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July/August 2012
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IDSA Journal Club
July-August 2012

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.


Vaccination for Herpes Zoster in Immunosuppressed Older Patients
Reviewed by George R. Thompson III, MD

The development of a live attenuated herpes zoster (HZ) vaccine has significantly reduced the incidence of HZ in immunocompetent patients. However, vaccination is currently contraindicated in those who are immunosuppressed secondary to concerns regarding the safety and effectiveness of a live viral vaccine in this population.

In the July 4 issue of The Journal of the American Medical Association, researchers performed a retrospective cohort analysis using Medicare beneficiaries diagnosed with an autoimmune disease (ankylosing spondylitis, inflammatory bowel disease, psoriatric arthritis/psoriasis or rheumatoid arthritis) to examine the possible association between receipt of the zoster vaccine and HZ incidence in the short-term (<42 days after vaccination) and long term (median of two years of follow-up).

Six hundred and thirty-three patients received immunosuppressive medications (TNF-α blockers, non-TNF biologics, DMARDS, and oral/or glucocorticoids) within 42 days of vaccination. There were no patients in this group who developed varicella, HZ, or meningitis/encephalitis. The adjusted hazard ratio for the vaccine was 0.61 at a median of two years of follow-up—findings suggesting vaccination is associated with a decreased risk of HZ.

These results suggest live-zoster vaccination may not be associated with increased risk of HZ shortly after vaccination in patients treated with immunosuppressive medications. The generalizability of these results to other immunosuppressed populations remains in question and further study in these groups will be needed. However, the authors’ results do call into question current recommendations that HZ vaccination is contraindicated in patients receiving immunosuppressive medications.

(Zhang et al. JAMA. 2012;208(1):43-49.)

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Management of Severe, Left-sided Infective Endocarditis: The Scales Tip Toward Early Surgery?
Reviewed by Kathryn E. Stephenson, MD, MPH

Left-sided, native-valve infective endocarditis is challenging to manage when it is complicated by severe valve disease and large vegetations. Early surgery may lead to a decrease in systemic embolism or progression to heart failure. There is concern, however, that surgery in the setting of active infection may have unacceptable adverse effects.

In the June 28 issue of the New England Journal of Medicine, investigators reported on a randomized clinical trial comparing early surgery versus conventional treatment for left-sided infective endocarditis complicated by severe valve disease and large vegetations. Seventy-six patients were enrolled from 2006-2011 at two medical centers in Korea. Patients were diagnosed with endocarditis according to the modified Duke criteria and were excluded from the study if they had absolute indications or contraindications to surgery.

In an intention-to-treat analysis, the authors report that patients who received conventional treatment were significantly more likely to die in the hospital or have an embolic event than patients who received early surgery (23 percent vs. 3 percent of patients, respectively; P=0.03). At six weeks, the rate of embolism was 21 percent in the conventional-treatment group compared to 0 percent in the surgery group (P=0.005). There was also no increase in operative mortality or recurrence of endocarditis in the surgery group. Interestingly, 77 percent of patients in the conventional-treatment group underwent surgery anyway because of worsened cardiac disease.

The authors conclude that early surgery is superior to conventional therapy for severe left-sided, native-valve endocarditis, primarily because surgery reduces the risk of systemic embolism. The strength of the study is its randomized design, though the number of patients enrolled was small. Also, viridans streptococci were the predominant pathogens isolated and the results may not be generalizable to other organisms. Nevertheless, this study suggests that all patients with severe, left-sided, native-valve endocarditis should be referred to medical centers with cardiac surgical experience.

(Kang et al. N Engl J Med. 2012;366:2466-73.)

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Safety and Efficacy of Pandemic Influenza A(H1N1) Vaccination
Reviewed by Jason Weinberg, MD

Vaccination against pandemic influenza A(H1H1) is safe in pregnant women and in young HIV-1-infected individuals, according to recent reports in The Journal of the American Medical Association (JAMA) and The Journal of Infectious Diseases (JID).

Morbidity and mortality associated with both seasonal and pandemic influenza infection is increased in pregnancy. Pregnant women were prioritized for vaccination during the recent pandemic, but fetal safety associated with vaccination during pregnancy against pandemic influenza A(H1N1) has been incompletely defined. In an observational cohort study in the July 11 issue of JAMA, the authors assessed adverse fetal outcomes in 6,989 infants whose mothers were exposed to an adjuvant-containing influenza A(H1N1)pdm09 vaccine during pregnancy. Using a propensity score matching approach to compare vaccine-exposed and vaccine-unexposed infants, the investigators demonstrated that there was no significant increase in the prevalence of major birth defects, risk of preterm birth, or risk of low birth weight.

