Infectious Diseases

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).

The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
 

Pathogens

Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.

Defining severe community-acquired pneumonia

The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.

Major criteria are:

• Septic shock requiring vasopressors.
• Respiratory failure requiring mechanical ventilation.

Minor criteria are:

• Respiratory rate greater than or equal to 30 breaths/min.
• Ratio of arterial O₂ partial pressure to fractional inspired O₂ less than or equal to 250.
• Multilobar infiltrates.
• Confusion/disorientation.
• Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
• Leukopenia (white blood cell count less than 4,000 cells/mcL).
• Thrombocytopenia (platelet count less than 100,000 mcL)
• Hypothermia (core temperature less than 36º C).
• Hypotension requiring aggressive fluid resuscitation.

Management and diagnostic testing

Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.

For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.

Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
 

Empiric antibiotic therapy

Healthy adults without comorbidities should be treated with monotherapy of either:

• Amoxicillin 1 g three times daily.
• OR doxycycline 100 mg twice daily.
• OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.

Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:

• Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
• OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).

Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:

• Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
• OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).

If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.

Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):

• Beta-lactam and macrolide.
• OR fluoroquinolone and beta-lactam.

It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.

Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
 

The bottom line

CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.

For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.

 

Reference

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).

The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
 

Pathogens

Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.

Defining severe community-acquired pneumonia

The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.

Major criteria are:

• Septic shock requiring vasopressors.
• Respiratory failure requiring mechanical ventilation.

Minor criteria are:

• Respiratory rate greater than or equal to 30 breaths/min.
• Ratio of arterial O₂ partial pressure to fractional inspired O₂ less than or equal to 250.
• Multilobar infiltrates.
• Confusion/disorientation.
• Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
• Leukopenia (white blood cell count less than 4,000 cells/mcL).
• Thrombocytopenia (platelet count less than 100,000 mcL)
• Hypothermia (core temperature less than 36º C).
• Hypotension requiring aggressive fluid resuscitation.

Management and diagnostic testing

Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.

For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.

Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
 

Empiric antibiotic therapy

Healthy adults without comorbidities should be treated with monotherapy of either:

• Amoxicillin 1 g three times daily.
• OR doxycycline 100 mg twice daily.
• OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.

Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:

• Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
• OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).

Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:

• Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
• OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).

If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.

Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):

• Beta-lactam and macrolide.
• OR fluoroquinolone and beta-lactam.

It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.

Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
 

The bottom line

CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.

For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.

 

Reference

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).

The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
 

Pathogens

Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.

Defining severe community-acquired pneumonia

The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.

Major criteria are:

• Septic shock requiring vasopressors.
• Respiratory failure requiring mechanical ventilation.

Minor criteria are:

• Respiratory rate greater than or equal to 30 breaths/min.
• Ratio of arterial O₂ partial pressure to fractional inspired O₂ less than or equal to 250.
• Multilobar infiltrates.
• Confusion/disorientation.
• Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
• Leukopenia (white blood cell count less than 4,000 cells/mcL).
• Thrombocytopenia (platelet count less than 100,000 mcL)
• Hypothermia (core temperature less than 36º C).
• Hypotension requiring aggressive fluid resuscitation.

Management and diagnostic testing

Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.

For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.

Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
 

Empiric antibiotic therapy

Healthy adults without comorbidities should be treated with monotherapy of either:

• Amoxicillin 1 g three times daily.
• OR doxycycline 100 mg twice daily.
• OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.

Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:

• Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
• OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).

Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:

• Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
• OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).

If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.

Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):

• Beta-lactam and macrolide.
• OR fluoroquinolone and beta-lactam.

It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.

Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
 

The bottom line

CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.

For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.

 

Reference

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.

Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

The 9-valent human papillomavirus vaccine (9vHPV) vaccine carries an extremely low rate of adverse events, most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.

MarianVejcik/Getty Images

“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.

James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.

The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”

The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.

Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.

Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.

The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.

“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.

The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.

Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.

The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).

There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.

There were eight reports of Guillain-Barré.

There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.

One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.

There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.

Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.

“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.

Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.

[email protected]

SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.

The 9-valent human papillomavirus vaccine (9vHPV) vaccine carries an extremely low rate of adverse events, most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.

MarianVejcik/Getty Images

“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.

James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.

The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”

The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.

Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.

Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.

The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.

“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.

The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.

Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.

The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).

There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.

There were eight reports of Guillain-Barré.

There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.

One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.

There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.

Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.

“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.

Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.

[email protected]

SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.

The 9-valent human papillomavirus vaccine (9vHPV) vaccine carries an extremely low rate of adverse events, most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.

MarianVejcik/Getty Images

“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.

James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.

The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”

The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.

Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.

Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.

The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.

“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.

The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.

Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.

The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).

There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.

There were eight reports of Guillain-Barré.

There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.

One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.

There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.

Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.

“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.

Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.

[email protected]

SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.

Infants born in a country with no endemic measles no longer received adequate protection against the disease from maternal antibodies when they were aged 6 months, according to new research.

FatCamera/E+/Getty Images

In fact, most of the 196 infants’ maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.

The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics.

“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.

The findings are not surprising for a setting in which measles has been eliminated and align with results from past research, Huong Q. McLean, PhD, MPH, of the Marshfield (Wis.) Clinic Research Institute and Walter A. Orenstein, MD, of Emory University in Atlanta wrote in an accompanying editorial (Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-2541).

However, this susceptibility prior to receiving the MMR has taken on a new significance more recently, Dr. McLean and Dr. Orenstein suggested.

“In light of increasing measles outbreaks during the past year reaching levels not recorded in the United States since 1992 and increased measles elsewhere, coupled with the risk of severe illness in infants, there is increased concern regarding the protection of infants against measles,” the editorialists wrote.

Dr. Science and colleagues tested serum samples from 196 term infants, all under 12 months old, for antibodies against measles. The sera had been previously collected at a single tertiary care center in Ontario for clinical testing and then stored. Measles has been eliminated in Canada since 1998.

The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days); 2 months (61-89 days); 3 months (90-119 days); 4 months; 5 months; 6-9 months; and 9-11 months.

Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.

To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test (PRNT) to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay (ELISA) because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.

When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL) , and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.

Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.

Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).

The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Dr. McLean and Dr. Orenstein noted in their editorial.

