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September 2008
Vol. 18, No. 9
Cover Stories
IDSA Journal Club, August 2008

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

For more from Clinical Infectious Diseases and The Journal of Infectious Diseases, see the "In the IDSA Journals" section of IDSA News.


Antibiotics for Sinusitis May Help a Little, Hurt a Lot

Melinda M. Pettigrew, PhD

Although antibiotics may provide some benefit for acute sinusitis, that small benefit comes with the cost of increased adverse events, according to two recent studies.

Antibiotic prescriptions for upper respiratory tract infections are common and often inappropriately prescribed. In the first study, in the September issue of The Lancet Infectious Diseases, Falagas et al. published a meta-analysis of 17 randomized controlled trials to compare the benefit of antibiotics for acute sinusitis compared to placebo. Antibiotics were associated with an 82 percent higher cure rate and faster resolution of symptoms. The number of disease complications and sinusitis recurrences did not differ between the two groups.

Unfortunately, the small benefit of antibiotics corresponded with an 87 percent rise in the risk for adverse events due to treatment. Amoxicllin was the antibiotic most often prescribed and gastrointestinal symptoms were the most common adverse event.

The authors note that the difference in the cure rate in the antibiotics group may have been smaller than might be expected because many of the patients treated with antibiotics likely had viral, not bacterial, sinusitis. Furthermore, even bacterial sinusitis symptoms can resolve quickly with or without antibiotics.  

Caution should be used when interpreting these data. The analysis included studies with a range of inclusion criteria and differing outcome definitions. Most of the studies focused on the resolution of symptoms during a short time period. Several of the studies excluded patents with severe disease, and these are the patients who are the most likely to develop complications. (Falagas et al., Lancet ID. 2008;8:543-55.)

The second study, which adds to the concerns about adverse events, appears in the September 15 issue of Clinical Infectious Diseases. It suggests that antibiotic prescriptions are responsible for more than 142,000 emergency department visits. Shehab et al. analyzed nationally representative surveillance data to estimate the risk of emergency department visits for adverse events associated with systemic antibiotics by drug and type of adverse event. They estimated that out of all emergency department visits for adverse drug events, 20 percent were related to antibiotics. Half of the events were due to penicillin and cephalosporins. The majority of adverse events were due to allergic reactions.

These data may underestimate the number of adverse events, since patients with mild reactions are unlikely to visit the emergency room. The data sources used in this study also may not capture all prescriptions. The authors did not assess whether the antibiotics were prescribed appropriately. (Shehab et al., Clin Infect Dis. 2008;47:735-743.)

Together these two important studies indicate that in addition to the threat to public health of antibiotic resistance, the potential for adverse events should be considered when clinicians are deciding how to treat individual patients. More research is needed so that clinicians can correctly identify patients with disease of bacterial origin and those who could benefit most from antimicrobial treatment, especially with regard to upper respiratory tract infections. Novel interventions to decrease the frequency of inappropriate antimicrobial prescribing are needed.

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Silver-coated Endotracheal Tubes: Not a Silver Bullet for VAP

Jason B. Weinberg, MD

Silver-coated endotracheal tubes decreased the rate of microbiologically confirmed ventilator-associated pneumonia (VAP) but had no effect on other important outcomes in a study in the August 20 issue of the Journal of the American Medical Association.

VAP is a substantial cause of morbidity, but there is not yet a prevention strategy that consistently eliminates this problem.  In this well-designed, multicenter, prospective study, patients expected to require mechanical ventilation for more than 24 hours were randomized to use either a standard, uncoated endotracheal tube or an endotracheal tube coated with silver.  Among all patients and patients intubated 24 hours or longer, use of the silver-coated endotracheal tube was associated with a 36 percent reduction in risk of microbiologically confirmed VAP, the study’s primary outcome.  This effect was not particularly robust, however, and the overall incidence of VAP in the study population was relatively low.

Post-hoc analyses suggested that VAP was associated with increased duration of intubation, ICU stay, and hospital stay.  Despite these results, use of the silver-coated endotracheal tube was not associated with improvements in these relevant secondary outcomes.  Unfortunately, other related measures such as antibiotic use and hospital charges were not assessed in the study.

Simple interventions that decrease the incidence of diseases such as VAP are clearly important goals.  If they prove effective, devices such as the silver-coated endotracheal tube used in this study are particularly appealing because they may provide the additional benefit of limiting antibiotic use and reducing the emergence of antibiotic-resistant organisms.  In this case, however, it seems that additional data is needed before silver-coated endotracheal tubes should be recommended in all cases. (Koleff et al.,  JAMA. 2008;300:805-13.)

