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

Fan Zhang; Danyang Peng; Faming He; Ying Liu; Binbin Zang; Yanqiu Gao; Chao Qin; Suping Guo; Yawei Qi; Xisheng Zheng; Lin Guo; Tingting Zhao; Yue Jin; Rongqi Su; Juan Du; Jiazhan Pan; Bingyu Qin; Huanzhang Shao

doi:10.1007/s40121-025-01176-5

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

Infect Dis Ther. 2025 Jun 29. doi: 10.1007/s40121-025-01176-5. Online ahead of print.

Authors

Fan Zhang^{1

2

3}, Danyang Peng⁴, Faming He⁵, Ying Liu⁶, Binbin Zang⁷, Yanqiu Gao⁸, Chao Qin⁹, Suping Guo¹⁰, Yawei Qi¹¹, Xisheng Zheng¹², Lin Guo¹³, Tingting Zhao^{1

2

3}, Yue Jin^{1

3}, Rongqi Su^{1

3}, Juan Du^{1

3}, Jiazhan Pan^{1

3}, Bingyu Qin^{1

2

3}, Huanzhang Shao^{14

15

16}

Affiliations

¹ Department of Critical Care Medicine, Henan Provincial People's Hospital, Weiwu Road No. 7, Zhengzhou, 450003, Henan, China.
² Department of Critical Care Medicine, People's Hospital of Zhengzhou University, Zhengzhou, China.
³ Henan Key Laboratory for Critical Care Medicine, Zhengzhou, China.
⁴ Department of Critical Care Medicine, Henan Provincial Chest Hospital, Zhengzhou, China.
⁵ Department of Cardiac Surgery Intensive Care, Henan Provincial Chest Hospital, Zhengzhou, China.
⁶ Department of Critical Care Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhenzhou, China.
⁷ Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, China.
⁸ Department of Respiratory Intensive Care Unit, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
⁹ Department of Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹⁰ Department of Cardiac Intensive Care Unit, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China.
¹¹ Department of Critical Care Medicine, Zhengzhou YIHE Hospital, Zhengzhou, China.
¹² Department of Critical Care Medicine, Nanyang Central Hospital, Nanyang, China.
¹³ Department of Critical Care Medicine, The 7th People's Hospital of Zhengzhou, Zhengzhou, China.
¹⁴ Department of Critical Care Medicine, Henan Provincial People's Hospital, Weiwu Road No. 7, Zhengzhou, 450003, Henan, China. shaohuanzhang@zzu.edu.cn.
¹⁵ Department of Critical Care Medicine, People's Hospital of Zhengzhou University, Zhengzhou, China. shaohuanzhang@zzu.edu.cn.
¹⁶ Henan Key Laboratory for Critical Care Medicine, Zhengzhou, China. shaohuanzhang@zzu.edu.cn.

PMID: 40581883
DOI: 10.1007/s40121-025-01176-5

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 .

Keywords: Carbapenem-resistant; Colistin sulfate; Infection; Intensive care; Multicenter.

Grants and funding

202300410458/Natural Science Foundation of Henan Province