Cleansing is one of the most important steps in any skin care routine, but the surfeit of products on the market can lead to patients selecting an inappropriate cleanser for their skin type. This can engender various adverse cutaneous effects, including xerosis, flaking, acne, and flare-ups of chronic skin conditions such as eczema and rosacea. For example, acne medications are better tolerated when the proper cleanser is used. Cleanser choice is particularly important for individuals with dry skin who have an impaired barrier and those with sensitive skin who are susceptible to inflammation. The following discussion focuses on the factors that practitioners should address with patients when recommending cleansing products to help them maximize their outcomes and maintain clear, healthy-looking skin.

TYPES OF CLEANSERS

Foaming agents

Anionic surface acting agents (surfactants or detergents) produce foam and display the greatest cleansing potency. (Table 1). Because these detergents remove lipids from the skin’s surface and protective bilayer membrane barrier, they should only be used only by individuals with increased sebum production. Ingredients in this category injure the skin barrier and make the skin more susceptible to irritant reactions.1 For example, the widely used compound sodium lauryl sulfate (SLS), which strips lipids from the skin, irritates the skin to such an extent that it is used in research labs to hinder the skin barrier to test “barrier repair products.” The “sulfate- free” trend originates from the irritation caused by SLS. The barrier disruption caused by SLS can be used to intentionally damage the skin barrier to allow increased penetration of chemical peeling products and other therapeutic agents. An alternative to SLS is sodium laureth sulfate (or sodium lauryl ether sulfate, also known as SLES), which exhibits foaming attributes but is less likely than SLS to cause irritation. We often use a foaming cleanser in our practice prior to injectable procedures to ensure that makeup and debris are removed from the skin, and to decrease the time needed for topical lidocaine to penetrate into the skin. If you adopt this strategy, you should follow the injectable procedure with a barrier repair moisturizer.

liza5450/Thinkstock

Nonfoaming agents

These agents were developed through efforts to reduce detergent irritancy. This class of cleansers includes superfatted soaps, combination bars (“combars”), syndet bars (composed of synthetic surfactants) and compounds that deposit lipids on the skin, such as creams, lotions and oils. Cream, milk, cold creams, and oil cleansers fall into this category. These products usually have a neutral pH, and include ingredients such as alkyl glyceryl, ether sulfonate, alpha olefin sulfonates, betaines, sulfosuccinates, sodium cocoyl monoglyceride sulfate, and sodium cocoyl isethionate. Organic nonfoaming agents are also available, and may include saponins, a large family of structurally related compounds derived from plant, and sucrose laurate. Nonfoaming cleansers are most appropriate for dry skin types. Oily skin types often report that they “do not feel clean” when they use these cleansers.

Hydroxy acid cleansers

Alpha hydroxy acids (AHAs) are well suited for use by individuals with dry skin because hydroxy acids act as humectants (water-soluble materials with high water absorption capabilities). These hydrophilic cleansers provide exfoliation, and are appropriate for individuals with dry skin and acne because their low pH contributes to an inhospitable microbiome for Propionibacterium acnes, making it harder for the bacteria to thrive. Importantly, the exfoliating activity imparted by hydroxy acids sets the stage for better penetration into the stratum corneum by ingredients applied subsequent to the cleanser. Alpha hydroxy acid cleansers do not dry out the skin the way that salicylic acid cleansers do because their hydrophilic nature makes them unable to penetrate through sebum.

Salicylic acid (SA) cleansers are a member of the aspirin family and therefore confer anti-inflammatory properties. Salicylic acid is lipophilic and can penetrate through the sebum derived lipids into pores. They are the most effective cleansers to unclog pores. Therefore, SA cleansers are ideal for use by individuals with oily, sensitive skin prone to acne, seborrheic dermatitis, or rosacea. The exfoliation yielded by salicylic acid also enhances skin barrier penetration by ingredients applied after its use and is well tolerated by individuals with oily skin. Dry skin types, especially those on retinoids and benzoyl peroxide, will not tolerate SA as well as they will AHA cleansers.

Antibacterial cleansers

Antibacterial cleansers contain ingredients that reduce P. acnes and other types of bacteria on the skin. These products include benzoyl peroxide (BP), silver, hypochlorous acid, and sodium hypochlorite. Benzoyl peroxide can be highly irritating and is not well tolerated by patients with dry skin. Silver has a long history, having been used as an antibacterial agent since the times of King Herod. On the other hand, hypochlorous acid and sodium hypochlorite are novel entrants in the cleansing realm, particularly for individuals with acne. In fact, sodium hypochlorite is formulated to be mild enough for daily use while still sufficiently effective for acne-prone skin.

CLEANSER CHOICE BY SKIN ISSUE

Acne

Recommending the right cleanser for acne-prone skin first depends on whether the patient has oily or dry skin. Individuals with dry skin and acne cannot tolerate drying acne medications. Choosing the correct cleanser and moisturizer can help acne patients be more compliant with the acne treatment plan because of fewer side effects. Dry skin acne types often need two different cleansers. For the morning cleanser, AHA cleansers such as glycolic acid are effective at managing dry. acne-prone skin because glycolic acid has a relatively low pH. P. acnes is less likely to grow on skin with a lower pH.

Hydroxy acids help prevent clogged pores and exfoliate dead skin, which helps prevent acne comedones. Glycolic acid also serves as a humectant ingredient. Creamy cleansers should be used once daily, preferably at night for patients who use makeup since these products are effective at makeup removal. Foaming cleansers should never be used on dry, acne-prone skin. Individuals with the acne subtype of sensitive skin should avoid using scrubs, loofahs, and other forms of mechanical exfoliation.

Patients with oily skin and acne are easier to treat than are dry types because they can better tolerate acne medications. I recommend a salicylic acid cleanser in the morning to unclog pores. The anti-inflammatory properties of salicylic acid help prevent the formation of papules and pustules that characterize acne. Twice-daily use of salicylic acid by patients with oily skin and acne may feel too drying when combined with acne medications such as a retinoid and benzoyl peroxide. If this is the case, a foaming cleanser can be used in the evening to remove dirt, makeup, sunscreen, and debris that can clog pores and exacerbate acne.

Rosacea

Most dry skin type rosacea patients flush red when they wash their face, even if they only use water. The friction alone is enough to cause them to react. Rosacea patients can skip the morning cleanse to help reduce this skin irritation and flushing. Instead they should apply their a.m. anti-redness products followed by a sunscreen appropriate for their skin type. In the evening, a soothing, nonfoaming cleanser with anti-inflammatory ingredients is the best choice to remove makeup, sunscreen, and any built-up dirt or bacteria from the skin’s surface. This should be followed by an anti-redness product that targets the inflammation caused by rosacea.

Anti-inflammatory ingredients that can be found in soothing cleansers and moisturizers for rosacea prone skin include argan oil, green tea, feverfew, chamomile, licorice extract, and aloe.

Patients with very oily skin who have rosacea need to cleanse twice daily to remove excess oil to prevent comedones and acne lesions. A foaming cleanser that contains anti-inflammatory ingredients such as green tea, feverfew, licorice extract, aloe, niacinamide, green tea, and salicylic acid are a good choice for oily rosacea prone skin types.

All rosacea patients should be counseled to avoid mechanical exfoliation, including cleansing scrubs, chemical exfoliants, and abrasive loofahs or cloths.

Eczema

Patients with eczema should choose the same nonfoaming cleansers recommended for dry skin. For patients with frequent skin infections, hypochlorite and silver are beneficial ingredients found in cleansers to help decrease skin bacteria and prevent infections. Foaming cleansers should never be used in eczema prone types.

Conclusion

Cleansers play an important role in skin care because they affect the skin barrier, pH of the skin, presence of bacteria, condition of the pores, and penetration of the post cleanser–applied ingredients. Knowing which cleansing product to use based on a patient’s skin type is critical to recommending the proper ingredients so that patients can achieve and maintain healthy skin.

Table 1. Ingredients used in foaming cleansers

Acyl glycinates

Acylglutamates

Alkyl acyl isethionates

Alkyl carboxylates

Alkyl ether sulfates

Alkyl ethoxy sulfates

Alkyl phosphates

Alkyl sulfates

Alkyl sulfonates

Alkyl sulfosuccinates

Alkyl taurates
 

Reference

1. Contact Dermatitis. 1995 Oct;33(4):217-25

Cleansing is one of the most important steps in any skin care routine, but the surfeit of products on the market can lead to patients selecting an inappropriate cleanser for their skin type. This can engender various adverse cutaneous effects, including xerosis, flaking, acne, and flare-ups of chronic skin conditions such as eczema and rosacea. For example, acne medications are better tolerated when the proper cleanser is used. Cleanser choice is particularly important for individuals with dry skin who have an impaired barrier and those with sensitive skin who are susceptible to inflammation. The following discussion focuses on the factors that practitioners should address with patients when recommending cleansing products to help them maximize their outcomes and maintain clear, healthy-looking skin.

TYPES OF CLEANSERS

Foaming agents

Anionic surface acting agents (surfactants or detergents) produce foam and display the greatest cleansing potency. (Table 1). Because these detergents remove lipids from the skin’s surface and protective bilayer membrane barrier, they should only be used only by individuals with increased sebum production. Ingredients in this category injure the skin barrier and make the skin more susceptible to irritant reactions.1 For example, the widely used compound sodium lauryl sulfate (SLS), which strips lipids from the skin, irritates the skin to such an extent that it is used in research labs to hinder the skin barrier to test “barrier repair products.” The “sulfate- free” trend originates from the irritation caused by SLS. The barrier disruption caused by SLS can be used to intentionally damage the skin barrier to allow increased penetration of chemical peeling products and other therapeutic agents. An alternative to SLS is sodium laureth sulfate (or sodium lauryl ether sulfate, also known as SLES), which exhibits foaming attributes but is less likely than SLS to cause irritation. We often use a foaming cleanser in our practice prior to injectable procedures to ensure that makeup and debris are removed from the skin, and to decrease the time needed for topical lidocaine to penetrate into the skin. If you adopt this strategy, you should follow the injectable procedure with a barrier repair moisturizer.

liza5450/Thinkstock

Nonfoaming agents

These agents were developed through efforts to reduce detergent irritancy. This class of cleansers includes superfatted soaps, combination bars (“combars”), syndet bars (composed of synthetic surfactants) and compounds that deposit lipids on the skin, such as creams, lotions and oils. Cream, milk, cold creams, and oil cleansers fall into this category. These products usually have a neutral pH, and include ingredients such as alkyl glyceryl, ether sulfonate, alpha olefin sulfonates, betaines, sulfosuccinates, sodium cocoyl monoglyceride sulfate, and sodium cocoyl isethionate. Organic nonfoaming agents are also available, and may include saponins, a large family of structurally related compounds derived from plant, and sucrose laurate. Nonfoaming cleansers are most appropriate for dry skin types. Oily skin types often report that they “do not feel clean” when they use these cleansers.

Hydroxy acid cleansers

Alpha hydroxy acids (AHAs) are well suited for use by individuals with dry skin because hydroxy acids act as humectants (water-soluble materials with high water absorption capabilities). These hydrophilic cleansers provide exfoliation, and are appropriate for individuals with dry skin and acne because their low pH contributes to an inhospitable microbiome for Propionibacterium acnes, making it harder for the bacteria to thrive. Importantly, the exfoliating activity imparted by hydroxy acids sets the stage for better penetration into the stratum corneum by ingredients applied subsequent to the cleanser. Alpha hydroxy acid cleansers do not dry out the skin the way that salicylic acid cleansers do because their hydrophilic nature makes them unable to penetrate through sebum.

Salicylic acid (SA) cleansers are a member of the aspirin family and therefore confer anti-inflammatory properties. Salicylic acid is lipophilic and can penetrate through the sebum derived lipids into pores. They are the most effective cleansers to unclog pores. Therefore, SA cleansers are ideal for use by individuals with oily, sensitive skin prone to acne, seborrheic dermatitis, or rosacea. The exfoliation yielded by salicylic acid also enhances skin barrier penetration by ingredients applied after its use and is well tolerated by individuals with oily skin. Dry skin types, especially those on retinoids and benzoyl peroxide, will not tolerate SA as well as they will AHA cleansers.

Antibacterial cleansers

Antibacterial cleansers contain ingredients that reduce P. acnes and other types of bacteria on the skin. These products include benzoyl peroxide (BP), silver, hypochlorous acid, and sodium hypochlorite. Benzoyl peroxide can be highly irritating and is not well tolerated by patients with dry skin. Silver has a long history, having been used as an antibacterial agent since the times of King Herod. On the other hand, hypochlorous acid and sodium hypochlorite are novel entrants in the cleansing realm, particularly for individuals with acne. In fact, sodium hypochlorite is formulated to be mild enough for daily use while still sufficiently effective for acne-prone skin.

CLEANSER CHOICE BY SKIN ISSUE

Acne

Recommending the right cleanser for acne-prone skin first depends on whether the patient has oily or dry skin. Individuals with dry skin and acne cannot tolerate drying acne medications. Choosing the correct cleanser and moisturizer can help acne patients be more compliant with the acne treatment plan because of fewer side effects. Dry skin acne types often need two different cleansers. For the morning cleanser, AHA cleansers such as glycolic acid are effective at managing dry. acne-prone skin because glycolic acid has a relatively low pH. P. acnes is less likely to grow on skin with a lower pH.

Hydroxy acids help prevent clogged pores and exfoliate dead skin, which helps prevent acne comedones. Glycolic acid also serves as a humectant ingredient. Creamy cleansers should be used once daily, preferably at night for patients who use makeup since these products are effective at makeup removal. Foaming cleansers should never be used on dry, acne-prone skin. Individuals with the acne subtype of sensitive skin should avoid using scrubs, loofahs, and other forms of mechanical exfoliation.

Patients with oily skin and acne are easier to treat than are dry types because they can better tolerate acne medications. I recommend a salicylic acid cleanser in the morning to unclog pores. The anti-inflammatory properties of salicylic acid help prevent the formation of papules and pustules that characterize acne. Twice-daily use of salicylic acid by patients with oily skin and acne may feel too drying when combined with acne medications such as a retinoid and benzoyl peroxide. If this is the case, a foaming cleanser can be used in the evening to remove dirt, makeup, sunscreen, and debris that can clog pores and exacerbate acne.

