Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins

BackgroundNephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria limited therapeutic options has resulted in increased use polymyxins.ObjectivesTo determine rates nephrotoxicity during treatment whether any factors influence these.Data sourcesMedline, Embase Cochrane Library databases were searched on 2 January 2020.Study eligibility criteriaStudies reporting and/or patients infections treated polymyxins included. Reviews, meta-analyses reports not English excluded.ParticipantsPatients hospitalized systemic or inhaled For comparative analyses, non–polymyxin-based regimens also included.MethodsMeta-analyses performed using a random-effects model; subgroup conducted where data permitted mixed-effects model.ResultsIn total, 237 randomized controlled trials, cohort case–control studies eligible for inclusion; most single-arm observational studies. Nephrotoxic events 35,569 receiving analysed. Overall rate was 0.282 (95% confidence interval (CI) 0.259–0.307). When excluding >50% received inhaled-only assessment by methods other than internationally recognized criteria (RIFLE, KDIGO AKIN), 0.391 CI 0.364–0.419). The odds greater therapies compared to (odds ratio 2.23 1.58–3.15); p < 0.001). Meta-analyses showed significant effect type, dose, patient age, number concomitant nephrotoxins diuretics, glycopeptides vasopressors nephrotoxicity. Polymyxin significantly different (p 0.051). overall therapy 0.030 0.020–0.043).ConclusionsPolymyxins higher risk regimens.