A Pharmacovigilance Study of adverse events associated with polymyxins based on the U.S. Food and Drug Administration adverse event reporting system (FAERS) database

Polymyxins, including both colistin and polymyxin B (PMB), have regained clinical attention as last-line treatment options for treating infections caused by multidrug-resistant (MDR) gram-negative bacteria. Nonetheless, concerns persist regarding the toxicity associated with polymyxins. The objective of this study was to explore the potential severe adverse events (AEs) associated with polymyxins and compare the disparities in AEs between these two agents. Records of AEs associated with colistin and PMB were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from 1 January 2004, to 31 December 2022. Disproportionality analyses using the reporting odds ratio (ROR) method were conducted to estimate the potential risk signals between a specific AE and a drug, from the High-Level Term (HLT) to the System Organ Class (SOC) level. Subgroup analyses were performed to adjust for potential factors in each HLT with a significant disproportionality. A total of 3,915 records involving 718 patients were analyzed for the utilization of colistin and PMB. Apart from the effects on the renal and blood systems, the disproportionality strength between the two agents varied significantly in several other organs and systems, including the skin and cardiovascular and nervous systems. Our findings revealed a higher disproportionality of renal and urinary disorders (ROR 1.62, 95% CI 1.01-2.59) and acute kidney injury (AKI) (ROR 1.75, 95% CI 1.07-2.87) in patients treated with colistin. Conversely, colistin exhibited a lower potential risk for inducing neurotoxicity when compared to PMB (ROR 0.47, 95% CI 0.30-0.73). Notably, seven cases of skin hyperpigmentation (SH) associated with intravenous PMB have been reported, whereas none have been reported with colistin. Over 80% of cases involving polymyxin-related AEs occurred during the first two weeks following the initiation of polymyxin therapies, with a median onset time of 4.5 days. No difference was observed in the time of onset of AEs between colistin and PMB. Patients treated with colistin displayed a higher potential risk of nephrotoxicity but a lower risk of neurotoxicity when compared to those treated with PMB. Clinicians should be vigilant in monitoring the AEs of hyperpigmentation disorders induced by PMB, as there have been reported cases associated with its use, whereas no instances of this AE were reported among colistin-treated patients. Nevertheless, further research, especially with larger sample sizes, is imperative to validate these findings.