Rosacea

Most dry skin type rosacea patients flush red when they wash their face, even if they only use water. The friction alone is enough to cause them to react. Rosacea patients can skip the morning cleanse to help reduce this skin irritation and flushing. Instead they should apply their a.m. anti-redness products followed by a sunscreen appropriate for their skin type. In the evening, a soothing, nonfoaming cleanser with anti-inflammatory ingredients is the best choice to remove makeup, sunscreen, and any built-up dirt or bacteria from the skin’s surface. This should be followed by an anti-redness product that targets the inflammation caused by rosacea.

Anti-inflammatory ingredients that can be found in soothing cleansers and moisturizers for rosacea prone skin include argan oil, green tea, feverfew, chamomile, licorice extract, and aloe.

Patients with very oily skin who have rosacea need to cleanse twice daily to remove excess oil to prevent comedones and acne lesions. A foaming cleanser that contains anti-inflammatory ingredients such as green tea, feverfew, licorice extract, aloe, niacinamide, green tea, and salicylic acid are a good choice for oily rosacea prone skin types.

All rosacea patients should be counseled to avoid mechanical exfoliation, including cleansing scrubs, chemical exfoliants, and abrasive loofahs or cloths.

Eczema

Patients with eczema should choose the same nonfoaming cleansers recommended for dry skin. For patients with frequent skin infections, hypochlorite and silver are beneficial ingredients found in cleansers to help decrease skin bacteria and prevent infections. Foaming cleansers should never be used in eczema prone types.

Conclusion

Cleansers play an important role in skin care because they affect the skin barrier, pH of the skin, presence of bacteria, condition of the pores, and penetration of the post cleanser–applied ingredients. Knowing which cleansing product to use based on a patient’s skin type is critical to recommending the proper ingredients so that patients can achieve and maintain healthy skin.

Table 1. Ingredients used in foaming cleansers

Acyl glycinates

Acylglutamates

Alkyl acyl isethionates

Alkyl carboxylates

Alkyl ether sulfates

Alkyl ethoxy sulfates

Alkyl phosphates

Alkyl sulfates

Alkyl sulfonates

Alkyl sulfosuccinates

Alkyl taurates
 

Reference

1. Contact Dermatitis. 1995 Oct;33(4):217-25

Cleansing is one of the most important steps in any skin care routine, but the surfeit of products on the market can lead to patients selecting an inappropriate cleanser for their skin type. This can engender various adverse cutaneous effects, including xerosis, flaking, acne, and flare-ups of chronic skin conditions such as eczema and rosacea. For example, acne medications are better tolerated when the proper cleanser is used. Cleanser choice is particularly important for individuals with dry skin who have an impaired barrier and those with sensitive skin who are susceptible to inflammation. The following discussion focuses on the factors that practitioners should address with patients when recommending cleansing products to help them maximize their outcomes and maintain clear, healthy-looking skin.

TYPES OF CLEANSERS

Foaming agents

Anionic surface acting agents (surfactants or detergents) produce foam and display the greatest cleansing potency. (Table 1). Because these detergents remove lipids from the skin’s surface and protective bilayer membrane barrier, they should only be used only by individuals with increased sebum production. Ingredients in this category injure the skin barrier and make the skin more susceptible to irritant reactions.1 For example, the widely used compound sodium lauryl sulfate (SLS), which strips lipids from the skin, irritates the skin to such an extent that it is used in research labs to hinder the skin barrier to test “barrier repair products.” The “sulfate- free” trend originates from the irritation caused by SLS. The barrier disruption caused by SLS can be used to intentionally damage the skin barrier to allow increased penetration of chemical peeling products and other therapeutic agents. An alternative to SLS is sodium laureth sulfate (or sodium lauryl ether sulfate, also known as SLES), which exhibits foaming attributes but is less likely than SLS to cause irritation. We often use a foaming cleanser in our practice prior to injectable procedures to ensure that makeup and debris are removed from the skin, and to decrease the time needed for topical lidocaine to penetrate into the skin. If you adopt this strategy, you should follow the injectable procedure with a barrier repair moisturizer.

liza5450/Thinkstock

Nonfoaming agents

These agents were developed through efforts to reduce detergent irritancy. This class of cleansers includes superfatted soaps, combination bars (“combars”), syndet bars (composed of synthetic surfactants) and compounds that deposit lipids on the skin, such as creams, lotions and oils. Cream, milk, cold creams, and oil cleansers fall into this category. These products usually have a neutral pH, and include ingredients such as alkyl glyceryl, ether sulfonate, alpha olefin sulfonates, betaines, sulfosuccinates, sodium cocoyl monoglyceride sulfate, and sodium cocoyl isethionate. Organic nonfoaming agents are also available, and may include saponins, a large family of structurally related compounds derived from plant, and sucrose laurate. Nonfoaming cleansers are most appropriate for dry skin types. Oily skin types often report that they “do not feel clean” when they use these cleansers.

Hydroxy acid cleansers

Alpha hydroxy acids (AHAs) are well suited for use by individuals with dry skin because hydroxy acids act as humectants (water-soluble materials with high water absorption capabilities). These hydrophilic cleansers provide exfoliation, and are appropriate for individuals with dry skin and acne because their low pH contributes to an inhospitable microbiome for Propionibacterium acnes, making it harder for the bacteria to thrive. Importantly, the exfoliating activity imparted by hydroxy acids sets the stage for better penetration into the stratum corneum by ingredients applied subsequent to the cleanser. Alpha hydroxy acid cleansers do not dry out the skin the way that salicylic acid cleansers do because their hydrophilic nature makes them unable to penetrate through sebum.

Salicylic acid (SA) cleansers are a member of the aspirin family and therefore confer anti-inflammatory properties. Salicylic acid is lipophilic and can penetrate through the sebum derived lipids into pores. They are the most effective cleansers to unclog pores. Therefore, SA cleansers are ideal for use by individuals with oily, sensitive skin prone to acne, seborrheic dermatitis, or rosacea. The exfoliation yielded by salicylic acid also enhances skin barrier penetration by ingredients applied after its use and is well tolerated by individuals with oily skin. Dry skin types, especially those on retinoids and benzoyl peroxide, will not tolerate SA as well as they will AHA cleansers.

Antibacterial cleansers

Antibacterial cleansers contain ingredients that reduce P. acnes and other types of bacteria on the skin. These products include benzoyl peroxide (BP), silver, hypochlorous acid, and sodium hypochlorite. Benzoyl peroxide can be highly irritating and is not well tolerated by patients with dry skin. Silver has a long history, having been used as an antibacterial agent since the times of King Herod. On the other hand, hypochlorous acid and sodium hypochlorite are novel entrants in the cleansing realm, particularly for individuals with acne. In fact, sodium hypochlorite is formulated to be mild enough for daily use while still sufficiently effective for acne-prone skin.

CLEANSER CHOICE BY SKIN ISSUE

Acne

Recommending the right cleanser for acne-prone skin first depends on whether the patient has oily or dry skin. Individuals with dry skin and acne cannot tolerate drying acne medications. Choosing the correct cleanser and moisturizer can help acne patients be more compliant with the acne treatment plan because of fewer side effects. Dry skin acne types often need two different cleansers. For the morning cleanser, AHA cleansers such as glycolic acid are effective at managing dry. acne-prone skin because glycolic acid has a relatively low pH. P. acnes is less likely to grow on skin with a lower pH.

Hydroxy acids help prevent clogged pores and exfoliate dead skin, which helps prevent acne comedones. Glycolic acid also serves as a humectant ingredient. Creamy cleansers should be used once daily, preferably at night for patients who use makeup since these products are effective at makeup removal. Foaming cleansers should never be used on dry, acne-prone skin. Individuals with the acne subtype of sensitive skin should avoid using scrubs, loofahs, and other forms of mechanical exfoliation.

Patients with oily skin and acne are easier to treat than are dry types because they can better tolerate acne medications. I recommend a salicylic acid cleanser in the morning to unclog pores. The anti-inflammatory properties of salicylic acid help prevent the formation of papules and pustules that characterize acne. Twice-daily use of salicylic acid by patients with oily skin and acne may feel too drying when combined with acne medications such as a retinoid and benzoyl peroxide. If this is the case, a foaming cleanser can be used in the evening to remove dirt, makeup, sunscreen, and debris that can clog pores and exacerbate acne.

Rosacea

Most dry skin type rosacea patients flush red when they wash their face, even if they only use water. The friction alone is enough to cause them to react. Rosacea patients can skip the morning cleanse to help reduce this skin irritation and flushing. Instead they should apply their a.m. anti-redness products followed by a sunscreen appropriate for their skin type. In the evening, a soothing, nonfoaming cleanser with anti-inflammatory ingredients is the best choice to remove makeup, sunscreen, and any built-up dirt or bacteria from the skin’s surface. This should be followed by an anti-redness product that targets the inflammation caused by rosacea.

Anti-inflammatory ingredients that can be found in soothing cleansers and moisturizers for rosacea prone skin include argan oil, green tea, feverfew, chamomile, licorice extract, and aloe.

Patients with very oily skin who have rosacea need to cleanse twice daily to remove excess oil to prevent comedones and acne lesions. A foaming cleanser that contains anti-inflammatory ingredients such as green tea, feverfew, licorice extract, aloe, niacinamide, green tea, and salicylic acid are a good choice for oily rosacea prone skin types.

All rosacea patients should be counseled to avoid mechanical exfoliation, including cleansing scrubs, chemical exfoliants, and abrasive loofahs or cloths.

Eczema

Patients with eczema should choose the same nonfoaming cleansers recommended for dry skin. For patients with frequent skin infections, hypochlorite and silver are beneficial ingredients found in cleansers to help decrease skin bacteria and prevent infections. Foaming cleansers should never be used in eczema prone types.

Conclusion

Cleansers play an important role in skin care because they affect the skin barrier, pH of the skin, presence of bacteria, condition of the pores, and penetration of the post cleanser–applied ingredients. Knowing which cleansing product to use based on a patient’s skin type is critical to recommending the proper ingredients so that patients can achieve and maintain healthy skin.

Table 1. Ingredients used in foaming cleansers

Acyl glycinates

Acylglutamates

Alkyl acyl isethionates

Alkyl carboxylates

Alkyl ether sulfates

Alkyl ethoxy sulfates

Alkyl phosphates

Alkyl sulfates

Alkyl sulfonates

Alkyl sulfosuccinates

Alkyl taurates
 

Reference

1. Contact Dermatitis. 1995 Oct;33(4):217-25

Take-Home Points

• SSIs after TJA pose a substantial burden on patients, surgeons, and the healthcare system.
• While different forms of preoperative skin preparation have shown varying outcomes after TJA, the importance of preoperative patient optimization (nutritional status, immune function, etc) cannot be overstated. 
• Intraoperative infection prevention measures include cutaneous preparation, gloving, body exhaust suits, surgical drapes, OR staff traffic and ventilation flow, and antibiotic-loaded cement. 
• Antibiotic prophylaxis for dental procedures in TJA patients continues to remain a controversial issue with conflicting recommendations.
• SSIs have considerable financial costs and require increased resource utilization. Given the significant economic burden associated with TJA infections, it is imperative for orthopedists to establish practical and cost-effective strategies to prevent these devastating complications.

Surgical-site infection (SSI), a potentially devastating complication of lower extremity total joint arthroplasty (TJA), is estimated to occur in 1% to 2.5% of cases annually.¹ Infection after TJA places a significant burden on patients, surgeons, and the healthcare system. Revision procedures that address infection after total hip arthroplasty (THA) are associated with more hospitalizations, more operations, longer hospital stay, and higher outpatient costs in comparison with primary THAs and revision surgeries for aseptic loosening.² If left untreated, a SSI can go deeper into the joint and develop into a periprosthetic infection, which can be disastrous and costly. A periprosthetic joint infection study that used 2001 to 2009 Nationwide Inpatient Sample (NIS) data found that the cost of revision procedures increased to $560 million from $320 million, and was projected to reach $1.62 billion by 2020.³ Furthermore, society incurs indirect costs as a result of patient disability and loss of wages and productivity.² Therefore, the issue of infection after TJA is even more crucial in our cost-conscious healthcare environment. 

Patient optimization, advances in surgical technique, sterile protocol, and operative procedures have been effective in reducing bacterial counts at incision sites and minimizing SSIs. As a result, infection rates have leveled off after rising for a decade.⁴ Although infection prevention modalities have their differences, routine use is fundamental and recommended by the Hospital Infection Control Practices Advisory Committee.⁵ Furthermore, both the US Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee^6,7 recently updated their SSI prevention guidelines by incorporating evidence-based methodology, an element missing from earlier recommendations.

The etiologies of postoperative SSIs have been discussed ad nauseam, but there are few reports summarizing the literature on infection prevention modalities. In this review, we identify and examine SSI prevention strategies as they relate to lower extremity TJA. Specifically, we discuss the literature on the preoperative, intraoperative, and postoperative actions that can be taken to reduce the incidence of SSIs after TJA. We also highlight the economic implications of SSIs that occur after TJA.

Methods

For this review, we performed a literature search with PubMed, EBSCOhost, and Scopus. We looked for reports published between the inception of each database and July 2016. Combinations of various search terms were used: surgical site, infection, total joint arthroplasty, knee, hip, preoperative, intraoperative, perioperative, postoperative, preparation, nutrition, ventilation, antibiotic, body exhaust suit, gloves, drain, costs, economic, and payment.

Our search identified 195 abstracts. Drs. Mistry and Chughtai reviewed these to determine which articles were relevant. For any uncertainties, consensus was reached with the help of Dr. Delanois. Of the 195 articles, 103 were potentially relevant, and 54 of the 103 were excluded for being not relevant to preventing SSIs after TJA or for being written in a language other than English. The references in the remaining articles were assessed, and those with potentially relevant titles were selected for abstract review. This step provided another 35 articles. After all exclusions, 48 articles remained. We discuss these in the context of preoperative, intraoperative, and postoperative measures and economic impact.

Results

Preoperative Measures

Skin Preparation. Preoperative skin preparation methods include standard washing and rinsing, antiseptic soaps, and iodine-based or chlorhexidine gluconate-based antiseptic showers or skin cloths. Iodine-based antiseptics are effective against a wide range of Gram-positive and Gram-negative bacteria, fungi, and viruses. These agents penetrate the cell wall, oxidize the microbial contents, and replace those contents with free iodine molecules.⁸ Iodophors are free iodine molecules associated with a polymer (eg, polyvinylpyrrolidone); the iodophor povidone-iodine is bactericidal.⁹ Chlorhexidine gluconate-based solutions are effective against many types of yeast, Gram-positive and Gram-negative bacteria, and a wide variety of viruses.⁹ Both solutions are useful. Patients with an allergy to iodine can use chlorhexidine. Table 1 summarizes the studies on preoperative measures for preventing SSIs.

