Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality, but there is little consensus on the appropriate duration of antibiotic therapy. Current guidelines recommend antibiotic regimens lasting from five to 14 days. Shorter courses of antibiotic therapy may improve patient compliance, reduce risk of medication related adverse effects, and minimize the risk of antimicrobial resistance.
Study design: Meta-analysis.
Synopsis: Authors included 15 randomized controlled trials from 1990 through 2004. They compared the efficacy of short-course (seven days or less) antibiotic monotherapy versus extended regimens (longer than seven days) in patients age 12 or older with mild to moderate CAP. They excluded trials with a significant number of patients with bronchitis, healthcare-associated pneumonias, and chronic obstructive pulmonary disease exacerbations. The primary outcome measure failed to achieve clinical improvement or cure. Secondary outcome measures included mortality, bacteriologic failure, and other adverse events.
The authors found no significant differences in the risk of clinical failure, risk of mortality, risk of bacteriologic failure, or risk of adverse events in the short-course versus extended-course antibiotic regimens. This was consistent among the four antibiotic classes in the study: beta-lactam, fluoroquinolone, ketolide, and macrolide.
Bottom line: This study found no differences between short-course and extended-course antibiotic regimens in the treatment of adults with mild to moderate CAP in regard to clinical success, mortality, bacteriologic success, and adverse events.
Citation: Li JZ, Winston LG, Moore DH, et al. Efficacy of short-course antibiotic regimens for CAP: A meta-analysis. Am J Med. 2007;120(9):783-790.
Background: Fondaparinux is a selective factor Xa inhibitor approved by the FDA for the treatment and prevention of venous thromboembolism. The Organization to Assess Strategies for Ischemic Syndromes (OASIS)-5 was a randomized, double-blind trial that demonstrated fondaparinux is similar to enoxaparin in reducing the risk of ischemic events, but substantially reduces major bleeding, long-term mortality, and morbidity.1
Study design: Subgroup analysis of a randomized, controlled trial.
Setting: Hospitals to which patients with non-ST-segment elevation acute coronary syndrome presented.
Synopsis: In a subgroup analysis of 19,979 in the OASIS-5 trial, patients were divided into quartiles based on their estimated creatinine clearance, calculated by using the Modification of Diet in Renal Disease formula.2 Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately, and as a composite end point at nine, 30, and 180 days.
At nine days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90, 95% confidence interval [CI], 0.73 to 1.11); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42, CI, 0.32 to 0.56). Statistically significant differences in major bleeding persisted at 30 and 180 days.
While there was a trend toward a reduction in the composite end point among all quartiles of glomerular filtration rate (GFR), the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. The authors concluded that the absolute differences in favor of fondaparinux (efficacy and safety) were most apparent in patients with a GFR less than 58 mL/min per 1.73 m2 and were largely the result in a reduction in bleeding events.
The subgroup analysis was not planned before the OASIS-5 data were collected, and the results have not been confirmed elsewhere. For patients managed with an early invasive strategy, catheter thrombosis occurred more often in those who received fondaparinux than enoxaparin alone. Fondaparinux is not FDA approved for this indication.