Pharmacovigilance signals and regional burden of antibiotic-associated Clostridioides difficile infection: a pharmacovigilance study and Global Burden of Disease Study 2023.

Background

Despite the substantial global burden of Clostridioides difficile infection (CDI) and its close relationship with antibiotic exposure, evidence characterizing drug- and age-specific risk patterns remains limited.

Objectives

This study aimed to characterize antibiotic-associated CDI by assessing drug- and age-specific signal patterns and geographic and temporal variations.

Methods

Using the FDA Adverse Event Reporting System (FAERS), antibiotic-associated CDI reports were identified and evaluated through disproportionality analyses (information component [IC] and reporting odds ratio [ROR]). The assessment was then extended to the population level using Global Burden of Disease Study (GBD) 2023 data to evaluate the WHO-regional CDI burden between 1990 and 2023, expressed as disability-adjusted life years (DALYs) and age-standardized DALY rates (ASDRs).

Results

Among 23,168,942 FAERS reports, 2,464 antibiotic-associated CDI cases were identified. A strong overall signal was detected (IC, 3.17; ROR, 10.56 [95% CI, 10.11-11.02]). Clindamycin showed the highest individual-level signal (IC, 4.85; ROR, 32.63 [95% CI, 28.76-37.02]), while penicillin combinations, carbapenems, and cephalosporins exhibited the strongest class-level signals. CDI signals peaked among adults aged ≥80 years (ROR, 19.58 [95% CI, 17.73-21.64]). The Region of the Americas recorded the highest CDI burden by 2023, with an ASDR of 10.69 (95% UI, 9.49-12.20) per 100,000 population.

Conclusions

FAERS identified antibiotic- and age-specific CDI reporting signals, while GBD 2023 showed substantial regional heterogeneity in population-level burden. These complementary findings underscore the potential value of clinically contextualized antibiotic stewardship, diagnostic vigilance in vulnerable populations, and region-sensitive CDI surveillance.