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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.
Novel Swine-Origin H1N1 Influenza and Severe Respiratory Disease: Compiling the Evidence
Reviewed by Christopher J. Graber, MD, MPH
The ability of the novel swine-origin H1N1 influenza virus (S-OIV) to cause severe respiratory disease was examined in two studies from the Aug. 13 issue of the New England Journal of Medicine.
One study compiled data from the 2,155 cases of severe pneumonia reported to the Mexican Ministry of Health in the early phase of the S-OIV outbreak, from March 24 to April 29. The authors found that, in comparison to influenza seasons from 2006 to 2008, the number of cases and deaths from severe pneumonia during the S-OIV outbreak period were much more frequent among those in the 5- to 59-year-old age group. Another study examined 18 cases of confirmed S-OIV infection with pneumonia at a tertiary facility in Mexico City from March 24 to April 24; 13 patients were between the ages of 5 and 50. Illness was typically severe. Ten required mechanical ventilation on admission, and seven died. (Chowell et al. N Engl J Med 2009;361:674-9 and Perez-Padilla et al. N Engl J Med 2009;361:680-9)
The ability of S-OIV to cause severe respiratory disease was further corroborated in two articles published in the July 24 issue of Science. The studies used ferret models to demonstrate that S-OIV infected structures in the lower respiratory tract to a much greater degree than seasonal influenza A/H1N1 viruses. (Munster et al. Science 2009;325;481-3 and Maines et al. Science 2009;325;484-7)
Taken together, these studies demonstrate the ability of S-OIV to cause severe respiratory disease, particularly in young to middle-aged individuals, potentially due to lack of significant pre-existing immunity to A/H1N1 viruses that were more common prior to the 1957 A/H2H2 pandemic. These findings have important ramifications for vaccination and infection control efforts as the 2009 influenza season progresses.
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Influenza Shedding: Keep Patients Isolated
Reviewed by Khalil Ghanem, MD, PhD
Influenza shedding among hospitalized, critically ill patients may be significant and prolonged despite the use of antivirals. The findings are from a new study published in the Aug. 15 issue of The Journal of Infectious Diseases.
The investigators prospectively studied 147 inpatients diagnosed with H3N2 influenza in Hong Kong. They obtained daily nose and throat samples from these patients for one week. Twenty-two percent had received influenza vaccine earlier in the season, and 75 percent received antivirals for their current infection. Major comorbidities (congestive heart failure, cerebrovascular disease, malignancy, and/or chronic liver or kidney disease) and use of corticosteroids were associated with slower viral clearance. Although initiation of antiviral therapy within four days of symptom onset was associated with enhanced viral clearance, approximately 30 percent of patients who received antivirals were still shedding on their seventh day in the hospital.
Whether these findings apply to novel H1N1 (or other influenza strains) is unknown, but such an extrapolation may not be unreasonable. During peak influenza season and in outbreak settings, hospitals may be overwhelmed with suspected cases, and isolation rooms may become scarce. This study highlights the importance of maintaining strict infection control measures even after patients are started on antivirals.
(Lee et al. J Infect Dis 2009; 200:492–500)
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MRSA Carriage and Household Transmission After Discharge: More Information, More Questions
Reviewed by Paul Pottinger, MD
The effort to detect methicillin-resistant Staphylococcus aureus (MRSA) colonization among hospitalized patients has led some to ask appropriate questions before going home: How long will I remain colonized? Are my family members at risk for colonization, too? If so, will they get sick, and what should I do to protect them?
A paper and accompanying editorial in the Aug. 10 issue of Archives of Internal Medicine may help physicians answer these questions. In this prospective study, 1,501 Paris hospital patients being discharged to home care settings were screened for MRSA via cultures of nares and chronic skin wounds: 148 (12.7 percent) were found to be MRSA positive. These patients and their household family contacts were then swabbed every three months until culture-negative. Nearly one in five (19.1 percent) of these contacts were found to be culture-positive during the study, although none developed clinical infection. Interestingly, spouses and those providing direct care were most likely to be culture-positive, whereas sharing a bed was not a strong independent risk factor. Decolonization techniques were not used, and the median time to culture-negativity among patients was 282 days. Contacts were also less likely to be culture-positive as time passed.
