Comparison of Adverse Events Associated With Six Common Antibiotics in Lower Respiratory Tract Infections Using the United States Food and Drug Administration Adverse Event Reporting System

TL;DR

This study compares the safety of six common antibiotics used for lung infections, finding that some drugs are linked to more serious side effects than others.

Contribution

The paper provides a comparative analysis of adverse event patterns for six antibiotics in lower respiratory tract infections using FDA reporting data.

Findings

Ciprofloxacin and clarithromycin had higher rates of serious adverse events compared to amoxicillin.

Dermatological disorders occurred early, while liver and kidney issues developed later during treatment.

No antibiotic showed consistently lower adverse event rates across all categories.

Abstract

Background

Lower respiratory tract infections (LRTIs) remain a major global health concern, contributing substantially to morbidity and mortality. Antibiotics are commonly prescribed for these infections, but their safety profiles may vary across drug classes and patient populations. Understanding patterns of reported adverse events (AEs) among patients with LRTIs could provide useful insights for pharmacovigilance.

Objectives

To explore and compare the safety profiles of six antibiotics frequently used for bacterial LRTIs using data from a spontaneous reporting database.

Methods

Data were obtained from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) to identify AEs associated with these antibiotics in cases referring to LRTIs. Given the limitations of spontaneous reporting systems (e.g., underreporting, reporting bias, absence of denominators), this study was designed as hypothesis-generating. Time to AE onset was determined by the interval between antibiotic initiation and AE occurrence for cases with complete date information. Reporting odds ratios (RORs) and adjusted RORs (aRORs) were calculated to compare reporting proportions among antibiotics, with each antibiotic sequentially used as the reference in pairwise comparisons. Adjusted analyses accounted for sex, age, and reporter country, and Bonferroni correction adjusted the significance threshold to 0.0033.

Results

Across 11,522 patients, a total of 664 serious AEs were identified. Ciprofloxacin exhibited the highest reporting proportion, with 89 of 809 patients (11.0%), followed by clarithromycin (129/1,572; 8.2%), azithromycin (132/2,048; 6.4%), amoxicillin (90/1,796; 5.0%), levofloxacin (198/4,604; 4.3%), and doxycycline (26/693; 3.8%). Ciprofloxacin and clarithromycin were associated with a higher frequency of serious AEs compared with amoxicillin. For non‑serious AEs, dermatological disorders were reported less frequently with azithromycin, doxycycline, clarithromycin, levofloxacin, and ciprofloxacin than with amoxicillin, whereas neurological disorders were more frequently reported for doxycycline, clarithromycin, levofloxacin, and ciprofloxacin. Dermatological and lung disorders tended to appear early, typically within the first day after treatment initiation, whereas liver and renal disorders developed later (median ≥ 2 days). No single antibiotic exhibited consistently lower reporting proportions across all AE categories.

Conclusions

This FAERS‑based analysis identified antibiotic‑specific differences in both overall and serious AE reporting among commonly used agents for LRTIs. Fluoroquinolones (levofloxacin, ciprofloxacin) and macrolides (clarithromycin, azithromycin) showed elevated serious AE reporting relative to amoxicillin, underscoring the need for careful benefit-risk assessment. These drug‑specific patterns and temporal characteristics may help inform targeted clinical monitoring and guide future pharmacoepidemiological research to verify these hypothesis‑generating findings.

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