Colistin Pharmacokinetics in Pediatric Cancer Patients in Egypt

Abstract

Background: Colistin has been reintroduced to clinical practice after the emergence of multidrug-resistant gram-negative (MDR-GN) and failure of other antibiotics. Pharmacokinetics and pharmacodynamic data in pediatric population are scarce. This study aimed to highlight the pharmacokinetics of 2 colistin doses, 2.5 and 5mg/kg/day, in febrile neutropenia pediatrics cancer patients regarding patient outcomes. Patients and methods: In a prospective, comparative study, patients suffering from MDR-GN infection were randomly recruited to receive either 2.5 or 5mg/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 (AUC24), and the ratio of AUC24 to the minimum inhibitory concentration (AUC24/MIC) were assessed. Results. 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 AUC24/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). Conclusion: The current study suggests that the LD may be as efficacious and safe as the HD in treating MDR-GN infection. However, LD colistin was associated with a shorter clearance time than HD colistin

Keywords

• colistin
• pediatric cancer patients
• mdr gram-negative infection
• plasma concentration
• pharmacokinetics