Intravenous colistin use for infections due to multidrug-resistant gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis

Abstract

Synopsis 26Background: Data are limited regarding the clinical effectiveness and safety of 27 intravenous colistin for treatment of infections by multidrug-resistant gram-negative 28 bacilli (MDR-GNB) in the paediatric intensive care unit (PICU). 29Methods: Systematic review of intravenous colistin use in critically ill paediatric 30 patients with MDR-GNB infection in PubMed, Scopus and Embase (through January 31 31 st , 2018). 32Results: Out of 1,181 citations, 7 studies were included on the use of intravenous 33 colistin for 405 patients in PICU. Majority of patients were diagnosed with lower 34 respiratory tract infections, with Acinetobacter baumannii being the predominant 35 pathogen. Colistin dosages ranged between 2.6-18 mg/kg/day, with none but one case 36 reporting a loading dose. Emergence of colistin-resistance during treatment was 37 reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 38 0.5% respectively, but concomitant medications and severe underlying illness limited 39 our ability to definitively associate use of colistin with nephrotoxicity. Crude 40 mortality was 29.5% (95%CI 21.7-38.1%), whereas infection-related mortality was 41 16.6% (95%CI 12.2-21.5%). 42 Conclusions: While the reported incidence of adverse events related to colistin were 43 low, reported mortality rates for infections by MDR-GNB in PICU were notable. In 44 addition to severity of disease and comorbidities, inadequate daily dosage and the 45 absence of a loading dose may have contributed to mortality. As the use of colistin for 46 treatment of MDR-GNB infections increases, it is imperative to understand whether 47 optimal dosing of colistin in paediatric patients differs across different age groups. As 48 such, future studies to establish the pharmacokinetic properties of colistin in different 49 paediatric settings are warranted. 50 51