed to the eventual discontinuation of their use. The history of alloplastic breast augmentation also included epoxy resin, shellac, beeswax, paraffin, rubber, petroleum jelly, and liquefied silicone. Outcomes were not good, and many patients ultimately needed mastectomy.⁷

The first modern breast prosthesis was developed in 1961, and since then, implant composition and design have evolved significantly.⁸

From silicone to saline, and back again

The first silicone gel implants, introduced in the early 1960s,^8–19 had high complication rates—some centers reported an incidence of capsular contracture of up to 70%.^8,11 This is a foreign body reaction in which pathologic scar tissue encases the implant, causing it to distort, appear misshapen, harden, and even become painful.¹¹ Attempts to minimize this reaction led to later generations of silicone implants with polyurethane shells.¹²

Inflatable implants filled with sterile saline solution were originally developed in France in 1965. Unlike silicone implants, saline implants have undergone minimal changes since their inception, and grew in popularity during the 1970s in view of the high rates of capsular contracture with silicone implants.⁸ However, saline implants have their own problems, and as they became increasingly popular, deflation and the unnatural feel of saline sparked a renewed interest in silicone gel.

By the late 1980s, the thinner-shelled generation of silicone implants displayed its own frustrating complications including implant rupture, capsular contracture, infection, and possible systemic and disseminated granulomatous disease. From 1992 to 2006, the US Food and Drug Administration (FDA) placed a moratorium on silicone implants due to concerns about a possible link with autoimmune and connective tissue diseases and the possible carcinogenic nature of silicone.

While silicone implants were prohibited in the United States, development continued abroad, and eventually the moratorium was lifted after several meta-analyses failed to reveal any link regarding the aforementioned concerns.¹³

Today, silicone gel implants dominate the world market.¹⁴ In the United States, approximately 60% of implants contain silicone gel filler, and trends are similar in Europe.⁷

Table 1 summarizes the evolution of silicone breast implants over the last 50 years.^2,6,11,12Table 2 lists the advantages and disadvantages of silicone and saline breast implants.^2,6,8,15

CURRENT IMPLANT OPTIONS

Currently, 3 companies (Allergan, Mentor, Sientra) manufacture and distribute breast implants and implant-associated products such as tissue expanders and sizers in the US market.⁶

Another company, Motiva, makes an implant that is available in Europe, Asia, and Australia, and the device is currently undergoing a 10-year clinical trial in the United States that began recruiting patients in 16 centers in April 2018.¹⁶ Pending final approval, the Cleveland Clinic Department of Plastic Surgery may be among the centers involved in the clinical trial of the Motiva implant. Innovations in the Motiva implant include a high-performance shell that maintains consistent strength and includes a proprietary barrier layer, improved silicone gel filler, 3-D imprinted surface texturing, and an implant shape that adapts with vertical and horizontal movement. It also contains radio-frequency identification transponders that can transmit data about the implant wirelessly.^17–19

Developed in the 1980s, texturing of the implant surface disrupts capsule formation around the prosthesis. Additionally, texturing stabilizes an anatomically shaped (teardrop) implant within the breast pocket, reducing malrotation.^20,21

The first textured implants were covered with polyurethane foam, but they were ultimately withdrawn from the US market because of concern for in vivo degradation to carcinogenic compounds. The focus subsequently turned to texturing implant shells by mechanically creating pores of different sizes. Smooth implants, by contrast, are manufactured by repeatedly dipping the implant shell into liquid silicone.²

The capsular contraction rate has been shown to be lower with textured silicone than with smooth silicone (number needed to treat = 7–9), and evidence suggests a lower risk of needing a secondary procedure.²¹

Form-stable vs fluid-form

Silicone is a polymer. The physical properties of polymers vary greatly and depend on the length of the individual chains and the degree to which those chains are cross-linked. Liquid silicone contains short chains and sparse cross-linking, resulting in an oily compound well suited for lubrication. Silicone gel contains longer chains and more cross-linking and is therefore more viscous.

In “form-stable” implants, the silicone interior has sufficient chain length and cross-linking to retain the designed shape even at rest,² but they require slightly larger incisions.⁷ “Fluid-form” refers to an implant with silicone filler with shorter chain length, less cross-linking, and more fluidity.⁶

Shell

As with silicone fillers, the properties of silicone implant shells also depend on chain length and cross-linking within the polymer. Silicone elastomer shells (Table 1) contain extensively cross-linked chains that impart a flexible yet rubbery character. Silicone elastomers can also be found in facial implants and tissue expanders.²

Implant shape (round vs anatomic)

The shape of an implant is determined by the gel distribution inside of it. To understand gel distribution and implant shape, one must understand the gel-shell ratio. This ratio increases as cohesivity of the filler increases, and it represents increased bonding of the gel filler to the shell and a preserved implant shape at rest.

The gel-shell ratio varies among manufacturers, and a less-viscous filler may be more prone to rippling or loss of upper pole fullness in some patients. For this reason, careful analysis, patient and implant selection, and discussion of complications remain paramount.²

No anatomically shaped implant is manufactured with a smooth shell, but rather with a textured shell that resists malrotation.^6,15 However, in the United States, 95% of patients receive round implants.¹⁶

PATIENT ASSESSMENT

Before breast augmentation surgery, the surgeon assesses a number of factors—physical and psychosocial—and helps the patient choose a type and size of implant. The surgeon and patient also plan where the implants will be placed—ie, above or beneath the chest wall muscle—and where the incisions will be made. Every decision is made in close consultation with the patient, taking into account the patient’s desires and expectations, as well as what the patient’s anatomy allows. An integral component of this shared decision-making process is a discussion of the possible complications, and often photographs to better illustrate what to expect postoperatively. 

Psychosocial factors

One must consider the patient’s psychology, motivations for surgery, and emotional stability. Here, we look for underlying body dysmorphic disorder; excessive or unusual encouragement to undergo the procedure by a spouse, friends, or others; a history of other aesthetic procedures; unrealistic expectations; and other factors influencing the desire to undergo this surgery.

Choosing an implant

Implant selection must take into account the patient’s height, weight,⁷ and overall body morphology: taller patients and those with wider hips or shoulders usually require larger implants. A reliable method for determining the appropriate implant must include the current breast shape, dimensions, volume, skin elasticity, soft-tissue thickness, and overall body habitus. Ultimately, the most important considerations include breast base diameter, implant volume,²⁰ and soft-tissue envelope.

Preoperative sizing can involve placing sample implants within a brassiere so that the patient can preview possible outcomes. This method is particularly effective in minimizing dissatisfaction because it shares ownership of the decision-making process.¹⁵

A computerized implant selection program available in Europe suggests a “best-fit” implant based on a clinician’s measurements.⁷

Traditionally, plastic surgeons place breast implants either beneath the pectoralis major muscle (submuscular placement) or over the pectoralis⁸ but beneath the glandular breast parenchyma (subglandular placement) (Figure 2).⁷

Advantages of submuscular placement are a smoother transition of the upper breast pole from the chest wall and less rippling visible through the skin, due to the additional muscular coverage of the implant. Another advantage is that capsular contraction rates are lower with submuscular placement, likely due to possible contamination of implants by lactiferous ductal microbes when accessing the subglandular plane.^14,20 Disadvantages are pronounced discomfort after surgery and animation deformities with muscle contraction, particularly in young, highly active patients.

A popular modification of submuscular placement involves creating a surgical dissection plane between the subglandular tissue and the pectoralis major fascia. This “dual­­plane” approach allows the parenchyma to retract superiorly and reduce breast ptosis.⁷

Incisions

Table 3 highlights important considerations with regard to incision location.^15,20,21

ANTIBIOTICS

Many surgeons give a single prophylactic dose of antibiotic before surgery, a practice that some studies have shown to be effective in reducing the risk of infection.¹⁵ However, the benefit of routine postoperative use of antibiotics remains unsubstantiated¹⁵: postoperative antibiotic use does not appear to protect against infection, capsular contracture, or overall complications in primary or secondary breast augmentation surgery.²⁰

PERIOPERATIVE PERIOD

At our institution, breast augmentation surgery is an ambulatory procedure—the patient goes home the same day unless circumstances such as pain control warrant admission. This is, however, according to surgeon preference, and differs on a case-by-case basis. General anesthesia is the standard of care.¹⁵

POSTOPERATIVE PERIOD

In the immediate postoperative period, patients are instructed to wear a surgical bra for up to 6 weeks to allow stable scarring. Early mobilization is encouraged.^7,15 Depending on the patient’s situation, recovery, and healing, she may be out of work for about 1 week, sometimes more, sometimes less. 

Additional instructions are surgeon-specific. However, the patient is instructed to avoid bathing, swimming, immersion in water, and wearing underwire brassieres that could impair healing of an inferior incision; instead, patients are often instructed to wear a surgical bra provided on the day of surgery until cleared in the clinic.

Showering is allowed the next day or the second day after surgery, and of course there is no driving while on narcotics. Additionally, patients are counseled extensively regarding hematoma formation and the signs and symptoms of infection.

Patients are typically seen in clinic 1 week after surgery.

The cost of surgery may be $5,000 to $6,000 but can vary significantly from center to center depending on who the patient sees and where, and whether the patient presents for breast reconstruction after cancer or repair of congenital anomalies, or in certain cases of transgender surgery. The patient is typically responsible for the fee, but again this depends on the patient, indications, and particular insurance concerns.

IMPLANT LONGEVITY AND RUPTURE

In the United States, implant rupture rates range from 1.1% to 17.7% at 6 to 10 years after primary augmentation, 2.9% to 14.7% after revision augmentation, 1.5% to 35.4% after primary breast reconstruction, and 0% to 19.6% after revision reconstruction.¹¹

Unfortunately, the existence of multiple implant manufacturers, numerous implant generations, and poorly standardized screening protocols and reporting systems make the true rate of implant rupture difficult to assess without definitive imaging or implant retrieval.¹¹

Damage from surgical instrumentation during implantation is the most common cause of silicone breast implant rupture (50% to 64% of cases).²² Other causes include underfilling and fold flaw from capsular contracture.

Leakage of silicone gel filler may be confined to the periprosthetic capsule (intracapsular rupture) or extend beyond and into the breast parenchyma (extracapsular rupture). One study reported that only 10% of intracapsular ruptures progressed extracapsularly, while 84% of patients with extracapsular involvement remained stable for up to 2 years,²³ indicating that intracapsular rupture may not portend worsening disease.¹¹

Implant rupture occurs silently in most cases, with no clinically detectable signs or symptoms. In other cases, patients may present with alterations in breast shape and size, sudden asymmetry, firmness, pronounced capsular contracture, contour irregularity, or pain.

Aside from physical examination, comprehensive diagnostic testing includes imaging—ultrasonography, mammography, computed tomography, and magnetic resonance imaging (MRI). Of these, MRI is the method of choice, with sensitivity and specificity exceeding 90% for detecting implant rupture.¹¹ Classic findings on MRI include the “linguine” sign from a deflating implant shell, or the teardrop sign from implant sagging. Classic findings on ultrasonography include the “snowstorm” sign of extracapsular rupture and the “stepladder” sign of intracapsular rupture.

Mammography effectively detects free silicone in breast tissue with extracapsular rupture (25% of ruptures according to some studies)²³; however, it cannot detect rupture within the implant capsule. As an aside, submuscular implant placement may interfere less with screening mammography than subglandular implants do.^14,24

Current FDA recommendations to detect implant rupture encourage women with silicone breast implants to undergo screening 3 years after implantation and then every 2 years thereafter; no long-term monitoring is suggested for saline implants.¹⁵ Many plastic surgeons evaluate silicone breast implant patients every 1 to 2 years for contracture and rupture.⁸ Of note, capsular contracture impairs the effectiveness of ultrasonography and may require MRI confirmation.¹¹

If implant rupture is confirmed, the current recommendation is to remove the implant and the capsule. Another implant may be placed depending on the patient’s preference. Rigorous washout remains a key feature of any surgical intervention for ruptured breast implants; however, in the event of extracapsular rupture, resection of silicone granulomas may also be required.¹¹

Reoperation rates for primary breast augmentation surgery approach 20% and are even higher for secondary augmentation over a patient’s lifetime—the highest rate of all aesthetic procedures.^7,14

Capsular contracture is the most common complication of breast augmentation,²⁵ typically presenting within the first postoperative year,^26,27 and the risk increases over time.²⁸ It occurs with both silicone and saline breast implants.