They discussed the rationale for various changes in the recommended schedule for measles immunization, based on changes in epidemiology of the disease and improved understanding of the immune response to vaccination since the vaccine became available in 1963. Then they posed the question of whether the recommendation should be revised again.

“Ideally, the schedule should minimize the risk of measles and its complications and optimize vaccine-induced protection,” Dr. McLean and Dr. Orenstein wrote.

They argued that the evidence cannot currently support changing the first MMR dose to a younger age because measles incidence in the United States remains extremely low outside of the extraordinary outbreaks in 2014 and 2019. Further, infants under 12 months of age make up less than 15% of measles cases during outbreaks, and unvaccinated people make up more than 70% of cases.

Rather, they stated, this new study emphasizes the importance of following the current schedule, with consideration of an earlier schedule only warranted during outbreaks.

“Health care providers must work to maintain high levels of coverage with 2 doses of MMR among vaccine-eligible populations and minimize pockets of susceptibility to prevent transmission to infants and prevent reestablishment of endemic transmission,” they concluded.

The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures. The editorialists had no external funding and no relevant financial disclosures.

SOURCE: Science M et al. Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-0630.

Infants born in a country with no endemic measles no longer received adequate protection against the disease from maternal antibodies when they were aged 6 months, according to new research.

FatCamera/E+/Getty Images

In fact, most of the 196 infants’ maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.

The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics.

“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.

The findings are not surprising for a setting in which measles has been eliminated and align with results from past research, Huong Q. McLean, PhD, MPH, of the Marshfield (Wis.) Clinic Research Institute and Walter A. Orenstein, MD, of Emory University in Atlanta wrote in an accompanying editorial (Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-2541).

However, this susceptibility prior to receiving the MMR has taken on a new significance more recently, Dr. McLean and Dr. Orenstein suggested.

“In light of increasing measles outbreaks during the past year reaching levels not recorded in the United States since 1992 and increased measles elsewhere, coupled with the risk of severe illness in infants, there is increased concern regarding the protection of infants against measles,” the editorialists wrote.

Dr. Science and colleagues tested serum samples from 196 term infants, all under 12 months old, for antibodies against measles. The sera had been previously collected at a single tertiary care center in Ontario for clinical testing and then stored. Measles has been eliminated in Canada since 1998.

The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days); 2 months (61-89 days); 3 months (90-119 days); 4 months; 5 months; 6-9 months; and 9-11 months.

Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.

To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test (PRNT) to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay (ELISA) because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.

When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL) , and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.

Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.

Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).

The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Dr. McLean and Dr. Orenstein noted in their editorial.

They discussed the rationale for various changes in the recommended schedule for measles immunization, based on changes in epidemiology of the disease and improved understanding of the immune response to vaccination since the vaccine became available in 1963. Then they posed the question of whether the recommendation should be revised again.

“Ideally, the schedule should minimize the risk of measles and its complications and optimize vaccine-induced protection,” Dr. McLean and Dr. Orenstein wrote.

They argued that the evidence cannot currently support changing the first MMR dose to a younger age because measles incidence in the United States remains extremely low outside of the extraordinary outbreaks in 2014 and 2019. Further, infants under 12 months of age make up less than 15% of measles cases during outbreaks, and unvaccinated people make up more than 70% of cases.

Rather, they stated, this new study emphasizes the importance of following the current schedule, with consideration of an earlier schedule only warranted during outbreaks.

“Health care providers must work to maintain high levels of coverage with 2 doses of MMR among vaccine-eligible populations and minimize pockets of susceptibility to prevent transmission to infants and prevent reestablishment of endemic transmission,” they concluded.

The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures. The editorialists had no external funding and no relevant financial disclosures.

SOURCE: Science M et al. Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-0630.

Infants born in a country with no endemic measles no longer received adequate protection against the disease from maternal antibodies when they were aged 6 months, according to new research.

FatCamera/E+/Getty Images

In fact, most of the 196 infants’ maternal measles antibodies had dropped below the protective threshold by 3 months of age – well before the recommended age of 12-15 months for the first dose of MMR vaccine.

The odds of inadequate protection doubled for each additional month of age, Michelle Science, MD, of the University of Toronto and associates reported in Pediatrics.

“The widening gap between loss of maternal antibodies and measles vaccination described in our study leaves infants vulnerable to measles for much of their infancy and highlights the need for further research to support public health policy,” Dr. Science and colleagues wrote.

The findings are not surprising for a setting in which measles has been eliminated and align with results from past research, Huong Q. McLean, PhD, MPH, of the Marshfield (Wis.) Clinic Research Institute and Walter A. Orenstein, MD, of Emory University in Atlanta wrote in an accompanying editorial (Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-2541).

However, this susceptibility prior to receiving the MMR has taken on a new significance more recently, Dr. McLean and Dr. Orenstein suggested.

“In light of increasing measles outbreaks during the past year reaching levels not recorded in the United States since 1992 and increased measles elsewhere, coupled with the risk of severe illness in infants, there is increased concern regarding the protection of infants against measles,” the editorialists wrote.

Dr. Science and colleagues tested serum samples from 196 term infants, all under 12 months old, for antibodies against measles. The sera had been previously collected at a single tertiary care center in Ontario for clinical testing and then stored. Measles has been eliminated in Canada since 1998.

The researchers randomly selected 25 samples for each of eight different age groups: up to 30 days old; 1 month (31-60 days); 2 months (61-89 days); 3 months (90-119 days); 4 months; 5 months; 6-9 months; and 9-11 months.

Just over half the babies (56%) were male, and 35% had an underlying condition, but none had conditions that might affect antibody levels. The conditions were primarily a developmental delay or otherwise affecting the central nervous system, liver, or gastrointestinal function. Mean maternal age was 32 years.

To ensure high test sensitivity, the researchers used the plaque-reduction neutralization test (PRNT) to test for measles-neutralizing antibodies instead of using enzyme-linked immunosorbent assay (ELISA) because “ELISA sensitivity decreases as antibody titers decrease,” Dr. Science and colleagues wrote. They used a neutralization titer of less than 192 mIU/mL as the threshold for protection against measles.

