Efficacy and safety of colistin loading dose: a meta-analysis

Objectives: Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity.

Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model.

Results: Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10-1.39] but not clinical (RR = 1.04, 95% CI = 0.87-1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90-1.91) and mortality (RR = 1.03, 95% CI = 0.82-1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias.

Conclusions: Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.