Investigation of tazobactam/piperacillin– or meropenem–induced liver injury based on retrospective observational study and the FDA Adverse Event Reporting System

Abstract Background Our objective was to evaluate the association between tazobactam/piperacillin or meropenem and liver injury by performing a retrospective observational study and a study using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods In a retrospective observational study, data of patients hospitalized in Mie University Hospital between 2010 and 2022 who initiated treatment with tazobactam/piperacillin or meropenem in the intensive care unit were extracted. Liver injury was defined as an elevated alanine aminotransferase (ALT) grade based on the Common Terminology Criteria for Adverse Events. The FAERS database between 2013 and 2022 were used. Results In the retrospective observational study, multivariate logistic regression analyses indicated that the risk factors for liver injury included administration period (odds ratio [OR] = 1.080, p = 0.005), sequential organ failure assessment score (OR = 1.133, p = 0.004), and ALT (OR = 1.042, p = 0.007). Male, age, the fourth–generation cephalosporin, carbapenem, β –lactam and β –lactamase inhibitor combination, and complication of sepsis were associated with liver injury ( p < 0.001). Conclusion The periodic monitoring of liver function is strongly recommended in patients receiving tazobactam/piperacillin or meropenem, particularly in those with multiple risk factors for liver injury.