When the researchers calculated the predicted standardized mean antibody titer for infants with a mother aged 32 years, they determined their mean to be 541 mIU/mL at 1 month, 142 mIU/mL at 3 months (below the measles threshold of susceptibility of 192 mIU/mL) , and 64 mIU/mL at 6 months. None of the infants had measles antibodies above the protective threshold at 6 months old, the authors noted.

Children’s odds of susceptibility to measles doubled for each additional month of age, after adjustment for infant sex and maternal age (odds ratio, 2.13). Children’s likelihood of susceptibility to measles modestly increased as maternal age increased in 5-year increments from 25 to 40 years.

Children with an underlying conditions had greater susceptibility to measles (83%), compared with those without a comorbidity (68%, P = .03). No difference in susceptibility existed between males and females or based on gestational age at birth (ranging from 37 to 41 weeks).

The Advisory Committee on Immunization Practices permits measles vaccination “as early as 6 months for infants who plan to travel internationally, infants with ongoing risk for exposure during measles outbreaks and as postexposure prophylaxis,” Dr. McLean and Dr. Orenstein noted in their editorial.

They discussed the rationale for various changes in the recommended schedule for measles immunization, based on changes in epidemiology of the disease and improved understanding of the immune response to vaccination since the vaccine became available in 1963. Then they posed the question of whether the recommendation should be revised again.

“Ideally, the schedule should minimize the risk of measles and its complications and optimize vaccine-induced protection,” Dr. McLean and Dr. Orenstein wrote.

They argued that the evidence cannot currently support changing the first MMR dose to a younger age because measles incidence in the United States remains extremely low outside of the extraordinary outbreaks in 2014 and 2019. Further, infants under 12 months of age make up less than 15% of measles cases during outbreaks, and unvaccinated people make up more than 70% of cases.

Rather, they stated, this new study emphasizes the importance of following the current schedule, with consideration of an earlier schedule only warranted during outbreaks.

“Health care providers must work to maintain high levels of coverage with 2 doses of MMR among vaccine-eligible populations and minimize pockets of susceptibility to prevent transmission to infants and prevent reestablishment of endemic transmission,” they concluded.

The research was funded by the Public Health Ontario Project Initiation Fund. The authors had no relevant financial disclosures. The editorialists had no external funding and no relevant financial disclosures.

SOURCE: Science M et al. Pediatrics. 2019 Nov 21. doi: 10.1542/peds.2019-0630.

To the Editor:

Papulonecrotic tuberculid (PNT) is a cutaneous hypersensitivity reaction to antigenic components of Mycobacterium species, most commonly Mycobacterium tuberculosis. According to a PubMed search of articles indexed for MEDLINE using the terms papulonecrotic tuberculid, Mycobacterium avium complex, and Mycobacterium, only 1 case of PNT secondary to infection with Mycobacterium avium complex (MAC) has been reported.^1,2 Papulonecrotic tuberculid classically presents with symmetrical, dusky red papules with necrosis on the extremities.³ Patients may or may not have associated symptoms of fever and weight loss. It is diagnosed through skin biopsy as well as identification of a distant source of mycobacterial infection. Papulonecrotic tuberculid is considered a reactive process to a distant site of mycobacterial infection, and skin lesions contain few, if any, mycobacteria.⁴

A 65-year-old man was admitted to the hospital for expedited workup of chronic fevers, 20-lb weight loss, and night sweats of 8 months’ duration. He had a medical history of myelodysplastic syndrome and autoimmune hemolytic anemia. During hospitalization, positron emission tomography revealed multilevel vertebral lytic and sclerotic lesions. Subsequent T10 vertebral biopsy showed necrotizing granulomatous inflammation with extensive necrosis and acid-fast bacilli–positive organisms. The patient was empirically started on rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for presumed M tuberculosis and placed on respiratory isolation.

Dermatology was consulted for a recurrent tender rash on the bilateral upper and lower extremities of 5 years’ duration. Physical examination revealed numerous erythematous papulonecrotic lesions in various states of healing on the bilateral upper and lower extremities (Figure 1). Three years prior to the current presentation, 2 lesions were biopsied and demonstrated leukocytoclastic vasculitis with neutrophilic panniculitis and vasculopathy. A presumptive diagnosis of Sweet syndrome was made given the history of myelodysplastic syndrome, though an infectious etiology could not be ruled out at that time. Concurrently, the patient was diagnosed with autoimmune hemolytic anemia and was started on prednisone. Initially, the skin lesions improved with prednisone but never fully resolved; however, as the dosage of oral steroids decreased, the skin lesions worsened and presented in larger numbers with more frequency. The patient was titrated down to prednisone 5 mg daily with no additional treatment of the skin lesions at that time.

Disseminated MAC infection also was on the differential for our patient; however, we felt it was less likely than PNT for several reasons. First, disseminated infection rarely presents with cutaneous involvement and is associated with pulmonary involvement in 90% of cases.^7-9 Second, the granuloma formation noted on our patient’s skin biopsy was not typical for disseminated MAC but is well described in cases of PNT.^4,8,9 Finally, in the rare cases in which cutaneous involvement has occurred with disseminated mycobacterial infections, skin biopsies typically revealed numerous Mycobacterium organisms.^8,10 In contrast, skin lesions associated with PNT usually reveal few, if any, organisms, as was seen with our patient.²

The patient’s initial biopsies also supported a diagnosis of PNT, as early lesions of PNT typically show leukocytoclastic vasculitis. His response to low and high doses of prednisone also fit well with a PNT diagnosis. In fact, a case of PNT secondary to Mycobacterium bovis similarly showed an improvement in the rash with high-dose steroids but progression with lower doses.¹¹ It is possible that our patient’s response to steroids complicated the diagnosis of his rash.

The treatment of PNT is clearance of the underlying infection. Macrolide antibiotics, such as clarithromycin and azithromycin, have the best efficacy against MAC, in combination with ethambutol and/or rifabutin.^6,12 Treatment duration should be 1 year. Amikacin or streptomycin may be added to this regimen during early treatment.⁶ Mycobacterium avium complex is resistant to many antibiotics, including typical antituberculosis drugs, and sensitivities should be identified at the onset of treatment.^11,12

Albeit rare, clinicians should be aware of PNT secondary to MAC or other mycobacterial infections. Because this condition is difficult to diagnose with varying histologic findings and often negative tissue cultures, a high index of suspicion is necessary when a patient presents with recurrent papulonecrotic lesions, especially in immunocompromised hosts and patients with exposure to mycobacteria.

