Antibiotics for community acquired pneumonia in adult outpatients.

BACKGROUND: Community-acquired pneumonia (CAP) is a common condition representing a significant disease burden for the community, particularly for the elderly. Because antibiotics are helpful in treating CAP, they are the standard treatment and CAP thus contributes significantly to antibiotic use, which is associated with the development of bacterial resistance and side-effects. Although several studies have been published concerning CAP and its treatment, the available data arises mainly from studies conducted in hospitalized patients and outpatients. There is no concise summary of the available evidence that can help clinicians in choosing the most appropriate antibiotic. OBJECTIVES: Our goal was to summarize the evidence currently available from randomized controlled trials (RCTs) concerning the efficacy of alternative antibiotic treatments for CAP in ambulatory patients above 12 years of age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003) which contains the Cochrane Acute Respiratory Infections Group's trial register; MEDLINE (January 1966 to September week 3, 2003), and EMBASE (January 1974 to March 2003). Studies were also identified by checking the bibliographies of studies and review articles retrieved as well as by perusing medical journals. To identify any additional published or unpublished studies, we contacted the following antibiotics manufacturers: Abbott, AstraZeneca, Aventis, Boehringer-Ingelheim, Bristol-Myers-Squibb, GlaxoSmithKline, Hoffmann-LaRoche, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Pharmacia, Sanofi, and Yamanouchi. No language restrictions were applied in any of the search strategies. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) in which one or more antibiotics were tested for the treatment of CAP in ambulatory adolescent or adult patients. Studies testing one or more antibiotic and reporting the diagnostic criteria used in selecting patients as well as the clinical outcomes achieved were included. No language restrictions were applied. DATA COLLECTION AND ANALYSIS: Data were extracted and study reports assessed by two independent reviewers (LMB and TJMV). Authors of studies were contacted as needed to resolve any ambiguities in the study reports. The data were analyzed using the Cochrane Collaboration's RevMan 4.2.2 Software. Differences between reviewers were resolved by discussion and consensus. MAIN RESULTS: Three randomized controlled trials involving a total of 622 patients aged 12 years and older diagnosed with community acquired pneumonia were included. The quality of the studies and of the reporting was variable. A variety of clinical, radiological and bacteriological diagnostic criteria and outcomes were reported. Overall there was no significant difference in the efficacy of the various antibiotics under study. REVIEWERS' CONCLUSIONS: Currently available evidence from RCTs is insufficient to make evidence-based recommendations for the choice of antibiotic to be used for the treatment of community acquired pneumonia in ambulatory patients. Pooling of study data was limited by the very low number of studies. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations.

Do statins cause cancer? A meta-analysis of large randomized clinical trials.

PURPOSE: Although the short-term safety and tolerability of statins has been well established, their potential carcinogenicity in the long term is still debated. The goal of this study was to determine whether long-term treatment with statins is associated with an increased risk of fatal and nonfatal cancers. METHODS: We searched the Medline database between January 1966 and December 1999 for randomized, controlled trials of human subjects in which monotherapy with a statin was compared with placebo. No language restrictions were applied. Only trials with a minimum treatment duration of 4 years and a minimum of 1,000 subjects were included. Studies that did not provide information on fatal or nonfatal cancers were excluded. Data on fatal and nonfatal cancers and all-cause mortality were extracted by a single nonblinded reviewer. Overall crude estimates of risk difference were computed by summing the numerators and denominators of trial-specific risk estimates. RESULTS: Five trials met the inclusion criteria. The estimated differences in absolute risk between treatment and placebo were as follows (negative risks indicate that treatment was safer than placebo): all nonfatal cancers, 0.0% (95% confidence interval [CI]: -0.8% to 0.8%); all fatal cancers, -0.1% (95% CI: -0.7% to 0.4%); all fatal and nonfatal cancers combined, -0.1% (95% CI: -1.0% to 0.7%); and all-cause mortality, -1.5% (95% CI: 2.8% to 0.2%). CONCLUSION: This study demonstrates no association between statin use over a 5-year period and the risk of fatal and nonfatal cancers. This conclusion is limited by the relatively short follow-up of the studies analyzed. Similar analyses of data from studies with longer follow-up periods would be valuable.