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.

• Impact of Vancomycin Exposure on Patients with MRSA Bacteremia
• Antibiotic Resistance in the Environment: From the Streets of India to the Grocery Store
• Preventing Health Care-Associated MRSA Infections: The Bundle Approach
• Alternate Hepatitis B Vaccine Strategies for HIV-Infected Patients

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.

Impact of Vancomycin Exposure on Patients with MRSA Bacteremia
Reviewed by Paul Pottinger, MD

The 2009 guidelines for vancomycin therapeutic monitoring suggest achieving trough concentrations of 15-20 mcg/ml when treating serious infections due to methicillin-resistant Staphylococcus aureus (MRSA) isolates, especially those with vancomycin minimum inhibitory concentrations (MICs) > 1 mcg/ml. This recommendation was based on mathematical modeling, animal data and limited human evidence. (Also see IDSA’s 2011 practice guidelines for MRSA treatment.)

A study published in the April 15 issue of Clinical Infectious Diseases provides more clinical data in support of this practice. In this retrospective case series, 320 patients with MRSA bacteremia were studied for risk factors for vancomycin failure (defined as death at 30 days, blood culture positivity at seven days or more, and persistent signs and symptoms of bacteremia at the end of therapy).

Perhaps the authors’ most striking finding was an overall composite failure rate of 52.5 percent.  Statistically significant independent risk factors for failure included infective endocarditis (adjusted odds ratio 4.6), nosocomial-acquired infection (AOR 2.2), an initial vancomycin trough < 15 mg/L (AOR 2.0), and a vancomycin MIC > 1 (AOR 1.5). There was also support for the guideline position that patients whose area under the serum drug concentration-versus-time curve (AUC)/MIC ratio is less than 400 will be more likely to suffer a clinical failure. In this paper, the authors’ analysis found higher failure rates among those whose AUC/MIC was < 421 (failure rate 61 percent vs. 49 percent, p = 0.38).

In addition to confirming the significant morbidity and mortality associated with MRSA bacteremia, this study provides additional evidence to support recommendations both to take into account MRSA vancomycin MICs when treating bacteremia and to dose vancomycin to achieve serum trough levels of 15-20 mg/L, especially in MRSA endocarditis.

(Kullar et al. Clin Infect Dis. 2011;52:975-81.)

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Antibiotic Resistance in the Environment: From the Streets of India to the Grocery Store
Reviewed by Christopher J. Graber, MD, MPH

Two studies, one in the May issue of Lancet Infectious Diseases and one in the May 15 issue of Clinical Infectious Diseases, highlight the growing problem of antimicrobial resistance in bacteria that reside outside of the human host.

The first study addresses the startling emergence of the New Delhi metallo-β-lactamase 1 (NDM-1) carbapenemase initially described in Enterobacteriaceae among patients in or recently returned from India and Pakistan (see October 2010 IDSA Journal Club). To follow up on the finding that some patients from whom bacteria carrying the NDM-1 gene had no health care exposure, this study sampled seepage water (i.e., water pools in streets and rivulets) and tap water from 171 and 50 sites, respectively, within a 12 km radius of central New Delhi for the presence of the NDM-1 gene by PCR and DNA probing.

The NDM-1 gene was found in 51 (30 percent) of the seepage samples and in two (4 percent) of the tap water samples. Bacteria with the NDM-1 gene could be cultivated from 12 seepage samples and two tap water samples, not only including Enterobacteriaceae but other species not previously described as NDM-1-positive, including Shigella boydii, Vibrio cholerae, Aeromonas, and several nonfermenters (including multiple Pseudomonas species) where the gene appeared to be less stable.

The second study sampled a total of 136 retail beef, chicken, pork, and turkey products from 26 grocery stores in Chicago; Washington, D.C.; Fort Lauderdale, Fla.; Los Angeles; and Flagstaff, Ariz. for the presence of S. aureus. Seventy-nine unique isolates were found in 64 samples; turkey (20/26, 77 percent) was mostly frequently contaminated.  While oxacillin resistance was found in only three isolates, tetracycline resistance was widespread (63 percent overall), particularly among isolates from turkey and pork. Ciprofloxacin resistance was frequent among isolates from chicken (61 percent).  Intermediate resistance to vancomycin was found in one isolate from pork.

These articles provide stark reminders that antimicrobial resistance can be found not only in bacteria that colonize and infect us but also among bacteria in the water we drink and the food we eat. The findings strongly suggest that the effort to curb the spread of antimicrobial resistance should be expanded past the human host.

(Walsh et al. Lancet Infect Dis. 2011;11:355-62 and Waters et al. Clin Infect Dis. 2011;52:1227-30.)