In some studies, the incidence exceeded 4% in the first 2 years after surgery,²⁹ and nearly 50% by 10 years.³⁰ Other studies found rates of 0% to 20% over 13 years.²⁰

The etiology is not well understood and is presumed to be multifactorial, with proposed mechanisms and factors that include bacterial contamination, surface texturing, the implant pocket selected, the incision type, drain placement, antibiotic use, and smoking.²⁵

A meta-analysis from 17,000 implants found that the risk of capsular contracture was significantly higher when an implant was placed in a subglandular pocket than in a submuscular pocket,^22,26 and that although texturing decreased capsular contracture compared with smooth implants, the effect was modest when a textured or smooth implant was placed in a submuscular location.²⁸ With regard to incision location, studies have reported that the incidence of capsular contracture is highest with transaxillary and periareolar incisions, and lowest with inframammary incisions.^20,21

The leading theory is that contamination of the implant (primarily from the mammary ducts) results in biofilm formation. Subclinical hematoma surrounding the implant may also provide key bacterial nutrients.²⁰

Textured implants induce a greater inflammatory response in the capsular tissue, resulting in a thicker capsule; however, contracture rates remain lower with textured than with smooth implants.^14,31 Interestingly, lower rates of capsular contracture have been observed with later-generation, cohesive-gel, form-stable implants than with those of earlier generations.¹²

Although more research is needed, silicone implants appear to confer a higher risk of capsular contracture than saline implants.^14,20

Irrigating the breast pocket intraoperatively with triple antibiotic solution (bacitracin, cefazolin, and gentamicin) before placing the implant may decrease the capsular contracture rate.^15,20

Treatments for capsular contracture include pocket modifications such as capsulotomy (making releasing, relaxing incisions in the scar capsule encasing the implant), capsulectomy (removing portions of or the entire capsule), and replacing the implant in the other pocket (ie, if the original implant was subglandular, the replacement is placed in the submuscular pocket). Patients who have contractures that fail to respond to these treatments may ultimately benefit from implant removal and autologous reconstruction (autoaugmentation) rather than implant replacement.^32,33

ADDITIONAL COMPLICATIONS

Other complications include infection, malposition, rippling, seroma, hematoma, and sensory alterations.

Irrigation during the implantation procedure with a triple antibiotic solution consisting of bacitracin, gentamycin, and cephalexin in normal saline decreases infection and seroma rates.^15,20,34

Some surgeons also choose to irrigate the pocket with a betadine solution, or to cleanse the skin with betadine and place sterile towels and redrape before inserting the implant. Additionally, many prefer using a sterile device much like a pastry funnel called a Keller funnel to insert the implant into the breast pocket.³⁵

Infection is less common with cosmetic augmentations than with implant-based breast reconstruction, likely because of healthier, well-vascularized tissue in patients undergoing cosmetic surgery than in those undergoing mastectomy.¹⁴

Seroma is thought to be a consequence of texturing, and more so with macro- vs microtexturing. Though poorly understood, an association between texturing and double capsules has also been reported.^12,20

After primary breast augmentation, 10-year follow-up rates of capsular contracture, seroma, rippling, and malposition vary across the 3 major silicone implant manufacturers.¹² Hematoma and infection occur in less than 1% of primary augmentation patients.¹⁵

Malposition of the implant over time is less frequent with textured implants because of the higher coefficient of friction compared with smooth implants^.6,8,15

Visible skin rippling may be a consequence of texturing and also of thin body habitus, eg, in patients with a body mass index less than 18.5 kg/m². If the soft-tissue layer of the breast is thin, the natural rippling of smooth saline implant shells are more likely to show when placed in the subglandular pocket. Form-stable implants, by contrast, resist rippling.^12,15

Large implants and extensive lateral dissection can cause alterations in nipple sensation and sensory loss within lower breast pole skin. Axillary incisions may traumatize or damage the intercostobrachial nerve, resulting in upper inner arm sensory aberrations.

Ultimately, the 10-year incidence of secondary surgery ranges from 0% to 36% and the 10-year incidence of capsular contracture ranges from 11% to 19%.¹⁵ Additional cosmetic complaints after augmentation with implants include enlargement of the areola and engorgement of breast veins.¹⁴

BREAST CANCER AND DETECTION

Patients with or without implants do not seem to differ with regard to breast cancer stage upon detection, tumor burden, recurrence, or survival. However, more patients with implants may present with palpable masses, invasive tumors, axillary metastasis, and falsely negative mammograms.

Breast implants may actually facilitate cancer detection on physical examination by providing a more dense or stable surface upon which to palpate the breast tissue. Although they do not necessarily impair mastectomy or breast reconstruction, they may result in an increased rate of revision surgery after breast conservation therapy.^24,36 Mammography remains the standard of care for radiologic diagnosis but can be further supported by MRI and ultrasonography if necessary in patients with implants.

Although concerns persist, multiple studies have demonstrated the safety of fourth- and fifth-generation silicone breast implants with regard to autoimmune disease.⁷

In various clinical studies in mastectomy patients who underwent breast reconstruction with either silicone implants or autologous tissue, no difference was found with regard to the incidence of autoimmune diseases.² Additionally, in meta-analyses of data from more than 87,000 women, no association was found between connective tissue disease and silicone breast implants.^2,11 One study^11,23 noted no increase in autoantibodies in patients with undamaged silicone implants vs patients who experienced rupture.

Studies have also demonstrated that in children born to mothers with breast implants, the risk of rheumatic disease, esophageal disorders, congenital malformations, and death during the perinatal period is comparable with that in controls.³⁷ Another study, examining breastfeeding in women with silicone breast implants, showed no significant difference in silicon levels (used as a proxy for silicone) in breast milk compared with controls without implants; silicon levels were found to be significantly higher in cow’s milk and store-bought formulas.³⁸

BREAST IMPLANT-ASSOCIATED ANAPLASTIC LARGE-CELL LYMPHOMA

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma that develops in tissue adjacent to breast implants. It typically presents as breast swelling 2 to 38 years (mean of 8 years) after implant insertion.^39,40 The swelling may be secondary to periprosthetic seroma formation or, more rarely, palpable disease in the axilla. Patients occasionally complain of pain and, rarely, constitutional symptoms.²⁰ BIA-ALCL is not a disease of the surrounding breast tissue, but rather of the fibrous periprosthetic capsule.²¹

Of note, there is no documented case involving smooth implants,^41–43 but it may be related to fifth-generation textured implants.⁶ At present, it is not possible to definitively state which implant is associated with this condition; hence, more data are needed, and this association is currently under study.

The absolute risk of BIA-ALCL was reported in a Dutch study³⁹ as 1 in 35,000 by age 50, 1 in 12,000 by age 70, and 1 in 7,000 by age 75, with a number needed to harm of 6,920. Overall lifetime risk was estimated at 1 in 30,000 for women with textured implants in a 2015 US study.⁴⁰ In comparison, breast cancer risk is about 1 in 8 women. There is no apparent predilection for patients who underwent cosmetic augmentation vs reconstruction, or who received silicone vs saline implants.

The diagnosis is confirmed by ultrasonographically guided fine-needle aspiration of seroma fluid and subsequent immunohistochemical testing for CD30-positive and ALK-negative T lymphocytes. Other than positron-emission tomography for staging after diagnosis confirmation, imaging is ineffective. Expert opinion does not recommend routine screening unless the aforementioned symptoms arise.

Treatment involves implant removal and total capsulectomy, with samples sent for pathology study with cytokeratin staining.¹² Of note, in all cases of BIA-ALCL in which the disease was limited to the circumscribed scar tissue of the breast capsule, complete surgical excision has proved curative, whereas incomplete capsulectomy portends a greater risk of recurrence and decreased survival.⁴⁴

In cases of advanced or recurrent ALCL, diagnosed late or inappropriately, the National Comprehensive Cancer Network recommends a multidisciplinary approach involving adjuvant chemotherapy and radiation.⁴⁴ Anecdotally, at our institution, we have recently treated several cases of advanced ALCL presenting with invasive chest wall masses with extirpative surgery and subsequent reconstruction with the assistance of our thoracic surgery colleagues, as well as the aforementioned multidisciplinary approach using adjuvant therapy.

The mechanism of this malignancy is currently under investigation, but the current theory implicates an exaggerated lymphoproliferative response to bacterial contamination of the capsule superimposed upon genetic factors in susceptible patients.^42,43

National societies advise plastic surgeons to discuss the risk of BIA-ALCL with all patients at the time of breast augmentation consultation and to report all confirmed cases to the PROFILE registry (Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology).⁴⁵

ARE PATIENTS HAPPIER AFTERWARD?

Studies have shown that after undergoing breast augmentation surgery, patients note improvement in body image, and satisfaction rates range from 85% to 95% with respect to self-confidence and body image.⁴⁶ An evaluation of patient responses on the validated BREAST-Q Augmentation Questionnaire showed the following satisfaction rates: breasts 83%, psychosocial well-being 88%, and sexual functioning 81%.¹⁵

Although epidemiologic studies have reported higher suicide rates in women with cosmetic breast implants, this likely stems from preoperative psychological factors and underscores the role of psychiatric referral in patients with a mental health history or in those whom the surgeon deems it necessary.⁴⁶

Several high-quality studies have demonstrated that quality of life and psychosocial functioning (including depression) markedly improve after breast augmentation surgery.⁴⁷ Among a cohort of Norwegian patients, breast implant surgery resulted in improved motivation to perform daily activities, as well as improved quality of life from both a psychosocial and aesthetic perspective.⁴⁸ Interestingly, a recent study reported that patients who underwent breast implant surgery alone reported greater satisfaction and psychosocial quality of life than patients who underwent combination breast augmentation and mastopexy (breast-lifting) surgery.⁴⁹

Additional data are needed to refine our understanding of the complex interplay between psychosocial factors before and after surgery in patients seeking and undergoing breast augmentation procedures.

Repeat cultures are indicated in specific scenarios, but for most patients, frequent and indiscriminate repetition after an initial positive culture is unnecessary and may be associated with excessive use of resources. Prospective studies and practice guidelines are needed to help further define the indications.

See related editorial

THE TENDENCY TO REPEAT CULTURES

Current literature lacks strong evidence for repeating previously positive blood cultures collected appropriately—ie, 10 mL of blood for aerobic culture and 10 mL for anaerobic culture from 2 different sites, and a positive result from both sets. However, because of the risk of serious complications of bacteremia, particularly in critically ill patients, many clinicians order multiple, repeated sets of blood cultures.

Tabriz et al¹ found that one-third of hospitalized patients got repeat cultures after an initial set, regardless of the result of the first set. Most (83.4%) of those cultures yielded no growth, 9.1% grew the same pathogen, and 5.0% were contaminated. Finding a new pathogen was rare, occurring in only 2.5% of repeated cultures.

Wiggers et al² reported an even higher number of repeat cultures ordered for patients who had an initially positive culture: 38.9%.² And in another study,³ half of the patients received more than 2 consecutive cultures.

Drawbacks

Unrestrained ordering of repeat blood cultures can increase the risk of a false-positive result, leading to more cultures, echocardiography, other imaging tests, and unnecessary antimicrobial therapy, all of which puts patients at risk of adverse effects of treatment and missed alternative diagnoses and increases the length and cost of hospitalization.⁴

Advantages

On the other hand, repeat blood cultures  may increase the diagnostic yield for conditions such as infective endocarditis and may have implications for the duration of antibiotic therapy.¹ The duration of therapy for bacteremia is usually determined from the last negative culture; hence, documenting clearance of bacteremia can determine a precise end-date for antibiotic therapy.

