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

BACKGROUND: Community-acquired pneumonia (CAP) is one of the top causes of life-years lost globally. The optimal empiric antibiotic therapy regimen is uncertain. Randomized controlled trials (RCTs) provide useful information about relative antibiotic effectiveness. METHODS: We systematically searched Medline, EMBASE, and CENTRAL for RCTs comparing at least two empiric antibiotic regimens in patients with CAP, to March 17, 2017. We performed a systematic review and network meta-analysis and network meta-regression using a Bayesian framework. We used GRADE to assess certainty in the effect estimates. RESULTS: From 18,056 citations, we included 303 RCTs. Most studies (69.9%) were not blinded. All networks had low global heterogeneity (I(2) 0%). There were 26,423 participants included in the analysis of mortality and 30,559 for treatment failure. Seven hundred and twenty-six (2.9%) participants died. Patients randomized to third generation cephalosporins alone had higher mortality than those randomized to early generation fluoroquinolones (risk ratio [RR] 2.08, 95% credible interval 1.17–3.90), later generation fluoroquinolones (RR 2.32, 1.44–4.26), and cephalosporin-fluoroquinolone combinations (RR 3.21, 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, 0.21–0.99). The evidence was similar for treatment failure. Β-lactam plus β-lactamase inhibitors (e.g., piperacillin–tazobactam), early generation cephalosporins, and daptomycin appeared to confer a higher risk of 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. CONCLUSION: In patients with CAP, an antibiotic regimen that includes a fluoroquinolone (and possibly a macrolide) may reduce mortality by ~1–2% compared with β-lactams (with or without a β-lactamase inhibitor) and cephalosporins alone. High quality, blinded and pragmatic randomized evidence would be helpful to increase certainty in the evidence. DISCLOSURES: All authors: No reported disclosures.