Incidence of nephrotoxicity associated with intravenous colistimethate sodium administration for the treatment of multidrug-resistant gram-negative bacterial infections

Abstract

Colistimethate sodium (CMS) is the inactive prodrug of colistin, CMS has a narrow antibacterial spectrum with concentration-dependent bactericidal activity against multidrug-resistant gram-negative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii. This study aimed to analyze potential correlations between clinical features and the development of CMS-induced nephrotoxicity. This retrospective cohort study was conducted in a tertiary-care university hospital between 1 January 2015 and 31 December 2019. A total of 163 patients received CMS therapy. 75 patients (46%) developed nephrotoxicity attributable to colistin treatment, although only 14 patients (8.6%) discontinued treatment for this reason. 95.7% of CMS were prescribed as target therapy. Acinetobacter baumannii spp. was the most commonly identified pathogen (72.4%) followed by P. aeruginosa (19.6%). Several risk factors associated with nephrotoxicity were identified, among these were age (HR 1.033, 95%CI 1.016–1.052, p < 0.001), Charlson Index (HR 1.158, 95%CI 1.0462–1.283; p = 0.005) and baseline creatinine level (HR 1.273, 95%CI 1.071–1.514, p = 0.006). In terms of in-hospital mortality, risk factors were age (HR 2.43, 95%CI 1.021–1.065, p < 0.001); Charlson Index (HR 1.274, 95%CI 1.116–1.454, p = 0.043), higher baseline creatinine levels (HR 1.391, 95%CI 1.084–1.785, p = 0.010) and nephrotoxicity due to CMS treatment (HR 5.383, 95%CI 3.126–9.276, p < 0.001). In-hospital mortality rate were higher in patients with nephrotoxicity (log rank test p < 0.001). In conclusion, the nephrotoxicity was reported in almost half of the patients. Its complex management, continuous renal dose adjustment and monitoring creatinine levels at least every 48 h leads to a high percentage of inappropriate use and treatment failure.