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October 2010
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IDSA Journal Club
October 2010

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.

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.

Widespread Presence of NDM-1 in Enterobacteriaceae in India, Pakistan, and the UK
Reviewed by Christopher J. Graber, MD, MPH

A new metallo-β-lactamase has become widespread among Enterobacteriaceae isolates throughout India and Pakistan and is now the most common carbapenemase in Enterobacteriaceae in the United Kingdom, according to a study published in the September issue of Lancet Infectious Diseases.

New Delhi metallo-β-lactamase 1 (NDM-1) was first described in 2009 and has sporadically been reported in Klebsiella pneumoniae and Escherichia coli isolated from patients in the United States, Sweden, Canada, the Netherlands, and Australia who had recently received medical care in India. The study authors found that, among 141 and 47 carbapenem-resistant Enterobacteriaceae isolates collected in 2009 in the Indian cities of Chennai and Haryana, 44 (31 percent ) and 26 (55 percent) were positive for NDM-1 by PCR. NDM-1 was also identified in Enterobacteriaceae from several other communities throughout India and Pakistan, typically occurring in community-acquired infections.

An analysis of 73 carbapenemase-producing Enterobacteriaceae isolates referred to the UK’s national reference laboratory in 2009 revealed the presence of NDM-1 in 32 (44 percent); at least 17 isolates were from patients who had traveled to India or Pakistan within the prior year. While the Chennai and UK NDM-1 isolates were clonally diverse Enterobacteriaceae (mostly E. coli and K. pneumoniae), the Haryana isolates represented a single clone of K. pneumoniae. 

All NDM-1-positive isolates were resistant to carbapenems (except two isolates with borderline meropenem susceptibility) and aminoglycosides; less than 10 percent were susceptible to aztreonam or ciprofloxacin. Approximately 60 percent were susceptible to tigecycline, and 90 percent were susceptible to colistin. The NDM-1 gene was mostly found on plasmids that were of highly variable size, though three UK isolates also carried the NDM-1 gene on their chromosome.

NDM-1 has clearly demonstrated ability for rapid spread. Its presence only further emphasizes the worldwide need for heightened efforts in antibiotic stewardship, infection control, and antibiotic drug development. There should be a heightened suspicion for these organisms among patients who have traveled to areas where NDM-1 is endemic.

(Kumarasamy et al. Lancet Infect Dis. 2010; 10: 597–602.)

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Excessive Diagnostic Testing and Broad Antibiotic Use for SSTIs
Reviewed by Nina Kim, MD, MSc

The incidence of skin and soft tissue infections (SSTIs) has increased substantially in both hospital and outpatient settings in recent years. Despite this, we have few contemporary studies that systematically catalogue the clinical spectrum and current management of these common infections. Investigators from the University of Colorado in Denver reveal some important and alarming findings in a study published in the Oct. 15 issue of Clinical Infectious Diseases.

They examined a total of 322 consecutive cases of SSTI during 2007, captured through ICD-9 coding from hospital discharge diagnoses and categorized as cellulitis (20 percent), cutaneous abscess (32 percent), and SSTI with complicating factors (48 percent), such as deep tissue infection, bacteremia, and diabetic or chronic ulcer. In the latter two groups, where a pathogen was identified through abscess drainage, tissue specimen, or blood, Staphylococcus aureus and streptococci comprised the overwhelming majority (97 percent).

Despite this well-established predominance, antibiotics with broad activity against gram-negative organisms were used in two-thirds of cases. The median duration of therapy was two weeks for all categories, regardless of severity—despite available evidence that suggests many patients, especially those with uncomplicated forms of SSTI, can be treated safely with shorter courses. Diagnostic tests of questionable utility in SSTI were routinely used. Serum inflammatory markers (erythrocyte sedimentation rate or C-reactive protein) were measured in 70 percent of cases and imaging studies, particularly plain radiography, were done in 94 percent of cellulitis cases.

Although this is a retrospective study at a single academic center, it is a thorough overview of current inpatient SSTI presentation and management that brings into sharp focus excesses in diagnostic testing and antimicrobial therapy unlikely to be isolated to this Denver institution. The study underscores the need to examine our own care settings and to conduct careful prospective studies that clarify the clinical care of SSTIs.

