169 | Microbiological resistance and clinical ineffectiveness: an investigation into amoxicillin and amoxicillin/clavulanate efficacy in real-world populations

Pierangela Irrera¹, Gabriella Frattima¹, Fabiola De Luca¹, Anna Paola Capra¹, Michela Campolo¹, Alessio Ardizzone², Emanuela Esposito¹ | ¹Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy; ²UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.

The global escalation of antimicrobial resistance (AMR) is a primary concern at the intersection of environmental microbiology and public health. Amoxicillin (AMX) and its combination with clavulanic acid (AMC) are vulnerable to evolving bacterial defense mechanisms, such as beta-lactamase production. Monitoring "drug ineffectiveness" in large-scale databases allows us to track the clinical manifestations of these microbiological shifts in real-world populations. This study leverages the FDA Adverse Event Reporting System (FAERS) to investigate the correlation between reported therapeutic failures and the underlying microbiological resistance patterns associated with AMX and AMC treatments. A retrospective analysis was performed using AERs (Adverse Event Reports) from the FAERS database analyzing the time frame from January 2019 to December 2024. A total of 23.895 Individual Case Safety Reports (ICSRs) related to amoxicillin or the fixed-dose combination of amoxicillin/clavulanic acid were identified in the FDA Adverse Event Reporting System (FAERS) during the period from January 2019 to 31 December 2024. Of these 21,643 were serious (including 1277 death cases) and 2,251 were not serious. Of these, 17,903 ICSRs were associated with amoxicillin about these 15,851 were serious case (including 784 death cases) and 2,052 were not serious. The other 5992 ICSRs involved the combination of amoxicillin/clavulanic acid. Of these 5,792 were serious (including 493 death cases) and 199 were not serious. The higher reporting frequency of ineffectiveness is underlined for combinated therapy (630 cases; 10,31%) while for amoxicillin even though there are more cases, the percentage is lower (878 cases; 4,90%). Antibiotic resistance is a critical public health issue worldwide, with significant implications not only for patient management. In recent years, the decreased effectiveness of currently available antibiotics could compromise healthcare systems, resulting in increased morbidity and mortality from infections and increased healthcare and social costs. The ineffectiveness of this molecule due to drug resistance represents an enormous cost to the Italian National Health System (NHS), estimated at approximately €2.4 billion per year. An economic analysis conducted by individual Italian regions shows that the combination of amoxicillin/clavulanic acid is among the ten active ingredients with the highest expenditure for the National Health System (NHS). Consumption was found to be higher in the Central and Southern regions compared to the Northern regions, where the figure has significantly decreased. Our study demonstrate that pharmacovigilance data can effectively mirror the biological reality of antibiotic resistance. The observed trends in clinical ineffectiveness emphasize the need for integrated surveillance systems that consider the environmental impact on microbiological evolution to preserve the remaining efficacy of beta-lactam antibiotics. However, only through an integrated approach, involving the healthcare sector, scientific research, and the general population, is it possible to develop effective strategies to limit the spread of resistance and maintain the effectiveness of antibiotics for future generations.