To the Editor:

Papulonecrotic tuberculid (PNT) is a cutaneous hypersensitivity reaction to antigenic components of Mycobacterium species, most commonly Mycobacterium tuberculosis. According to a PubMed search of articles indexed for MEDLINE using the terms papulonecrotic tuberculid, Mycobacterium avium complex, and Mycobacterium, only 1 case of PNT secondary to infection with Mycobacterium avium complex (MAC) has been reported.^1,2 Papulonecrotic tuberculid classically presents with symmetrical, dusky red papules with necrosis on the extremities.³ Patients may or may not have associated symptoms of fever and weight loss. It is diagnosed through skin biopsy as well as identification of a distant source of mycobacterial infection. Papulonecrotic tuberculid is considered a reactive process to a distant site of mycobacterial infection, and skin lesions contain few, if any, mycobacteria.⁴

A 65-year-old man was admitted to the hospital for expedited workup of chronic fevers, 20-lb weight loss, and night sweats of 8 months’ duration. He had a medical history of myelodysplastic syndrome and autoimmune hemolytic anemia. During hospitalization, positron emission tomography revealed multilevel vertebral lytic and sclerotic lesions. Subsequent T10 vertebral biopsy showed necrotizing granulomatous inflammation with extensive necrosis and acid-fast bacilli–positive organisms. The patient was empirically started on rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for presumed M tuberculosis and placed on respiratory isolation.

Dermatology was consulted for a recurrent tender rash on the bilateral upper and lower extremities of 5 years’ duration. Physical examination revealed numerous erythematous papulonecrotic lesions in various states of healing on the bilateral upper and lower extremities (Figure 1). Three years prior to the current presentation, 2 lesions were biopsied and demonstrated leukocytoclastic vasculitis with neutrophilic panniculitis and vasculopathy. A presumptive diagnosis of Sweet syndrome was made given the history of myelodysplastic syndrome, though an infectious etiology could not be ruled out at that time. Concurrently, the patient was diagnosed with autoimmune hemolytic anemia and was started on prednisone. Initially, the skin lesions improved with prednisone but never fully resolved; however, as the dosage of oral steroids decreased, the skin lesions worsened and presented in larger numbers with more frequency. The patient was titrated down to prednisone 5 mg daily with no additional treatment of the skin lesions at that time.

Disseminated MAC infection also was on the differential for our patient; however, we felt it was less likely than PNT for several reasons. First, disseminated infection rarely presents with cutaneous involvement and is associated with pulmonary involvement in 90% of cases.^7-9 Second, the granuloma formation noted on our patient’s skin biopsy was not typical for disseminated MAC but is well described in cases of PNT.^4,8,9 Finally, in the rare cases in which cutaneous involvement has occurred with disseminated mycobacterial infections, skin biopsies typically revealed numerous Mycobacterium organisms.^8,10 In contrast, skin lesions associated with PNT usually reveal few, if any, organisms, as was seen with our patient.²

The patient’s initial biopsies also supported a diagnosis of PNT, as early lesions of PNT typically show leukocytoclastic vasculitis. His response to low and high doses of prednisone also fit well with a PNT diagnosis. In fact, a case of PNT secondary to Mycobacterium bovis similarly showed an improvement in the rash with high-dose steroids but progression with lower doses.¹¹ It is possible that our patient’s response to steroids complicated the diagnosis of his rash.

The treatment of PNT is clearance of the underlying infection. Macrolide antibiotics, such as clarithromycin and azithromycin, have the best efficacy against MAC, in combination with ethambutol and/or rifabutin.^6,12 Treatment duration should be 1 year. Amikacin or streptomycin may be added to this regimen during early treatment.⁶ Mycobacterium avium complex is resistant to many antibiotics, including typical antituberculosis drugs, and sensitivities should be identified at the onset of treatment.^11,12

Albeit rare, clinicians should be aware of PNT secondary to MAC or other mycobacterial infections. Because this condition is difficult to diagnose with varying histologic findings and often negative tissue cultures, a high index of suspicion is necessary when a patient presents with recurrent papulonecrotic lesions, especially in immunocompromised hosts and patients with exposure to mycobacteria.

To the Editor:

Papulonecrotic tuberculid (PNT) is a cutaneous hypersensitivity reaction to antigenic components of Mycobacterium species, most commonly Mycobacterium tuberculosis. According to a PubMed search of articles indexed for MEDLINE using the terms papulonecrotic tuberculid, Mycobacterium avium complex, and Mycobacterium, only 1 case of PNT secondary to infection with Mycobacterium avium complex (MAC) has been reported.^1,2 Papulonecrotic tuberculid classically presents with symmetrical, dusky red papules with necrosis on the extremities.³ Patients may or may not have associated symptoms of fever and weight loss. It is diagnosed through skin biopsy as well as identification of a distant source of mycobacterial infection. Papulonecrotic tuberculid is considered a reactive process to a distant site of mycobacterial infection, and skin lesions contain few, if any, mycobacteria.⁴

A 65-year-old man was admitted to the hospital for expedited workup of chronic fevers, 20-lb weight loss, and night sweats of 8 months’ duration. He had a medical history of myelodysplastic syndrome and autoimmune hemolytic anemia. During hospitalization, positron emission tomography revealed multilevel vertebral lytic and sclerotic lesions. Subsequent T10 vertebral biopsy showed necrotizing granulomatous inflammation with extensive necrosis and acid-fast bacilli–positive organisms. The patient was empirically started on rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for presumed M tuberculosis and placed on respiratory isolation.

