Nephrotoxicity risks of colistin-combination therapy: a USFDA adverse event reporting system analysis using disproportionality and interaction assessment

Colistin, a last-resort antimicrobial, is often used in combination with other drugs to treat multidrug-resistant infections, but its nephrotoxic potential raises concerns, especially in combination therapies. A retrospective analysis was performed on 29,163,222 reports from the USFDA Adverse Event Reporting System (AERS), identifying 125 reports meeting inclusion criteria for acute renal failure (ARF) associated with colistin-antimicrobial combinations. Disproportionality analysis using frequentists and Bayesian techniques were employed to evaluate ARF risk. Drug interaction and clinical outcomes were assessed using the Interaction-Adjusted SignalScores (INTSS) and mortality data, respectively. The results showed significantly higher ARF risk for colistin combinations with ceftazidime, vancomycin, meropenem, and tigecycline, with particularly strong signals observed for colistin-ceftazidime combinations, corroborated by INTSS. Mortality rates were paradoxically higher in patients receiving colistin without nephrotoxic antimicrobials. Comprehensive signal detection metrics highlighted a consistent ARF risk for several other antimicrobial combinations. Clinical outcomes analysis revealed a complex relationship between combination therapy choices and patient mortality. Colistin combinations with certain antimicrobials, especially ceftazidime, vancomycin, and tigecycline, carry significantly higher nephrotoxicity risks, warranting careful clinical consideration. Rigorous renal monitoring protocols are essential in managing these therapies, particularly in critically ill patients.