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Preventing Health Care-Associated MRSA Infections: The Bundle Approach
Reviewed by Ed Dominguez, MD

How to reduce health care-associated methicillin-resistant Staphylococcus aureus (MRSA) infections remains a challenge without a clear answer. By using an “MRSA bundle,” a Veterans Affairs (VA) center in Pittsburgh reduced these infections by 60 percent on a surgical ward and by 75 percent in a surgical ICU in a four-year pilot study, ending in 2007. The bundle included universal nasal surveillance, hand hygiene, contact precautions for patients colonized or infected with MRSA, and a change in infection control philosophy that places responsibility on all personnel with patient contact. A report in the April 14 issue of The New England Journal of Medicine describes the results of a much larger study conducted after this bundle was subsequently implemented at 150 VA centers nationwide.

During the study period, from 2007 to 2010, 1.9 million patient admissions/discharges/transfers occurred from ICUs and non-ICUs, accounting for 8.3 million patient-days. The mean age was 62.6 years, and 95 percent of the patients were men. By the end of the study, admission screening increased from 82 percent to 96 percent, and transfer/discharge screening increased from 72 percent to 93 percent. The mean monthly prevalence of colonization or infection upon admission was 13.6 percent. MRSA prevalence was greater in non-ICU patients than in ICU patients (15.7 percent vs. 14.5 percent, P<0.001).

In ICUs, the MRSA bundle decreased the rates of health care-associated infections by 62 percent, from 1.64 per 1,000 patient-days to 0.62 per 1,000 patient-days (P<0.001). The rates in non-ICUs fell 45 percent, from 0.47 per 1,000 patient-days to 0.26 per 1,000 patient-days (P<0.001). Furthermore, the rates of MRSA transmission fell in ICUs by 17 percent and in non-ICUs by 21 percent (P<0.001 for both). Finally, investigators observed declines in the rates of bloodstream infections (including catheter-associated), pneumonia (nosocomial and ventilator-associated), urinary tract infections, and wound infections. It is unclear which elements of the bundle were most effective and whether pre-existing infection control initiatives contributed to the observed improvement. Nonetheless, the results suggest a multifaceted approach is warranted and perhaps efficacious.

(Jain et al. New Engl J Med. 2011; 364:1419-1430.)

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Alternate Hepatitis B Vaccine Strategies for HIV-Infected Patients
Reviewed by Christian B. Ramers, MD, MPH

Chronic hepatitis B infection is more common in HIV-infected individuals than the general public and greatly increases the risk of liver-related mortality in these patients. Unfortunately, vaccination response rates are diminished in this population, especially in those with a low CD4 nadir, ongoing HIV replication, and older age. Several strategies have been employed to address these lower rates, including higher vaccine doses, alternate schedules, intradermal route for administration, and adjuvant use. A study in the April 13, 2011 issue of The Journal of the American Medical Association compares two of these strategies with the standard three-dose schedule in a randomized controlled trial.

Investigators enrolled and randomized 437 HIV-infected patients without hepatitis B immunity to receive the standard three shot (20 mcg) hepatitis B vaccine series (IM20x3, n = 145), a double-dose (40 mcg) four-shot series (IM40x4, n = 148), or a lower-dose (4 mcg) four-shot intradermal series (ID4x4, n = 144). Patients with CD4 counts < 200 cells/mm³ were excluded, as were those co-infected with hepatitis C. The main outcomes were the percentage of responders in each group, defined by the presence of > 10 mIU/mL of anti-HBs antibody at week 28 of the study.

A significantly higher percentage of patients in the double-dose group (IM40x4, 82 percent) and the intradermal group (ID4x4, 77 percent) developed protective antibodies than did the standard group (IM20x3 65 percent, p < 0.001 and p = 0.02, respectively). Female sex, lower age, no active smoking, higher baseline CD4 count, and undetectable viral load were associated with response at 28 weeks. Adjusted odds ratios for response rates compared to the standard IM20x3 regimen were 3.58 (95 percent CI 1.92-6.67) for the IM40x4 schedule and 2.09 (95 percent CI 1.18-3.68) for the ID4x4 schedule. 

This study suggests two alternatives that could achieve higher rates of seroconversion in HIV-infected patients. Importantly, this trial did not address the notoriously difficult subgroup of patients with CD4 < 200. Also, of particular relevance to resource-limited settings, the intradermal route may achieve acceptably high protection rates using less reagent, allowing greater scale-up of this effective prevention tool. Given these results, future guidelines should consider these alternate strategies.

(Launay et al.  JAMA. 2011 Apr 13; 305(14):1432-1440.)

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