Identifying the Best Initial Oral Antibiotics for Adults with Community-Acquired Pneumonia: A Network Meta-Analysis

Abstract

Background: The objective of this network meta-analysis was to compare rates of clinical response and mortality for empiric oral antibiotic regimens in adults with mild-moderate community-acquired pneumonia (CAP).

Methods: We searched PubMed, Cochrane, and the reference lists of systematic reviews and clinical guidelines. We included randomized trials of adults with radiologically confirmed mild to moderate CAP initially treated orally and reporting clinical cure or mortality. Abstracts and studies were reviewed in parallel for inclusion in the analysis and for data abstraction. We performed separate analyses by antibiotic medications and antibiotic classes and present the results through network diagrams and forest plots sorted by p-scores. We assessed the quality of each study using the Cochrane Risk of Bias framework, as well as global and local inconsistency.

Results: We identified 24 studies with 9361 patients: six at low risk of bias, six at unclear risk, and 12 at high risk. Nemonoxacin, levofloxacin, and telithromycin were most likely to achieve clinical response (p-score 0.79, 0.71, and 0.69 respectively), while penicillin and amoxicillin were least likely to achieve clinical response. Levofloxacin, nemonoxacin, azithromycin, and amoxicillin-clavulanate were most likely to be associated with lower mortality (p-score 0.85, 0.75, 0.74, and 0.68 respectively). By antibiotic class, quinolones and macrolides were most effective for clinical response (0.71 and 0.70 respectively), with amoxicillin-clavulanate plus macrolides and beta-lactams being less effective (p-score 0.11 and 0.22). Quinolones were most likely to be associated with lower mortality (0.63). All confidence intervals were broad and partially overlapping.

Conclusion: We observed trends toward a better clinical response and lower mortality for quinolones as empiric antibiotics for CAP, but found no conclusive evidence of any antibiotic being clearly more effective than another. More trials are needed to inform guideline recommendations on the most effective antibiotic regimens for outpatients with mild to moderate CAP.

Keywords: antibiotics; clinical response; community-acquired pneumonia; guidelines; mortality; network meta-analysis; outpatient; pneumonia.

Figure 1

Traffic light and summary plot (unweighted) for risk of bias assessment of included studies. See Appendix Table 3 for the specific definitions and criteria used; “other sources of bias” refers to industry bias. Plots in this figure were drawn using the R-based shiny web app risk of bias VISualization tool (robvis). *Only included in alternate inclusion criteria analysis summarized in Appendix Figures 2–5.

Figure 2

Network diagram (left) and forest plot (right) for clinical response as the outcome by medication in patients with mild or moderate CAP using the oral route initially.

Figure 3

Network diagram (left) and forest plot (right) for overall mortality as the outcome by medication in patients with mild or moderate CAP using the oral route initially.

Figure 4

Network diagram (left) and forest plot (right) for clinical response as the outcome by antibiotic class in patients with mild or moderate CAP using the oral route initially. Abbreviations: QUIN, quinolone; MAC, macrolide; AC, amoxicillin-clavulanate; CEPH + MAC, cephalosporin + macrolide; CEPH, cephalosporin; PLEURO, pleuromodulin; KETO, ketolide; AC + MAC, amoxicillin-clavulanate + macrolide; BETA, beta-lactam.

Figure 5

Network diagram (left) and forest plot (right) for mortality as the outcome by antibiotic class in patients with mild or moderate CAP using the oral route initially.