There is no shortage of evidence of the efficacy of these antiseptics in minimizing the incidence of SSIs. Hayek and colleagues¹⁰ prospectively analyzed use of different preoperative skin preparation methods in 2015 patients. Six weeks after surgery, the infection rate was significantly lower with use of chlorhexidine than with use of an unmedicated bar of soap or placebo cloth (9% vs 11.7% and 12.8%, respectively; P < .05). In a study of 100 patients, Murray and colleagues¹¹ found the overall bacterial culture rate was significantly lower for those who used a 2% chlorhexidine gluconate cloth before shoulder surgery than for those who took a standard shower with soap (66% vs 94%; P = .0008). Darouiche and colleagues¹² found the overall SSI rate was significantly lower for 409 surgical patients prepared with chlorhexidine-alcohol than for 440 prepared with povidone-iodine (9.5% vs 16.1%; P = .004; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85).

Chlorhexidine gluconate-impregnated cloths have also had promising results, which may be attributed to general ease of use and potentially improved patient adherence. Zywiel and colleagues¹³ reported no SSIs in 136 patients who used these cloths at home before total knee arthroplasty (TKA) and 21 SSIs (3.0%) in 711 patients who did not use the cloths. In a study of 2545 THA patients, Kapadia and colleagues¹⁴ noted a significantly lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths than with only in-hospital perioperative skin preparation (0.5% vs 1.7%; P = .04). In 2293 TKAs, Johnson and colleagues¹⁵ similarly found a lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths (0.6% vs 2.2%; P = .02). In another prospective, randomized trial, Kapadia and colleagues16 compared 275 patients who used chlorhexidine cloths the night before and the morning of lower extremity TJA surgery with 279 patients who underwent standard-of-care preparation (preadmission bathing with antibacterial soap and water). The chlorhexidine cohort had a lower overall incidence of infection (0.4% vs 2.9%; P = .049), and the standard-of-care cohort had a stronger association with infection (odds ratio [OR], 8.15; 95% CI, 1.01-65.6). 

Patient Optimization. Poor nutritional status may compromise immune function, potentially resulting in delayed healing, increased risk of infection, and, ultimately, negative postoperative outcomes. Malnutrition can be diagnosed on the basis of a prealbumin level of <15 mg/dL (normal, 15-30 mg/dL), a serum albumin level of <3.4 g/dL (normal, 3.4-5.4 g/dL), or a total lymphocyte count under 1200 cells/μL (normal, 3900-10,000 cells/μL).^17-19 Greene and colleagues¹⁸ found that patients with preoperative malnutrition had up to a 7-fold higher rate of infection after TJA. In a study of 135 THAs and TKAs, Alfargieny and colleagues²⁰ found preoperative serum albumin was the only nutritional biomarker predictive of SSI (P = .011). Furthermore, patients who take immunomodulating medications (eg, for inflammatory arthropathies) should temporarily discontinue them before surgery in order to lower their risk of infection.²¹ 

Smoking is well established as a major risk factor for poor outcomes after surgery. It is postulated that the vasoconstrictive effects of nicotine and the hypoxic effects of carbon monoxide contribute to poor wound healing.²² In a meta-analysis of 4 studies, Sørensen²³ found smokers were at increased risk for wound complications (OR, 2.27; 95% CI, 1.82-2.84), delayed wound healing and dehiscence (OR, 2.07; 95% CI, 1.53-2.81), and infection (OR, 1.79; 95% CI, 1.57-2.04). Moreover, smoking cessation decreased the incidence of SSIs (OR, 0.43; 95% CI, 0.21-0.85). A meta- analysis by Wong and colleagues²⁴ revealed an inflection point for improved outcomes in patients who abstained from smoking for at least 4 weeks before surgery. Risk of infection was lower for these patients than for current smokers (OR, 0.69; 95% CI, 0.56-0.84).

Other comorbidities contribute to SSIs as well. In their analysis of American College of Surgeons National Surgical Quality Improvement Program registry data on 25,235 patients who underwent primary and revision lower extremity TJA, Pugely and colleagues²⁵ found that, in the primary TJA cohort, body mass index (BMI) of >40 kg/m2 (OR, 1.9; 95% CI, 1.3-2.9), electrolyte disturbance (OR, 2.4; 95% CI, 1.0-6.0), and hypertension diagnosis (OR, 1.5; 95% CI, 1.1-2.0) increased the risk of SSI within 30 days. Furthermore, diabetes mellitus delays collagen synthesis, impairs lymphocyte function, and impairs wound healing, which may lead to poor recovery and higher risk of infection.²⁶ In a study of 167 TKAs performed in 115 patients with type 2 diabetes mellitus, Han and Kang²⁶ found that wound complications were 6 times more likely in those with hemoglobin A1c (HbA1c) levels higher than 8% than in those with lower HbA1c levels (OR, 6.07; 95% CI, 1.12-33.0). In a similar study of 462 patients with diabetes, Hwang and colleagues²⁷ found a higher likelihood of superficial SSIs in patients with HbA1c levels >8% (OR, 6.1; 95% CI, 1.6-23.4; P = .008). This association was also found in patients with a fasting blood glucose level of >200 mg/dL (OR, 9.2; 95% CI, 2.2-38.2; P = .038).

Methicillin-resistant Staphylococcus aureus (MRSA) is thought to account for 10% to 25% of all periprosthetic infections in the United States.28 Nasal colonization by this pathogen increases the risk for SSIs; however, decolonization protocols have proved useful in decreasing the rates of colonization. Moroski and colleagues²⁹ assessed the efficacy of a preoperative 5-day course of intranasal mupirocin in 289 primary or revision TJA patients. Before surgery, 12 patients had positive MRSA cultures, and 44 had positive methicillin-sensitive S aureus (MSSA) cultures. On day of surgery, a significant reduction in MRSA (P = .0073) and MSSA (P = .0341) colonization was noted. Rao and colleagues³⁰ found that the infection rate decreased from 2.7% to 1.2% in 2284 TJA patients treated with a decolonization protocol (P = .009). 

Intraoperative Measures

Cutaneous Preparation. The solutions used in perioperative skin preparation are similar to those used preoperatively: povidone-iodine, alcohol, and chlorhexidine. The efficacy of these preparations varies. Table 2 summarizes the studies on intraoperative measures for preventing SSIs.

The literature also highlights the importance of technique in incision-site preparation. In a prospective study, Morrison and colleagues³³ randomly assigned 600 primary TJA patients to either (1) use of alcohol and povidone-iodine before draping, with additional preparation with iodine povacrylex (DuraPrep) and isopropyl alcohol before application of the final drape (300-patient intervention group) or (2) only use of alcohol and povidone-iodine before draping (300-patient control group). At the final follow-up, the incidence of SSI was significantly lower in the intervention group than in the control group (1.8% vs 6.5%; P = .015). In another study that assessed perioperative skin preparation methods, Brown and colleagues34 found that airborne bacteria levels in operating rooms were >4 times higher with patients whose legs were prepared by a scrubbed, gowned leg-holder than with patients whose legs were prepared by an unscrubbed, ungowned leg-holder (P = .0001).

Hair Removal. Although removing hair from surgical sites is common practice, the literature advocating it varies. A large comprehensive review³⁵ revealed no increased risk of SSI with removing vs not removing hair (RR, 1.65; 95% CI, 0.85-3.19). On the other hand, some hair removal methods may affect the incidence of infection. For example, use of electric hair clippers is presumed to reduce the risk of SSIs, whereas traditional razors may compromise the epidermal barriers and create a pathway for bacterial colonization.^5,36,37 In the aforementioned review,³⁵ SSIs were more than twice as likely to occur with hair removed by shaving than with hair removed by electric clippers (RR, 2.02; 95% CI, 1.21-3.36). Cruse and Foord³⁸ found a higher rate of SSIs with hair removed by shaving than with hair removed by clipping (2.3% vs 1.7%). Most surgeons agree that, if given the choice, they would remove hair with electric clippers rather than razors.

Gloves. Almost all orthopedists double their gloves for TJA cases. Over several studies, the incidence of glove perforation during orthopedic procedures has ranged from 3.6% to 26%,^39-41 depending on the operating room personnel and glove layering studied. Orthopedists must know this startling finding, as surgical glove perforation is associated with an increase in the rate of SSIs, from 1.7% to 5.7%.³⁸ Carter and colleagues⁴² found the highest risk of glove perforation occurs when double-gloved attending surgeons, adult reconstruction fellows, and registered nurses initially assist during primary and revision TJA. In their study, outer and inner glove layers were perforated 2.5% of the time. All outer-layer perforations were noticed, but inner-layer perforations went unnoticed 81% of the time, which poses a potential hazard for both patients and healthcare personnel. In addition, there was a significant increase in the incidence of glove perforations for attending surgeons during revision TJA vs primary TJA (8.9% vs 3.7%; P = .04). This finding may be expected given the complexity of revision procedures, the presence of sharp bony and metal edges, and the longer operative times. Giving more attention to glove perforations during arthroplasties may mitigate the risk of SSI. As soon as a perforation is noticed, the glove should be removed and replaced.

Body Exhaust Suits. Early TJAs had infection rates approaching 10%.⁴³ Bacterial-laden particles shed from surgical staff were postulated to be the cause,^44,45 and this idea prompted the development of new technology, such as body exhaust suits, which have demonstrated up to a 20-fold reduction in airborne bacterial contamination and decreased incidence of deep infection, from 1% to 0.1%, as compared with conventional surgical attire.⁴⁶ However, the efficacy of these suits was recently challenged. Hooper and colleagues⁴⁷ assessed >88,000 TJA cases in the New Zealand Joint Registry and found a significant increase in early revision THA for deep infection with vs without use of body exhaust suits (0.186% vs 0.064%; P < .0001). The incidence of revision TKAs for deep infections with use of these suits was similar (0.243% vs 0.098%; P < .001). Many of the surgeons surveyed indicated their peripheral vision was limited by the suits, which may contribute to sterile field contamination. By contrast, Miner and colleagues⁴⁸ were unable to determine an increased risk of SSI with use of body exhaust suits (RR, 0.75; 95% CI, 0.34-1.62), though there was a trend toward more infections without suits. Moreover, these suits are effective in reducing mean air bacterial counts (P = .014), but it is not known if this method correlates with mean wound bacterial counts (r = –.011) and therefore increases the risk of SSI.⁴⁹

Surgical Drapes. Surgical draping, including cloths, iodine-impregnated materials, and woven or unwoven materials, is the standard of care worldwide. The particular draping technique usually varies by surgeon. Plastic drapes are better barriers than cloth drapes, as found in a study by Blom and colleagues⁵⁰: Bacterial growth rates were almost 10 times higher with use of wet woven cloth drapes than with plastic surgical drapes. These findings were supported in another, similar study by Blom and colleagues⁵¹: Wetting drapes with blood or normal saline enhanced bacterial penetration. In addition, wetting drapes with chlorhexidine or iodine reduced but did not eliminate bacterial penetration. Fairclough and colleagues⁵² emphasized that iodine-impregnated drapes reduced surgical-site bacterial contamination from 15% to 1.6%. However, a Cochrane review⁵³ found these drapes had no effect on the SSI rate (RR, 1.03; 95% CI, 0.06-1.66; P = .89), though the risk of infection was slightly higher with adhesive draping than with no drape (RR, 1.23; 95% CI, 1.02-1.48; P = .03).

Ventilation Flow. Laminar-airflow systems are widely used to prevent SSIs after TJA. Horizontal-flow and vertical-flow ventilation provides and maintains ultra-clean air in the operating room. Evans⁵⁴ found the bacterial counts in the air and the wound were lower with laminar airflow than without this airflow. The amount of airborne bacterial colony-forming units and dust large enough to carry bacteria was reduced to 1 or 2 particles more than 2 μm/m3 with use of a typical laminar- airflow system. In comparing 3922 TKA patients in laminar-airflow operating rooms with 4133 patients in conventional rooms, Lidwell and colleagues⁴⁶ found a significantly lower incidence of SSIs in patients in laminar-airflow operating rooms (0.6% vs 2.3%; P < .001).

Conversely, Miner and colleagues⁴⁸ did not find a lower risk of SSI with laminar-airflow systems (RR, 1.57; 95% CI, 0.75-3.31). In addition, in their analysis of >88,000 cases from the New Zealand Joint Registry, Hooper and colleagues⁴⁷ found that the incidence of early infections was higher with laminar-airflow systems than with standard airflow systems for both TKA (0.193% vs 0.100%; P = .019) and THA (0.148% vs 0.061%; P < .001). They postulated that vertically oriented airflow may have transmitted contaminated particles into the surgical sites. Additional evidence may be needed to resolve these conflicting findings and determine whether clean-air practices provide significant clinical benefit in the operating room.

Staff Traffic Volume. When staff enters or exits the operating room or makes extra movements during a procedure, airflow near the wound is disturbed and no longer able to remove sufficient airborne pathogens from the sterile field. The laminar- airflow pattern may be disrupted each time the operating room doors open and close, potentially allowing airborne pathogens to be introduced near the patient. Lynch and colleagues⁵⁵ found the operating room door opened almost 50 times per hour, and it took about 20 seconds to close each time. As a result, the door may remain open for up to 20 minutes per case, causing substantial airflow disruption and potentially ineffective removal of airborne bacterial particles. Similarly, Young and O’Regan⁵⁶ found the operating room door opened about 19 times per hour and took 20 seconds to close each time. The theater door was open an estimated 10.7% of each hour of sterile procedure. Presence of more staff also increases airborne bacterial counts. Pryor and Messmer⁵⁷ evaluated a cohort of 2864 patients to determine the effect of number of personnel in the operating theater on the incidence of SSIs. Infection rates were 6.27% with >17 different people entering the room and 1.52% with <9 different people entering the room. Restricting the number of people in the room may be one of the easiest and most efficient ways to prevent SSI.

