# A Population-Based Cohort Study on the Association Between Oral Third-Generation Cephalosporins and Other Antimicrobial Prescriptions and Adverse Events: Findings From the Shizuoka Kokuho Database Study

## TL;DR

This study found that certain oral antibiotics, including third-generation cephalosporins, are linked to increased risk of antibiotic-related adverse events in Japan.

## Contribution

The study provides population-level evidence linking specific oral antimicrobial prescriptions to adverse events using a large health database.

## Key findings

- Third-generation cephalosporins increased risk of adverse events (HR: 1.14).
- Tetracyclines and aminoglycosides showed higher risk (HR: 2.14 and 8.36 respectively).
- Older age and male gender were additional risk factors for adverse events.

## Abstract

Introduction: The rise of drug-resistant bacteria and associated adverse events have been linked to inappropriate antibiotic use. In Japan, inappropriate prescriptions of oral antimicrobials might be prevalent and contribute to this issue. This study explored the association between oral third-generation cephalosporins and other antimicrobials with adverse events in the Japanese population.

Methods: We conducted a population-based cohort study using a large-scale database, i.e., the Shizuoka Kokuho Database. This study included individuals with health checkup records, with the observation period for each participant ranging from insurance enrollment or April 2012 to insurance withdrawal or September 2020. The primary outcome was hospitalization with clinically important antibiotic-related adverse events (ciArAEs) based on the International Classification of Diseases, Tenth Revision (ICD-10) codes. In addition, we executed a multivariable analysis employing potential predictive factors selected from comorbidities, prescribed antimicrobials, and health checkup results.

Results: Of the 685,161 individuals included in the analysis, 2,557 had ciArAEs. Third-generation cephalosporins (HR: 1.14, 95% CI: 1.01-1.29), tetracyclines (HR: 2.14, 95% CI: 1.47-3.13), and aminoglycosides (HR: 8.36, 95% CI: 1.18-59.2) were identified as potential predictive factors for ciArAEs among oral antimicrobial agents. Additional predictive factors included older age, males, intravenous penicillin, and various comorbidities.

Conclusions: By utilizing a large-scale database, we demonstrated the relationship between the use of antimicrobial agents, including oral third-generation cephalosporins, and ciArAEs. This finding underscores the need for enhanced prescription practices and further antimicrobial resistance and adverse events studies.