Bacteremia due to Staphylococcus aureus and to endovascular and epidural sources has been found to be independently associated with persistent bacteremia, detected in 6.6% of 1,801 index cases of bacteremia in a retrospective cohort study.² An endovascular source (adjusted odds ratio [OR] 7.66, 95% confidence interval [CI] 2.30–25.48), an epidural source (adjusted OR 26.99, 95% CI, 1.91–391.08), and S aureus bacteremia (adjusted OR 4.49, 95% CI 1.88–10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1%, P =  .006), viridans group streptococci (1.7%, P =  .035), and beta-hemolytic streptococci (0%, P = .028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 hours of the index event (29.7% vs 52.5%, P < .001).²

Repeating blood cultures after an initial positive result is superfluous, except in certain situations.

Suspected endovascular infection

Patients with endocarditis, thrombophlebitis, an indwelling device for epidural access, or a cardiovascular implantable electronic device should have repeat cultures after an initial positive culture. Implantable electronic device infection is suspected in the following cases: sustained positive blood culture (> 24 hours); relapsing bacteremia despite a course of appropriate antibiotic therapy; presence of an implantable cardioverter defibrillator; presence of a prosthetic cardiac valve; and an episode of bacteremia within 3 months of device placement.⁵

S aureus bacteremia

Repeat blood culture is warranted for S aureus bacteremia regardless of methicillin susceptibility.¹ But persistent methicillin-resistant S aureus (MRSA) bacteremia changes the management of these patients.⁶ For example, the source of infection should be identified, followed by debridement or drainage, and then either high-dose or combination antimicrobial therapy.⁶ Infective endocarditis from persistent MRSA bacteremia is an indication for surgery.⁶

Persistent S aureus bacteremia may change the duration of therapy, as the common practice is to continue treating uncomplicated gram-positive bacteremia for 14 days from the date of the first negative culture. Infection leading to infective endocarditis increases the duration of antibiotic therapy to at least 4 weeks.

Candidemia

Candidemia is an absolute indication for repeat blood culture.⁷ Patients with persistent candidemia should undergo imaging of the genitourinary tract, liver, and spleen as part of the evaluation for a deep-tissue source of infection.⁷ Also, if the patient is initially treated with an echinocandin, therapy can be transitioned to fluconazole if the isolate is azole-susceptible, the patient’s condition is clinically stable, and repeat cultures are negative.⁷ Therefore, repeating cultures has therapeutic implications.

Confirming response to therapy

In patients with infective endocarditis or other endovascular infection caused by S aureus, Enterococcus species, or gram-negative bacilli,¹ repeat blood culture should be done to confirm therapeutic response. Patients with infective endocarditis whose condition is stable can be discharged to receive outpatient parenteral antibiotic therapy. However, patients with uncontrolled heart failure, systemic emboli, abscess, persistent fever, or persistently positive cultures are not candidates for outpatient therapy and require repeat cultures.⁸

Multidrug-resistant gram-negative bacilli

Bacteremia due to multidrug-resistant gram-negative bacilli requires repeat blood cultures to document clearance of bacteremia and to ensure the efficacy of antibiotics, as these organisms pose a higher risk of treatment failure, and combination synergistic regimens may be needed if bacteremia does not clear.

Febrile neutropenia

Blood cultures are important in the management of febrile neutropenia. In a study by Rosenblum et al,⁹ repeat cultures were positive in 10.9% of patients with febrile neutropenia after an initial negative culture, but many of those organisms were of low pathogenicity, and a significant proportion were coagulase-negative staphylococci.¹⁰ Another study showed that the frequency of detecting new pathogens by repeat culture in recurrent febrile neutropenia was higher than that in persistent febrile neutropenia (8% vs 2%) (P = .0491); a history of recent bacteremia was identified as a significant predictor of positive culture in recurrent febrile neutropenia.¹¹

Persistent or new infection

Persistence of fever, leukocytosis, or other signs of infection 72 hours after appropriate antibiotic therapy is started requires follow-up blood cultures.

New episode of sepsis. A new episode of sepsis should be confirmed¹² using the systemic inflammatory response syndrome criteria, the newer definition of Sepsis-related Organ Failure Assessment (SOFA) in the intensive-care unit, or the quick SOFA in general units. If the patient develops new signs of sepsis after response to treatment for initial bacteremia, repeat blood cultures should be considered.

Central line-associated bloodstream infection requires repeat cultures.¹³ Persistence of bacteremia in this type of infection extends the duration of therapy, as most clinicians determine treatment duration from the last negative culture. Persistent bacteremia also influences the decision to salvage or remove the catheter. Microbiologic clearance of bacteremia on blood culture can also guide the time of reinsertion if the catheter was removed.

Concern for an unresolved focus of infection such as abscess, joint infection, or retained catheter is an indication for repeat blood cultures.

Bacteremia of unknown source. In clinical practice, we encounter scenarios in which blood cultures are positive but no source can be identified. In those situations, it is important to repeat blood cultures to document clearance. If bacteremia persists, we need to continue searching for the source.

Repeat blood cultures are not routinely indicated in patients with streptococcal bacteremia, uncomplicated gram-negative bacteremia, and bacteremia associated with localized infection such as cellulitis, community-acquired pneumonia, or pyelonephritis.^2,4 A study of patients with gram-negative bacteremia found that 17 repeated cultures needed to be drawn to yield 1 positive culture.¹⁴

Isolated fever or leukocytosis does not accurately predict bacteremia.⁴ A study that excluded neutropenic and intensive-care patients reported none of the initially negative cultures to be positive when repeated.¹⁵

Ordering repeat cultures in response to persistent fever is a common practice, even though fever is typical in the first 72 hours of antibiotic therapy. Such cultures rarely if ever reveal new pathogens, and results can be predicted based on cultures before the start of antibiotics.¹⁵ For patients on antibiotics, physicians should therefore wait for results of the preantibiotic cultures rather than order new cultures in response to persistent fever.¹⁵

WOULD WE MISS PERSISTENT BACTEREMIA?

In theory, not repeating blood cultures could miss persistent bacteremia, but this is unlikely if the concerns discussed above are considered. Further, persistent bacteremia would result in clinical signs and symptoms that should prompt repeat cultures.

FREQUENCY OF REPEAT BLOOD CULTURES

There are no evidence-based guidelines for the frequency of repeating cultures. The Infectious Diseases Society of America recommends repeating blood cultures 2 to 4 days after the index positive culture in the case of multidrug-resistant S aureus bacteremia, and every day or every other day for candidemia.^6,7,9

A study evaluating the practice patterns of repeating cultures after an initial bacteremia showed that 34.7% were done within 24 hours and 44.7% were done in 2 to 4 days.¹ There is no evidence that repeating blood cultures daily is necessary in these patients. As a general rule, it should be done 48 to 72 hours after a positive culture.

Repeat cultures are indicated in specific scenarios, but for most patients, frequent and indiscriminate repetition after an initial positive culture is unnecessary and may be associated with excessive use of resources. Prospective studies and practice guidelines are needed to help further define the indications.

See related editorial

THE TENDENCY TO REPEAT CULTURES

Current literature lacks strong evidence for repeating previously positive blood cultures collected appropriately—ie, 10 mL of blood for aerobic culture and 10 mL for anaerobic culture from 2 different sites, and a positive result from both sets. However, because of the risk of serious complications of bacteremia, particularly in critically ill patients, many clinicians order multiple, repeated sets of blood cultures.

Tabriz et al¹ found that one-third of hospitalized patients got repeat cultures after an initial set, regardless of the result of the first set. Most (83.4%) of those cultures yielded no growth, 9.1% grew the same pathogen, and 5.0% were contaminated. Finding a new pathogen was rare, occurring in only 2.5% of repeated cultures.

Wiggers et al² reported an even higher number of repeat cultures ordered for patients who had an initially positive culture: 38.9%.² And in another study,³ half of the patients received more than 2 consecutive cultures.

Drawbacks

Unrestrained ordering of repeat blood cultures can increase the risk of a false-positive result, leading to more cultures, echocardiography, other imaging tests, and unnecessary antimicrobial therapy, all of which puts patients at risk of adverse effects of treatment and missed alternative diagnoses and increases the length and cost of hospitalization.⁴

Advantages

On the other hand, repeat blood cultures  may increase the diagnostic yield for conditions such as infective endocarditis and may have implications for the duration of antibiotic therapy.¹ The duration of therapy for bacteremia is usually determined from the last negative culture; hence, documenting clearance of bacteremia can determine a precise end-date for antibiotic therapy.

Bacteremia due to Staphylococcus aureus and to endovascular and epidural sources has been found to be independently associated with persistent bacteremia, detected in 6.6% of 1,801 index cases of bacteremia in a retrospective cohort study.² An endovascular source (adjusted odds ratio [OR] 7.66, 95% confidence interval [CI] 2.30–25.48), an epidural source (adjusted OR 26.99, 95% CI, 1.91–391.08), and S aureus bacteremia (adjusted OR 4.49, 95% CI 1.88–10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1%, P =  .006), viridans group streptococci (1.7%, P =  .035), and beta-hemolytic streptococci (0%, P = .028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 hours of the index event (29.7% vs 52.5%, P < .001).²

Repeating blood cultures after an initial positive result is superfluous, except in certain situations.

Suspected endovascular infection

Patients with endocarditis, thrombophlebitis, an indwelling device for epidural access, or a cardiovascular implantable electronic device should have repeat cultures after an initial positive culture. Implantable electronic device infection is suspected in the following cases: sustained positive blood culture (> 24 hours); relapsing bacteremia despite a course of appropriate antibiotic therapy; presence of an implantable cardioverter defibrillator; presence of a prosthetic cardiac valve; and an episode of bacteremia within 3 months of device placement.⁵

S aureus bacteremia

Repeat blood culture is warranted for S aureus bacteremia regardless of methicillin susceptibility.¹ But persistent methicillin-resistant S aureus (MRSA) bacteremia changes the management of these patients.⁶ For example, the source of infection should be identified, followed by debridement or drainage, and then either high-dose or combination antimicrobial therapy.⁶ Infective endocarditis from persistent MRSA bacteremia is an indication for surgery.⁶

Persistent S aureus bacteremia may change the duration of therapy, as the common practice is to continue treating uncomplicated gram-positive bacteremia for 14 days from the date of the first negative culture. Infection leading to infective endocarditis increases the duration of antibiotic therapy to at least 4 weeks.

Candidemia

Candidemia is an absolute indication for repeat blood culture.⁷ Patients with persistent candidemia should undergo imaging of the genitourinary tract, liver, and spleen as part of the evaluation for a deep-tissue source of infection.⁷ Also, if the patient is initially treated with an echinocandin, therapy can be transitioned to fluconazole if the isolate is azole-susceptible, the patient’s condition is clinically stable, and repeat cultures are negative.⁷ Therefore, repeating cultures has therapeutic implications.

Confirming response to therapy

In patients with infective endocarditis or other endovascular infection caused by S aureus, Enterococcus species, or gram-negative bacilli,¹ repeat blood culture should be done to confirm therapeutic response. Patients with infective endocarditis whose condition is stable can be discharged to receive outpatient parenteral antibiotic therapy. However, patients with uncontrolled heart failure, systemic emboli, abscess, persistent fever, or persistently positive cultures are not candidates for outpatient therapy and require repeat cultures.⁸

Multidrug-resistant gram-negative bacilli

Bacteremia due to multidrug-resistant gram-negative bacilli requires repeat blood cultures to document clearance of bacteremia and to ensure the efficacy of antibiotics, as these organisms pose a higher risk of treatment failure, and combination synergistic regimens may be needed if bacteremia does not clear.

Febrile neutropenia

Blood cultures are important in the management of febrile neutropenia. In a study by Rosenblum et al,⁹ repeat cultures were positive in 10.9% of patients with febrile neutropenia after an initial negative culture, but many of those organisms were of low pathogenicity, and a significant proportion were coagulase-negative staphylococci.¹⁰ Another study showed that the frequency of detecting new pathogens by repeat culture in recurrent febrile neutropenia was higher than that in persistent febrile neutropenia (8% vs 2%) (P = .0491); a history of recent bacteremia was identified as a significant predictor of positive culture in recurrent febrile neutropenia.¹¹

Persistent or new infection

Persistence of fever, leukocytosis, or other signs of infection 72 hours after appropriate antibiotic therapy is started requires follow-up blood cultures.

