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.

• Persistent Cognitive and Functional Deficits Following Sepsis
• Adenovirus 36 and Childhood Obesity: Causal or Innocent Bystander?
• HIV Epidemic Unabated in the MSM Population
• CHG‐Impregnated Cloths and Preventing SSTIs: More Research Needed
• Study Suggests Voriconazole as Reasonable Option for Invasive Fusariosis

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.

Persistent Cognitive and Functional Deficits Following Sepsis
Reviewed by Jason Weinberg, MD

Severe sepsis in older patients was independently associated with long-term cognitive and functional deficits in a study in the Oct. 27 edition of the Journal of the American Medical Association.

Using data from a longstanding cohort study of older Americans, the authors prospectively identified 516 patients with a mean age of 76.9 years who survived hospitalizations with severe sepsis, based on information from Medicare claims.  Data were drawn from ongoing biennial surveys of these patients and 4,517 other patients who survived hospitalizations without sepsis to assess their functional and cognitive status before and after hospitalization.

Severe sepsis was associated with an increase in moderate to severe cognitive impairment, along with an increase in the number of functional limitations and the rate of developing those limitations.  Increases in functional limitations were greatest in patients with better baseline function before sepsis, with a mean of 1.5 new limitations per person.  The results were consistent through a variety of subgroup and sensitivity analyses. Increased cognitive and functional impairment persisted in sepsis survivors for at least eight years.

Important questions remain, including uncertainty about specific mechanisms linking sepsis to long-term functional deficits.  The authors suggest plausible explanations, including effects of inflammation, ischemia, and reperfusion on muscle and nerve injury that could contribute to long-term deficits.  Importantly, these factors are likely to be potentially preventable or treatable.  Despite the uncertainty, this study clearly demonstrates that the consequences of sepsis are substantial and extend well beyond an acute episode, even when antibiotic therapy is successful.

(Iwashyna et al. JAMA. 2010; 304(16):1787-1794.)

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Adenovirus 36 and Childhood Obesity: Causal or Innocent Bystander?
Reviewed by George R. Thompson III, MD

Genetic factors likely play an important role in the development of childhood obesity; however these risks alone cannot explain the rapid increase in the prevalence of this condition. The concept of a viral contribution to obesity has recently emerged, and adenovirus 36 (AD36) has been implicated in animal models. The authors of a study in the October issue of Pediatrics sought to determine the incidence of AD36 antibodies in non-obese and obese children and to correlate the severity of obesity with AD36 serostatus.

This single-center study enrolled 124 children (57 non-obese, 67 obese) between the ages of 8 and 18.  Fifteen percent of the children were AD36-positive; those who were AD36-positive were significantly older and had a significantly greater median body mass index (BMI) than children who were AD36-negative. In a secondary analysis, obese children who were AD36-positive had a significantly greater mean BMI and, on average, weighed 16.1 kg more than obese children who were AD36-negative.

These results support an association between the presence of AD36-specific antibodies and obesity in children. The nearly threefold difference in levels of AD36-positivity between obese and non-obese children is comparable to data previously described in adults and lends further credit to a viral contribution to obesity.  Although proadipogenic effects of AD36 have been described in animal models, causality in humans has yet to be demonstrated despite the biologic plausibility. Additional research, including longitudinal data, will be needed to determine the timing of AD36 infection and how exposure relates to human obesity.

(Gabbert et al.  Pediatrics. 2010; 126(4):721-726.)

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HIV Epidemic Unabated in the MSM Population
Reviewed by Jonathan Li, MD

Men who have sex with men (MSM) have historically been one of the highest risk populations for HIV infection in the United States.  A sobering new study published in the Sept. 24 issue of the Centers for Disease Control and Prevention (CDC)’s Morbidity and Mortality Weekly Report evaluated the prevalence of HIV in this population group and surveyed the participants’ knowledge of their HIV status.

In 2008, CDC’s National HIV Behavioral Surveillance system (NHBS) performed an anonymous cross-sectional study of more than 8,000 MSM participants.  The study found an HIV prevalence of 19 percent, with the highest rates in the non-Hispanic black population (28 percent), followed by Hispanics (18 percent), and the non-Hispanic white population (17 percent).  Forty-four percent were unaware of their infection, including 63 percent of those aged 18-29 years old and 54 percent of minorities.  

