Systematic Review and Network Meta-Analysis of Randomized Trials of Antibiotic Therapy for Community-Acquired Pneumonia

Conference Correspondent - IDWeek 2018

In this report, the authors systematically searched the Medline, EMBASE, and CENTRAL databases for randomized clinical trials (RCTs) comparing at least 2 empiric antibiotic regimens in patients with community-acquired pneumonia (CAP), and then performed a systematic review and network meta-analysis and network metaregression using a Bayesian framework, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence to assess certainty in the effect estimates.

From 18,056 citations, 303 RCTs were included. Most studies (69.9%) were not blinded. All networks had low global heterogeneity (I2 0%). A total of 26,423 participants were included in the analysis of mortality, and 30,559 for treatment failure.

Patients randomized to third-generation cephalosporins alone had greater mortality than those randomized to early-generation fluoroquinolones (risk ratio [RR], 2.08; 95% credible interval [CI], 1.17-3.90), later-generation fluoroquinolones (RR, 2.32; CI, 1.44-4.26), and cephalosporin-fluoroquinolone combinations (RR, 3.21; CI, 0.99-12.49). Participants who were randomized to a cephalosporin plus macrolide were less likely to die than those who received a third-generation cephalosporin alone (RR, 0.47; CI, 0.21-0.99). The evidence was similar for treatment failure. Treatment with beta-lactam plus beta-lactamase inhibitors (eg, piperacillin-tazobactam), early generation cephalosporins, and daptomycin appeared to result in a higher risk for mortality and/or treatment failure than most other antibiotic regimens, including third-generation cephalosporins alone. For key comparisons, the GRADE quality of evidence was low or moderate.

In patients with CAP, an antibiotic regimen that includes a fluoroquinolone (and possibly a macrolide) may reduce mortality by approximately 1% to 2% compared with beta-lactams (with or without a beta-lactamase inhibitor) and cephalosporins alone. High-quality, blinded, and pragmatic randomized evidence would be helpful to increase certainty in the evidence.

Source: Siemieniuk R, et al. IDWeek 2018. Abstract 747.

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