Colistin Pharmacokinetics in Pediatric Cancer Patients in Egypt

Abstract

Colistin has been reintroduced to clinical practice after the emergence of multidrug-resistant gram-negative (MDR-GN) and the failure of other antibiotics. Pharmacokinetics and pharmacodynamic data in the pediatric population are scarce. This study aimed to highlight the pharmacokinetics of 2 colistin doses, 2.5, and 5 mg/kg/day, in febrile neutropenia pediatric cancer patients regarding patient outcomes. In a prospective, comparative study, patients suffering from MDR-GN infection were randomly recruited to receive either 2.5 or 5 mg/kg/day colistin doses. The demographic, microbiological, and treatment outcomes were collected before and after treatment. Colistin levels were determined using HPLC/MS/MS. Peak, trough, area under the concentration-time curve (AUC 24 ), and the ratio of AUC 24 to the minimum inhibitory concentration (AUC 24 /MIC) were assessed. Clinical cure was achieved in 14 (77.8%) cases in the Low-Dose (LD) group vs. 13 (81.3%) in the High-Dose (HD) group. Four (25%) patients vs. 4 (33.3%) in the LD and HD group (P= 0.69) attained an optimal plasma AUC 24 /MIC, respectively, while the therapeutic level of colistin was reached in all patients in the LD group compared to 14/16 (87.5%) in the HD group. Microbiological eradication was achieved in 93.8% and 91.6% of patients in the LD and HD groups, respectively. However, the median time to clearance was significantly lower in the LD group, 4 days vs. 7 days in the HD group (P= 0.022). In conclusion, the current study suggests that LD may be as efficacious and safe as HD in treating MDR-GN infection. However, LD colistin was associated with a shorter clearance time than HD colistin.