Systemic Antibiotic Prophylaxis. Perioperative antibiotic use is vital in minimizing the risk of infection after TJA. The Surgical Care Improvement Project recommended beginning the first antimicrobial dose either within 60 minutes before surgical incision (for cephalosporin) or within 2 hours before incision (for vancomycin) and discontinuing the prophylactic antimicrobial agents within 24 hours after surgery ends.^58,59 However, Gorenoi and colleagues⁶⁰ were unable to recommend a way to select particular antibiotics, as they found no difference in the effectiveness of various antibiotic agents used in TKA. A systematic review by AlBuhairan and colleagues⁶¹ revealed that antibiotic prophylaxis (vs no prophylaxis) reduced the absolute risk of a SSI by 8% and the relative risk by 81% (P < 0.0001). These findings are supported by evidence of the efficacy of perioperative antibiotics in reducing the incidence of SSI.^62,63 Antibiotic regimens should be based on susceptibility and availability, depending on hospital prevalence of infections. Even more, patients should receive prophylaxis in a timely manner. Finally, bacteriostatic antibiotics (vancomycin) should not be used on their own for preoperative prophylaxis.

Antibiotic Cement. Antibiotic-loaded bone cement (ALBC), which locally releases antimicrobials in high concentration, is often used in revision joint arthroplasty, but use in primary joint arthroplasty remains controversial. In a study of THA patients, Parvizi and colleagues64 found infection rates of 1.2% with 2.3% with and without use of ALBC, respectively. Other studies have had opposing results. Namba and colleagues⁶⁵ evaluated 22,889 primary TKAs, 2030 (8.9%) of which used ALBC. The incidence of deep infection was significantly higher with ALBC than with regular bone cement (1.4% vs 0.7%; P = .002). In addition, a meta- analysis of >6500 primary TKA patients, by Zhou and colleagues,⁶⁶ revealed no significant difference in the incidence of deep SSIs with use of ALBC vs regular cement (1.32% vs 1.89%; RR, 0.75; 95% CI, 0.43-1.33; P = .33). More evidence is needed to determine the efficacy of ALBC in primary TJA. International Consensus Meeting on Periprosthetic Joint Infection participants recommended use of ALBC in high-risk patients, including patients who are obese or immunosuppressed or have diabetes or a prior history of infection.⁶⁷

Postoperative Measures

Antibiotic Prophylaxis. The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) have suggestions for antibiotic prophylaxis for patients at increased risk for infection. As of 2015, the ADA no longer recommends antibiotic prophylaxis for patients with prosthetic joint implants,68 whereas the AAOS considers all patients with TJA to be at risk.⁶⁹

Although recommendations exist, the actual risk of infection resulting from dental procedures and the role of antibiotic prophylaxis are not well defined. Berbari and colleagues⁷¹ found that antibiotic prophylaxis in high- or low-risk dental procedures did not decrease the risk of subsequent THA infection (OR, 0.9; 95% CI, 0.5-1.6) or TKA infection (OR, 1.2; 95% CI, 0.7-2.2). Moreover, the risk of infection was no higher for patients who had a prosthetic hip or knee and underwent a high- or low-risk dental procedure without antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4-1.6) than for similar patients who did not undergo a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Some studies highlight the low level of evidence supporting antibiotic prophylaxis during dental procedures.^72,73 However, there is no evidence of adverse effects of antibiotic prophylaxis. Given the potential high risk of infection after such procedures, a more robust body of evidence is needed to reach consensus.

Evacuation Drain Management. Prolonged use of surgical evacuation drains may be a risk factor for SSI. Therefore, early drain removal is paramount. Higher infection rates with prolonged drain use have been found in patients with persistent wound drainage, including malnourished, obese, and over-anticoagulated patients. Patients with wounds persistently draining for >1 week should undergo superficial wound irrigation and débridement. Jaberi and colleagues⁷⁴ assessed 10,325 TJA patients and found that the majority of persistent drainage ceased within 1 week with use of less invasive measures, including oral antibiotics and local wound care. Furthermore, only 28% of patients with persistent drainage underwent surgical débridement. It is unclear if this practice alone is appropriate. Infection should always be suspected and treated aggressively, and cultures should be obtained from synovial fluid before antibiotics are started, unless there is an obvious superficial infection that does not require further work-up.⁶⁷

Economic Impact

SSIs remain a significant healthcare issue, and the social and financial costs are staggering. Without appropriate measures in place, these complications will place a larger burden on the healthcare system primarily as a result of longer hospital stays, multiple procedures, and increased resource utilization.⁷⁵ Given the risk of progression to prosthetic joint infection, early preventive interventions must be explored.

Improved patient selection may be an important factor in reducing SSIs. In an analysis of 8494 joint arthroplasties, Malinzak and colleagues⁸⁰ noted that patients with a BMI of >50 kg/m2 had an increased OR of infection of 21.3 compared to those with BMI <50 kg/m2. Wagner and colleagues⁸¹ analyzed 21,361 THAs and found that, for every BMI unit over 25 kg/m2, there was an 8% increased risk of joint infection (P < .001). Although it is unknown if there is an association between reduction in preoperative BMI and reduction in postoperative complication risk, it may still be worthwhile and cost-effective to modify this and similar risk factors before elective procedures.

Market forces are becoming a larger consideration in healthcare and are being driven by provider competition.⁸² Treatment outcomes, quality of care, and healthcare prices have gained attention as a means of estimating potential costs.⁸³ In 2011, the Centers for Medicare & Medicaid Services (CMS) advanced the Bundled Payments for Care Improvement (BPCI) initiative, which aimed to provide better coordinated care of higher quality and lower cost.⁸⁴ This led to development of the Comprehensive Care for Joint Replacement (CJR) program, which gives beneficiaries flexibility in choosing services and ensures that providers adhere to required standards. During its 5-year test period beginning in 2016, the CJR program is projected to save CMS $153 million.⁸⁴ Under this program, the institution where TJA is performed is responsible for all the costs of related care from time of surgery through 90 days after hospital discharge—which is known as an “episode of care.” If the cost incurred during an episode exceeds an established target cost (as determined by CMS), the hospital must repay Medicare the difference. Conversely, if the cost of an episode is less than the established target cost, the hospital is rewarded with the difference. Bundling payments for a single episode of care in this manner is thought to incentivize providers and hospitals to give patients more comprehensive and coordinated care. Given the substantial economic burden associated with joint arthroplasty infections, it is imperative for orthopedists to establish practical and cost-effective strategies that can prevent these disastrous complications.

Conclusion

SSIs are a devastating burden to patients, surgeons, and other healthcare providers. In recent years, new discoveries and innovations have helped mitigate the incidence of these complications of THA and TKA. However, the incidence of SSIs may rise with the increasing use of TJAs and with the development of new drug-resistant pathogens. In addition, the increasing number of TJAs performed on overweight and high-risk patients means the costs of postoperative infections will be substantial. With new reimbursement models in place, hospitals and providers are being held more accountable for the care they deliver during and after TJA. Consequently, more emphasis should be placed on techniques that are proved to minimize the incidence of SSIs.

Take-Home Points

• SSIs after TJA pose a substantial burden on patients, surgeons, and the healthcare system.
• While different forms of preoperative skin preparation have shown varying outcomes after TJA, the importance of preoperative patient optimization (nutritional status, immune function, etc) cannot be overstated. 
• Intraoperative infection prevention measures include cutaneous preparation, gloving, body exhaust suits, surgical drapes, OR staff traffic and ventilation flow, and antibiotic-loaded cement. 
• Antibiotic prophylaxis for dental procedures in TJA patients continues to remain a controversial issue with conflicting recommendations.
• SSIs have considerable financial costs and require increased resource utilization. Given the significant economic burden associated with TJA infections, it is imperative for orthopedists to establish practical and cost-effective strategies to prevent these devastating complications.

Surgical-site infection (SSI), a potentially devastating complication of lower extremity total joint arthroplasty (TJA), is estimated to occur in 1% to 2.5% of cases annually.¹ Infection after TJA places a significant burden on patients, surgeons, and the healthcare system. Revision procedures that address infection after total hip arthroplasty (THA) are associated with more hospitalizations, more operations, longer hospital stay, and higher outpatient costs in comparison with primary THAs and revision surgeries for aseptic loosening.² If left untreated, a SSI can go deeper into the joint and develop into a periprosthetic infection, which can be disastrous and costly. A periprosthetic joint infection study that used 2001 to 2009 Nationwide Inpatient Sample (NIS) data found that the cost of revision procedures increased to $560 million from $320 million, and was projected to reach $1.62 billion by 2020.³ Furthermore, society incurs indirect costs as a result of patient disability and loss of wages and productivity.² Therefore, the issue of infection after TJA is even more crucial in our cost-conscious healthcare environment. 

Patient optimization, advances in surgical technique, sterile protocol, and operative procedures have been effective in reducing bacterial counts at incision sites and minimizing SSIs. As a result, infection rates have leveled off after rising for a decade.⁴ Although infection prevention modalities have their differences, routine use is fundamental and recommended by the Hospital Infection Control Practices Advisory Committee.⁵ Furthermore, both the US Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee^6,7 recently updated their SSI prevention guidelines by incorporating evidence-based methodology, an element missing from earlier recommendations.

The etiologies of postoperative SSIs have been discussed ad nauseam, but there are few reports summarizing the literature on infection prevention modalities. In this review, we identify and examine SSI prevention strategies as they relate to lower extremity TJA. Specifically, we discuss the literature on the preoperative, intraoperative, and postoperative actions that can be taken to reduce the incidence of SSIs after TJA. We also highlight the economic implications of SSIs that occur after TJA.

Methods

For this review, we performed a literature search with PubMed, EBSCOhost, and Scopus. We looked for reports published between the inception of each database and July 2016. Combinations of various search terms were used: surgical site, infection, total joint arthroplasty, knee, hip, preoperative, intraoperative, perioperative, postoperative, preparation, nutrition, ventilation, antibiotic, body exhaust suit, gloves, drain, costs, economic, and payment.

Our search identified 195 abstracts. Drs. Mistry and Chughtai reviewed these to determine which articles were relevant. For any uncertainties, consensus was reached with the help of Dr. Delanois. Of the 195 articles, 103 were potentially relevant, and 54 of the 103 were excluded for being not relevant to preventing SSIs after TJA or for being written in a language other than English. The references in the remaining articles were assessed, and those with potentially relevant titles were selected for abstract review. This step provided another 35 articles. After all exclusions, 48 articles remained. We discuss these in the context of preoperative, intraoperative, and postoperative measures and economic impact.

Results

Preoperative Measures

Skin Preparation. Preoperative skin preparation methods include standard washing and rinsing, antiseptic soaps, and iodine-based or chlorhexidine gluconate-based antiseptic showers or skin cloths. Iodine-based antiseptics are effective against a wide range of Gram-positive and Gram-negative bacteria, fungi, and viruses. These agents penetrate the cell wall, oxidize the microbial contents, and replace those contents with free iodine molecules.⁸ Iodophors are free iodine molecules associated with a polymer (eg, polyvinylpyrrolidone); the iodophor povidone-iodine is bactericidal.⁹ Chlorhexidine gluconate-based solutions are effective against many types of yeast, Gram-positive and Gram-negative bacteria, and a wide variety of viruses.⁹ Both solutions are useful. Patients with an allergy to iodine can use chlorhexidine. Table 1 summarizes the studies on preoperative measures for preventing SSIs.

There is no shortage of evidence of the efficacy of these antiseptics in minimizing the incidence of SSIs. Hayek and colleagues¹⁰ prospectively analyzed use of different preoperative skin preparation methods in 2015 patients. Six weeks after surgery, the infection rate was significantly lower with use of chlorhexidine than with use of an unmedicated bar of soap or placebo cloth (9% vs 11.7% and 12.8%, respectively; P < .05). In a study of 100 patients, Murray and colleagues¹¹ found the overall bacterial culture rate was significantly lower for those who used a 2% chlorhexidine gluconate cloth before shoulder surgery than for those who took a standard shower with soap (66% vs 94%; P = .0008). Darouiche and colleagues¹² found the overall SSI rate was significantly lower for 409 surgical patients prepared with chlorhexidine-alcohol than for 440 prepared with povidone-iodine (9.5% vs 16.1%; P = .004; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85).

Chlorhexidine gluconate-impregnated cloths have also had promising results, which may be attributed to general ease of use and potentially improved patient adherence. Zywiel and colleagues¹³ reported no SSIs in 136 patients who used these cloths at home before total knee arthroplasty (TKA) and 21 SSIs (3.0%) in 711 patients who did not use the cloths. In a study of 2545 THA patients, Kapadia and colleagues¹⁴ noted a significantly lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths than with only in-hospital perioperative skin preparation (0.5% vs 1.7%; P = .04). In 2293 TKAs, Johnson and colleagues¹⁵ similarly found a lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths (0.6% vs 2.2%; P = .02). In another prospective, randomized trial, Kapadia and colleagues16 compared 275 patients who used chlorhexidine cloths the night before and the morning of lower extremity TJA surgery with 279 patients who underwent standard-of-care preparation (preadmission bathing with antibacterial soap and water). The chlorhexidine cohort had a lower overall incidence of infection (0.4% vs 2.9%; P = .049), and the standard-of-care cohort had a stronger association with infection (odds ratio [OR], 8.15; 95% CI, 1.01-65.6). 

Patient Optimization. Poor nutritional status may compromise immune function, potentially resulting in delayed healing, increased risk of infection, and, ultimately, negative postoperative outcomes. Malnutrition can be diagnosed on the basis of a prealbumin level of <15 mg/dL (normal, 15-30 mg/dL), a serum albumin level of <3.4 g/dL (normal, 3.4-5.4 g/dL), or a total lymphocyte count under 1200 cells/μL (normal, 3900-10,000 cells/μL).^17-19 Greene and colleagues¹⁸ found that patients with preoperative malnutrition had up to a 7-fold higher rate of infection after TJA. In a study of 135 THAs and TKAs, Alfargieny and colleagues²⁰ found preoperative serum albumin was the only nutritional biomarker predictive of SSI (P = .011). Furthermore, patients who take immunomodulating medications (eg, for inflammatory arthropathies) should temporarily discontinue them before surgery in order to lower their risk of infection.²¹ 

Smoking is well established as a major risk factor for poor outcomes after surgery. It is postulated that the vasoconstrictive effects of nicotine and the hypoxic effects of carbon monoxide contribute to poor wound healing.²² In a meta-analysis of 4 studies, Sørensen²³ found smokers were at increased risk for wound complications (OR, 2.27; 95% CI, 1.82-2.84), delayed wound healing and dehiscence (OR, 2.07; 95% CI, 1.53-2.81), and infection (OR, 1.79; 95% CI, 1.57-2.04). Moreover, smoking cessation decreased the incidence of SSIs (OR, 0.43; 95% CI, 0.21-0.85). A meta- analysis by Wong and colleagues²⁴ revealed an inflection point for improved outcomes in patients who abstained from smoking for at least 4 weeks before surgery. Risk of infection was lower for these patients than for current smokers (OR, 0.69; 95% CI, 0.56-0.84).

