Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults

Background Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. Methods We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18–64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2–90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Results Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10–0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25–0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09–0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Conclusions Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.