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July/August 2011
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IDSA Journal Club
July-August 2011

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.

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.

Effects of Surgical vs. N-95 Masks and Evidence for Transocular Entry of Seasonal Influenza
Reviewed by Christopher J. Graber, MD, MPH

A recent study in The Journal of Infectious Diseases raises important issues regarding transmission of seasonal influenza, most notably that transocular entry may play a role in transmission.

The investigators recruited 28 healthy volunteers to be exposed to aerosolized live attenuated influenza vaccine (2009/10 seasonal FluMist) in an airtight chamber for 20 minutes and be assigned to one of the following groups: no barrier precautions, ocular exposure only (with subjects breathing air from outside the chamber), surgical mask with and without eye protection, and N-95 respirators with and without eye protection. A nasal wash was performed immediately after exposure, from which quantitative reverse-transcriptase PCR for a portion of the M gene of influenza A was performed.

The largest amount of viral RNA was found in the nasal washes of the subjects with no barrier precautions and with surgical masks without eye protection; all participants in these groups had positive nasal washes. Three of four subjects in the ocular exposure only group had positive nasal washes, though the absolute amount of RNA present was very low. Though eye protection did not prevent anyone wearing a surgical mask from having a positive nasal wash, it did reduce the amount of RNA present approximately four-fold. In the N-95 respirator group, eye protection was associated with a lower number of subjects having positive nasal washes (one of five versus three of five subjects) and an approximately eight-fold reduction in amount of RNA present. Five- to ten-fold reductions in amount of RNA present were seen in those wearing the N-95 respirators compared to surgical masks.

While this was a small study, it adds important data to the ongoing debate of how best to protect health care workers from influenza exposure and suggests the need for further study on the role of eye protection.

(Bischoff et al. J Infect Dis 2011; 204:193-9)

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Antibiotic Overuse: Spotlight on Acute Pediatric Visits for Asthma
Reviewed by Christian B. Ramers, MD, MPH

Visits to primary care providers, emergency departments, and pediatricians are often due to acute respiratory tract infections, especially in children with asthma or a prior history of wheezing.  Because most of these are caused by viruses, antibiotics are generally not recommended in the management of acute asthma. Yet this may be a unique patient population in which a large proportion of unwarranted antibiotic use occurs. Two studies in the June issue of the Journal of Pediatrics highlight this persistent problem and quantify the troublesome frequency of antibiotic use in this setting.

In the first study, American investigators analyzed data from two large nationally representative databases of ambulatory and emergency visits. Analysis was restricted to patients < 18 years of age with a primary diagnosis of asthma. Between 1998 and 2007, there were 5,198 visits in the dataset, and 15.6 percent of them involved an antibiotic prescription without a co-existing diagnosis to justify such a prescription. In a multivariate analysis, factors associated with antibiotic prescription included concomitant steroid prescription (odds ratio (OR) 2.69, 95 percent confidence interval (CI) 1.68-4.30) and visit during a winter month (OR 1.92, 95 percent CI 1.05-3.52). Patients seen in an emergency department were less likely to receive antibiotics (OR 0.46, 95 percent CI 0.26-0.89). 

In another study, investigators in Belgium used a health insurance database covering 44 percent of the country’s population. Restricting the analysis to children, the dataset included 892,841 individuals, and ambulatory visits were analyzed for one calendar year. Overall, 44.2 percent of these children received an antibiotic prescription. Children were significantly more likely to receive an antibiotic if they were prescribed an asthma drug (bronchodilator or leukotriene antagonist) on the same day (OR 1.90, 95 percent CI 1.89-1.91). Overall, among children who received an asthma drug, 34.6 percent also received an antibiotic prescription.

Both studies underscore the particular importance of acute visits for asthma symptoms in the over-prescription of antibiotics. Although unlikely to have any effect on outcomes, antibiotics are often co-prescribed with asthma medications, up to 15 to 35 percent of the time. Efforts to decrease unnecessary antibiotic prescriptions in primary and ambulatory settings should focus on this particular population.

(Paul et al. J Pediatr. 2011; 127: 1014-1021 and De Boeck et al. J Pediatr 2011; 127:1022-1026.)