Other comorbidities contribute to SSIs as well. In their analysis of American College of Surgeons National Surgical Quality Improvement Program registry data on 25,235 patients who underwent primary and revision lower extremity TJA, Pugely and colleagues²⁵ found that, in the primary TJA cohort, body mass index (BMI) of >40 kg/m2 (OR, 1.9; 95% CI, 1.3-2.9), electrolyte disturbance (OR, 2.4; 95% CI, 1.0-6.0), and hypertension diagnosis (OR, 1.5; 95% CI, 1.1-2.0) increased the risk of SSI within 30 days. Furthermore, diabetes mellitus delays collagen synthesis, impairs lymphocyte function, and impairs wound healing, which may lead to poor recovery and higher risk of infection.²⁶ In a study of 167 TKAs performed in 115 patients with type 2 diabetes mellitus, Han and Kang²⁶ found that wound complications were 6 times more likely in those with hemoglobin A1c (HbA1c) levels higher than 8% than in those with lower HbA1c levels (OR, 6.07; 95% CI, 1.12-33.0). In a similar study of 462 patients with diabetes, Hwang and colleagues²⁷ found a higher likelihood of superficial SSIs in patients with HbA1c levels >8% (OR, 6.1; 95% CI, 1.6-23.4; P = .008). This association was also found in patients with a fasting blood glucose level of >200 mg/dL (OR, 9.2; 95% CI, 2.2-38.2; P = .038).

Methicillin-resistant Staphylococcus aureus (MRSA) is thought to account for 10% to 25% of all periprosthetic infections in the United States.28 Nasal colonization by this pathogen increases the risk for SSIs; however, decolonization protocols have proved useful in decreasing the rates of colonization. Moroski and colleagues²⁹ assessed the efficacy of a preoperative 5-day course of intranasal mupirocin in 289 primary or revision TJA patients. Before surgery, 12 patients had positive MRSA cultures, and 44 had positive methicillin-sensitive S aureus (MSSA) cultures. On day of surgery, a significant reduction in MRSA (P = .0073) and MSSA (P = .0341) colonization was noted. Rao and colleagues³⁰ found that the infection rate decreased from 2.7% to 1.2% in 2284 TJA patients treated with a decolonization protocol (P = .009). 

Intraoperative Measures

Cutaneous Preparation. The solutions used in perioperative skin preparation are similar to those used preoperatively: povidone-iodine, alcohol, and chlorhexidine. The efficacy of these preparations varies. Table 2 summarizes the studies on intraoperative measures for preventing SSIs.

The literature also highlights the importance of technique in incision-site preparation. In a prospective study, Morrison and colleagues³³ randomly assigned 600 primary TJA patients to either (1) use of alcohol and povidone-iodine before draping, with additional preparation with iodine povacrylex (DuraPrep) and isopropyl alcohol before application of the final drape (300-patient intervention group) or (2) only use of alcohol and povidone-iodine before draping (300-patient control group). At the final follow-up, the incidence of SSI was significantly lower in the intervention group than in the control group (1.8% vs 6.5%; P = .015). In another study that assessed perioperative skin preparation methods, Brown and colleagues34 found that airborne bacteria levels in operating rooms were >4 times higher with patients whose legs were prepared by a scrubbed, gowned leg-holder than with patients whose legs were prepared by an unscrubbed, ungowned leg-holder (P = .0001).

Hair Removal. Although removing hair from surgical sites is common practice, the literature advocating it varies. A large comprehensive review³⁵ revealed no increased risk of SSI with removing vs not removing hair (RR, 1.65; 95% CI, 0.85-3.19). On the other hand, some hair removal methods may affect the incidence of infection. For example, use of electric hair clippers is presumed to reduce the risk of SSIs, whereas traditional razors may compromise the epidermal barriers and create a pathway for bacterial colonization.^5,36,37 In the aforementioned review,³⁵ SSIs were more than twice as likely to occur with hair removed by shaving than with hair removed by electric clippers (RR, 2.02; 95% CI, 1.21-3.36). Cruse and Foord³⁸ found a higher rate of SSIs with hair removed by shaving than with hair removed by clipping (2.3% vs 1.7%). Most surgeons agree that, if given the choice, they would remove hair with electric clippers rather than razors.

Gloves. Almost all orthopedists double their gloves for TJA cases. Over several studies, the incidence of glove perforation during orthopedic procedures has ranged from 3.6% to 26%,^39-41 depending on the operating room personnel and glove layering studied. Orthopedists must know this startling finding, as surgical glove perforation is associated with an increase in the rate of SSIs, from 1.7% to 5.7%.³⁸ Carter and colleagues⁴² found the highest risk of glove perforation occurs when double-gloved attending surgeons, adult reconstruction fellows, and registered nurses initially assist during primary and revision TJA. In their study, outer and inner glove layers were perforated 2.5% of the time. All outer-layer perforations were noticed, but inner-layer perforations went unnoticed 81% of the time, which poses a potential hazard for both patients and healthcare personnel. In addition, there was a significant increase in the incidence of glove perforations for attending surgeons during revision TJA vs primary TJA (8.9% vs 3.7%; P = .04). This finding may be expected given the complexity of revision procedures, the presence of sharp bony and metal edges, and the longer operative times. Giving more attention to glove perforations during arthroplasties may mitigate the risk of SSI. As soon as a perforation is noticed, the glove should be removed and replaced.

Body Exhaust Suits. Early TJAs had infection rates approaching 10%.⁴³ Bacterial-laden particles shed from surgical staff were postulated to be the cause,^44,45 and this idea prompted the development of new technology, such as body exhaust suits, which have demonstrated up to a 20-fold reduction in airborne bacterial contamination and decreased incidence of deep infection, from 1% to 0.1%, as compared with conventional surgical attire.⁴⁶ However, the efficacy of these suits was recently challenged. Hooper and colleagues⁴⁷ assessed >88,000 TJA cases in the New Zealand Joint Registry and found a significant increase in early revision THA for deep infection with vs without use of body exhaust suits (0.186% vs 0.064%; P < .0001). The incidence of revision TKAs for deep infections with use of these suits was similar (0.243% vs 0.098%; P < .001). Many of the surgeons surveyed indicated their peripheral vision was limited by the suits, which may contribute to sterile field contamination. By contrast, Miner and colleagues⁴⁸ were unable to determine an increased risk of SSI with use of body exhaust suits (RR, 0.75; 95% CI, 0.34-1.62), though there was a trend toward more infections without suits. Moreover, these suits are effective in reducing mean air bacterial counts (P = .014), but it is not known if this method correlates with mean wound bacterial counts (r = –.011) and therefore increases the risk of SSI.⁴⁹

Surgical Drapes. Surgical draping, including cloths, iodine-impregnated materials, and woven or unwoven materials, is the standard of care worldwide. The particular draping technique usually varies by surgeon. Plastic drapes are better barriers than cloth drapes, as found in a study by Blom and colleagues⁵⁰: Bacterial growth rates were almost 10 times higher with use of wet woven cloth drapes than with plastic surgical drapes. These findings were supported in another, similar study by Blom and colleagues⁵¹: Wetting drapes with blood or normal saline enhanced bacterial penetration. In addition, wetting drapes with chlorhexidine or iodine reduced but did not eliminate bacterial penetration. Fairclough and colleagues⁵² emphasized that iodine-impregnated drapes reduced surgical-site bacterial contamination from 15% to 1.6%. However, a Cochrane review⁵³ found these drapes had no effect on the SSI rate (RR, 1.03; 95% CI, 0.06-1.66; P = .89), though the risk of infection was slightly higher with adhesive draping than with no drape (RR, 1.23; 95% CI, 1.02-1.48; P = .03).

Ventilation Flow. Laminar-airflow systems are widely used to prevent SSIs after TJA. Horizontal-flow and vertical-flow ventilation provides and maintains ultra-clean air in the operating room. Evans⁵⁴ found the bacterial counts in the air and the wound were lower with laminar airflow than without this airflow. The amount of airborne bacterial colony-forming units and dust large enough to carry bacteria was reduced to 1 or 2 particles more than 2 μm/m3 with use of a typical laminar- airflow system. In comparing 3922 TKA patients in laminar-airflow operating rooms with 4133 patients in conventional rooms, Lidwell and colleagues⁴⁶ found a significantly lower incidence of SSIs in patients in laminar-airflow operating rooms (0.6% vs 2.3%; P < .001).

Conversely, Miner and colleagues⁴⁸ did not find a lower risk of SSI with laminar-airflow systems (RR, 1.57; 95% CI, 0.75-3.31). In addition, in their analysis of >88,000 cases from the New Zealand Joint Registry, Hooper and colleagues⁴⁷ found that the incidence of early infections was higher with laminar-airflow systems than with standard airflow systems for both TKA (0.193% vs 0.100%; P = .019) and THA (0.148% vs 0.061%; P < .001). They postulated that vertically oriented airflow may have transmitted contaminated particles into the surgical sites. Additional evidence may be needed to resolve these conflicting findings and determine whether clean-air practices provide significant clinical benefit in the operating room.

Staff Traffic Volume. When staff enters or exits the operating room or makes extra movements during a procedure, airflow near the wound is disturbed and no longer able to remove sufficient airborne pathogens from the sterile field. The laminar- airflow pattern may be disrupted each time the operating room doors open and close, potentially allowing airborne pathogens to be introduced near the patient. Lynch and colleagues⁵⁵ found the operating room door opened almost 50 times per hour, and it took about 20 seconds to close each time. As a result, the door may remain open for up to 20 minutes per case, causing substantial airflow disruption and potentially ineffective removal of airborne bacterial particles. Similarly, Young and O’Regan⁵⁶ found the operating room door opened about 19 times per hour and took 20 seconds to close each time. The theater door was open an estimated 10.7% of each hour of sterile procedure. Presence of more staff also increases airborne bacterial counts. Pryor and Messmer⁵⁷ evaluated a cohort of 2864 patients to determine the effect of number of personnel in the operating theater on the incidence of SSIs. Infection rates were 6.27% with >17 different people entering the room and 1.52% with <9 different people entering the room. Restricting the number of people in the room may be one of the easiest and most efficient ways to prevent SSI.

Systemic Antibiotic Prophylaxis. Perioperative antibiotic use is vital in minimizing the risk of infection after TJA. The Surgical Care Improvement Project recommended beginning the first antimicrobial dose either within 60 minutes before surgical incision (for cephalosporin) or within 2 hours before incision (for vancomycin) and discontinuing the prophylactic antimicrobial agents within 24 hours after surgery ends.^58,59 However, Gorenoi and colleagues⁶⁰ were unable to recommend a way to select particular antibiotics, as they found no difference in the effectiveness of various antibiotic agents used in TKA. A systematic review by AlBuhairan and colleagues⁶¹ revealed that antibiotic prophylaxis (vs no prophylaxis) reduced the absolute risk of a SSI by 8% and the relative risk by 81% (P < 0.0001). These findings are supported by evidence of the efficacy of perioperative antibiotics in reducing the incidence of SSI.^62,63 Antibiotic regimens should be based on susceptibility and availability, depending on hospital prevalence of infections. Even more, patients should receive prophylaxis in a timely manner. Finally, bacteriostatic antibiotics (vancomycin) should not be used on their own for preoperative prophylaxis.

Antibiotic Cement. Antibiotic-loaded bone cement (ALBC), which locally releases antimicrobials in high concentration, is often used in revision joint arthroplasty, but use in primary joint arthroplasty remains controversial. In a study of THA patients, Parvizi and colleagues64 found infection rates of 1.2% with 2.3% with and without use of ALBC, respectively. Other studies have had opposing results. Namba and colleagues⁶⁵ evaluated 22,889 primary TKAs, 2030 (8.9%) of which used ALBC. The incidence of deep infection was significantly higher with ALBC than with regular bone cement (1.4% vs 0.7%; P = .002). In addition, a meta- analysis of >6500 primary TKA patients, by Zhou and colleagues,⁶⁶ revealed no significant difference in the incidence of deep SSIs with use of ALBC vs regular cement (1.32% vs 1.89%; RR, 0.75; 95% CI, 0.43-1.33; P = .33). More evidence is needed to determine the efficacy of ALBC in primary TJA. International Consensus Meeting on Periprosthetic Joint Infection participants recommended use of ALBC in high-risk patients, including patients who are obese or immunosuppressed or have diabetes or a prior history of infection.⁶⁷

Postoperative Measures

Antibiotic Prophylaxis. The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) have suggestions for antibiotic prophylaxis for patients at increased risk for infection. As of 2015, the ADA no longer recommends antibiotic prophylaxis for patients with prosthetic joint implants,68 whereas the AAOS considers all patients with TJA to be at risk.⁶⁹

Although recommendations exist, the actual risk of infection resulting from dental procedures and the role of antibiotic prophylaxis are not well defined. Berbari and colleagues⁷¹ found that antibiotic prophylaxis in high- or low-risk dental procedures did not decrease the risk of subsequent THA infection (OR, 0.9; 95% CI, 0.5-1.6) or TKA infection (OR, 1.2; 95% CI, 0.7-2.2). Moreover, the risk of infection was no higher for patients who had a prosthetic hip or knee and underwent a high- or low-risk dental procedure without antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4-1.6) than for similar patients who did not undergo a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Some studies highlight the low level of evidence supporting antibiotic prophylaxis during dental procedures.^72,73 However, there is no evidence of adverse effects of antibiotic prophylaxis. Given the potential high risk of infection after such procedures, a more robust body of evidence is needed to reach consensus.