The study lacks definitive proof of transmission from patient to household contacts: Antecedent cultures were not available, and molecular typing was not performed, although antibiotic resistance profiles were identical among patients and contacts, and were “consistent with hospital-acquired strains.” Nevertheless, some reasonable conclusions are possible: As in the hospital, MRSA can be spread via direct contact from patients to care providers at home; transmission is rarely associated with genuine infection (zero cases in this series); even without decolonization efforts, the rate of culture-positivity falls with time; and the rationale to protect contacts from acquiring colonization seems tried and true: diligent hand hygiene, especially after direct patient care.
(Lucet et al. Arch Intern Med 2009;169(15):1372-1378 and Winston et al. Arch Intern Med 2009;169(15):1379-1380)
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Cefazolin Failure in Patients With MSSA Infections: A Possible Cause
Reviewed by Sara Cosgrove, MD
Cefazolin may fail to treat some patients with methicillin susceptible Staphylococcus aureus (MSSA) infections and high organism burdens, such as bacteremia and endocarditis, according to a study in the August issue of Antimicrobial Agents and Chemotherapy.
Most S. aureus isolates produce beta-lactamases, and production of Type A beta-lactamase in large amounts has been associated in previous investigations with cefazolin failure, particularly in patients with high-inoculum infections. The authors of this study evaluated 98 strains of MSSA from patients with soft tissue infection, hospital-acquired pneumonia, endocarditis, and bacteremia. The researchers found that 87 percent of MSSA isolates produced a beta-lactamase: 26 percent produced Type A, 15 percent produced Type B, and 46 percent produced Type C. An inoculum effect against cefazolin, in which the minimum inhibitory concentrations (MICs) of cefazolin are in the non-susceptible range (≥ 16 mcg/mL) with a 107 CFU/mL inoculum, was seen in 19 (19 percent) of isolates. The inoculum effect with cefazolin was most prominent among Type A beta-lactamase producers, with 36 percent of these strains showing an inoculum effect.
In a subgroup of patients with MSSA bacteremia on hemodialysis who received cefazolin, three of six patients whose treatment failed had evidence of a pronounced inoculum effect, while none of the six patients who were cured had evidence of such an effect (p = 0.09). Although not statistically significant, this finding suggests that some patients may be at risk for cefazolin failure despite having MSSA, and that patients who receive cefazolin for serious infections should be monitored carefully for relapse of infection, particularly those on hemodialysis.
The authors do not offer additional reasons why cefazolin treatment may have failed, such as inadequate or missed doses, or inadequate drug levels. Unfortunately, there is not an easy way for laboratories to identify strains showing an inoculum effect. The authors note a semiquantitative nitrocefin disk reaction using a concentration of cells from overnight culture identified most Type A beta-lactamase producing strains but not Type C producing strains.
(Nannini et al. Antimicrob Agents Chemother 2009;53(8): 3437-3441)
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Corticosteroids and Antivirals for Bell Palsy
Reviewed by Jason Weinberg, MD
Corticosteroid use is associated with a reduced risk for poor outcomes in Bell palsy patients, according to a meta-analysis described in the Sept. 2 issue of the Journal of the American Medical Association.
The report’s authors reviewed data from a combined total of 2,786 patients from 18 trials evaluating the use of corticosteroids, antiviral agents, or both in the treatment of Bell palsy. When used alone, corticosteroids led to minimal adverse effects and were associated with a statistically significant reduction in the risk of unsatisfactory facial recovery, the primary outcome defined by the authors of the meta-analysis. Corticosteroids also reduced the risk of secondary outcomes such as short-term unsatisfactory recovery, synkinesis, and autonomic dysfunction. Many of the patients included in the meta-analysis came from just two recent randomized controlled trials. However, the results were consistent across many studies, and the effect was strong.
In contrast, the analysis showed no significant benefit for antiviral agents when used alone. Antiviral agents were associated with reduced risk for unsatisfactory outcome when used in conjunction with corticosteroids. This reduction in risk was not statistically significant, however, and the evidence supporting the effect was not as strong as that supporting the benefit of corticosteroids.
The potential synergistic effects of antiviral agents combined with corticosteroids are biologically plausible for those cases of Bell palsy caused by susceptible viruses, but previous studies have drawn conflicting conclusions regarding their benefit. We will need to wait for more data to make conclusions about whether or not antiviral agents provide added benefit when combined with corticosteroids. However, using well-defined inclusion criteria and providing clear descriptions of the quality of the evidence supporting its conclusions, this meta-analysis provides strong support for the use of corticosteroids for Bell palsy in clinical practice.
(de Almeida et al. JAMA 2009;302:985-993)
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