Comparative Safety of Different Antibiotic Regimens for the Treatment of Outpatient Community-Acquired Pneumonia Among Otherwise Healthy Adults.

Abstract

Evidence is limited on 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, nonelderly adults. We conducted an active-comparator new-user cohort study (2007-2019) of commercially insured adults aged 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 to 90 days (eg, renal failure [14 days]). We estimated risk differences [RDs] per 1000 treatment episodes and risk ratios using propensity score-weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. 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 with macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (eg, β-lactam: nausea/vomiting/abdominal pain [RD per 1000, 3.20; 95% CI, 0.99-5.73]; non-Clostridioides difficile diarrhea [RD per 1000, 4.61; 95% CI, 2.47-6.82]; vulvovaginal candidiasis/vaginitis [RD per 1000, 3.57; 95% CI, 0.87, 6.88]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. 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.