Influenza infection can also be more severe in HIV-1-infected individuals. However, antibody responses to seasonal influenza vaccine are less robust in the setting of HIV infection. To determine whether vaccination against pandemic influenza A(H1N1) was safe and effective in young HIV-1-infected patients, investigators in a study in the Aug. 1 edition of JID conducted an uncontrolled trial in which 55 patients aged 4 to 24 years who were perinatally infected with HIV-1 received two doses of a high-dose (30 μg), adjuvant-free monovalent vaccine. Very few adverse events were observed following vaccination. Seroresponse [≥ four-fold rise in hemagglutinin inhibition (HAI) titers] was noted in between 79.6 percent and 84.8 percent of patients depending on age, and seroprotection (HAI titers ≥ 40) was detected in between 79.6 percent and 85.1 percent of patients. In general, these responses were less robust than in previous studies with HIV-uninfected children.

Vaccination against pandemic influenza A(H1N1) is not without risk. In a separate study in the July 11 issue of JAMA, administration of an adjuvant-containing monovalent vaccine was associated with a small increased risk of Guillain-Barré syndrome. Longer-term safety data in infants whose mothers were vaccinated during pregnancy is still needed. Likewise, additional data confirming the safety and efficacy of vaccination in patients with greater immunocompromise due to HIV infection will be helpful. Collectively, however, these recent reports suggest that vaccination against pandemic influenza A(H1N1) is likely to be safe in these at-risk populations.

(Pasternak et al. JAMA 2012; 308(2):165-174; De Wals et al. JAMA 2012; 308(2):175-181; Flynn et al. J Infect Dis 2012; 206:421-30.)

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Persistence of Non-gonococcal Urethritis: Common and Dependent on Organism and Antibiotic Treatment
Reviewed by Jonathan Li, MD

Non-gonococcal urethritis (NGU) is the most common cause of urethritis in men in the United States. A multicenter randomized controlled study conducted in four sexually transmitted disease clinics and published last year evaluated optimal treatment. This trial randomized 305 heterosexual men to treatment with doxycycline or azithromycin alone or each in conjunction with tinidazole. The results showed no significant clinical benefit from tinidazole and overall similar clinical cure rates between azithromycin and doxycycline. A follow-up analysis published in the Aug. 1 issue of The Journal of Infectious Diseases evaluated the persistence of NGU after treatment.

Among the 293 evaluable participants, 44 percent were found to have Chlamydia trachomatis, 31 percent had Mycoplasma genitalium, 13 percent had Trichomonas vaginalis, and 28 percent had none of the three organisms detected. Persistence rates differed by organism and treatment regimen. Four weeks after the initial treatment, Chlamydia trachomatis persisted in 12 percent of participants, and Mycoplasma genitalium persisted in 44 percent. Chlamydia trachomatis was more likely to be detected at follow-up after treatment with azithromycin than after treatment with doxycycline (23 percent vs. 5 percent, P=0.01). In contrast, persistence of Mycoplasma genitalium was more common in those treated with doxycycline compared to those treated with azithromycin (68 percent vs. 33 percent, P=0.001). Persistent detection of organisms was significantly associated with the presence of urethral discharge and elevated inflammatory cells on urethral smear.

Current Centers for Disease Control and Prevention guidelines recommend either azithromycin or doxycycline for the empiric treatment of non-gonococcal urethritis. These data suggest that doxycycline may be preferred when Chlamydia trachomatis infection has been confirmed. However, azithromycin is likely to remain popular for empiric treatment given its simplicity of dosing (including ease of directly observed therapy) as well as the overall comparable efficacy with doxycycline in the primary analysis of the trial.

(Seña et al. Clin Infect Dis. 2011; 52:163-70.)

For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

Aug. 15

  • Hot Spring Hazard–Microsporidial Keratitis
  • Can Linezolid be Safely Used in Patients Receiving Serotonergic Drugs?

Aug. 1

  • Tropheryma whipplei Endocarditis
  • Aneurysms, Vascular Grafts, and Q Fever

July 15

  • Hot-Foot Syndrome
  • Nocardia Resistant to Trimethoprim-Sulfamethoxazole? Maybe Not
  • Vancomycin in Real Life

July 1

  • Mechanism of Action of Amphotericin B: Another Dogma Falls
  • Treatment of Infections Due to Methicillin-Susceptible Staphylococcus aureus (MSSA): Cephalosporins Versus Semisynthetic Penicillins


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