747. Antibiotic therapy for community-acquired pneumonia: a systematic review and network meta-analysis of randomized trials
Session: Poster Abstract Session: Respiratory Infections: Viral
Thursday, October 4, 2018
Room: S Poster Hall
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 (I2 0%). There were 26,423 participants included in the analysis of mortality and 30,559 for treatment failure. 726 (2.9%) participants died. Patients randomized to 3rd 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 3rd generation cephalosporin alone (RR 0.47, 0.21-0.99). The evidence was similar for treatment failure. Beta-lactam plus beta-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 3rd 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 approximately 1-2% compared to 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.

Reed Siemieniuk, MD, PhD(c)1, Yung Lee, BHSc2, Isaac Bogoch, MD3, Romina Brignardello-Petersen, DDS MSc PhD2, Yutong Fei, MD PhD4, Paul Alexander, PhD5, Theresa Aves, RN MSc2, Dena Zeraatkar, BHSc2, Behnam Sadeghirad, PharmD MPH2, Xun Li, MD4, Nathan Evaniew, MD PhD2, Neera Bhatnagar, MLIS2, Bram Rochwerg, MD MSc2, Gordon Guyatt, MD MSc2 and Mark Loeb, MD, MSc2, (1)Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada, (2)McMaster University, Hamilton, ON, Canada, (3)University Health Network, Toronto, ON, Canada, (4)Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China, (5)Infectious Diseases Society of America, Arlington, VA

Disclosures:

R. Siemieniuk, None

Y. Lee, None

I. Bogoch, None

R. Brignardello-Petersen, None

Y. Fei, None

P. Alexander, None

T. Aves, None

D. Zeraatkar, None

B. Sadeghirad, None

X. Li, None

N. Evaniew, None

N. Bhatnagar, None

B. Rochwerg, None

G. Guyatt, None

M. Loeb, None

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