These results are startling and are comparable to the estimated 18 percent adult HIV prevalence rate in South Africa.  Unfortunately, they are also not significantly changed from a similar survey performed in 2004-2005.  These findings reinforce the importance of HIV education, especially for the youth and minority populations.  Clinicians should be encouraged to adhere to CDC recommendations that sexually active MSM be tested for HIV annually.

(Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Sept. 24, 2010 / 59(SS08);1-37.)

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CHG-Impregnated Cloths and Preventing SSTIs: More Research Needed
Reviewed by Sara Cosgrove, MD

Although many practitioners currently recommend skin decolonization for prevention of recurrent skin and soft tissue infections (SSTIs), data supporting this practice are limited. According to a study published in the December issue of Infection Control and Hospital Epidemiology, cleansing with 2 percent chlorhexidine gluconate (CHG)-impregnated cloths three times a week was ineffective in preventing SSTIs among Marine officer candidates.

Participants were cluster randomized by platoon to apply 2 percent CHG cloths (N = 781) or control cloths (N= 781) immediately after showering during their 6-10 week training classes. They were followed daily for evidence of SSTI.  Compliance, defined as use of at least 50 percent of the wipes, was relatively low: 63 percent in the CHG group and 67 percent in the control group.  Fifty-six (rate = 0.094) SSTIs occurred in the CHG group, and 44 (rate = 0.071) occurred in the control group; 80 percent occurred in the first four weeks of follow up. Although subjects treated with CHG cloths had lower rates of skin colonization than those treated with control cloths, overall rates of methicillin-sensitive Staphylococcus aureus (MSSA) (49.9  percent vs. 60.8 percent) and methicillin-resistant Staphylococcus aureus (MRSA) (2.6 percent vs. 6.0 percent) colonization were high. The authors speculate the negative study results may have been due to a combination of poor compliance and reduction of the CHG effect due to frequent showering.

The study is the first to evaluate the use of CHG bathing in an outpatient population, and its results suggest that CHG bathing alone does not reduce SSTI rates, particularly if compliance is not high. Further studies are needed to understand the role of more frequent CHG use and its use in combination with mupirocin.

(Whitman et al. Infect Control Hosp Epidemiol. 2010;31:1207–1215.)

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Study Suggests Voriconazole as Reasonable Option for Invasive Fusariosis
Reviewed by Khalil Ghanem, MD, PhD

The optimal treatment for invasive fusariosis is unknown. Although voriconazole was approved in 2002 for treating Fusarium infections, the available data were limited. In a retrospective study of 73 cases in the October issue of Antimicrobial Agents and Chemotherapy, voriconazole appeared to be a reasonable option.

The cases were collected from the Pfizer voriconazole clinical database and the French National Reference Center for Mycoses and Antifungals database. Efficacy was based on investigator assessment at the end of therapy: A complete or partial response was classified as a success. The median age of the patients was 43 years, 92 percent had a proven Fusarium infection, 60 percent had hematologic malignancies, 64 percent were neutropenic, and 78 percent were treated with voriconazole after failing therapy with another antifungal agent.

Success was achieved in 47 percent of patients (median duration of therapy was 57 days). In 16 percent, concomitant antifungal therapy was administered simultaneously or shortly after voriconazole therapy. Combination therapy did not improve outcomes. Neutropenic patients had a lower response rate (5 percent) than non-neutropenic patients (63 percent). Although not statistically significant, response rates varied by Fusarium species and by site of infection (0 percent survival for brain infections vs. 64 percent survival for lung infections). For amphotericin derivatives, published efficacy rates range from 32 percent for amphotericin B to 46 percent for amphotericin B lipid complex.

The data must be interpreted cautiously given the retrospective study design and the small sample size. The study suggests voriconazole may be considered an option for fusariosis, but the optimal treatment of Fusarium infections remains unknown. Combination therapy, often recommended when treating fusariosis, should not be abandoned based on this small study.

(Lortholary et al. Antimicrob Agents and Chemother. 2010; 54: 4446- 4450.)

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