New episode of sepsis. A new episode of sepsis should be confirmed¹² using the systemic inflammatory response syndrome criteria, the newer definition of Sepsis-related Organ Failure Assessment (SOFA) in the intensive-care unit, or the quick SOFA in general units. If the patient develops new signs of sepsis after response to treatment for initial bacteremia, repeat blood cultures should be considered.

Central line-associated bloodstream infection requires repeat cultures.¹³ Persistence of bacteremia in this type of infection extends the duration of therapy, as most clinicians determine treatment duration from the last negative culture. Persistent bacteremia also influences the decision to salvage or remove the catheter. Microbiologic clearance of bacteremia on blood culture can also guide the time of reinsertion if the catheter was removed.

Concern for an unresolved focus of infection such as abscess, joint infection, or retained catheter is an indication for repeat blood cultures.

Bacteremia of unknown source. In clinical practice, we encounter scenarios in which blood cultures are positive but no source can be identified. In those situations, it is important to repeat blood cultures to document clearance. If bacteremia persists, we need to continue searching for the source.

Repeat blood cultures are not routinely indicated in patients with streptococcal bacteremia, uncomplicated gram-negative bacteremia, and bacteremia associated with localized infection such as cellulitis, community-acquired pneumonia, or pyelonephritis.^2,4 A study of patients with gram-negative bacteremia found that 17 repeated cultures needed to be drawn to yield 1 positive culture.¹⁴

Isolated fever or leukocytosis does not accurately predict bacteremia.⁴ A study that excluded neutropenic and intensive-care patients reported none of the initially negative cultures to be positive when repeated.¹⁵

Ordering repeat cultures in response to persistent fever is a common practice, even though fever is typical in the first 72 hours of antibiotic therapy. Such cultures rarely if ever reveal new pathogens, and results can be predicted based on cultures before the start of antibiotics.¹⁵ For patients on antibiotics, physicians should therefore wait for results of the preantibiotic cultures rather than order new cultures in response to persistent fever.¹⁵

WOULD WE MISS PERSISTENT BACTEREMIA?

In theory, not repeating blood cultures could miss persistent bacteremia, but this is unlikely if the concerns discussed above are considered. Further, persistent bacteremia would result in clinical signs and symptoms that should prompt repeat cultures.

FREQUENCY OF REPEAT BLOOD CULTURES

There are no evidence-based guidelines for the frequency of repeating cultures. The Infectious Diseases Society of America recommends repeating blood cultures 2 to 4 days after the index positive culture in the case of multidrug-resistant S aureus bacteremia, and every day or every other day for candidemia.^6,7,9

A study evaluating the practice patterns of repeating cultures after an initial bacteremia showed that 34.7% were done within 24 hours and 44.7% were done in 2 to 4 days.¹ There is no evidence that repeating blood cultures daily is necessary in these patients. As a general rule, it should be done 48 to 72 hours after a positive culture.

Repeat cultures are indicated in specific scenarios, but for most patients, frequent and indiscriminate repetition after an initial positive culture is unnecessary and may be associated with excessive use of resources. Prospective studies and practice guidelines are needed to help further define the indications.

See related editorial

THE TENDENCY TO REPEAT CULTURES

Current literature lacks strong evidence for repeating previously positive blood cultures collected appropriately—ie, 10 mL of blood for aerobic culture and 10 mL for anaerobic culture from 2 different sites, and a positive result from both sets. However, because of the risk of serious complications of bacteremia, particularly in critically ill patients, many clinicians order multiple, repeated sets of blood cultures.

Tabriz et al¹ found that one-third of hospitalized patients got repeat cultures after an initial set, regardless of the result of the first set. Most (83.4%) of those cultures yielded no growth, 9.1% grew the same pathogen, and 5.0% were contaminated. Finding a new pathogen was rare, occurring in only 2.5% of repeated cultures.

Wiggers et al² reported an even higher number of repeat cultures ordered for patients who had an initially positive culture: 38.9%.² And in another study,³ half of the patients received more than 2 consecutive cultures.

Drawbacks

Unrestrained ordering of repeat blood cultures can increase the risk of a false-positive result, leading to more cultures, echocardiography, other imaging tests, and unnecessary antimicrobial therapy, all of which puts patients at risk of adverse effects of treatment and missed alternative diagnoses and increases the length and cost of hospitalization.⁴

Advantages

On the other hand, repeat blood cultures  may increase the diagnostic yield for conditions such as infective endocarditis and may have implications for the duration of antibiotic therapy.¹ The duration of therapy for bacteremia is usually determined from the last negative culture; hence, documenting clearance of bacteremia can determine a precise end-date for antibiotic therapy.

Bacteremia due to Staphylococcus aureus and to endovascular and epidural sources has been found to be independently associated with persistent bacteremia, detected in 6.6% of 1,801 index cases of bacteremia in a retrospective cohort study.² An endovascular source (adjusted odds ratio [OR] 7.66, 95% confidence interval [CI] 2.30–25.48), an epidural source (adjusted OR 26.99, 95% CI, 1.91–391.08), and S aureus bacteremia (adjusted OR 4.49, 95% CI 1.88–10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1%, P =  .006), viridans group streptococci (1.7%, P =  .035), and beta-hemolytic streptococci (0%, P = .028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 hours of the index event (29.7% vs 52.5%, P < .001).²

Repeating blood cultures after an initial positive result is superfluous, except in certain situations.

Suspected endovascular infection

Patients with endocarditis, thrombophlebitis, an indwelling device for epidural access, or a cardiovascular implantable electronic device should have repeat cultures after an initial positive culture. Implantable electronic device infection is suspected in the following cases: sustained positive blood culture (> 24 hours); relapsing bacteremia despite a course of appropriate antibiotic therapy; presence of an implantable cardioverter defibrillator; presence of a prosthetic cardiac valve; and an episode of bacteremia within 3 months of device placement.⁵

S aureus bacteremia

Repeat blood culture is warranted for S aureus bacteremia regardless of methicillin susceptibility.¹ But persistent methicillin-resistant S aureus (MRSA) bacteremia changes the management of these patients.⁶ For example, the source of infection should be identified, followed by debridement or drainage, and then either high-dose or combination antimicrobial therapy.⁶ Infective endocarditis from persistent MRSA bacteremia is an indication for surgery.⁶

Persistent S aureus bacteremia may change the duration of therapy, as the common practice is to continue treating uncomplicated gram-positive bacteremia for 14 days from the date of the first negative culture. Infection leading to infective endocarditis increases the duration of antibiotic therapy to at least 4 weeks.

Candidemia

Candidemia is an absolute indication for repeat blood culture.⁷ Patients with persistent candidemia should undergo imaging of the genitourinary tract, liver, and spleen as part of the evaluation for a deep-tissue source of infection.⁷ Also, if the patient is initially treated with an echinocandin, therapy can be transitioned to fluconazole if the isolate is azole-susceptible, the patient’s condition is clinically stable, and repeat cultures are negative.⁷ Therefore, repeating cultures has therapeutic implications.

Confirming response to therapy

In patients with infective endocarditis or other endovascular infection caused by S aureus, Enterococcus species, or gram-negative bacilli,¹ repeat blood culture should be done to confirm therapeutic response. Patients with infective endocarditis whose condition is stable can be discharged to receive outpatient parenteral antibiotic therapy. However, patients with uncontrolled heart failure, systemic emboli, abscess, persistent fever, or persistently positive cultures are not candidates for outpatient therapy and require repeat cultures.⁸

Multidrug-resistant gram-negative bacilli

Bacteremia due to multidrug-resistant gram-negative bacilli requires repeat blood cultures to document clearance of bacteremia and to ensure the efficacy of antibiotics, as these organisms pose a higher risk of treatment failure, and combination synergistic regimens may be needed if bacteremia does not clear.

Febrile neutropenia

Blood cultures are important in the management of febrile neutropenia. In a study by Rosenblum et al,⁹ repeat cultures were positive in 10.9% of patients with febrile neutropenia after an initial negative culture, but many of those organisms were of low pathogenicity, and a significant proportion were coagulase-negative staphylococci.¹⁰ Another study showed that the frequency of detecting new pathogens by repeat culture in recurrent febrile neutropenia was higher than that in persistent febrile neutropenia (8% vs 2%) (P = .0491); a history of recent bacteremia was identified as a significant predictor of positive culture in recurrent febrile neutropenia.¹¹

Persistent or new infection

Persistence of fever, leukocytosis, or other signs of infection 72 hours after appropriate antibiotic therapy is started requires follow-up blood cultures.

New episode of sepsis. A new episode of sepsis should be confirmed¹² using the systemic inflammatory response syndrome criteria, the newer definition of Sepsis-related Organ Failure Assessment (SOFA) in the intensive-care unit, or the quick SOFA in general units. If the patient develops new signs of sepsis after response to treatment for initial bacteremia, repeat blood cultures should be considered.

Central line-associated bloodstream infection requires repeat cultures.¹³ Persistence of bacteremia in this type of infection extends the duration of therapy, as most clinicians determine treatment duration from the last negative culture. Persistent bacteremia also influences the decision to salvage or remove the catheter. Microbiologic clearance of bacteremia on blood culture can also guide the time of reinsertion if the catheter was removed.

Concern for an unresolved focus of infection such as abscess, joint infection, or retained catheter is an indication for repeat blood cultures.

Bacteremia of unknown source. In clinical practice, we encounter scenarios in which blood cultures are positive but no source can be identified. In those situations, it is important to repeat blood cultures to document clearance. If bacteremia persists, we need to continue searching for the source.

Repeat blood cultures are not routinely indicated in patients with streptococcal bacteremia, uncomplicated gram-negative bacteremia, and bacteremia associated with localized infection such as cellulitis, community-acquired pneumonia, or pyelonephritis.^2,4 A study of patients with gram-negative bacteremia found that 17 repeated cultures needed to be drawn to yield 1 positive culture.¹⁴

Isolated fever or leukocytosis does not accurately predict bacteremia.⁴ A study that excluded neutropenic and intensive-care patients reported none of the initially negative cultures to be positive when repeated.¹⁵

Ordering repeat cultures in response to persistent fever is a common practice, even though fever is typical in the first 72 hours of antibiotic therapy. Such cultures rarely if ever reveal new pathogens, and results can be predicted based on cultures before the start of antibiotics.¹⁵ For patients on antibiotics, physicians should therefore wait for results of the preantibiotic cultures rather than order new cultures in response to persistent fever.¹⁵

WOULD WE MISS PERSISTENT BACTEREMIA?

In theory, not repeating blood cultures could miss persistent bacteremia, but this is unlikely if the concerns discussed above are considered. Further, persistent bacteremia would result in clinical signs and symptoms that should prompt repeat cultures.

FREQUENCY OF REPEAT BLOOD CULTURES

There are no evidence-based guidelines for the frequency of repeating cultures. The Infectious Diseases Society of America recommends repeating blood cultures 2 to 4 days after the index positive culture in the case of multidrug-resistant S aureus bacteremia, and every day or every other day for candidemia.^6,7,9

A study evaluating the practice patterns of repeating cultures after an initial bacteremia showed that 34.7% were done within 24 hours and 44.7% were done in 2 to 4 days.¹ There is no evidence that repeating blood cultures daily is necessary in these patients. As a general rule, it should be done 48 to 72 hours after a positive culture.

Bacteremia is common and associated with significant morbidity and mortality. Bloodstream infections rank among the leading causes of death in North America and Europe.¹

See related article

In this issue, Mushtaq et al² contend that follow-up blood cultures after initial bacteremia are not needed for most hospitalized patients. Not repeating blood cultures after initial bacteremia has been proposed to decrease hospitalization length, consultations, and healthcare costs in some clinical settings. However, without follow-up cultures, it can be difficult to assess the adequacy of treatment of bacteremia and associated underlying infections.

