Abstract
ABSTRACT
Background and Aims
Amoxicillin, alone or combined with clavulanic acid, is widely used for the treatment of bacterial infections. While clavulanic acid expands amoxicillin's antibacterial spectrum by inhibiting β‐lactamases, differences in their real‐world safety profiles and reporting patterns remain relevant for pharmacovigilance and antimicrobial surveillance. This study aimed to characterize and compare adverse event reporting associated with amoxicillin and amoxicillin/clavulanic acid and to explore reporting signals involving Preferred Terms potentially associated with reduced treatment effectiveness.
Methods
Adverse drug reaction reports recorded in the FDA Adverse Event Reporting System (FAERS) Public Dashboard between 2022 and 2025 were analyzed. Disproportionality analyses were performed at the MedDRA Preferred Term level using Reporting Odds Ratios, Proportional Reporting Ratios, and Information Component‐based methods. Selected Preferred Terms were further evaluated through direct comparison between the two therapies.
Results
Amoxicillin was predominantly associated with hypersensitivity and cutaneous adverse event signals, whereas amoxicillin/clavulanic acid showed a stronger hepatobiliary reporting profile, including signals for drug‐induced liver injury, cholestasis, and hepatic cytolysis. Direct comparison confirmed distinct reporting patterns, with relatively stronger liver‐related signals for the combination therapy and stronger hypersensitivity‐related signals for amoxicillin alone. Preferred Terms potentially associated with reduced treatment effectiveness or antimicrobial resistance were identified in both groups; however, these reporting signals may reflect heterogeneous clinical scenarios and should not be interpreted as evidence of confirmed therapeutic failure or microbiological resistance.
Conclusion
These findings support the use of pharmacovigilance databases as complementary tools for antibiotic safety monitoring and for identifying reporting patterns that may warrant further investigation, including reports suggestive of reduced treatment effectiveness. However, such signals should be interpreted cautiously, as they do not establish reduced antimicrobial effectiveness or antimicrobial resistance and may reflect a variety of underlying clinical and therapeutic factors.