Dermatology was consulted for a recurrent tender rash on the bilateral upper and lower extremities of 5 years’ duration. Physical examination revealed numerous erythematous papulonecrotic lesions in various states of healing on the bilateral upper and lower extremities (Figure 1). Three years prior to the current presentation, 2 lesions were biopsied and demonstrated leukocytoclastic vasculitis with neutrophilic panniculitis and vasculopathy. A presumptive diagnosis of Sweet syndrome was made given the history of myelodysplastic syndrome, though an infectious etiology could not be ruled out at that time. Concurrently, the patient was diagnosed with autoimmune hemolytic anemia and was started on prednisone. Initially, the skin lesions improved with prednisone but never fully resolved; however, as the dosage of oral steroids decreased, the skin lesions worsened and presented in larger numbers with more frequency. The patient was titrated down to prednisone 5 mg daily with no additional treatment of the skin lesions at that time.

Disseminated MAC infection also was on the differential for our patient; however, we felt it was less likely than PNT for several reasons. First, disseminated infection rarely presents with cutaneous involvement and is associated with pulmonary involvement in 90% of cases.^7-9 Second, the granuloma formation noted on our patient’s skin biopsy was not typical for disseminated MAC but is well described in cases of PNT.^4,8,9 Finally, in the rare cases in which cutaneous involvement has occurred with disseminated mycobacterial infections, skin biopsies typically revealed numerous Mycobacterium organisms.^8,10 In contrast, skin lesions associated with PNT usually reveal few, if any, organisms, as was seen with our patient.²

The patient’s initial biopsies also supported a diagnosis of PNT, as early lesions of PNT typically show leukocytoclastic vasculitis. His response to low and high doses of prednisone also fit well with a PNT diagnosis. In fact, a case of PNT secondary to Mycobacterium bovis similarly showed an improvement in the rash with high-dose steroids but progression with lower doses.¹¹ It is possible that our patient’s response to steroids complicated the diagnosis of his rash.

The treatment of PNT is clearance of the underlying infection. Macrolide antibiotics, such as clarithromycin and azithromycin, have the best efficacy against MAC, in combination with ethambutol and/or rifabutin.^6,12 Treatment duration should be 1 year. Amikacin or streptomycin may be added to this regimen during early treatment.⁶ Mycobacterium avium complex is resistant to many antibiotics, including typical antituberculosis drugs, and sensitivities should be identified at the onset of treatment.^11,12

Albeit rare, clinicians should be aware of PNT secondary to MAC or other mycobacterial infections. Because this condition is difficult to diagnose with varying histologic findings and often negative tissue cultures, a high index of suspicion is necessary when a patient presents with recurrent papulonecrotic lesions, especially in immunocompromised hosts and patients with exposure to mycobacteria.

NEW ORLEANS – The incidence of acute otitis media has decreased by 25% to 35% in the past decade, thanks largely to the widespread and near universal use of the pneumococcal conjugate vaccine, according to Ellen R. Wald, MD.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

“To a smaller degree, it is also attributable to the use of influenza vaccine, and to the use of more stringent diagnostic criteria,” Dr. Wald, who chairs the department of pediatrics at the University of Wisconsin, Madison, said at the annual meeting of the American Academy of Pediatrics. “The fact that we are decreasing the number of episodes of otitis media in children in the first year of life means that we’re going to have fewer otitis-prone children and therefore less of a need for tympanostomy tubes, either as a solution to the problem of recurrence of acute otitis media (AOM) or for the problem of persistent effusion.”

The best way to limit antimicrobial use is for clinicians to increase their ability to differentiate AOM from otitis media with effusion (OME), said Dr. Wald, pediatrician-in-chief at the American Family Children’s Hospital in Madison. She noted that OME is a nonbacterial inflammatory state that usually resolves spontaneously. It tends to occur before or after AOM, and often without ever progressing to AOM. “Its principal importance is as a cause of hearing loss and as a confounder in the diagnosis AOM,” she explained. “Because it is a nonbacterial process, antibiotics are not indicated in the management of OME. In contrast, children with AOM have a bacterial infection that will benefit from the use of antimicrobials.”*

Middle ear effusion is common to both OME and AOM, she continued. To discriminate between the two conditions, clinicians must look for signs of acute inflammation of the tympanic membrane, “which we expect to see in AOM,” she said. “The most powerful sign of inflammation of the tympanic membrane is distinct fullness or bulging of the tympanic membrane on exam.”

Dr. Wald advises clinicians to be as systematic as possible when conducting the otoscopic exam, by looking at color and classifying it as pink, gray, white, yellow, red, amber, or blue, and by documenting the position as neutral, retracted, full, or bulging. “When we gauge how light passes through the tympanic membrane, we judge it as translucent, opaque, or partially opaque, and mobility as normal, decreased, or absent,” she added. “When we find decreased or absent mobility of the tympanic membrane, it tells us that we have fluid in the middle ear, but it does not discriminate between AOM and OME.”

Advances in digital otoscopy are helping pediatricians to improve their diagnostic skills. An early device, the iPhone otoscope by CellScope, uses an iOS smartphone to capture images and videos of the external ear canal and eardrum. “The image is pretty much the same as that seen through the eye of a hand-held otoscope,” Dr. Wald said. “The problem with this particular design is that the speculum is kind of large. It does still require the removal of cerumen, and the smartphone is kind of awkward to use as a handle during an otoscopic exam.”

A new digital otoscope called Wispr was unveiled at the AAP meeting. First developed at the University of Wisconsin and now marketed by WiscMed, Wispr delivers high-resolution views of the eardrum in even small or partially obstructed ear canals with one-button image and video capture. WiscMed was founded by Jim Berbee, MD, MBA, an engineer turned emergency medicine physician.

“One of the advantages of this particular model is that it handles a lot more like a usual otoscope and can be attached to the rechargeable handles that are commercially available,” Dr. Wald said. “It has an extremely tiny speculum. Within the head, there is even a smaller camera that allows the photographs to be taken. Because the speculum is so tiny, it allows the device to sometimes avoid the presence of cerumen, or sometimes go through it and still obtain an image.”

[email protected]

*This article was updated 12/13/2019

NEW ORLEANS – The incidence of acute otitis media has decreased by 25% to 35% in the past decade, thanks largely to the widespread and near universal use of the pneumococcal conjugate vaccine, according to Ellen R. Wald, MD.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

“To a smaller degree, it is also attributable to the use of influenza vaccine, and to the use of more stringent diagnostic criteria,” Dr. Wald, who chairs the department of pediatrics at the University of Wisconsin, Madison, said at the annual meeting of the American Academy of Pediatrics. “The fact that we are decreasing the number of episodes of otitis media in children in the first year of life means that we’re going to have fewer otitis-prone children and therefore less of a need for tympanostomy tubes, either as a solution to the problem of recurrence of acute otitis media (AOM) or for the problem of persistent effusion.”