GRAM-NEGATIVE ORGANISMS

Results of retrospective studies indicate that follow-up cultures may not be routinely needed for gram-negative bacteremia. In a review by Canzoneri et al of 383 cases with subsequent follow-up cultures,³ 55 (14%) were positive. The mean duration of bacteremia was 2.8 days (range 1 to 15 days). Of the 55 persistently positive blood cultures, only 8 (15%) were caused by gram-negative organisms. Limitations to this study included the lack of patient outcome data, a low event rate, and the retrospective design.⁴

In a retrospective case-control study of follow-up cultures for 862 episodes of Klebsiella pneumoniae bacteremia,⁵ independent risk factors for persistent bacteremia were intra-abdominal infection, higher Charlson comorbidity index score, solid-organ transplant, and unfavorable treatment response.

These studies confirm that persistent bacteremia is uncommon with gram-negative organisms. They also support using comorbidities and treatment response to guide the ordering of follow-up blood cultures.

WHEN IS FOLLOW-UP CULTURE USEFUL?

Although follow-up blood cultures may not be needed routinely in patients with gram- negative bacteremia, it would be difficult to extrapolate this to gram-positive organisms, especially Staphylococcus aureus.

In Canzoneri et al,³ 43 (78%) of the 55 positive follow-up cultures were due to gram-positive organisms. Factors associated with positive follow-up cultures were concurrent fever, presence of a central intravenous line, end-stage renal disease on hemodialysis, and diabetes mellitus. In addition, infectious disease consultation to decide the need for follow-up cultures for S aureus bacteremia has been associated with fewer deaths, fewer relapses, and lower readmission rates.^6,7

In certain clinical scenarios, follow-up blood cultures can provide useful information, such as when the source of bacteremia is endocarditis or cardiac device infection, a vascular graft, or an intravascular line. In the Infectious Diseases Society of America guidelines for diagnosis and management of catheter-related bloodstream infections, persistent or relapsing bacteremia for some organisms is a criterion for removal of a long-term central venous catheter.⁸

Follow-up cultures are especially useful when the focus of infection is protected from antibiotic penetration, such as in the central nervous system, joints, and abdominal or other abscess. These foci may require drainage for cure. In these cases or in the setting of unfavorable clinical treatment response, follow-up blood cultures showing persistent bacteremia can prompt a search for unaddressed or incompletely addressed foci of infection and allow for source control.

The timing of follow-up cultures is generally 1 to 2 days after the initial culture. Although Mushtaq et al propose a different approach, traditional teaching has been that the last blood culture should not be positive, and this leads to ordering follow-up blood cultures until clearance of bacteremia is documented.

Bacteremia is common and associated with significant morbidity and mortality. Bloodstream infections rank among the leading causes of death in North America and Europe.¹

See related article

In this issue, Mushtaq et al² contend that follow-up blood cultures after initial bacteremia are not needed for most hospitalized patients. Not repeating blood cultures after initial bacteremia has been proposed to decrease hospitalization length, consultations, and healthcare costs in some clinical settings. However, without follow-up cultures, it can be difficult to assess the adequacy of treatment of bacteremia and associated underlying infections.

GRAM-NEGATIVE ORGANISMS

Results of retrospective studies indicate that follow-up cultures may not be routinely needed for gram-negative bacteremia. In a review by Canzoneri et al of 383 cases with subsequent follow-up cultures,³ 55 (14%) were positive. The mean duration of bacteremia was 2.8 days (range 1 to 15 days). Of the 55 persistently positive blood cultures, only 8 (15%) were caused by gram-negative organisms. Limitations to this study included the lack of patient outcome data, a low event rate, and the retrospective design.⁴

In a retrospective case-control study of follow-up cultures for 862 episodes of Klebsiella pneumoniae bacteremia,⁵ independent risk factors for persistent bacteremia were intra-abdominal infection, higher Charlson comorbidity index score, solid-organ transplant, and unfavorable treatment response.

These studies confirm that persistent bacteremia is uncommon with gram-negative organisms. They also support using comorbidities and treatment response to guide the ordering of follow-up blood cultures.

WHEN IS FOLLOW-UP CULTURE USEFUL?

Although follow-up blood cultures may not be needed routinely in patients with gram- negative bacteremia, it would be difficult to extrapolate this to gram-positive organisms, especially Staphylococcus aureus.

In Canzoneri et al,³ 43 (78%) of the 55 positive follow-up cultures were due to gram-positive organisms. Factors associated with positive follow-up cultures were concurrent fever, presence of a central intravenous line, end-stage renal disease on hemodialysis, and diabetes mellitus. In addition, infectious disease consultation to decide the need for follow-up cultures for S aureus bacteremia has been associated with fewer deaths, fewer relapses, and lower readmission rates.^6,7

In certain clinical scenarios, follow-up blood cultures can provide useful information, such as when the source of bacteremia is endocarditis or cardiac device infection, a vascular graft, or an intravascular line. In the Infectious Diseases Society of America guidelines for diagnosis and management of catheter-related bloodstream infections, persistent or relapsing bacteremia for some organisms is a criterion for removal of a long-term central venous catheter.⁸

Follow-up cultures are especially useful when the focus of infection is protected from antibiotic penetration, such as in the central nervous system, joints, and abdominal or other abscess. These foci may require drainage for cure. In these cases or in the setting of unfavorable clinical treatment response, follow-up blood cultures showing persistent bacteremia can prompt a search for unaddressed or incompletely addressed foci of infection and allow for source control.

The timing of follow-up cultures is generally 1 to 2 days after the initial culture. Although Mushtaq et al propose a different approach, traditional teaching has been that the last blood culture should not be positive, and this leads to ordering follow-up blood cultures until clearance of bacteremia is documented.

Bacteremia is common and associated with significant morbidity and mortality. Bloodstream infections rank among the leading causes of death in North America and Europe.¹

See related article

In this issue, Mushtaq et al² contend that follow-up blood cultures after initial bacteremia are not needed for most hospitalized patients. Not repeating blood cultures after initial bacteremia has been proposed to decrease hospitalization length, consultations, and healthcare costs in some clinical settings. However, without follow-up cultures, it can be difficult to assess the adequacy of treatment of bacteremia and associated underlying infections.

GRAM-NEGATIVE ORGANISMS

Results of retrospective studies indicate that follow-up cultures may not be routinely needed for gram-negative bacteremia. In a review by Canzoneri et al of 383 cases with subsequent follow-up cultures,³ 55 (14%) were positive. The mean duration of bacteremia was 2.8 days (range 1 to 15 days). Of the 55 persistently positive blood cultures, only 8 (15%) were caused by gram-negative organisms. Limitations to this study included the lack of patient outcome data, a low event rate, and the retrospective design.⁴

In a retrospective case-control study of follow-up cultures for 862 episodes of Klebsiella pneumoniae bacteremia,⁵ independent risk factors for persistent bacteremia were intra-abdominal infection, higher Charlson comorbidity index score, solid-organ transplant, and unfavorable treatment response.

These studies confirm that persistent bacteremia is uncommon with gram-negative organisms. They also support using comorbidities and treatment response to guide the ordering of follow-up blood cultures.

WHEN IS FOLLOW-UP CULTURE USEFUL?

Although follow-up blood cultures may not be needed routinely in patients with gram- negative bacteremia, it would be difficult to extrapolate this to gram-positive organisms, especially Staphylococcus aureus.

In Canzoneri et al,³ 43 (78%) of the 55 positive follow-up cultures were due to gram-positive organisms. Factors associated with positive follow-up cultures were concurrent fever, presence of a central intravenous line, end-stage renal disease on hemodialysis, and diabetes mellitus. In addition, infectious disease consultation to decide the need for follow-up cultures for S aureus bacteremia has been associated with fewer deaths, fewer relapses, and lower readmission rates.^6,7

In certain clinical scenarios, follow-up blood cultures can provide useful information, such as when the source of bacteremia is endocarditis or cardiac device infection, a vascular graft, or an intravascular line. In the Infectious Diseases Society of America guidelines for diagnosis and management of catheter-related bloodstream infections, persistent or relapsing bacteremia for some organisms is a criterion for removal of a long-term central venous catheter.⁸

Follow-up cultures are especially useful when the focus of infection is protected from antibiotic penetration, such as in the central nervous system, joints, and abdominal or other abscess. These foci may require drainage for cure. In these cases or in the setting of unfavorable clinical treatment response, follow-up blood cultures showing persistent bacteremia can prompt a search for unaddressed or incompletely addressed foci of infection and allow for source control.

The timing of follow-up cultures is generally 1 to 2 days after the initial culture. Although Mushtaq et al propose a different approach, traditional teaching has been that the last blood culture should not be positive, and this leads to ordering follow-up blood cultures until clearance of bacteremia is documented.

Study Overview

Objective. To assess whether procalcitonin-guided antibiotic usage results in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

Design. Multi-center 1:1 randomized trial.

Setting and participants. This study was conducted at 14 academic hospitals in the United States between 2014 and 2017 in which procalcitonin assay was not routinely used. All adult patients in the emergency department with an initial diagnosis of acute lower respiratory tract infection without a decision to give or withhold antibiotics because of uncertainty regarding the need for antibiotics were included in the study. Patients were excluded if antibiotics were unlikely to be held in their case, such as if there was a need for mechanical ventilation or known severe immunosuppression, and if procalcitonin could be falsely elevated (chronic dialysis, metastatic cancer, surgery in the past 7 days).

Intervention. Patients were randomly assigned to receive guideline-based care using procalcitonin (procalcitonin group) or usual care (usual-care group). In the procalcitonin group, the procalcitonin assay results, and the procalcitonin treatment guidelines were provided to the treating physician. The guideline used previously established cutoffs (procalcitonin level of < 0.1 µg/L, antibiotics were strongly discouraged; 0.1 to 0.25 µg/L, antibiotics were discouraged; 0.25 to 0.5 µg/L, antibiotics were recommended; and > 0.5 µg/L, antibiotics were strongly recommended). Procalcitonin was measured initially in the emergency department. If the patient was hospitalized, procalcitonin was again measured 6 to 24 hours later, and on hospital days 3, 5, and 7. To implement this intervention, a multifaceted approach was used, which included sending letters to local primary care providers describing the trial, ensuring rapid delivery of procalcitonin results by tracking and coordinating blood samples with routine morning draws, and embedding the procalcitonin results and guidelines into the sites’ electronic health records. In the usual-care group, procalcitonin levels at enrollment were measured but not disclosed to clinicians. In both treatment groups, clinicians retained autonomy regarding care decisions.

Main outcome measures. The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. The primary safety outcome was any adverse effects that could be attributable to withholding antibiotics in lower respiratory tract infections, within 30 days after enrollment. Secondary outcomes included admission to the intensive care unit (ICU), subsequent emergency department visits by day 30, and quality of life as assessed with the Airway Questionnaire 20.

Main results. 8360 patients with acute lower respiratory tract infection who presented to the emergency department were screened for eligibility; of these, 1664 patients underwent randomization. Ultimately, 1656 patients were included in the final analysis cohort (826 in the procalcitonin group and 830 in the usual-care group), because 8 patients withdrew. Of the cohort, 1345 (81.2%) patients completed the full 30-day follow up. Baseline characteristics were similar between the treatment groups. In the procalcitonin group, clinicians received the procalcitonin results for 95.9% of the patients. As a result of clinical care, 2.2% of the patients in the usual-care group also had procalcitonin testing. Clinicians adhered to the procalcitonin guideline recommendations for 64.8% of the procalcitonin group.

There was no significant difference in the intention-treat-treat analysis between the procalcitonin group and the usual-care group in antibiotic days during the first 30 days (mean antibiotic days, 4.2 and 4.3 days, respectively [95% confidence interval {CI}, –0.6 to 0.5; P = 0.87]). Within 30 days there was no significant difference in the proportion of patients with adverse outcomes in the procalcitonin group and usual-care group (11.7% and 13.1%, respectively [95% CI, –4.6 to 1.7]; P < 0.01 for noninferiority). There was no significant difference between the procalcitonin and usual-care groups for any of the secondary outcomes.