(Jenkins et. al. Clin Infect Dis. 2010; 51:895-903.)

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HPV Vaccine Safe and Immunogenic in HIV-Infected Men
Reviewed by Shireesha Dhanireddy, MD

The quadrivalent human papillomavirus (HPV) vaccine is safe and immunogenic in HIV-infected men, according to a study in the Oct. 15 issue of The Journal of Infectious Diseases.

The single-arm, open-label, multicenter trial included male patients from eight clinical trial sites in the U.S. The patients were HIV-infected men > 18 years old with CD4 counts > 200 cells/uL and HIV-1 RNA levels < 200 copies/mL on antiretroviral or with CD4 counts > 350 cells/uL, not on treatment, and without history of anal cancer or high-grade squamous anal intraepithelial neoplasm (HGAIN). Individuals were also excluded if HPV 16 and 18 were detected by PCR of anal swabs. Subjects received vaccine at entry, week 8, and week 24. The primary endpoints included immunogenicity, determined by antibody titer to vaccine serotypes, as well as the development of serious vaccine-related adverse events.

Of the 235 eligible patients, a significant number were excluded based on the presence of HGAIN at baseline. One hundred patients were eligible for the per-protocol analysis. Participants achieved a > 95 percent response rate based on anti-HPV antibodies to vaccine serotypes. No serious adverse events were associated with the vaccine.

Interestingly, a significant proportion (60-78 percent) of men were seronegative for at least one vaccine serotype at baseline, suggesting that despite age and history of sexual intercourse, HIV-positive men may still benefit from HPV vaccine. A significant proportion of men (nearly 30 percent) were excluded based on the presence of high-grade lesions at baseline, however. A limitation of this study is that the median CD4 count of participants was >500 cells/uL, which may explain the high rates of response compared to other vaccines.

This study shows that quadrivalent HPV vaccine may be given safely to HIV-infected men with relatively preserved CD4 counts. However, clinical efficacy data is still lacking.

(Wilkin et al. J Infect Dis. 2010;202:1246-1253.)

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Survival of Hepatitis C Virus in Syringes
Reviewed by Ed Dominguez, MD

Harm reduction programs have reduced the incidence of HIV infection among intravenous drug users (IDUs) but not for hepatitis C virus infection (HCV). The estimated probability of HCV transmission via this route is five-fold to twenty-fold higher than for HIV. In the Oct. 1 issue of The Journal of Infectious Diseases, researchers determined the viability of HCV in two types of commonly used syringes at different temperatures over time.

The team measured infectivity via a microculture assay. Syringes were loaded with blood spiked with HCV, duplicating the common sequence used by IDUs. The syringes were then assayed for virus immediately or stored at 4°C, 22°C, and 37°C for up to 63 days. Low void volumes (2 microliters) were investigated with U-100 1-ml insulin syringes and high void volumes (32 microliters) with 1-ml tuberculin syringes. The researchers recovered HCV in 5 percent of insulin syringes stored at 4°C for up to seven days. No virus was recovered from those stored at 22°C and 37°C after one day of storage. Infectivity declined almost as rapidly. Syringes stored at 4°C showed 92 percent reduction at day seven, while those stored at 37°C showed 96 percent reduction at day one.

This inverse relationship between temperature and HCV survival was more pronounced in the high void volume syringes. Although HCV infectivity decreased by at least 90 percent after one day of storage at all temperatures, syringes stored at 4°C showed consistently higher infectivity than those stored at other temperatures through the first 21 days.

Harm reduction programs, such as syringe exchange, have reduced the circulation time of used syringes to < 3 days. However, this seminal study suggests that HCV infectivity may persist beyond that time, particularly in high void volume syringes and in syringes stored at 4°C. Public health recommendations for preventing HCV in IDUs will need to be reevaluated in light of this finding.

(Paintsil et al. J Infect Dis. 2010; 202(7):981-3.)

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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:

Nov. 15

  • Meningitis and Pituitary Function
  • Herpes Zoster Vaccine in Patients with Previous Shingles

Nov. 1

  • More False‐Positive Immunoglobulin (Ig) M Antibody Test Results: Coccidioidomycosis
  • Noncirrhotic Portal Hypertension Possibly Related to Didanosine Therapy
  • Itraconazole Can Give You the Shakes

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