The efficacy and safety of colistimethate sodium in the treatment of carbapenem-resistant Gram-negative bacilli: a real-world observational study.

Abstract

As carbapenem-resistant Gram-negative bacilli (CR-GNB) has spread worldwide, colistimethate sodium (CMS) has been reintroduced into clinic, yet high-quality evidence remains scarce; therefore, this study-the first prospective, observational investigation in China-was designed to evaluate the clinical efficacy and safety of CMS in treating CR-GNB. Between November 2021 and November 2023, nine ICUs in Henan Province consecutively enrolled 222 patients aged ≥14 years with culture-confirmed CR-GNB infection who were planned to receive ≥7 days of intravenous CMS. The primary efficacy endpoints were clinical response and 30-day all-cause mortality; the main safety endpoint was CMS-associated acute kidney injury (AKI). The overall clinical response rate was 82.5% (95% CI: 76.6%-87.3%), consisting of 17.1% complete resolution and 65.4% partial clinical improvement. The microbiological response rate was 79.0%, the bacterial clearance rate was 72.8%, and the 30-day all-cause mortality was 19.8%. Subgroup analyses showed that CR-GNB patients with single-site infection, isolated pulmonary infection, or monomicrobial infection achieved significantly better clinical efficacy. Multivariable regression analysis revealed that higher APACHE II scores (OR = 0.91), multi-site infection (OR = 0.26), and polymicrobial infection (OR = 0.35) were independent risk factors for poor clinical response. Meanwhile, multi-site infection (OR = 4.19) and polymicrobial infection (OR = 2.94) served as independent risk factors for 30-day all-cause mortality. In terms of safety, the overall incidence of adverse events (AEs) was 3.6%, and the incidence of acute kidney injury (AKI) was 20.4%, mostly classified as KDIGO stage I. In addition, patients with elevated baseline serum creatinine demonstrated a significantly higher risk of AKI. Overall, CMS-based regimens achieved favorable efficacy in ICU patients with CR-GNB infections, with an acceptable overall safety profile.