Conclusion. A procalcitonin-directed antibiotic administration guideline did not result in fewer antibiotic days than did usual-care among patients with suspected lower respiratory tract infection.

Commentary

Procalcitonin is a serum biomarker synthesized in thyroid neuroendocrine cells and is the precursor to calcitonin.¹ It is undetectable in healthy human serum, but in the setting of systemic inflammation caused by bacterial infection, procalcitonin synthesis is induced in many tissues. Since its discovery in 1970, procalcitonin’s potential utility has been sought in various settings, such as guiding the initiation and/or discontinuation of antibiotics.²

In a prospective randomized trial in patients with an acute chronic obstructive pulmonary disease (COPD) exacerbation, treatment success was not better with antibiotics than placebo in patients with a procalcitonin level < 0.1 µg/L.³ Others replicated these results in COPD patients with acute exacerbation of COPD.⁴ Another small randomized trial showed that using procalcitonin in intensive care patients reduced antibiotic duration.⁵ Another small study found similar results in their critical care setting.⁶ Procalcitonin-guided antibiotic treatment produced similar results in patients with aspiration pneumonia.⁷ In summary, previously published studies nearly uniformly report reduced antibiotic duration or initiation using procalcitonin cutoffs without increasing adverse events.

In the current study, Huang and colleagues conducted a multi-center randomized trial in 14 academic US hospitals, while simultaneously attempting quality improvement methods for implementing and maximizing compliance with procalcitonin guidelines for local physicians. This study was able to achieve approximately 65% compliance with the guideline, which is relatively lower than in previously reported studies using procalcitonin guidelines. This study was larger and involved more hospitals than the other studies. Interestingly, this study did not find statistically significant differences in antibiotic usage or duration between the procalcitonin group compared to the usual-care group. While this result can be partially explained by the low rate of compliance with the guideline, the result may actually reflect the real-life pattern of procalcitonin guideline usage in clinicians. These results suggest that procalcitonin-based guidelines attempting to reduce antibiotic usage and exposure may be of low value, contrasting with findings from previous studies.

The Huang et al study is well-designed, had a low rate of follow-up loss and withdrawal, was conducted mostly at urban academic hospitals that had a high level of adherence to Joint Commission pneumonia core measures, and had appropriate statistical analyses; however, several factors should be considered when applying the results of this study to clinical practice. First, the large majority (80.1%) of the study cohort had final diagnoses of a COPD exacerbation, asthma exacerbation, or acute bronchitis. These patients had a moderate degree of disease (required hospitalization in 59% of patients with a mean hospital length of stay of 5 days), but their symptoms were severe enough for the patients to present to the emergency department. Patients with a suspected nonrespiratory infection or a milder degree of infection, especially in the ambulatory care setting, may have different antibiotic prescribing patterns. Also, patients in the ambulatory care setting likely have different causal organisms of their diagnosis. Second, this study excluded patients with severe disease who required ICU admission with either septic shock or respiratory failure, patients with pre-existing diseases that placed them at high risk (eg, immunosuppressed patients), and/or patients who had complications of their infection with either a lung abscess or empyema. This pattern of exclusion was widely similar to the other previous procalcitonin studies, which shows that procalcitonin guidelines should not be applied blindly in critically ill patients, even those not requiring ICU admission. Third, patients were excluded from the study if they were on chronic dialysis, had metastatic cancer, or had a recent surgery because of possible elevation of procalcitonin levels without a bacterial infection.

In conclusion, the current study did not find any difference in antibiotic exposure throughout the course of care (including discharge or hospitalization) of patients with a lower respiratory tract infection who presented to the emergency department when a procalcitonin guideline was implemented. The results of the current study raise questions regarding the new trend of widely accepting procalcitonin-based antibiotic usage.

Applications for Clinical Practice

Procalcitonin is a relatively new marker that is released during a systemic bacterial infection. While prior studies have supported systematic use of procalcitonin-based guidelines to initiate and discontinue antibiotics in order to limit antibiotic exposure, clinicians should be mindful that a procalcitonin antibiotic guideline may be useful in specific patients and should only be used in combination with usual clinical judgment. Clinicians must also recognize the medical conditions that may falsely elevate the procalcitonin level. Most important, the procalcitonin level should not be used as the sole indication to withhold antibiotics in an otherwise appropriately indicated clinical scenario.

—Minkyung Kwon, MD, Scott A. Helgeson, MD, and Vichaya Arunthari, MD
Pulmonary and Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL

Study Overview

Objective. To assess whether procalcitonin-guided antibiotic usage results in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

Design. Multi-center 1:1 randomized trial.

Setting and participants. This study was conducted at 14 academic hospitals in the United States between 2014 and 2017 in which procalcitonin assay was not routinely used. All adult patients in the emergency department with an initial diagnosis of acute lower respiratory tract infection without a decision to give or withhold antibiotics because of uncertainty regarding the need for antibiotics were included in the study. Patients were excluded if antibiotics were unlikely to be held in their case, such as if there was a need for mechanical ventilation or known severe immunosuppression, and if procalcitonin could be falsely elevated (chronic dialysis, metastatic cancer, surgery in the past 7 days).

Intervention. Patients were randomly assigned to receive guideline-based care using procalcitonin (procalcitonin group) or usual care (usual-care group). In the procalcitonin group, the procalcitonin assay results, and the procalcitonin treatment guidelines were provided to the treating physician. The guideline used previously established cutoffs (procalcitonin level of < 0.1 µg/L, antibiotics were strongly discouraged; 0.1 to 0.25 µg/L, antibiotics were discouraged; 0.25 to 0.5 µg/L, antibiotics were recommended; and > 0.5 µg/L, antibiotics were strongly recommended). Procalcitonin was measured initially in the emergency department. If the patient was hospitalized, procalcitonin was again measured 6 to 24 hours later, and on hospital days 3, 5, and 7. To implement this intervention, a multifaceted approach was used, which included sending letters to local primary care providers describing the trial, ensuring rapid delivery of procalcitonin results by tracking and coordinating blood samples with routine morning draws, and embedding the procalcitonin results and guidelines into the sites’ electronic health records. In the usual-care group, procalcitonin levels at enrollment were measured but not disclosed to clinicians. In both treatment groups, clinicians retained autonomy regarding care decisions.

Main outcome measures. The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. The primary safety outcome was any adverse effects that could be attributable to withholding antibiotics in lower respiratory tract infections, within 30 days after enrollment. Secondary outcomes included admission to the intensive care unit (ICU), subsequent emergency department visits by day 30, and quality of life as assessed with the Airway Questionnaire 20.

Main results. 8360 patients with acute lower respiratory tract infection who presented to the emergency department were screened for eligibility; of these, 1664 patients underwent randomization. Ultimately, 1656 patients were included in the final analysis cohort (826 in the procalcitonin group and 830 in the usual-care group), because 8 patients withdrew. Of the cohort, 1345 (81.2%) patients completed the full 30-day follow up. Baseline characteristics were similar between the treatment groups. In the procalcitonin group, clinicians received the procalcitonin results for 95.9% of the patients. As a result of clinical care, 2.2% of the patients in the usual-care group also had procalcitonin testing. Clinicians adhered to the procalcitonin guideline recommendations for 64.8% of the procalcitonin group.

There was no significant difference in the intention-treat-treat analysis between the procalcitonin group and the usual-care group in antibiotic days during the first 30 days (mean antibiotic days, 4.2 and 4.3 days, respectively [95% confidence interval {CI}, –0.6 to 0.5; P = 0.87]). Within 30 days there was no significant difference in the proportion of patients with adverse outcomes in the procalcitonin group and usual-care group (11.7% and 13.1%, respectively [95% CI, –4.6 to 1.7]; P < 0.01 for noninferiority). There was no significant difference between the procalcitonin and usual-care groups for any of the secondary outcomes.

Conclusion. A procalcitonin-directed antibiotic administration guideline did not result in fewer antibiotic days than did usual-care among patients with suspected lower respiratory tract infection.

Commentary

Procalcitonin is a serum biomarker synthesized in thyroid neuroendocrine cells and is the precursor to calcitonin.¹ It is undetectable in healthy human serum, but in the setting of systemic inflammation caused by bacterial infection, procalcitonin synthesis is induced in many tissues. Since its discovery in 1970, procalcitonin’s potential utility has been sought in various settings, such as guiding the initiation and/or discontinuation of antibiotics.²

In a prospective randomized trial in patients with an acute chronic obstructive pulmonary disease (COPD) exacerbation, treatment success was not better with antibiotics than placebo in patients with a procalcitonin level < 0.1 µg/L.³ Others replicated these results in COPD patients with acute exacerbation of COPD.⁴ Another small randomized trial showed that using procalcitonin in intensive care patients reduced antibiotic duration.⁵ Another small study found similar results in their critical care setting.⁶ Procalcitonin-guided antibiotic treatment produced similar results in patients with aspiration pneumonia.⁷ In summary, previously published studies nearly uniformly report reduced antibiotic duration or initiation using procalcitonin cutoffs without increasing adverse events.

In the current study, Huang and colleagues conducted a multi-center randomized trial in 14 academic US hospitals, while simultaneously attempting quality improvement methods for implementing and maximizing compliance with procalcitonin guidelines for local physicians. This study was able to achieve approximately 65% compliance with the guideline, which is relatively lower than in previously reported studies using procalcitonin guidelines. This study was larger and involved more hospitals than the other studies. Interestingly, this study did not find statistically significant differences in antibiotic usage or duration between the procalcitonin group compared to the usual-care group. While this result can be partially explained by the low rate of compliance with the guideline, the result may actually reflect the real-life pattern of procalcitonin guideline usage in clinicians. These results suggest that procalcitonin-based guidelines attempting to reduce antibiotic usage and exposure may be of low value, contrasting with findings from previous studies.

The Huang et al study is well-designed, had a low rate of follow-up loss and withdrawal, was conducted mostly at urban academic hospitals that had a high level of adherence to Joint Commission pneumonia core measures, and had appropriate statistical analyses; however, several factors should be considered when applying the results of this study to clinical practice. First, the large majority (80.1%) of the study cohort had final diagnoses of a COPD exacerbation, asthma exacerbation, or acute bronchitis. These patients had a moderate degree of disease (required hospitalization in 59% of patients with a mean hospital length of stay of 5 days), but their symptoms were severe enough for the patients to present to the emergency department. Patients with a suspected nonrespiratory infection or a milder degree of infection, especially in the ambulatory care setting, may have different antibiotic prescribing patterns. Also, patients in the ambulatory care setting likely have different causal organisms of their diagnosis. Second, this study excluded patients with severe disease who required ICU admission with either septic shock or respiratory failure, patients with pre-existing diseases that placed them at high risk (eg, immunosuppressed patients), and/or patients who had complications of their infection with either a lung abscess or empyema. This pattern of exclusion was widely similar to the other previous procalcitonin studies, which shows that procalcitonin guidelines should not be applied blindly in critically ill patients, even those not requiring ICU admission. Third, patients were excluded from the study if they were on chronic dialysis, had metastatic cancer, or had a recent surgery because of possible elevation of procalcitonin levels without a bacterial infection.

In conclusion, the current study did not find any difference in antibiotic exposure throughout the course of care (including discharge or hospitalization) of patients with a lower respiratory tract infection who presented to the emergency department when a procalcitonin guideline was implemented. The results of the current study raise questions regarding the new trend of widely accepting procalcitonin-based antibiotic usage.

Applications for Clinical Practice

Procalcitonin is a relatively new marker that is released during a systemic bacterial infection. While prior studies have supported systematic use of procalcitonin-based guidelines to initiate and discontinue antibiotics in order to limit antibiotic exposure, clinicians should be mindful that a procalcitonin antibiotic guideline may be useful in specific patients and should only be used in combination with usual clinical judgment. Clinicians must also recognize the medical conditions that may falsely elevate the procalcitonin level. Most important, the procalcitonin level should not be used as the sole indication to withhold antibiotics in an otherwise appropriately indicated clinical scenario.

