In this feature, a panel of IDSA members identifies and critiques important new infectious diseases studies in the current literature that have a significant impact on the practice of infectious diseases medicine.
Linezolid for Catheter-Related Bloodstream Infections? Caution Advised.
Linezolid was reported to be non-inferior to vancomycin when treating catheter insertion-site and catheter-related bloodstream infections (CRBSI ) in a randomized, open-label, phase III study published in the January 15 issue of Clinical Infectious Diseases. However, the study has significant limitations.
This multicenter study recruited 739 patients with suspected catheter-related infection. Of 164 patients with catheter-site infections treated with linezolid, 89.6 percent achieved successful microbiological outcomes one to two weeks after therapy, compared to 89.9 percent of 151 patients in the vancomycin group. Of those patients with CRBSI, 86.3 percent of the 95 patients treated with linezolid and 90.5 percent of the 74 treated with vancomycin achieved successful outcomes. These results met non-inferiority criteria. There was a trend for increased mortality in the linezolid group. Side-effects related to bone-marrow toxicity were similar in both groups.
Clinicians should be aware that the linezolid package insert states that it should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections. Aside from that fact, this study had several limitations that must be taken into account. Most significantly, the power to detect a clinically meaningful difference between the two arms was very limited given the small sample size in the CRBSI populations. This is a crucial point because the risk of making a Type II error is high (i.e. saying that no difference exists when it does). Efficacy of linezolid for Staphylococcus aureus CRBSI cannot be inferred from this study because only a quarter of patients had S. aureus infection.
Given the long clinical experience we have with vancomycin, it should still be the primary agent to treat gram-positive CRBSI. This study offers data to suggest that linezolid may be an alternative in salvage situations.
(Wilcox et a., Clin Infect Dis. 2009;48:203-212.)
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Flu—Not Flu Shot—Associated with GBS
Seasonal influenza vaccination is not associated with an increased risk of Guillain-Barre syndrome (GBS) but recent influenza-like illness (
ILI) is significantly associated with GBS, according to a study in the February 1 edition of the American Journal of Epidemiology.
The authors studied data recorded in the General Practice Research Database in the United Kingdom, one of the world’s largest primary care databases, holding data on 5.7 percent of the
UK population. The study employed a self-controlled case series methodology: Cases act as their own controls, contributing time to both the control and risk periods depending on whether and when they receive an influenza vaccine or have an
ILI. This design overcomes some of the usual problems with a cohort study such as cofounding due to essential differences between patients who receive vaccinations and those who do not.
Researchers analyzed 775 episodes of GBS in 690 patients; 169 had at least one influenza vaccine, 69 had at least one pneumococcal vaccine, and 99 had at least one
ILI. The relative incidence of GBS within 90 days of influenza vaccination was 0.76 (95% confidence interval 0.41-1.40), while the relative incidence of GBS within 90 days of an
ILI was 7.35 (95% confidence interval 9.37-29.54). Results were similar when the analysis was repeated using a subset of validated cases.
This study provides important data to refute the notion that influenza vaccine increases risk of GBS and to support the association between GBS and antecedent respiratory illness. In addition, it provides a possible explanation for the perception of a relationship between influenza vaccination and GBS: Influenza vaccination season coincides with ILI season; thus, patients who develop GBS after receiving influenza vaccine are also at risk for having had an
ILI prior to exposure, which may represent the true risk factor.
(Stowe et al., Am J Epidemiol. 2009;169:382-388.)
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No Convincing Benefit of Steroids for Virus-Induced Wheezing in Children
Oral prednisolone treatment of children with virus-induced wheezing did not provide any clear benefit according to a study in the January 22 issue of The New England Journal of Medicine.
In this randomized, double-blind study, 687 young children with virus-induced wheezing who presented to an emergency department or were referred to a hospital received a 5-day course of either oral prednisolone or placebo. Although well tolerated, steroid treatment was not associated with significant differences in the time to hospital discharge, use of a bronchodilator, or severity of symptoms. No differences emerged when results were stratified by symptom severity or when the analysis was limited to patients classified as being at high risk for having asthma later in life, although this was a very small subgroup in the study. Of note, diagnostics were not performed to document the presence of a virus in these patients and allow the investigators to determine whether steroids would provide benefit for patients infected with a specific virus.
In a separate article in the same issue, Ducharme and colleagues report on the preemptive use of an inhaled steroid or placebo in 129 young children beginning at the onset of a respiratory illness. The use of high-dose fluticasone reduced the use of rescue oral steroids (8 percent of the fluticasone group vs. 18 percent of the placebo group) and was associated with small reductions in symptom severity and duration. However, children with virus-induced wheezing who received steroids were noted to have smaller gains in height and weight.
Some controversy still remains regarding the use of steroids in patients with virus-induced wheezing. Together, though, these studies suggest that steroids provide little clear benefit for patients with mild or moderate disease and can be associated with concerning side effects.
(Panickar et al. N Engl J Med. 2009;360:329-38 and Ducharme et al. N Engl J Med. 2009; 360:339-53.)
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Using Hair to Monitor Therapeutic Drug Levels
Examining hair samples may provide a useful, non-invasive way to monitor antiretroviral drug concentrations, particularly in the developing world, according to a study published ahead of print in AIDS.
The Women’s Interagency HIV Study (WIHS), a prospective cohort of HIV-infected women, found that protease inhibitor (PI) levels in small hair samples were the strongest independent predictor of virologic success, defined as a viral load (VL) less than 80 copies/mL or a 2 log or more drop in VL from when starting antiretrovirals (ARV).
Drug levels in hair offer an advantage of providing an estimate of an average level of medication exposure rather than a single plasma drug concentration. Also, hair is easy to collect, store, and ship.
The authors set out to examine the relationship between concentrations of lopinavir (LPV)/ritnoavir (RTV) and atazanavir (ATV) in hair and initial virologic outcomes. Between October 2003 and October 2006, 224 participants at several sites in the
United States had hair samples collected and analyzed for levels of the target new PI at the semiannual WIHS visit.
The study revealed that participants initiating LPV/RTV who had hair levels in the top tertile were 40 times more likely to have virologic success compared to the bottom tertile. Variables such as adherence, age, race, starting viral load and CD4 count, and prior PI experience were controlled at the time of analysis. In women starting ATV, virologic suppression was 8 times more likely for those with hair concentrations in the top tertile compared to the bottom tertile.
This non-invasive approach for assessing ARV exposure may be most useful in resource-limited settings, but can be considered in situations where specimen collection is difficult such as in pediatrics, or when drug exposure is unpredictable such as pregnancy.
(Gandhi et al., AIDS 2009;23, published ahead of print.)
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