ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacoepidemiology
This article is part of the Research TopicInnovative Approaches in Pharmacovigilance: Enhancing Detection and Analysis of Adverse Drug Reactions in Clinical and Real-World SettingsView all 13 articles
Will the Introduction of β-Lactamase Inhibitors Alter the Adverse Event Profile of Parent Penicillins Antibiotics? A Pharmacovigilance Study Based on Amoxicillin-Clavulanate and Ampicillin-Sulbactam
Provisionally accepted
- 1Central Hospital of Shaoyang, Shaoyang, China
- 2The Second Affiliated Hospital of Wannan Medical College, Wuhu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: This study aimed to investigate whether the introduction of β -lactamase inhibitors (BLIs) alters the adverse event (AE) profiles of parent penicillin antibiotics, using real-world pharmacovigilance data. Methods: A disproportionality analysis was conducted using reports from the FDA Adverse Event Reporting System (FAERS) database (2004-2024). The research compared the safety profiles of amoxicillin versus amoxicillin-clavulanate (ACP) and ampicillin versus ampicillin-sulbactam(ASS) by employing multiple statistical methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). The signals were considered significant only when meeting multiple algorithm criteria (ROR, PRR, BCPNN, EBGM). Subgroup analyses by age and gender were performed. Results: Analysis of over 200,000 reports revealed distinct AE spectra. ACP demonstrated a significantly stronger association with hepatobiliary disorders (e.g., drug-induced liver injury, ROR 35.41) compared to amoxicillin alone (ROR 4.98). In contrast, amoxicillin monotherapy showed stronger signals for certain immune-mediated skin reactions. For ampicillin, monotherapy was strongly linked to pregnancy/perinatal events, whereas ASS showed higher risks for gastrointestinal disorders (e.g., hemorrhagic enterocolitis), specific skin reactions, and allergic events. Subgroup analyses indicated that hepatobiliary and renal risks with ACP were more prominent in males and the elderly (≥60 years), while severe skin reactions with ampicillin were more frequent in females. Conclusion: The addition of BLIs significantly may modify the AE profiles of parent penicillins, introducing distinct organ-specific risks. These findings underscore the necessity for personalized risk assessment and monitoring in clinical practice, tailored to the specific combination agent and patient demographics.
Keywords: Adverse event, Amoxicillin-clavulanate, Ampicillin-Sulbactam, FAERS, β-lactamase inhibitors
Received: 20 Dec 2025; Accepted: 12 Feb 2026.
Copyright: © 2026 He, Liao, Xiao, Zhou, Huang and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sheng Wei
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.