Colistin-induced acute kidney injury in neonates with sepsis and its association with plasma colistin concentration: a prospective cohort study
摘要
Colistin is increasingly used as a reserve antibiotic for multidrug-resistant (MDR) Gram-negative infections. However, colistin-induced acute kidney injury (AKI) is under-reported in neonates with sepsis.
ObjectivesTo evaluate the association and causality between colistin use and AKI in neonatal sepsis, and to explore the correlation between steady-state plasma colistin concentration and AKI development.
MethodsIn this prospective cohort study, neonates receiving colistin for proven or probable sepsis were enrolled. Exclusion criteria included major congenital anomalies and death within 72 h of life. Causality of colistin-induced AKI was assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria. Steady-state colistin levels were measured after the sixth dose. AKI was defined and staged according to KDIGO guidelines.
ResultsA total of 40 neonates were enrolled (mean gestational age: 29.3 ± 3.1 weeks). The mean duration of colistin therapy was 10.1 ± 0.8 days. AKI occurred in 28/40 (70%), of whom 13 had moderate-to-severe AKI. According to WHO-UMC criteria, 10/28 (35%) AKI cases were classified as “possible” colistin-induced nephrotoxicity. The median (IQR) steady-state colistin concentration was 1.08 (0.53,2.53) mg/L overall. Plasma colistin levels were higher in neonates with “possible” nephrotoxicity (median: 2.09 mg/L) compared with those classified as “unlikely/unclassifiable” (0.95 mg/L) and the non-AKI group (1.04 mg/L) (p = 0.3). Thirteen neonates (33%) died during hospitalization.
ConclusionPossible colistin induced AKI was seen in nearly one third cases. Higher steady-state plasma colistin levels was seen in the possible colistin-induced AKI group, highlighting the need for therapeutic drug monitoring and cautious use in this vulnerable population.