The best way to limit antimicrobial use is for clinicians to increase their ability to differentiate AOM from otitis media with effusion (OME), said Dr. Wald, pediatrician-in-chief at the American Family Children’s Hospital in Madison. She noted that OME is a nonbacterial inflammatory state that usually resolves spontaneously. It tends to occur before or after AOM, and often without ever progressing to AOM. “Its principal importance is as a cause of hearing loss and as a confounder in the diagnosis AOM,” she explained. “Because it is a nonbacterial process, antibiotics are not indicated in the management of OME. In contrast, children with AOM have a bacterial infection that will benefit from the use of antimicrobials.”*

Middle ear effusion is common to both OME and AOM, she continued. To discriminate between the two conditions, clinicians must look for signs of acute inflammation of the tympanic membrane, “which we expect to see in AOM,” she said. “The most powerful sign of inflammation of the tympanic membrane is distinct fullness or bulging of the tympanic membrane on exam.”

Dr. Wald advises clinicians to be as systematic as possible when conducting the otoscopic exam, by looking at color and classifying it as pink, gray, white, yellow, red, amber, or blue, and by documenting the position as neutral, retracted, full, or bulging. “When we gauge how light passes through the tympanic membrane, we judge it as translucent, opaque, or partially opaque, and mobility as normal, decreased, or absent,” she added. “When we find decreased or absent mobility of the tympanic membrane, it tells us that we have fluid in the middle ear, but it does not discriminate between AOM and OME.”

Advances in digital otoscopy are helping pediatricians to improve their diagnostic skills. An early device, the iPhone otoscope by CellScope, uses an iOS smartphone to capture images and videos of the external ear canal and eardrum. “The image is pretty much the same as that seen through the eye of a hand-held otoscope,” Dr. Wald said. “The problem with this particular design is that the speculum is kind of large. It does still require the removal of cerumen, and the smartphone is kind of awkward to use as a handle during an otoscopic exam.”

A new digital otoscope called Wispr was unveiled at the AAP meeting. First developed at the University of Wisconsin and now marketed by WiscMed, Wispr delivers high-resolution views of the eardrum in even small or partially obstructed ear canals with one-button image and video capture. WiscMed was founded by Jim Berbee, MD, MBA, an engineer turned emergency medicine physician.

“One of the advantages of this particular model is that it handles a lot more like a usual otoscope and can be attached to the rechargeable handles that are commercially available,” Dr. Wald said. “It has an extremely tiny speculum. Within the head, there is even a smaller camera that allows the photographs to be taken. Because the speculum is so tiny, it allows the device to sometimes avoid the presence of cerumen, or sometimes go through it and still obtain an image.”

[email protected]

*This article was updated 12/13/2019

NEW ORLEANS – The incidence of acute otitis media has decreased by 25% to 35% in the past decade, thanks largely to the widespread and near universal use of the pneumococcal conjugate vaccine, according to Ellen R. Wald, MD.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

“To a smaller degree, it is also attributable to the use of influenza vaccine, and to the use of more stringent diagnostic criteria,” Dr. Wald, who chairs the department of pediatrics at the University of Wisconsin, Madison, said at the annual meeting of the American Academy of Pediatrics. “The fact that we are decreasing the number of episodes of otitis media in children in the first year of life means that we’re going to have fewer otitis-prone children and therefore less of a need for tympanostomy tubes, either as a solution to the problem of recurrence of acute otitis media (AOM) or for the problem of persistent effusion.”

The best way to limit antimicrobial use is for clinicians to increase their ability to differentiate AOM from otitis media with effusion (OME), said Dr. Wald, pediatrician-in-chief at the American Family Children’s Hospital in Madison. She noted that OME is a nonbacterial inflammatory state that usually resolves spontaneously. It tends to occur before or after AOM, and often without ever progressing to AOM. “Its principal importance is as a cause of hearing loss and as a confounder in the diagnosis AOM,” she explained. “Because it is a nonbacterial process, antibiotics are not indicated in the management of OME. In contrast, children with AOM have a bacterial infection that will benefit from the use of antimicrobials.”*

Middle ear effusion is common to both OME and AOM, she continued. To discriminate between the two conditions, clinicians must look for signs of acute inflammation of the tympanic membrane, “which we expect to see in AOM,” she said. “The most powerful sign of inflammation of the tympanic membrane is distinct fullness or bulging of the tympanic membrane on exam.”

Dr. Wald advises clinicians to be as systematic as possible when conducting the otoscopic exam, by looking at color and classifying it as pink, gray, white, yellow, red, amber, or blue, and by documenting the position as neutral, retracted, full, or bulging. “When we gauge how light passes through the tympanic membrane, we judge it as translucent, opaque, or partially opaque, and mobility as normal, decreased, or absent,” she added. “When we find decreased or absent mobility of the tympanic membrane, it tells us that we have fluid in the middle ear, but it does not discriminate between AOM and OME.”

Advances in digital otoscopy are helping pediatricians to improve their diagnostic skills. An early device, the iPhone otoscope by CellScope, uses an iOS smartphone to capture images and videos of the external ear canal and eardrum. “The image is pretty much the same as that seen through the eye of a hand-held otoscope,” Dr. Wald said. “The problem with this particular design is that the speculum is kind of large. It does still require the removal of cerumen, and the smartphone is kind of awkward to use as a handle during an otoscopic exam.”

A new digital otoscope called Wispr was unveiled at the AAP meeting. First developed at the University of Wisconsin and now marketed by WiscMed, Wispr delivers high-resolution views of the eardrum in even small or partially obstructed ear canals with one-button image and video capture. WiscMed was founded by Jim Berbee, MD, MBA, an engineer turned emergency medicine physician.

“One of the advantages of this particular model is that it handles a lot more like a usual otoscope and can be attached to the rechargeable handles that are commercially available,” Dr. Wald said. “It has an extremely tiny speculum. Within the head, there is even a smaller camera that allows the photographs to be taken. Because the speculum is so tiny, it allows the device to sometimes avoid the presence of cerumen, or sometimes go through it and still obtain an image.”