—Minkyung Kwon, MD, Scott A. Helgeson, MD, and Vichaya Arunthari, MD
Pulmonary and Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL

Study Overview

Objective. To assess whether procalcitonin-guided antibiotic usage results in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events.

Design. Multi-center 1:1 randomized trial.

Setting and participants. This study was conducted at 14 academic hospitals in the United States between 2014 and 2017 in which procalcitonin assay was not routinely used. All adult patients in the emergency department with an initial diagnosis of acute lower respiratory tract infection without a decision to give or withhold antibiotics because of uncertainty regarding the need for antibiotics were included in the study. Patients were excluded if antibiotics were unlikely to be held in their case, such as if there was a need for mechanical ventilation or known severe immunosuppression, and if procalcitonin could be falsely elevated (chronic dialysis, metastatic cancer, surgery in the past 7 days).

Intervention. Patients were randomly assigned to receive guideline-based care using procalcitonin (procalcitonin group) or usual care (usual-care group). In the procalcitonin group, the procalcitonin assay results, and the procalcitonin treatment guidelines were provided to the treating physician. The guideline used previously established cutoffs (procalcitonin level of < 0.1 µg/L, antibiotics were strongly discouraged; 0.1 to 0.25 µg/L, antibiotics were discouraged; 0.25 to 0.5 µg/L, antibiotics were recommended; and > 0.5 µg/L, antibiotics were strongly recommended). Procalcitonin was measured initially in the emergency department. If the patient was hospitalized, procalcitonin was again measured 6 to 24 hours later, and on hospital days 3, 5, and 7. To implement this intervention, a multifaceted approach was used, which included sending letters to local primary care providers describing the trial, ensuring rapid delivery of procalcitonin results by tracking and coordinating blood samples with routine morning draws, and embedding the procalcitonin results and guidelines into the sites’ electronic health records. In the usual-care group, procalcitonin levels at enrollment were measured but not disclosed to clinicians. In both treatment groups, clinicians retained autonomy regarding care decisions.

Main outcome measures. The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. The primary safety outcome was any adverse effects that could be attributable to withholding antibiotics in lower respiratory tract infections, within 30 days after enrollment. Secondary outcomes included admission to the intensive care unit (ICU), subsequent emergency department visits by day 30, and quality of life as assessed with the Airway Questionnaire 20.

Main results. 8360 patients with acute lower respiratory tract infection who presented to the emergency department were screened for eligibility; of these, 1664 patients underwent randomization. Ultimately, 1656 patients were included in the final analysis cohort (826 in the procalcitonin group and 830 in the usual-care group), because 8 patients withdrew. Of the cohort, 1345 (81.2%) patients completed the full 30-day follow up. Baseline characteristics were similar between the treatment groups. In the procalcitonin group, clinicians received the procalcitonin results for 95.9% of the patients. As a result of clinical care, 2.2% of the patients in the usual-care group also had procalcitonin testing. Clinicians adhered to the procalcitonin guideline recommendations for 64.8% of the procalcitonin group.

There was no significant difference in the intention-treat-treat analysis between the procalcitonin group and the usual-care group in antibiotic days during the first 30 days (mean antibiotic days, 4.2 and 4.3 days, respectively [95% confidence interval {CI}, –0.6 to 0.5; P = 0.87]). Within 30 days there was no significant difference in the proportion of patients with adverse outcomes in the procalcitonin group and usual-care group (11.7% and 13.1%, respectively [95% CI, –4.6 to 1.7]; P < 0.01 for noninferiority). There was no significant difference between the procalcitonin and usual-care groups for any of the secondary outcomes.

Conclusion. A procalcitonin-directed antibiotic administration guideline did not result in fewer antibiotic days than did usual-care among patients with suspected lower respiratory tract infection.

Commentary

Procalcitonin is a serum biomarker synthesized in thyroid neuroendocrine cells and is the precursor to calcitonin.¹ It is undetectable in healthy human serum, but in the setting of systemic inflammation caused by bacterial infection, procalcitonin synthesis is induced in many tissues. Since its discovery in 1970, procalcitonin’s potential utility has been sought in various settings, such as guiding the initiation and/or discontinuation of antibiotics.²

In a prospective randomized trial in patients with an acute chronic obstructive pulmonary disease (COPD) exacerbation, treatment success was not better with antibiotics than placebo in patients with a procalcitonin level < 0.1 µg/L.³ Others replicated these results in COPD patients with acute exacerbation of COPD.⁴ Another small randomized trial showed that using procalcitonin in intensive care patients reduced antibiotic duration.⁵ Another small study found similar results in their critical care setting.⁶ Procalcitonin-guided antibiotic treatment produced similar results in patients with aspiration pneumonia.⁷ In summary, previously published studies nearly uniformly report reduced antibiotic duration or initiation using procalcitonin cutoffs without increasing adverse events.

In the current study, Huang and colleagues conducted a multi-center randomized trial in 14 academic US hospitals, while simultaneously attempting quality improvement methods for implementing and maximizing compliance with procalcitonin guidelines for local physicians. This study was able to achieve approximately 65% compliance with the guideline, which is relatively lower than in previously reported studies using procalcitonin guidelines. This study was larger and involved more hospitals than the other studies. Interestingly, this study did not find statistically significant differences in antibiotic usage or duration between the procalcitonin group compared to the usual-care group. While this result can be partially explained by the low rate of compliance with the guideline, the result may actually reflect the real-life pattern of procalcitonin guideline usage in clinicians. These results suggest that procalcitonin-based guidelines attempting to reduce antibiotic usage and exposure may be of low value, contrasting with findings from previous studies.

The Huang et al study is well-designed, had a low rate of follow-up loss and withdrawal, was conducted mostly at urban academic hospitals that had a high level of adherence to Joint Commission pneumonia core measures, and had appropriate statistical analyses; however, several factors should be considered when applying the results of this study to clinical practice. First, the large majority (80.1%) of the study cohort had final diagnoses of a COPD exacerbation, asthma exacerbation, or acute bronchitis. These patients had a moderate degree of disease (required hospitalization in 59% of patients with a mean hospital length of stay of 5 days), but their symptoms were severe enough for the patients to present to the emergency department. Patients with a suspected nonrespiratory infection or a milder degree of infection, especially in the ambulatory care setting, may have different antibiotic prescribing patterns. Also, patients in the ambulatory care setting likely have different causal organisms of their diagnosis. Second, this study excluded patients with severe disease who required ICU admission with either septic shock or respiratory failure, patients with pre-existing diseases that placed them at high risk (eg, immunosuppressed patients), and/or patients who had complications of their infection with either a lung abscess or empyema. This pattern of exclusion was widely similar to the other previous procalcitonin studies, which shows that procalcitonin guidelines should not be applied blindly in critically ill patients, even those not requiring ICU admission. Third, patients were excluded from the study if they were on chronic dialysis, had metastatic cancer, or had a recent surgery because of possible elevation of procalcitonin levels without a bacterial infection.

In conclusion, the current study did not find any difference in antibiotic exposure throughout the course of care (including discharge or hospitalization) of patients with a lower respiratory tract infection who presented to the emergency department when a procalcitonin guideline was implemented. The results of the current study raise questions regarding the new trend of widely accepting procalcitonin-based antibiotic usage.

Applications for Clinical Practice

Procalcitonin is a relatively new marker that is released during a systemic bacterial infection. While prior studies have supported systematic use of procalcitonin-based guidelines to initiate and discontinue antibiotics in order to limit antibiotic exposure, clinicians should be mindful that a procalcitonin antibiotic guideline may be useful in specific patients and should only be used in combination with usual clinical judgment. Clinicians must also recognize the medical conditions that may falsely elevate the procalcitonin level. Most important, the procalcitonin level should not be used as the sole indication to withhold antibiotics in an otherwise appropriately indicated clinical scenario.

—Minkyung Kwon, MD, Scott A. Helgeson, MD, and Vichaya Arunthari, MD
Pulmonary and Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL

Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.

s-c-s/Thinkstock

A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.

Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.

As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.

Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.

Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).

“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.

The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.

[email protected]

Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.

s-c-s/Thinkstock

A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.

Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.

As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.

Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.

Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).

“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.

The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.

[email protected]

Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.

s-c-s/Thinkstock

A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.

Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.

As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.

Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.

Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).

“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.

The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.

[email protected]

Dermatologists are prescribing fewer antibiotics for acne and rosacea, but prescribing after dermatologic surgery has increased in the past decade.

In a study published online Jan. 16 in JAMA Dermatology, researchers report the results of a cross-sectional analysis of antibiotic prescribing by 11,986 dermatologists between 2008 and 2016, using commercial claims data.

The analysis showed that, over this period of time, the overall rate of antibiotic prescribing by dermatologists decreased by 36.6%, from 3.36 courses per 100 dermatologist visits to 2.13 courses. In particular, antibiotic prescribing for acne decreased by 28.1%, from 11.76 courses per 100 visits to 8.45 courses, and for rosacea it decreased by 18.1%, from 10.89 courses per 100 visits to 8.92 courses.

John S. Barbieri, MD, of the department of dermatology, University of Pennsylvania, and his coauthors described the overall decline in antibiotic prescribing as “encouraging,” considering that in 2013 dermatologists were identified as the “most frequent prescribers of oral antibiotics per clinician.” The decline resulted in an estimated 480,000 fewer antibiotic courses a year, they noted.

“Much of the decrease in extended courses of antibiotic therapy is associated with visits for acne and rosacea,” they wrote. “Although recent guidelines suggest limiting the duration of therapy in this patient population, course duration has remained stable over time, suggesting that this decrease may be due to fewer patients being treated with antibiotics rather than patients being treated for a shorter duration.”

However, the rate of oral antibiotic prescriptions associated with surgical visits increased by 69.6%, from 3.92 courses per 100 visits to 6.65. This increase was concerning, given the risk of surgical-site infections was low, the authors pointed out. “In addition, a 2008 advisory statement on antibiotic prophylaxis recommends single-dose perioperative antibiotics for patients at increased risk of surgical-site infection,” they added.

The study also noted a 35.3% increase in antibiotic prescribing for cysts and a 3.2% increase for hidradenitis suppurativa.

Over the entire study period, nearly 1 million courses of oral antibiotics were prescribed. Doxycycline hyclate accounted for around one quarter of prescriptions, as did minocycline, while 19.9% of prescriptions were for cephalexin.

“Given the low rate of infectious complications, even for Mohs surgery, and the lack of evidence to support the use of prolonged rather than single-dose perioperative regimens, the postoperative courses of antibiotics identified in this study may increase risks to patients without substantial benefits,” they added.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal Skin Diseases. No conflicts of interest were declared.

SOURCE: Barbieri J et al. JAMA Dermatology. 2019 Jan 16. doi: 10.1001/jamadermatol.2018.4944.

Dermatologists are prescribing fewer antibiotics for acne and rosacea, but prescribing after dermatologic surgery has increased in the past decade.

In a study published online Jan. 16 in JAMA Dermatology, researchers report the results of a cross-sectional analysis of antibiotic prescribing by 11,986 dermatologists between 2008 and 2016, using commercial claims data.

The analysis showed that, over this period of time, the overall rate of antibiotic prescribing by dermatologists decreased by 36.6%, from 3.36 courses per 100 dermatologist visits to 2.13 courses. In particular, antibiotic prescribing for acne decreased by 28.1%, from 11.76 courses per 100 visits to 8.45 courses, and for rosacea it decreased by 18.1%, from 10.89 courses per 100 visits to 8.92 courses.

John S. Barbieri, MD, of the department of dermatology, University of Pennsylvania, and his coauthors described the overall decline in antibiotic prescribing as “encouraging,” considering that in 2013 dermatologists were identified as the “most frequent prescribers of oral antibiotics per clinician.” The decline resulted in an estimated 480,000 fewer antibiotic courses a year, they noted.