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Rapid HIV Testing in the Emergency Room: Interpret Positive Tests Carefully

Khalil G. Ghanem, MD

While rapid HIV tests are a quick, easy, and highly sensitive way to broaden HIV screening, an article in the August 5 issue of Annals of Internal Medicine shows that one commonly used oral test gave more false positives than the manufacturer advertised.

The number of new cases of HIV in the United States has been relatively stable (although underestimated) for over a decade.  Many who are HIV-infected are unaware of their diagnosis. This has led to expanded screening efforts to try and identify these patients and bring them to care. One such effort is rapid HIV testing in the emergency room (ER).

Walensky et al. report the results of rapid screening of 849 adults in an ER in Boston using the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test.  The investigators found 39 positive results. Confirmatory testing using Western Blot, EIA, and HIV-RNA testing revealed that only five of these 31 tests were true positives. (Eight patients declined follow-up testing.) The specificity of the test was found to be 96.9 percent, somewhat lower than the 99 percent specificity suggested by the manufacturer. Confirmatory Western blot was conclusive in only 50 percent of patients on the first attempt. The addition of HIV-1 RNA testing improved the rate of conclusive results to 96 percent.

There are several lessons to be learned. Negative rapid HIV tests may be reassuring, but positive rapid tests need to be confirmed before discussing the results with patients. A confirmatory testing approach must be in place to deal with positive test results; in a significant number of cases, Western blot testing alone may not offer immediate clarification. HIV-RNA testing on positive rapid test results and indeterminate initial Western blot tests may provide a more rapid answer than the current CDC-recommended approach of repeating the Western blot four weeks later.

This study should not dissuade us from performing rapid HIV testing in the ER or other such venues; indeed, patients with a reactive  screening test had an eight- to 32-fold increased odds of HIV infection compared with the pretest odds; it should, however, encourage a reasoned approach to dealing with positive test results.  (Walensky et al., Ann Intern Med. 2008;149;153-160.)

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Long-term Prognosis after West Nile Virus Infection

Khalil G. Ghanem, MD

Physical and mental outcome measures appear to normalize within approximately one year in patients with West Nile virus (WNV), according to a study published in the August 19 issue of Annals of Internal Medicine. Women, those with neuroinvasive disease, and patients with multiple co-morbid conditions took longer to recover.  

The investigators followed 156 patients diagnosed with WNV for a median of 203 days. They included patients with neuroinvasive (both meningitis and encephalitis) and non-neuroinvasive disease. The outcome measures consisted of scores on the Physical Component Summary and Mental Component Summary of the Short Form-36, Depression Anxiety Stress Scale, and Fatigue Severity Scale.

Within about a year, patients recovered to levels of physical and mental functions similar to the general population. Patients who did not have significant co-morbid conditions were more likely to recover physical and mental functions faster; men were more likely to recover mental function faster than women.

ID clinicians are frequently called upon to discuss prognosis of illnesses with patients and their families. This study should help frame the discussion as it relates to WNV. A few limitations are worth highlighting: only 156 of 367 potential participants were enrolled; seven patients died before enrollment; and seven patients who had acute flaccid paralysis were excluded from the prognostic curves. Whether these limitations biased the results towards better outcomes is unclear but should be kept in mind. (Loeb et al., Ann Intern Med. 2008;149:232-241.)

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Does Repeated Use of Single-dose Nevirapine Increase Resistance?

Sabrina Renee Kendrick, MD

In a small study in the August 15 issue of the Journal of Infectious Diseases, Flys et al. report that repeated use of single-dose (SD) nevirapine (NVP) to prevent mother-to-child transmission of HIV does not appear to influence NVP resistance.

Researchers in Uganda compared the emergence and persistence of NVP-resistant HIV strains in 57 women who had not received SD NVP in a prior pregnancy to 34 pregnant women who had. NVP resistance was studied in samples collected from these two groups of women and their 17 HIV-infected infants at fixed times after SD NVP administration.

The authors found no significant difference in the proportion of women in whom NVP resistance was detected, the types of resistance mutations, or the frequency and level of the K103N resistance mutation at six weeks or six months post partum. Infants born to SD NVP-naïve and SD NVP-experienced women also had similar proportions of NVP resistance.

The small sample sizes in this study limited the power to detect significant differences in NVP resistance between the comparison groups. Therefore, caution is advised when interpreting the data. (Flys et al., Journ Infect Dis. 2008;198:465-469.)

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