Evacuation Drain Management. Prolonged use of surgical evacuation drains may be a risk factor for SSI. Therefore, early drain removal is paramount. Higher infection rates with prolonged drain use have been found in patients with persistent wound drainage, including malnourished, obese, and over-anticoagulated patients. Patients with wounds persistently draining for >1 week should undergo superficial wound irrigation and débridement. Jaberi and colleagues⁷⁴ assessed 10,325 TJA patients and found that the majority of persistent drainage ceased within 1 week with use of less invasive measures, including oral antibiotics and local wound care. Furthermore, only 28% of patients with persistent drainage underwent surgical débridement. It is unclear if this practice alone is appropriate. Infection should always be suspected and treated aggressively, and cultures should be obtained from synovial fluid before antibiotics are started, unless there is an obvious superficial infection that does not require further work-up.⁶⁷

Economic Impact

SSIs remain a significant healthcare issue, and the social and financial costs are staggering. Without appropriate measures in place, these complications will place a larger burden on the healthcare system primarily as a result of longer hospital stays, multiple procedures, and increased resource utilization.⁷⁵ Given the risk of progression to prosthetic joint infection, early preventive interventions must be explored.

Improved patient selection may be an important factor in reducing SSIs. In an analysis of 8494 joint arthroplasties, Malinzak and colleagues⁸⁰ noted that patients with a BMI of >50 kg/m2 had an increased OR of infection of 21.3 compared to those with BMI <50 kg/m2. Wagner and colleagues⁸¹ analyzed 21,361 THAs and found that, for every BMI unit over 25 kg/m2, there was an 8% increased risk of joint infection (P < .001). Although it is unknown if there is an association between reduction in preoperative BMI and reduction in postoperative complication risk, it may still be worthwhile and cost-effective to modify this and similar risk factors before elective procedures.

Market forces are becoming a larger consideration in healthcare and are being driven by provider competition.⁸² Treatment outcomes, quality of care, and healthcare prices have gained attention as a means of estimating potential costs.⁸³ In 2011, the Centers for Medicare & Medicaid Services (CMS) advanced the Bundled Payments for Care Improvement (BPCI) initiative, which aimed to provide better coordinated care of higher quality and lower cost.⁸⁴ This led to development of the Comprehensive Care for Joint Replacement (CJR) program, which gives beneficiaries flexibility in choosing services and ensures that providers adhere to required standards. During its 5-year test period beginning in 2016, the CJR program is projected to save CMS $153 million.⁸⁴ Under this program, the institution where TJA is performed is responsible for all the costs of related care from time of surgery through 90 days after hospital discharge—which is known as an “episode of care.” If the cost incurred during an episode exceeds an established target cost (as determined by CMS), the hospital must repay Medicare the difference. Conversely, if the cost of an episode is less than the established target cost, the hospital is rewarded with the difference. Bundling payments for a single episode of care in this manner is thought to incentivize providers and hospitals to give patients more comprehensive and coordinated care. Given the substantial economic burden associated with joint arthroplasty infections, it is imperative for orthopedists to establish practical and cost-effective strategies that can prevent these disastrous complications.

Conclusion

SSIs are a devastating burden to patients, surgeons, and other healthcare providers. In recent years, new discoveries and innovations have helped mitigate the incidence of these complications of THA and TKA. However, the incidence of SSIs may rise with the increasing use of TJAs and with the development of new drug-resistant pathogens. In addition, the increasing number of TJAs performed on overweight and high-risk patients means the costs of postoperative infections will be substantial. With new reimbursement models in place, hospitals and providers are being held more accountable for the care they deliver during and after TJA. Consequently, more emphasis should be placed on techniques that are proved to minimize the incidence of SSIs.

Take-Home Points

• SSIs after TJA pose a substantial burden on patients, surgeons, and the healthcare system.
• While different forms of preoperative skin preparation have shown varying outcomes after TJA, the importance of preoperative patient optimization (nutritional status, immune function, etc) cannot be overstated. 
• Intraoperative infection prevention measures include cutaneous preparation, gloving, body exhaust suits, surgical drapes, OR staff traffic and ventilation flow, and antibiotic-loaded cement. 
• Antibiotic prophylaxis for dental procedures in TJA patients continues to remain a controversial issue with conflicting recommendations.
• SSIs have considerable financial costs and require increased resource utilization. Given the significant economic burden associated with TJA infections, it is imperative for orthopedists to establish practical and cost-effective strategies to prevent these devastating complications.

Surgical-site infection (SSI), a potentially devastating complication of lower extremity total joint arthroplasty (TJA), is estimated to occur in 1% to 2.5% of cases annually.¹ Infection after TJA places a significant burden on patients, surgeons, and the healthcare system. Revision procedures that address infection after total hip arthroplasty (THA) are associated with more hospitalizations, more operations, longer hospital stay, and higher outpatient costs in comparison with primary THAs and revision surgeries for aseptic loosening.² If left untreated, a SSI can go deeper into the joint and develop into a periprosthetic infection, which can be disastrous and costly. A periprosthetic joint infection study that used 2001 to 2009 Nationwide Inpatient Sample (NIS) data found that the cost of revision procedures increased to $560 million from $320 million, and was projected to reach $1.62 billion by 2020.³ Furthermore, society incurs indirect costs as a result of patient disability and loss of wages and productivity.² Therefore, the issue of infection after TJA is even more crucial in our cost-conscious healthcare environment. 

Patient optimization, advances in surgical technique, sterile protocol, and operative procedures have been effective in reducing bacterial counts at incision sites and minimizing SSIs. As a result, infection rates have leveled off after rising for a decade.⁴ Although infection prevention modalities have their differences, routine use is fundamental and recommended by the Hospital Infection Control Practices Advisory Committee.⁵ Furthermore, both the US Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee^6,7 recently updated their SSI prevention guidelines by incorporating evidence-based methodology, an element missing from earlier recommendations.

The etiologies of postoperative SSIs have been discussed ad nauseam, but there are few reports summarizing the literature on infection prevention modalities. In this review, we identify and examine SSI prevention strategies as they relate to lower extremity TJA. Specifically, we discuss the literature on the preoperative, intraoperative, and postoperative actions that can be taken to reduce the incidence of SSIs after TJA. We also highlight the economic implications of SSIs that occur after TJA.

Methods

For this review, we performed a literature search with PubMed, EBSCOhost, and Scopus. We looked for reports published between the inception of each database and July 2016. Combinations of various search terms were used: surgical site, infection, total joint arthroplasty, knee, hip, preoperative, intraoperative, perioperative, postoperative, preparation, nutrition, ventilation, antibiotic, body exhaust suit, gloves, drain, costs, economic, and payment.

Our search identified 195 abstracts. Drs. Mistry and Chughtai reviewed these to determine which articles were relevant. For any uncertainties, consensus was reached with the help of Dr. Delanois. Of the 195 articles, 103 were potentially relevant, and 54 of the 103 were excluded for being not relevant to preventing SSIs after TJA or for being written in a language other than English. The references in the remaining articles were assessed, and those with potentially relevant titles were selected for abstract review. This step provided another 35 articles. After all exclusions, 48 articles remained. We discuss these in the context of preoperative, intraoperative, and postoperative measures and economic impact.

Results

Preoperative Measures

Skin Preparation. Preoperative skin preparation methods include standard washing and rinsing, antiseptic soaps, and iodine-based or chlorhexidine gluconate-based antiseptic showers or skin cloths. Iodine-based antiseptics are effective against a wide range of Gram-positive and Gram-negative bacteria, fungi, and viruses. These agents penetrate the cell wall, oxidize the microbial contents, and replace those contents with free iodine molecules.⁸ Iodophors are free iodine molecules associated with a polymer (eg, polyvinylpyrrolidone); the iodophor povidone-iodine is bactericidal.⁹ Chlorhexidine gluconate-based solutions are effective against many types of yeast, Gram-positive and Gram-negative bacteria, and a wide variety of viruses.⁹ Both solutions are useful. Patients with an allergy to iodine can use chlorhexidine. Table 1 summarizes the studies on preoperative measures for preventing SSIs.

There is no shortage of evidence of the efficacy of these antiseptics in minimizing the incidence of SSIs. Hayek and colleagues¹⁰ prospectively analyzed use of different preoperative skin preparation methods in 2015 patients. Six weeks after surgery, the infection rate was significantly lower with use of chlorhexidine than with use of an unmedicated bar of soap or placebo cloth (9% vs 11.7% and 12.8%, respectively; P < .05). In a study of 100 patients, Murray and colleagues¹¹ found the overall bacterial culture rate was significantly lower for those who used a 2% chlorhexidine gluconate cloth before shoulder surgery than for those who took a standard shower with soap (66% vs 94%; P = .0008). Darouiche and colleagues¹² found the overall SSI rate was significantly lower for 409 surgical patients prepared with chlorhexidine-alcohol than for 440 prepared with povidone-iodine (9.5% vs 16.1%; P = .004; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85).

Chlorhexidine gluconate-impregnated cloths have also had promising results, which may be attributed to general ease of use and potentially improved patient adherence. Zywiel and colleagues¹³ reported no SSIs in 136 patients who used these cloths at home before total knee arthroplasty (TKA) and 21 SSIs (3.0%) in 711 patients who did not use the cloths. In a study of 2545 THA patients, Kapadia and colleagues¹⁴ noted a significantly lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths than with only in-hospital perioperative skin preparation (0.5% vs 1.7%; P = .04). In 2293 TKAs, Johnson and colleagues¹⁵ similarly found a lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths (0.6% vs 2.2%; P = .02). In another prospective, randomized trial, Kapadia and colleagues16 compared 275 patients who used chlorhexidine cloths the night before and the morning of lower extremity TJA surgery with 279 patients who underwent standard-of-care preparation (preadmission bathing with antibacterial soap and water). The chlorhexidine cohort had a lower overall incidence of infection (0.4% vs 2.9%; P = .049), and the standard-of-care cohort had a stronger association with infection (odds ratio [OR], 8.15; 95% CI, 1.01-65.6). 

Patient Optimization. Poor nutritional status may compromise immune function, potentially resulting in delayed healing, increased risk of infection, and, ultimately, negative postoperative outcomes. Malnutrition can be diagnosed on the basis of a prealbumin level of <15 mg/dL (normal, 15-30 mg/dL), a serum albumin level of <3.4 g/dL (normal, 3.4-5.4 g/dL), or a total lymphocyte count under 1200 cells/μL (normal, 3900-10,000 cells/μL).^17-19 Greene and colleagues¹⁸ found that patients with preoperative malnutrition had up to a 7-fold higher rate of infection after TJA. In a study of 135 THAs and TKAs, Alfargieny and colleagues²⁰ found preoperative serum albumin was the only nutritional biomarker predictive of SSI (P = .011). Furthermore, patients who take immunomodulating medications (eg, for inflammatory arthropathies) should temporarily discontinue them before surgery in order to lower their risk of infection.²¹ 

Smoking is well established as a major risk factor for poor outcomes after surgery. It is postulated that the vasoconstrictive effects of nicotine and the hypoxic effects of carbon monoxide contribute to poor wound healing.²² In a meta-analysis of 4 studies, Sørensen²³ found smokers were at increased risk for wound complications (OR, 2.27; 95% CI, 1.82-2.84), delayed wound healing and dehiscence (OR, 2.07; 95% CI, 1.53-2.81), and infection (OR, 1.79; 95% CI, 1.57-2.04). Moreover, smoking cessation decreased the incidence of SSIs (OR, 0.43; 95% CI, 0.21-0.85). A meta- analysis by Wong and colleagues²⁴ revealed an inflection point for improved outcomes in patients who abstained from smoking for at least 4 weeks before surgery. Risk of infection was lower for these patients than for current smokers (OR, 0.69; 95% CI, 0.56-0.84).

Other comorbidities contribute to SSIs as well. In their analysis of American College of Surgeons National Surgical Quality Improvement Program registry data on 25,235 patients who underwent primary and revision lower extremity TJA, Pugely and colleagues²⁵ found that, in the primary TJA cohort, body mass index (BMI) of >40 kg/m2 (OR, 1.9; 95% CI, 1.3-2.9), electrolyte disturbance (OR, 2.4; 95% CI, 1.0-6.0), and hypertension diagnosis (OR, 1.5; 95% CI, 1.1-2.0) increased the risk of SSI within 30 days. Furthermore, diabetes mellitus delays collagen synthesis, impairs lymphocyte function, and impairs wound healing, which may lead to poor recovery and higher risk of infection.²⁶ In a study of 167 TKAs performed in 115 patients with type 2 diabetes mellitus, Han and Kang²⁶ found that wound complications were 6 times more likely in those with hemoglobin A1c (HbA1c) levels higher than 8% than in those with lower HbA1c levels (OR, 6.07; 95% CI, 1.12-33.0). In a similar study of 462 patients with diabetes, Hwang and colleagues²⁷ found a higher likelihood of superficial SSIs in patients with HbA1c levels >8% (OR, 6.1; 95% CI, 1.6-23.4; P = .008). This association was also found in patients with a fasting blood glucose level of >200 mg/dL (OR, 9.2; 95% CI, 2.2-38.2; P = .038).

Methicillin-resistant Staphylococcus aureus (MRSA) is thought to account for 10% to 25% of all periprosthetic infections in the United States.28 Nasal colonization by this pathogen increases the risk for SSIs; however, decolonization protocols have proved useful in decreasing the rates of colonization. Moroski and colleagues²⁹ assessed the efficacy of a preoperative 5-day course of intranasal mupirocin in 289 primary or revision TJA patients. Before surgery, 12 patients had positive MRSA cultures, and 44 had positive methicillin-sensitive S aureus (MSSA) cultures. On day of surgery, a significant reduction in MRSA (P = .0073) and MSSA (P = .0341) colonization was noted. Rao and colleagues³⁰ found that the infection rate decreased from 2.7% to 1.2% in 2284 TJA patients treated with a decolonization protocol (P = .009). 

Intraoperative Measures

Cutaneous Preparation. The solutions used in perioperative skin preparation are similar to those used preoperatively: povidone-iodine, alcohol, and chlorhexidine. The efficacy of these preparations varies. Table 2 summarizes the studies on intraoperative measures for preventing SSIs.

The literature also highlights the importance of technique in incision-site preparation. In a prospective study, Morrison and colleagues³³ randomly assigned 600 primary TJA patients to either (1) use of alcohol and povidone-iodine before draping, with additional preparation with iodine povacrylex (DuraPrep) and isopropyl alcohol before application of the final drape (300-patient intervention group) or (2) only use of alcohol and povidone-iodine before draping (300-patient control group). At the final follow-up, the incidence of SSI was significantly lower in the intervention group than in the control group (1.8% vs 6.5%; P = .015). In another study that assessed perioperative skin preparation methods, Brown and colleagues34 found that airborne bacteria levels in operating rooms were >4 times higher with patients whose legs were prepared by a scrubbed, gowned leg-holder than with patients whose legs were prepared by an unscrubbed, ungowned leg-holder (P = .0001).

