Incidence of Nephrotoxicity Associated with Intravenous Colistimethate Sodium Administration for the Treatment of Multidrug-resistant Gram-negative Bacterial Infections

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 P. 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 baumanii spp. was the most commonly identified pathogen (72.4%) followed by Pseudomonas aeruginosa (19.6%). Several risk factors associated with nephrotoxicity were identified, among these were Charlson Index (OR 1.29, 95%CI 1.02–1.62; p = 0.032); admission to the ICU (OR 4.25, 95%CI 1.63–11.07, p = 0.003) and cumulative dose per patient (OR 1.03, 95% CI 1.01–1.05, p = 0.003). In terms of in-hospital mortality, risk factors were male sex (OR 2.43, 95%CI 1.06–5.56, p = 0.035); age (OR 1.03, 95%CI 1.01–1.05, p = 0.043) and higher maintenance doses (OR 1.21, 95%CI 1.03–1.43, p = 0.023). Nephrotoxicity due to CMS treatment was not related to mortality (OR 1.42, 95%CI 0.68–2.99, p = 0.351). In conclusion, it was shown once again that CMS is a drug with a high incidence of nephrotoxicity. Its complex management, administering the loading dose and monitoring creatinine at least every 48 hours, with consequent adjustment of the maintenance dosage, leads to a high percentage of inappropriate use.