Colistin Sulfate-Based Combination Therapy for Infections Caused by Carbapenem-Resistant Organisms in Intensive Care Units: A Multicenter, Prospective, Observational Clinical Trial

硫酸粘菌素联合疗法治疗重症监护病房中由碳青霉烯类耐药菌引起的感染:一项多中心、前瞻性、观察性临床试验

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Abstract

INTRODUCTION: With the rapid spread of carbapenem-resistant Gram-negative bacterial infections, polymyxins have reemerged as a critical "salvage" antibiotic option. METHODS: This multicenter observational study assessed the effectiveness and safety of colistin sulfate-based treatment for carbapenem-resistant organism (CRO) infections in patients in intensive care across ten clinical sites in China. Clinical and microbiological responses, 28-day all-cause mortality, and associated risk factors were analyzed. Nephrotoxicity was assessed using Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Of 240 critically ill adult patients with confirmed CRO infection, 91.3% had pulmonary infection, and 77.1% and 52.5% achieved clinical and microbiological response, respectively. Subgroup analyses showed associations between outcomes and patient age and colistin sulfate treatment duration. The 28-day all-cause mortality was 27.1%. Clinical response and mortality were significantly associated with Sequential Organ Failure Assessment (SOFA) score and colistin sulfate treatment duration. Analysis of the receiver operating characteristic (ROC) curve revealed that the thresholds for colistin treatment duration for predicting clinical response and survival were > 9.5 days (area under the curve [AUC] > 0.7). Nephrotoxicity was reported in 13.1% of patients not receiving continuous renal replacement therapy (CRRT), with no significant duration-dependent increase. Post-treatment serum creatinine (Scr) levels remained stable or improved across all renal function subgroups. CONCLUSIONS: Colistin sulfate in combination with other antimicrobials can be considered a reasonable and safe treatment option for CRO infections. Understanding the factors involved in this potential beneficial treatment can enable more careful follow-up of patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2100044866. Registered on 30 March 2021, https://www.chictr.org.cn/showproj.html?proj=124119 .

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