Hair Removal. Although removing hair from surgical sites is common practice, the literature advocating it varies. A large comprehensive review³⁵ revealed no increased risk of SSI with removing vs not removing hair (RR, 1.65; 95% CI, 0.85-3.19). On the other hand, some hair removal methods may affect the incidence of infection. For example, use of electric hair clippers is presumed to reduce the risk of SSIs, whereas traditional razors may compromise the epidermal barriers and create a pathway for bacterial colonization.^5,36,37 In the aforementioned review,³⁵ SSIs were more than twice as likely to occur with hair removed by shaving than with hair removed by electric clippers (RR, 2.02; 95% CI, 1.21-3.36). Cruse and Foord³⁸ found a higher rate of SSIs with hair removed by shaving than with hair removed by clipping (2.3% vs 1.7%). Most surgeons agree that, if given the choice, they would remove hair with electric clippers rather than razors.

Gloves. Almost all orthopedists double their gloves for TJA cases. Over several studies, the incidence of glove perforation during orthopedic procedures has ranged from 3.6% to 26%,^39-41 depending on the operating room personnel and glove layering studied. Orthopedists must know this startling finding, as surgical glove perforation is associated with an increase in the rate of SSIs, from 1.7% to 5.7%.³⁸ Carter and colleagues⁴² found the highest risk of glove perforation occurs when double-gloved attending surgeons, adult reconstruction fellows, and registered nurses initially assist during primary and revision TJA. In their study, outer and inner glove layers were perforated 2.5% of the time. All outer-layer perforations were noticed, but inner-layer perforations went unnoticed 81% of the time, which poses a potential hazard for both patients and healthcare personnel. In addition, there was a significant increase in the incidence of glove perforations for attending surgeons during revision TJA vs primary TJA (8.9% vs 3.7%; P = .04). This finding may be expected given the complexity of revision procedures, the presence of sharp bony and metal edges, and the longer operative times. Giving more attention to glove perforations during arthroplasties may mitigate the risk of SSI. As soon as a perforation is noticed, the glove should be removed and replaced.

Body Exhaust Suits. Early TJAs had infection rates approaching 10%.⁴³ Bacterial-laden particles shed from surgical staff were postulated to be the cause,^44,45 and this idea prompted the development of new technology, such as body exhaust suits, which have demonstrated up to a 20-fold reduction in airborne bacterial contamination and decreased incidence of deep infection, from 1% to 0.1%, as compared with conventional surgical attire.⁴⁶ However, the efficacy of these suits was recently challenged. Hooper and colleagues⁴⁷ assessed >88,000 TJA cases in the New Zealand Joint Registry and found a significant increase in early revision THA for deep infection with vs without use of body exhaust suits (0.186% vs 0.064%; P < .0001). The incidence of revision TKAs for deep infections with use of these suits was similar (0.243% vs 0.098%; P < .001). Many of the surgeons surveyed indicated their peripheral vision was limited by the suits, which may contribute to sterile field contamination. By contrast, Miner and colleagues⁴⁸ were unable to determine an increased risk of SSI with use of body exhaust suits (RR, 0.75; 95% CI, 0.34-1.62), though there was a trend toward more infections without suits. Moreover, these suits are effective in reducing mean air bacterial counts (P = .014), but it is not known if this method correlates with mean wound bacterial counts (r = –.011) and therefore increases the risk of SSI.⁴⁹

Surgical Drapes. Surgical draping, including cloths, iodine-impregnated materials, and woven or unwoven materials, is the standard of care worldwide. The particular draping technique usually varies by surgeon. Plastic drapes are better barriers than cloth drapes, as found in a study by Blom and colleagues⁵⁰: Bacterial growth rates were almost 10 times higher with use of wet woven cloth drapes than with plastic surgical drapes. These findings were supported in another, similar study by Blom and colleagues⁵¹: Wetting drapes with blood or normal saline enhanced bacterial penetration. In addition, wetting drapes with chlorhexidine or iodine reduced but did not eliminate bacterial penetration. Fairclough and colleagues⁵² emphasized that iodine-impregnated drapes reduced surgical-site bacterial contamination from 15% to 1.6%. However, a Cochrane review⁵³ found these drapes had no effect on the SSI rate (RR, 1.03; 95% CI, 0.06-1.66; P = .89), though the risk of infection was slightly higher with adhesive draping than with no drape (RR, 1.23; 95% CI, 1.02-1.48; P = .03).

Ventilation Flow. Laminar-airflow systems are widely used to prevent SSIs after TJA. Horizontal-flow and vertical-flow ventilation provides and maintains ultra-clean air in the operating room. Evans⁵⁴ found the bacterial counts in the air and the wound were lower with laminar airflow than without this airflow. The amount of airborne bacterial colony-forming units and dust large enough to carry bacteria was reduced to 1 or 2 particles more than 2 μm/m3 with use of a typical laminar- airflow system. In comparing 3922 TKA patients in laminar-airflow operating rooms with 4133 patients in conventional rooms, Lidwell and colleagues⁴⁶ found a significantly lower incidence of SSIs in patients in laminar-airflow operating rooms (0.6% vs 2.3%; P < .001).

Conversely, Miner and colleagues⁴⁸ did not find a lower risk of SSI with laminar-airflow systems (RR, 1.57; 95% CI, 0.75-3.31). In addition, in their analysis of >88,000 cases from the New Zealand Joint Registry, Hooper and colleagues⁴⁷ found that the incidence of early infections was higher with laminar-airflow systems than with standard airflow systems for both TKA (0.193% vs 0.100%; P = .019) and THA (0.148% vs 0.061%; P < .001). They postulated that vertically oriented airflow may have transmitted contaminated particles into the surgical sites. Additional evidence may be needed to resolve these conflicting findings and determine whether clean-air practices provide significant clinical benefit in the operating room.

Staff Traffic Volume. When staff enters or exits the operating room or makes extra movements during a procedure, airflow near the wound is disturbed and no longer able to remove sufficient airborne pathogens from the sterile field. The laminar- airflow pattern may be disrupted each time the operating room doors open and close, potentially allowing airborne pathogens to be introduced near the patient. Lynch and colleagues⁵⁵ found the operating room door opened almost 50 times per hour, and it took about 20 seconds to close each time. As a result, the door may remain open for up to 20 minutes per case, causing substantial airflow disruption and potentially ineffective removal of airborne bacterial particles. Similarly, Young and O’Regan⁵⁶ found the operating room door opened about 19 times per hour and took 20 seconds to close each time. The theater door was open an estimated 10.7% of each hour of sterile procedure. Presence of more staff also increases airborne bacterial counts. Pryor and Messmer⁵⁷ evaluated a cohort of 2864 patients to determine the effect of number of personnel in the operating theater on the incidence of SSIs. Infection rates were 6.27% with >17 different people entering the room and 1.52% with <9 different people entering the room. Restricting the number of people in the room may be one of the easiest and most efficient ways to prevent SSI.

Systemic Antibiotic Prophylaxis. Perioperative antibiotic use is vital in minimizing the risk of infection after TJA. The Surgical Care Improvement Project recommended beginning the first antimicrobial dose either within 60 minutes before surgical incision (for cephalosporin) or within 2 hours before incision (for vancomycin) and discontinuing the prophylactic antimicrobial agents within 24 hours after surgery ends.^58,59 However, Gorenoi and colleagues⁶⁰ were unable to recommend a way to select particular antibiotics, as they found no difference in the effectiveness of various antibiotic agents used in TKA. A systematic review by AlBuhairan and colleagues⁶¹ revealed that antibiotic prophylaxis (vs no prophylaxis) reduced the absolute risk of a SSI by 8% and the relative risk by 81% (P < 0.0001). These findings are supported by evidence of the efficacy of perioperative antibiotics in reducing the incidence of SSI.^62,63 Antibiotic regimens should be based on susceptibility and availability, depending on hospital prevalence of infections. Even more, patients should receive prophylaxis in a timely manner. Finally, bacteriostatic antibiotics (vancomycin) should not be used on their own for preoperative prophylaxis.

Antibiotic Cement. Antibiotic-loaded bone cement (ALBC), which locally releases antimicrobials in high concentration, is often used in revision joint arthroplasty, but use in primary joint arthroplasty remains controversial. In a study of THA patients, Parvizi and colleagues64 found infection rates of 1.2% with 2.3% with and without use of ALBC, respectively. Other studies have had opposing results. Namba and colleagues⁶⁵ evaluated 22,889 primary TKAs, 2030 (8.9%) of which used ALBC. The incidence of deep infection was significantly higher with ALBC than with regular bone cement (1.4% vs 0.7%; P = .002). In addition, a meta- analysis of >6500 primary TKA patients, by Zhou and colleagues,⁶⁶ revealed no significant difference in the incidence of deep SSIs with use of ALBC vs regular cement (1.32% vs 1.89%; RR, 0.75; 95% CI, 0.43-1.33; P = .33). More evidence is needed to determine the efficacy of ALBC in primary TJA. International Consensus Meeting on Periprosthetic Joint Infection participants recommended use of ALBC in high-risk patients, including patients who are obese or immunosuppressed or have diabetes or a prior history of infection.⁶⁷

Postoperative Measures

Antibiotic Prophylaxis. The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) have suggestions for antibiotic prophylaxis for patients at increased risk for infection. As of 2015, the ADA no longer recommends antibiotic prophylaxis for patients with prosthetic joint implants,68 whereas the AAOS considers all patients with TJA to be at risk.⁶⁹

Although recommendations exist, the actual risk of infection resulting from dental procedures and the role of antibiotic prophylaxis are not well defined. Berbari and colleagues⁷¹ found that antibiotic prophylaxis in high- or low-risk dental procedures did not decrease the risk of subsequent THA infection (OR, 0.9; 95% CI, 0.5-1.6) or TKA infection (OR, 1.2; 95% CI, 0.7-2.2). Moreover, the risk of infection was no higher for patients who had a prosthetic hip or knee and underwent a high- or low-risk dental procedure without antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4-1.6) than for similar patients who did not undergo a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Some studies highlight the low level of evidence supporting antibiotic prophylaxis during dental procedures.^72,73 However, there is no evidence of adverse effects of antibiotic prophylaxis. Given the potential high risk of infection after such procedures, a more robust body of evidence is needed to reach consensus.

Evacuation Drain Management. Prolonged use of surgical evacuation drains may be a risk factor for SSI. Therefore, early drain removal is paramount. Higher infection rates with prolonged drain use have been found in patients with persistent wound drainage, including malnourished, obese, and over-anticoagulated patients. Patients with wounds persistently draining for >1 week should undergo superficial wound irrigation and débridement. Jaberi and colleagues⁷⁴ assessed 10,325 TJA patients and found that the majority of persistent drainage ceased within 1 week with use of less invasive measures, including oral antibiotics and local wound care. Furthermore, only 28% of patients with persistent drainage underwent surgical débridement. It is unclear if this practice alone is appropriate. Infection should always be suspected and treated aggressively, and cultures should be obtained from synovial fluid before antibiotics are started, unless there is an obvious superficial infection that does not require further work-up.⁶⁷

Economic Impact

SSIs remain a significant healthcare issue, and the social and financial costs are staggering. Without appropriate measures in place, these complications will place a larger burden on the healthcare system primarily as a result of longer hospital stays, multiple procedures, and increased resource utilization.⁷⁵ Given the risk of progression to prosthetic joint infection, early preventive interventions must be explored.

Improved patient selection may be an important factor in reducing SSIs. In an analysis of 8494 joint arthroplasties, Malinzak and colleagues⁸⁰ noted that patients with a BMI of >50 kg/m2 had an increased OR of infection of 21.3 compared to those with BMI <50 kg/m2. Wagner and colleagues⁸¹ analyzed 21,361 THAs and found that, for every BMI unit over 25 kg/m2, there was an 8% increased risk of joint infection (P < .001). Although it is unknown if there is an association between reduction in preoperative BMI and reduction in postoperative complication risk, it may still be worthwhile and cost-effective to modify this and similar risk factors before elective procedures.

Market forces are becoming a larger consideration in healthcare and are being driven by provider competition.⁸² Treatment outcomes, quality of care, and healthcare prices have gained attention as a means of estimating potential costs.⁸³ In 2011, the Centers for Medicare & Medicaid Services (CMS) advanced the Bundled Payments for Care Improvement (BPCI) initiative, which aimed to provide better coordinated care of higher quality and lower cost.⁸⁴ This led to development of the Comprehensive Care for Joint Replacement (CJR) program, which gives beneficiaries flexibility in choosing services and ensures that providers adhere to required standards. During its 5-year test period beginning in 2016, the CJR program is projected to save CMS $153 million.⁸⁴ Under this program, the institution where TJA is performed is responsible for all the costs of related care from time of surgery through 90 days after hospital discharge—which is known as an “episode of care.” If the cost incurred during an episode exceeds an established target cost (as determined by CMS), the hospital must repay Medicare the difference. Conversely, if the cost of an episode is less than the established target cost, the hospital is rewarded with the difference. Bundling payments for a single episode of care in this manner is thought to incentivize providers and hospitals to give patients more comprehensive and coordinated care. Given the substantial economic burden associated with joint arthroplasty infections, it is imperative for orthopedists to establish practical and cost-effective strategies that can prevent these disastrous complications.

Conclusion

SSIs are a devastating burden to patients, surgeons, and other healthcare providers. In recent years, new discoveries and innovations have helped mitigate the incidence of these complications of THA and TKA. However, the incidence of SSIs may rise with the increasing use of TJAs and with the development of new drug-resistant pathogens. In addition, the increasing number of TJAs performed on overweight and high-risk patients means the costs of postoperative infections will be substantial. With new reimbursement models in place, hospitals and providers are being held more accountable for the care they deliver during and after TJA. Consequently, more emphasis should be placed on techniques that are proved to minimize the incidence of SSIs.

Clinical question: How accurate are doctors and nurses at predicting survival and functional outcomes in critically ill patients?

Background: Doctors have been shown to have moderate accuracy at predicting in-hospital mortality in critically ill patients; however, little is known about their ability to predict longer-term outcomes.