“Much of the decrease in extended courses of antibiotic therapy is associated with visits for acne and rosacea,” they wrote. “Although recent guidelines suggest limiting the duration of therapy in this patient population, course duration has remained stable over time, suggesting that this decrease may be due to fewer patients being treated with antibiotics rather than patients being treated for a shorter duration.”

However, the rate of oral antibiotic prescriptions associated with surgical visits increased by 69.6%, from 3.92 courses per 100 visits to 6.65. This increase was concerning, given the risk of surgical-site infections was low, the authors pointed out. “In addition, a 2008 advisory statement on antibiotic prophylaxis recommends single-dose perioperative antibiotics for patients at increased risk of surgical-site infection,” they added.

The study also noted a 35.3% increase in antibiotic prescribing for cysts and a 3.2% increase for hidradenitis suppurativa.

Over the entire study period, nearly 1 million courses of oral antibiotics were prescribed. Doxycycline hyclate accounted for around one quarter of prescriptions, as did minocycline, while 19.9% of prescriptions were for cephalexin.

“Given the low rate of infectious complications, even for Mohs surgery, and the lack of evidence to support the use of prolonged rather than single-dose perioperative regimens, the postoperative courses of antibiotics identified in this study may increase risks to patients without substantial benefits,” they added.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal Skin Diseases. No conflicts of interest were declared.

SOURCE: Barbieri J et al. JAMA Dermatology. 2019 Jan 16. doi: 10.1001/jamadermatol.2018.4944.

Dermatologists are prescribing fewer antibiotics for acne and rosacea, but prescribing after dermatologic surgery has increased in the past decade.

In a study published online Jan. 16 in JAMA Dermatology, researchers report the results of a cross-sectional analysis of antibiotic prescribing by 11,986 dermatologists between 2008 and 2016, using commercial claims data.

The analysis showed that, over this period of time, the overall rate of antibiotic prescribing by dermatologists decreased by 36.6%, from 3.36 courses per 100 dermatologist visits to 2.13 courses. In particular, antibiotic prescribing for acne decreased by 28.1%, from 11.76 courses per 100 visits to 8.45 courses, and for rosacea it decreased by 18.1%, from 10.89 courses per 100 visits to 8.92 courses.

John S. Barbieri, MD, of the department of dermatology, University of Pennsylvania, and his coauthors described the overall decline in antibiotic prescribing as “encouraging,” considering that in 2013 dermatologists were identified as the “most frequent prescribers of oral antibiotics per clinician.” The decline resulted in an estimated 480,000 fewer antibiotic courses a year, they noted.

“Much of the decrease in extended courses of antibiotic therapy is associated with visits for acne and rosacea,” they wrote. “Although recent guidelines suggest limiting the duration of therapy in this patient population, course duration has remained stable over time, suggesting that this decrease may be due to fewer patients being treated with antibiotics rather than patients being treated for a shorter duration.”

However, the rate of oral antibiotic prescriptions associated with surgical visits increased by 69.6%, from 3.92 courses per 100 visits to 6.65. This increase was concerning, given the risk of surgical-site infections was low, the authors pointed out. “In addition, a 2008 advisory statement on antibiotic prophylaxis recommends single-dose perioperative antibiotics for patients at increased risk of surgical-site infection,” they added.

The study also noted a 35.3% increase in antibiotic prescribing for cysts and a 3.2% increase for hidradenitis suppurativa.

Over the entire study period, nearly 1 million courses of oral antibiotics were prescribed. Doxycycline hyclate accounted for around one quarter of prescriptions, as did minocycline, while 19.9% of prescriptions were for cephalexin.

“Given the low rate of infectious complications, even for Mohs surgery, and the lack of evidence to support the use of prolonged rather than single-dose perioperative regimens, the postoperative courses of antibiotics identified in this study may increase risks to patients without substantial benefits,” they added.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal Skin Diseases. No conflicts of interest were declared.

SOURCE: Barbieri J et al. JAMA Dermatology. 2019 Jan 16. doi: 10.1001/jamadermatol.2018.4944.

LAS VEGAS – Gynecologist Michael S. Baggish, MD, offered tips about diagnosis and treatment of vulvar conditions at the Pelvic Anatomy and Gynecologic Surgery Symposium.

Pubic lice

Treat with malathion 0.5% lotion (Ovide), permethrin 1%-5% (Nix), or lindane 1% (Kwell). Be aware that the U.S. Library of Medicine cautions that lindane can cause serious side effects, and patients should use it only “if there is some reason you cannot use the other medications or if you have tried the other medications and they have not worked.”

Pruritus (itchy skin)

Eliminate possible contact allergens such as soaps, detergents, and undergarments. Swabs with 2% acetic acid solution can assist with general hygiene. It’s important to address secondary infections, and control of diet and stress may be helpful.

Folliculitis (inflammation of hair follicles)

A salt water bath can be helpful. Try 2 cups of “Instant Ocean” – a sea salt product for aquariums – in a shallow bath twice daily.

It can be treated with silver sulfadiazine (Silvadene) cream (three times daily and at bedtime) or clindamycin (Cleocin) cream (three times daily and at bedtime).

Consider a systemic drug after culture results come back if needed.
 

Lichen sclerosus (a skin inflammation also known as white spot disease)

“I see a lot of lichen sclerosus,” Dr. Baggish said. “Every single practice day, I’m seeing two or three [cases].”

Topical treatments include testosterone cream (which has low efficacy) and topical corticosteroid creams and ointments (the standard treatment).

Other treatments provide better and more consistent results: Etretinate (Tegison), a retinoid that is expensive and can produce serious side effects, and injectable dexamethasone (Decadron), which can stop progression.

Be aware that 10% of patients with this condition may develop squamous cell carcinoma. Monitor for any changes in appearance and biopsy if needed.

Behçet’s disease (a blood vessel inflammation disorder also known as silk road disease)

This rare condition can cause mouth and genital ulcers and uveitis (eye inflammation). For treatment, start 40 mg prednisone for 2-3 days, then 20 mg for 2 days, then 10 mg for 4 days, then stop. Start treatment immediately if there are signs of an oral lesion.

Fox-Fordyce disease (an inflammatory response that blocks sweat ducts and causes intense itching)

Treatment includes estrogen (2.5 mg per day) and tretinoin (Retin-A, apply once daily), usually given together. Suggest that patients try the Instant Ocean salt water treatment in the bath once daily (see details above under folliculitis entry).

Genital warts

Vaporize the warts via laser. “If they look like they’re recurring, I put them on interferon for 3 months because otherwise they just keep recurring,” Dr. Baggish said. “You could put topical treatments on them, but they’ll recur.”

Dr. Baggish, of the University of California, San Francisco, had no relevant financial disclosures. The meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

LAS VEGAS – Gynecologist Michael S. Baggish, MD, offered tips about diagnosis and treatment of vulvar conditions at the Pelvic Anatomy and Gynecologic Surgery Symposium.

Pubic lice

Treat with malathion 0.5% lotion (Ovide), permethrin 1%-5% (Nix), or lindane 1% (Kwell). Be aware that the U.S. Library of Medicine cautions that lindane can cause serious side effects, and patients should use it only “if there is some reason you cannot use the other medications or if you have tried the other medications and they have not worked.”

Pruritus (itchy skin)

Eliminate possible contact allergens such as soaps, detergents, and undergarments. Swabs with 2% acetic acid solution can assist with general hygiene. It’s important to address secondary infections, and control of diet and stress may be helpful.

Folliculitis (inflammation of hair follicles)

A salt water bath can be helpful. Try 2 cups of “Instant Ocean” – a sea salt product for aquariums – in a shallow bath twice daily.

It can be treated with silver sulfadiazine (Silvadene) cream (three times daily and at bedtime) or clindamycin (Cleocin) cream (three times daily and at bedtime).

Consider a systemic drug after culture results come back if needed.
 

Lichen sclerosus (a skin inflammation also known as white spot disease)

“I see a lot of lichen sclerosus,” Dr. Baggish said. “Every single practice day, I’m seeing two or three [cases].”

Topical treatments include testosterone cream (which has low efficacy) and topical corticosteroid creams and ointments (the standard treatment).

Other treatments provide better and more consistent results: Etretinate (Tegison), a retinoid that is expensive and can produce serious side effects, and injectable dexamethasone (Decadron), which can stop progression.

Be aware that 10% of patients with this condition may develop squamous cell carcinoma. Monitor for any changes in appearance and biopsy if needed.

Behçet’s disease (a blood vessel inflammation disorder also known as silk road disease)

This rare condition can cause mouth and genital ulcers and uveitis (eye inflammation). For treatment, start 40 mg prednisone for 2-3 days, then 20 mg for 2 days, then 10 mg for 4 days, then stop. Start treatment immediately if there are signs of an oral lesion.

Fox-Fordyce disease (an inflammatory response that blocks sweat ducts and causes intense itching)

Treatment includes estrogen (2.5 mg per day) and tretinoin (Retin-A, apply once daily), usually given together. Suggest that patients try the Instant Ocean salt water treatment in the bath once daily (see details above under folliculitis entry).

Genital warts

Vaporize the warts via laser. “If they look like they’re recurring, I put them on interferon for 3 months because otherwise they just keep recurring,” Dr. Baggish said. “You could put topical treatments on them, but they’ll recur.”

Dr. Baggish, of the University of California, San Francisco, had no relevant financial disclosures. The meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

LAS VEGAS – Gynecologist Michael S. Baggish, MD, offered tips about diagnosis and treatment of vulvar conditions at the Pelvic Anatomy and Gynecologic Surgery Symposium.

Pubic lice

Treat with malathion 0.5% lotion (Ovide), permethrin 1%-5% (Nix), or lindane 1% (Kwell). Be aware that the U.S. Library of Medicine cautions that lindane can cause serious side effects, and patients should use it only “if there is some reason you cannot use the other medications or if you have tried the other medications and they have not worked.”

Pruritus (itchy skin)

Eliminate possible contact allergens such as soaps, detergents, and undergarments. Swabs with 2% acetic acid solution can assist with general hygiene. It’s important to address secondary infections, and control of diet and stress may be helpful.

Folliculitis (inflammation of hair follicles)

A salt water bath can be helpful. Try 2 cups of “Instant Ocean” – a sea salt product for aquariums – in a shallow bath twice daily.

It can be treated with silver sulfadiazine (Silvadene) cream (three times daily and at bedtime) or clindamycin (Cleocin) cream (three times daily and at bedtime).

Consider a systemic drug after culture results come back if needed.
 

Lichen sclerosus (a skin inflammation also known as white spot disease)

“I see a lot of lichen sclerosus,” Dr. Baggish said. “Every single practice day, I’m seeing two or three [cases].”

Topical treatments include testosterone cream (which has low efficacy) and topical corticosteroid creams and ointments (the standard treatment).

Other treatments provide better and more consistent results: Etretinate (Tegison), a retinoid that is expensive and can produce serious side effects, and injectable dexamethasone (Decadron), which can stop progression.

Be aware that 10% of patients with this condition may develop squamous cell carcinoma. Monitor for any changes in appearance and biopsy if needed.

Behçet’s disease (a blood vessel inflammation disorder also known as silk road disease)

This rare condition can cause mouth and genital ulcers and uveitis (eye inflammation). For treatment, start 40 mg prednisone for 2-3 days, then 20 mg for 2 days, then 10 mg for 4 days, then stop. Start treatment immediately if there are signs of an oral lesion.

Fox-Fordyce disease (an inflammatory response that blocks sweat ducts and causes intense itching)

Treatment includes estrogen (2.5 mg per day) and tretinoin (Retin-A, apply once daily), usually given together. Suggest that patients try the Instant Ocean salt water treatment in the bath once daily (see details above under folliculitis entry).

Genital warts

Vaporize the warts via laser. “If they look like they’re recurring, I put them on interferon for 3 months because otherwise they just keep recurring,” Dr. Baggish said. “You could put topical treatments on them, but they’ll recur.”

Dr. Baggish, of the University of California, San Francisco, had no relevant financial disclosures. The meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.