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E. coli Outbreak in Germany: A Preliminary Report
Reviewed by Rachel Simmons, MD

A report published online in the New England Journal of Medicine provided preliminary information on the large E. coli outbreak in Germany. As of June 18, 2011, more than 3,200 cases were reported, including 39 deaths (3.3 percent) and 810 associated cases (25.1 percent) of hemolytic uremic syndrome (HUS). HUS occurred overwhelmingly in adults (89 percent) in this outbreak, and women made up the majority of case patients with HUS (68 percent) and with Shiga-toxin producing E. coli gastroenteritis (58.8 percent). 

Bloody diarrhea (96 percent) and abdominal pain (89 percent) were the most common clinical symptoms in adults. As expected, patients with HUS had significantly higher creatinine levels (2.6 mg/dl versus 0.8) and lower platelet counts (88.3 billions/liter versus 245.3) during the illness compared to those patients who did not develop HUS. In a small prospective cohort, no features or laboratory tests were identified that could predict the development of HUS.

The outbreak strain is O104:H4, has the gene for Shiga-toxin 2 variant (stx2a), and also carries virulence-factor genes for enteroaggregative E. coli. A subset of isolates has been analyzed by pulse-field gel electrophoresis, and the bacteria are indistinguishable from each other. The outbreak strain contains both an extended-spectrum beta-lactamase (ESBL) complex and the beta-lactamase TEM-1; is resistant to beta-lactam antibiotics, third generation cephalosporins, and nalidixic acid; and is susceptible to ciprofloxacin and carbapenems.

This large outbreak has several unique features. The rate of HUS among adults was quite high, and for unclear reasons, women were overrepresented among those with gastroenteritis and with HUS. In addition, the outbreak stain not only carried a Shiga-toxin gene, but also genes typically associated with enteroaggregative E. coli. This combination may have contributed to its increased virulence. Additional information about this bacteria and its source is eagerly anticipated. 

(Frank et al. N Engl J Med. published online June 22, 2011)

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Dexamethasone in CAP May Shorten Length of Hospital Stay
Reviewed by Nina Kim, MD, MSc

Community-acquired pneumonia (CAP) remains among the leading causes of death in the U.S., and hospitalization rates for pneumonia appear to be increasing, particularly in the elderly. Overwhelming inflammatory reactions can contribute to this high morbidity and mortality. Investigators from the Netherlands sought to examine whether corticosteroids added to antibiotics could accelerate recovery from pneumonia. Their results appear in the June 11 issue of the Lancet.

The double-blind trial enrolled 304 patients who met criteria for CAP and who were randomized to receive either dexamethasone 5 mg or placebo intravenously once daily for four days, initiated no later than 12 hours from admission. Individuals with known congenital or acquired immunodeficiency or who were on immunosuppressive medications including corticosteroids or chemotherapy were excluded. The primary endpoint was length of hospital stay (LOS) with time censored at discharge, death, or transfer to the intensive care unit (ICU).

The dexamethasone group had a shorter median LOS compared with the placebo group – 6.5 versus 7.5 days (95 percent confidence interval (CI) for difference in medians: 0-2 days, P=0.048) – a difference that remained after adjusting for baseline characteristics, yielding a hazard ratio of 1.46 favoring the dexamethasone group for earlier discharge (95 percent CI, 1.13-1.89). There was no difference in hospital mortality, rates of transfer to ICU, empyema or pleural effusion, or readmission.

This study is the largest randomized-controlled trial to date of corticosteroids in CAP. This modest reduction in LOS came at some cost, as hyperglycemia was not surprisingly more common among those who received dexamethasone. Gastric perforation also occurred in one dexamethasone-treated patient three days into therapy – a temporal association that is difficult to dismiss. These results may also not be generalizable, considering only 11 percent of these patients received a macrolide, an agent more widely used in the U.S. for CAP and known to have immunomodulatory properties.

(Meijvis et. al. Lancet 2011; 377:2023-30.)

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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:

July 15

  • PCR for Invasive Aspergillosis
  • A New Central Nervous System Syndrome in HIV-Infected Patients?
  • KSHV—A Master Manipulator

July 1

  • MRSA in the Supermarket
  • XMRV—The Answer Is In
  • Gonorrhea Is a Little Bit Human

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