Study design: Prospective cohort study.

Six-month follow-up was completed for 299 patients. Accuracy was highest when either physicians or nurses expressed confidence in their predictions; doctors confident in their predications of 6-month survival had a positive likelihood ratio of 33.00 (95% CI, 8.34-130.63). Both doctors and nurses least accurately predicted cognitive function (positive LR, 2.36; 95% CI, 1.36-4.12; negative LR, 0.75; 95% CI, 0.61-0.92 for doctors, positive LR, 1.50; 95% CI, 0.86-2.60; negative LR, 0.88; 95% CI, 0.73-1.06 for nurses), while doctors most accurately predicated 6-month mortality (positive LR, 5.91; 95% CI, 3.74-9.32; negative LR, 0.41; 95% CI, 0.33-0.52) and nurses most accurately predicted in-hospital mortality (positive LR, 4.71; 95% CI, 2.94-7.56; negative LR, 0.6; 95% CI,0.49-0.75).

Bottom line: Doctors and nurses were better at predicting mortality than they were at predicting cognition, and their predicted outcomes were most accurate when they expressed a high degree of confidence in the predictions.

Citation: Detsky ME, Harhay MO, Bayard DF, et al. Discriminative accuracy of physician and nurse predictions for survival and functional outcomes 6 months after an ICU admission. JAMA. 2017;317(21):2187-95.

Dr. Herscher is assistant professor, division of hospital medicine, Icahn School of Medicine of the Mount Sinai Health System.

Clinical question: How accurate are doctors and nurses at predicting survival and functional outcomes in critically ill patients?

Background: Doctors have been shown to have moderate accuracy at predicting in-hospital mortality in critically ill patients; however, little is known about their ability to predict longer-term outcomes.

Study design: Prospective cohort study.

Six-month follow-up was completed for 299 patients. Accuracy was highest when either physicians or nurses expressed confidence in their predictions; doctors confident in their predications of 6-month survival had a positive likelihood ratio of 33.00 (95% CI, 8.34-130.63). Both doctors and nurses least accurately predicted cognitive function (positive LR, 2.36; 95% CI, 1.36-4.12; negative LR, 0.75; 95% CI, 0.61-0.92 for doctors, positive LR, 1.50; 95% CI, 0.86-2.60; negative LR, 0.88; 95% CI, 0.73-1.06 for nurses), while doctors most accurately predicated 6-month mortality (positive LR, 5.91; 95% CI, 3.74-9.32; negative LR, 0.41; 95% CI, 0.33-0.52) and nurses most accurately predicted in-hospital mortality (positive LR, 4.71; 95% CI, 2.94-7.56; negative LR, 0.6; 95% CI,0.49-0.75).

Bottom line: Doctors and nurses were better at predicting mortality than they were at predicting cognition, and their predicted outcomes were most accurate when they expressed a high degree of confidence in the predictions.

Citation: Detsky ME, Harhay MO, Bayard DF, et al. Discriminative accuracy of physician and nurse predictions for survival and functional outcomes 6 months after an ICU admission. JAMA. 2017;317(21):2187-95.

Dr. Herscher is assistant professor, division of hospital medicine, Icahn School of Medicine of the Mount Sinai Health System.

Clinical question: How accurate are doctors and nurses at predicting survival and functional outcomes in critically ill patients?

Background: Doctors have been shown to have moderate accuracy at predicting in-hospital mortality in critically ill patients; however, little is known about their ability to predict longer-term outcomes.

Study design: Prospective cohort study.

Six-month follow-up was completed for 299 patients. Accuracy was highest when either physicians or nurses expressed confidence in their predictions; doctors confident in their predications of 6-month survival had a positive likelihood ratio of 33.00 (95% CI, 8.34-130.63). Both doctors and nurses least accurately predicted cognitive function (positive LR, 2.36; 95% CI, 1.36-4.12; negative LR, 0.75; 95% CI, 0.61-0.92 for doctors, positive LR, 1.50; 95% CI, 0.86-2.60; negative LR, 0.88; 95% CI, 0.73-1.06 for nurses), while doctors most accurately predicated 6-month mortality (positive LR, 5.91; 95% CI, 3.74-9.32; negative LR, 0.41; 95% CI, 0.33-0.52) and nurses most accurately predicted in-hospital mortality (positive LR, 4.71; 95% CI, 2.94-7.56; negative LR, 0.6; 95% CI,0.49-0.75).

Bottom line: Doctors and nurses were better at predicting mortality than they were at predicting cognition, and their predicted outcomes were most accurate when they expressed a high degree of confidence in the predictions.

Citation: Detsky ME, Harhay MO, Bayard DF, et al. Discriminative accuracy of physician and nurse predictions for survival and functional outcomes 6 months after an ICU admission. JAMA. 2017;317(21):2187-95.

Dr. Herscher is assistant professor, division of hospital medicine, Icahn School of Medicine of the Mount Sinai Health System.

Is scarlet fever—long thought to be eradicated—reemerging as a health threat? China, the United Kingdom, and Hong Kong have seen upsurges in scarlet fever cases in the past few years.

Hong Kong has seen a more than 10-fold increase over the previous incidence rate. In a study of 7,266 patients aged ≤ 14 years (3,304 with laboratory-confirmed diagnosis), researchers from University of Hong Kong found a “sharp peak” in 2011: 1,438 cases were reported, exceeding the total number of 1,117 in the previous 6 years. Since then, the annual number of reported cases has remained at a “relatively high level,” the researchers say, with an average of 14.5 cases per 10,000 children during 2012-2015.

The elevated pattern was more apparent in children aged ≤ 5 years. In that age group, annual incidence averaged 3.3 per 10,000 during 2005-2010, then jumped dramatically to 23.9 per 10,000 in 2011. It dropped slightly to 18.1 per 10,000 in 2012-2015.

The cause is unclear, the researchers say. They cite 1 report that suggests toxin acquisition and multidrug resistance may have contributed. School is probably a major transmission site. Incidence was higher among younger children entering school and during school days. The researchers say boys were more at risk than girls, possibly because they have more physical interactions or poorer personal hygiene. Thus, school-based control measures—especially for boys aged 3 to 5 years—could be “particularly important.”

Is scarlet fever—long thought to be eradicated—reemerging as a health threat? China, the United Kingdom, and Hong Kong have seen upsurges in scarlet fever cases in the past few years.

Hong Kong has seen a more than 10-fold increase over the previous incidence rate. In a study of 7,266 patients aged ≤ 14 years (3,304 with laboratory-confirmed diagnosis), researchers from University of Hong Kong found a “sharp peak” in 2011: 1,438 cases were reported, exceeding the total number of 1,117 in the previous 6 years. Since then, the annual number of reported cases has remained at a “relatively high level,” the researchers say, with an average of 14.5 cases per 10,000 children during 2012-2015.

The elevated pattern was more apparent in children aged ≤ 5 years. In that age group, annual incidence averaged 3.3 per 10,000 during 2005-2010, then jumped dramatically to 23.9 per 10,000 in 2011. It dropped slightly to 18.1 per 10,000 in 2012-2015.

The cause is unclear, the researchers say. They cite 1 report that suggests toxin acquisition and multidrug resistance may have contributed. School is probably a major transmission site. Incidence was higher among younger children entering school and during school days. The researchers say boys were more at risk than girls, possibly because they have more physical interactions or poorer personal hygiene. Thus, school-based control measures—especially for boys aged 3 to 5 years—could be “particularly important.”

Is scarlet fever—long thought to be eradicated—reemerging as a health threat? China, the United Kingdom, and Hong Kong have seen upsurges in scarlet fever cases in the past few years.

Hong Kong has seen a more than 10-fold increase over the previous incidence rate. In a study of 7,266 patients aged ≤ 14 years (3,304 with laboratory-confirmed diagnosis), researchers from University of Hong Kong found a “sharp peak” in 2011: 1,438 cases were reported, exceeding the total number of 1,117 in the previous 6 years. Since then, the annual number of reported cases has remained at a “relatively high level,” the researchers say, with an average of 14.5 cases per 10,000 children during 2012-2015.

The elevated pattern was more apparent in children aged ≤ 5 years. In that age group, annual incidence averaged 3.3 per 10,000 during 2005-2010, then jumped dramatically to 23.9 per 10,000 in 2011. It dropped slightly to 18.1 per 10,000 in 2012-2015.

The cause is unclear, the researchers say. They cite 1 report that suggests toxin acquisition and multidrug resistance may have contributed. School is probably a major transmission site. Incidence was higher among younger children entering school and during school days. The researchers say boys were more at risk than girls, possibly because they have more physical interactions or poorer personal hygiene. Thus, school-based control measures—especially for boys aged 3 to 5 years—could be “particularly important.”

Medicine Media Relations

ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.

Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.

Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).

The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.

TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.

The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.

Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”

The researchers identified 691 VTEs during the 299,767 person-years of follow-up.

A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”

Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”

The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.

“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.

“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”

Medicine Media Relations

ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.

Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.

Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).

The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.

TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.

The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.

Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”

The researchers identified 691 VTEs during the 299,767 person-years of follow-up.

A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”

Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”

The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.

“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.

“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”

Medicine Media Relations

ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.

Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.

Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).

The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.

TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.

The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.

Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”

The researchers identified 691 VTEs during the 299,767 person-years of follow-up.

A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”

Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”

The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.

“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.

“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).

Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).

The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).

Phase 3 trials

Rurioctocog alfa pegol has been studied in 3 phase 3 trials.

One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.

Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.

A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).

Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).

The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).

Phase 3 trials

Rurioctocog alfa pegol has been studied in 3 phase 3 trials.

One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.

Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.

A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).

Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).

The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).

Phase 3 trials

Rurioctocog alfa pegol has been studied in 3 phase 3 trials.

One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.

Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.

A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).

The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The EC previously approved BV to treat:

• Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Adults with CD30+ HL at increased risk of relapse or progression following ASCT
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).

The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The EC previously approved BV to treat:

• Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Adults with CD30+ HL at increased risk of relapse or progression following ASCT
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).

The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

The EC previously approved BV to treat:

• Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• Adults with CD30+ HL at increased risk of relapse or progression following ASCT
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.

Phase 3 trial

The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.

The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.

Phase 3 trial

The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.

The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Photo by Chad McNeeley

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).

The CHMP’s opinion will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.

Phase 3 trial

The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.

The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

The Food and Drug Administration has approved a supplemental new drug application for cariprazine (Vraylar) for maintenance treatment of adults with schizophrenia, the drug’s licensor, Allergan, announced Nov. 13. The drug was approved in 2015 for the acute treatment of schizophrenia or for manic or mixed episodes of bipolar I disorder in adults.

The efficacy of the atypical antipsychotic for maintenance treatment of schizophrenia was demonstrated by a 72-week multinational, double-blind, randomized study of a stabilized cariprazine dose of 3, 6, or 9 mg daily, compared with placebo. The daily dose had a significant effect on the study’s primary endpoint – time to relapse. Nearly twice as many placebo-treated patients as cariprazine-treated patients relapsed (49.5% vs. 29.7%).

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The Food and Drug Administration has approved a supplemental new drug application for cariprazine (Vraylar) for maintenance treatment of adults with schizophrenia, the drug’s licensor, Allergan, announced Nov. 13. The drug was approved in 2015 for the acute treatment of schizophrenia or for manic or mixed episodes of bipolar I disorder in adults.

The efficacy of the atypical antipsychotic for maintenance treatment of schizophrenia was demonstrated by a 72-week multinational, double-blind, randomized study of a stabilized cariprazine dose of 3, 6, or 9 mg daily, compared with placebo. The daily dose had a significant effect on the study’s primary endpoint – time to relapse. Nearly twice as many placebo-treated patients as cariprazine-treated patients relapsed (49.5% vs. 29.7%).

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The Food and Drug Administration has approved a supplemental new drug application for cariprazine (Vraylar) for maintenance treatment of adults with schizophrenia, the drug’s licensor, Allergan, announced Nov. 13. The drug was approved in 2015 for the acute treatment of schizophrenia or for manic or mixed episodes of bipolar I disorder in adults.

The efficacy of the atypical antipsychotic for maintenance treatment of schizophrenia was demonstrated by a 72-week multinational, double-blind, randomized study of a stabilized cariprazine dose of 3, 6, or 9 mg daily, compared with placebo. The daily dose had a significant effect on the study’s primary endpoint – time to relapse. Nearly twice as many placebo-treated patients as cariprazine-treated patients relapsed (49.5% vs. 29.7%).

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Coverage with recommended vaccines for children aged 19-35 months generally remained high and stable in 2016, but problems persisted, said Holly A. Hill, MD, PhD, and her associates at the National Center for Immunization and Respiratory Diseases, Atlanta.

Coverage still was below 90% for vaccines that needed booster doses during the second year of life (four or more doses of DTaP and pneumococcal conjugate vaccine [PCV] and Haemophilus influenzae type b [Hib] full series) and for other recommended vaccines (hepatitis B [HepB] birth dose, rotavirus, and hepatitis A [HepA]), they reported in Morbidity and Mortality Weekly Report.

copyright Sean Locke/iStockphoto.com

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Coverage with recommended vaccines for children aged 19-35 months generally remained high and stable in 2016, but problems persisted, said Holly A. Hill, MD, PhD, and her associates at the National Center for Immunization and Respiratory Diseases, Atlanta.

Coverage still was below 90% for vaccines that needed booster doses during the second year of life (four or more doses of DTaP and pneumococcal conjugate vaccine [PCV] and Haemophilus influenzae type b [Hib] full series) and for other recommended vaccines (hepatitis B [HepB] birth dose, rotavirus, and hepatitis A [HepA]), they reported in Morbidity and Mortality Weekly Report.

copyright Sean Locke/iStockphoto.com

[email protected]

Coverage with recommended vaccines for children aged 19-35 months generally remained high and stable in 2016, but problems persisted, said Holly A. Hill, MD, PhD, and her associates at the National Center for Immunization and Respiratory Diseases, Atlanta.

Coverage still was below 90% for vaccines that needed booster doses during the second year of life (four or more doses of DTaP and pneumococcal conjugate vaccine [PCV] and Haemophilus influenzae type b [Hib] full series) and for other recommended vaccines (hepatitis B [HepB] birth dose, rotavirus, and hepatitis A [HepA]), they reported in Morbidity and Mortality Weekly Report.

copyright Sean Locke/iStockphoto.com

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