[email protected]

*This article was updated 12/13/2019

BOSTON – Some of the most notable abstracts presented here at the annual meeting of the American Association for the Study of Liver Diseases dealt with key topics including the natural history of hepatitis B virus, novel treatment approaches, and prevention, according to Marc Ghany, MD.

Andrew Bowser/MDedge News

During a special hepatitis debriefing session held on the last day of the conference, Dr. Ghany reviewed his key selections in hepatitis B virus (HBV) research, including the following:
 

Natural history

Steatohepatitis may worsen HBV-related liver injury, according to results of an analysis of liver biopsies from adult patients enrolled in a North American cohort study (Abstract 162). Investigators found that steatohepatitis was associated with a 1.6-fold increased risk of advanced fibrosis.

“For all patients with hepatitis B, I think it’s important to screen and manage metabolic abnormalities to prevent liver disease progression,” said Dr. Ghany, who is with the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was evaluated in two notable studies, Dr. Ghany said, including one that found no difference in risk of HCC development among white patients who received long-term entecavir versus those who received long-term tenofovir (Abstract 454). This stands in contrast to a previous and controversial finding, according to investigators, that HCC incidence was lower in Asian patients treated with tenofovir versus those treated with entecavir.

In the other study, investigators found that dual-antiplatelet therapy (DAPT) was associated with a lower risk of HCC versus aspirin monotherapy in patients with chronic hepatitis B (Abstract 934). Antiplatelet therapy was associated with a near 20% reduction in HCC risk, while DAPT as compared with aspirin monotherapy was linked to a near 30% reduction. “These are very provocative findings,” Dr. Ghany said. “Of course they need to be confirmed, but if so, may open new avenues of HCC chemoprevention.”
 

Novel therapies

Several new and promising drugs are undergoing clinical trials, including JNJ-64530440 (JNJ-0440), a novel class N capsid assembly modulator. In phase 1a data presented here at The Liver Meeting, the treatment was safe, well tolerated, and resulted in potent inhibition of viral replication (Abstract 0089). “We await further studies on its effect on functional cure,” Dr. Ghany told attendees.

Another treatment to watch is GSK3389404 (GSK404), a liver-targeted antisense oligonucleotide; in a phase 2 placebo-controlled study in patients with chronic hepatitis B on stable nucleos(t)ide therapy, this treatment had acceptable safety and produced dose-dependent declines in hepatitis B surface antigen (HBsAg), according to investigators (Abstract 0695). Dr. Ghany said this constitutes “proof of principle” that antisense oligonucleotides can decrease HBsAg levels.

In a phase 2 randomized, placebo-controlled study in virally suppressed adults with chronic hepatitis B, the toll-like receptor 8 (TLR8) agonist GS-9688 was safe and well tolerated, and resulted in dose-dependent pharmacodynamic changes, with 5% of patients experiencing a 1 log₁₀ IU/mL or greater decline in HBsAg levels or an HBsAg loss by week 24 (Abstract 0697). This is a “promising approach” that merits further study, according to Dr. Ghany.
 

Prevention: Vaccination and screening

A trivalent HBV vaccine is superior to monovalent vaccine, according to results from the double-blind, randomized, controlled, phase 3 PROTECT study presented here at the meeting (Abstract LP13). Known as Sci-B-Vac, the mammalian cell-derived trivalent vaccine had higher response rates versus the recombinant monovalent vaccine Engerix-B in difficult-to-vaccinate populations, according to Dr. Ghany.

A separate report based on a national health insurance cohort study in Korea demonstrated that regular follow-up, that is to say, every 3-6 months, significantly reduced liver cancer–related mortality (Abstract 0159). Patients compliant with screening in the study not only had a 44% reduction in risk of death from HCC, but also were more likely to receive curative treatments (23.1% versus 15.1%). “Notwithstanding the limitations or cohort studies, I think these data reinforce the need to screen patients with chronic hepatitis B,” Dr. Ghany said.

He provided no disclosures in his presentation.

BOSTON – Some of the most notable abstracts presented here at the annual meeting of the American Association for the Study of Liver Diseases dealt with key topics including the natural history of hepatitis B virus, novel treatment approaches, and prevention, according to Marc Ghany, MD.

Andrew Bowser/MDedge News

During a special hepatitis debriefing session held on the last day of the conference, Dr. Ghany reviewed his key selections in hepatitis B virus (HBV) research, including the following:
 

Natural history

Steatohepatitis may worsen HBV-related liver injury, according to results of an analysis of liver biopsies from adult patients enrolled in a North American cohort study (Abstract 162). Investigators found that steatohepatitis was associated with a 1.6-fold increased risk of advanced fibrosis.

“For all patients with hepatitis B, I think it’s important to screen and manage metabolic abnormalities to prevent liver disease progression,” said Dr. Ghany, who is with the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was evaluated in two notable studies, Dr. Ghany said, including one that found no difference in risk of HCC development among white patients who received long-term entecavir versus those who received long-term tenofovir (Abstract 454). This stands in contrast to a previous and controversial finding, according to investigators, that HCC incidence was lower in Asian patients treated with tenofovir versus those treated with entecavir.

In the other study, investigators found that dual-antiplatelet therapy (DAPT) was associated with a lower risk of HCC versus aspirin monotherapy in patients with chronic hepatitis B (Abstract 934). Antiplatelet therapy was associated with a near 20% reduction in HCC risk, while DAPT as compared with aspirin monotherapy was linked to a near 30% reduction. “These are very provocative findings,” Dr. Ghany said. “Of course they need to be confirmed, but if so, may open new avenues of HCC chemoprevention.”
 

Novel therapies

Several new and promising drugs are undergoing clinical trials, including JNJ-64530440 (JNJ-0440), a novel class N capsid assembly modulator. In phase 1a data presented here at The Liver Meeting, the treatment was safe, well tolerated, and resulted in potent inhibition of viral replication (Abstract 0089). “We await further studies on its effect on functional cure,” Dr. Ghany told attendees.

Another treatment to watch is GSK3389404 (GSK404), a liver-targeted antisense oligonucleotide; in a phase 2 placebo-controlled study in patients with chronic hepatitis B on stable nucleos(t)ide therapy, this treatment had acceptable safety and produced dose-dependent declines in hepatitis B surface antigen (HBsAg), according to investigators (Abstract 0695). Dr. Ghany said this constitutes “proof of principle” that antisense oligonucleotides can decrease HBsAg levels.

In a phase 2 randomized, placebo-controlled study in virally suppressed adults with chronic hepatitis B, the toll-like receptor 8 (TLR8) agonist GS-9688 was safe and well tolerated, and resulted in dose-dependent pharmacodynamic changes, with 5% of patients experiencing a 1 log₁₀ IU/mL or greater decline in HBsAg levels or an HBsAg loss by week 24 (Abstract 0697). This is a “promising approach” that merits further study, according to Dr. Ghany.
 

Prevention: Vaccination and screening

A trivalent HBV vaccine is superior to monovalent vaccine, according to results from the double-blind, randomized, controlled, phase 3 PROTECT study presented here at the meeting (Abstract LP13). Known as Sci-B-Vac, the mammalian cell-derived trivalent vaccine had higher response rates versus the recombinant monovalent vaccine Engerix-B in difficult-to-vaccinate populations, according to Dr. Ghany.

A separate report based on a national health insurance cohort study in Korea demonstrated that regular follow-up, that is to say, every 3-6 months, significantly reduced liver cancer–related mortality (Abstract 0159). Patients compliant with screening in the study not only had a 44% reduction in risk of death from HCC, but also were more likely to receive curative treatments (23.1% versus 15.1%). “Notwithstanding the limitations or cohort studies, I think these data reinforce the need to screen patients with chronic hepatitis B,” Dr. Ghany said.

He provided no disclosures in his presentation.

BOSTON – Some of the most notable abstracts presented here at the annual meeting of the American Association for the Study of Liver Diseases dealt with key topics including the natural history of hepatitis B virus, novel treatment approaches, and prevention, according to Marc Ghany, MD.

Andrew Bowser/MDedge News

During a special hepatitis debriefing session held on the last day of the conference, Dr. Ghany reviewed his key selections in hepatitis B virus (HBV) research, including the following:
 

Natural history

Steatohepatitis may worsen HBV-related liver injury, according to results of an analysis of liver biopsies from adult patients enrolled in a North American cohort study (Abstract 162). Investigators found that steatohepatitis was associated with a 1.6-fold increased risk of advanced fibrosis.

“For all patients with hepatitis B, I think it’s important to screen and manage metabolic abnormalities to prevent liver disease progression,” said Dr. Ghany, who is with the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was evaluated in two notable studies, Dr. Ghany said, including one that found no difference in risk of HCC development among white patients who received long-term entecavir versus those who received long-term tenofovir (Abstract 454). This stands in contrast to a previous and controversial finding, according to investigators, that HCC incidence was lower in Asian patients treated with tenofovir versus those treated with entecavir.

In the other study, investigators found that dual-antiplatelet therapy (DAPT) was associated with a lower risk of HCC versus aspirin monotherapy in patients with chronic hepatitis B (Abstract 934). Antiplatelet therapy was associated with a near 20% reduction in HCC risk, while DAPT as compared with aspirin monotherapy was linked to a near 30% reduction. “These are very provocative findings,” Dr. Ghany said. “Of course they need to be confirmed, but if so, may open new avenues of HCC chemoprevention.”
 

Novel therapies

Several new and promising drugs are undergoing clinical trials, including JNJ-64530440 (JNJ-0440), a novel class N capsid assembly modulator. In phase 1a data presented here at The Liver Meeting, the treatment was safe, well tolerated, and resulted in potent inhibition of viral replication (Abstract 0089). “We await further studies on its effect on functional cure,” Dr. Ghany told attendees.

Another treatment to watch is GSK3389404 (GSK404), a liver-targeted antisense oligonucleotide; in a phase 2 placebo-controlled study in patients with chronic hepatitis B on stable nucleos(t)ide therapy, this treatment had acceptable safety and produced dose-dependent declines in hepatitis B surface antigen (HBsAg), according to investigators (Abstract 0695). Dr. Ghany said this constitutes “proof of principle” that antisense oligonucleotides can decrease HBsAg levels.

In a phase 2 randomized, placebo-controlled study in virally suppressed adults with chronic hepatitis B, the toll-like receptor 8 (TLR8) agonist GS-9688 was safe and well tolerated, and resulted in dose-dependent pharmacodynamic changes, with 5% of patients experiencing a 1 log₁₀ IU/mL or greater decline in HBsAg levels or an HBsAg loss by week 24 (Abstract 0697). This is a “promising approach” that merits further study, according to Dr. Ghany.
 

Prevention: Vaccination and screening

A trivalent HBV vaccine is superior to monovalent vaccine, according to results from the double-blind, randomized, controlled, phase 3 PROTECT study presented here at the meeting (Abstract LP13). Known as Sci-B-Vac, the mammalian cell-derived trivalent vaccine had higher response rates versus the recombinant monovalent vaccine Engerix-B in difficult-to-vaccinate populations, according to Dr. Ghany.

A separate report based on a national health insurance cohort study in Korea demonstrated that regular follow-up, that is to say, every 3-6 months, significantly reduced liver cancer–related mortality (Abstract 0159). Patients compliant with screening in the study not only had a 44% reduction in risk of death from HCC, but also were more likely to receive curative treatments (23.1% versus 15.1%). “Notwithstanding the limitations or cohort studies, I think these data reinforce the need to screen patients with chronic hepatitis B,” Dr. Ghany said.

He provided no disclosures in his presentation.

BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.

Will Pass/MDedge News

This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.

“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”

To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.

Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).

While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.

“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.

Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.

“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”

In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.

“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”

The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.

SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.

BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.

Will Pass/MDedge News

This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.

“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”

To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.

Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).

While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.

“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.

Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.

“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”

In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.

“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”

The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.

SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.

BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.

Will Pass/MDedge News

This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.

“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”

To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.

Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).

While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.

“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.

Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.

“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”

In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.

“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”

The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.

SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.