Clinical efficacy and nephrotoxicity of intravenous colistin sulfate in the treatment of carbapenem-resistant gram-negative bacterial infections: a retrospective cohort study

Background Carbapenem-resistant gram-negative bacteria (CR-GNB) are becoming increasingly important bacterial pathogens in critically ill patients. Several clinicians use Intravenous colistin sulfate to treat infections due to CR-GNB, although the clinical data is limited. The aim of our retrospective observational study was to evaluate the effectiveness and nephrotoxicity of intravenous colistin sulfate in the treatment of CR-GNB infections. Methods Fifty critically ill intensive care patients with infections due to CR-GNB were retrospectively enrolled between January 2020 and December 2021 in the Zhejiang Provincial People’s Hospital. Favorable clinical response rate, bacterial clearance rate, nephrotoxicity, and 28-day mortality were evaluated. Results The overall favorable clinical response rate was 58%, the bacterial clearance rate was 40%, and the 28-day all-cause mortality was 44%. Temperature, neutrophil count, C-reaction protein (CRP), procalcitonin (PCT), creatinine (Cr), and lactate levels were also significantly decreased (P<0.05). The major adverse reaction is nephrotoxicity, and renal function was evaluated on the day before and after treatment with colistin sulfate. Possible nephrotoxicity was observed in three patients (6%). Backward logistic regression was conducted to determine risk factors for the nephrotoxicity of colistin sulfate, the result showed there were no significant differences in the duration and dose of colistin sulfate. Conclusions Our results provide evidence for the positive clinical efficacy and safety of colistin sulfate. Appropriate use of colistin sulfate may be viable and safe in the treatment of severe infections caused by CR-GNB.

[1]  Q. Pei,et al.  Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients , 2022, Frontiers in Pharmacology.

[2]  G. Lin,et al.  Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy , 2022, Frontiers in Pharmacology.

[3]  G. Lin,et al.  Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug‐resistant Acinetobacter baumannii induced post‐neurosurgical ventriculitis , 2022, British journal of clinical pharmacology.

[4]  Zhenshun Cheng,et al.  Risk factors for polymyxin B-associated acute kidney injury. , 2022, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[5]  R. Jiang,et al.  Efficacy and safety of polymyxin B in carbapenem-resistant gram-negative organisms infections , 2021, BMC Infectious Diseases.

[6]  Shujun Zhou,et al.  Treatment of pulmonary infection of extensively drug-resistant Acinetobacter baumannii with intravenous colistin sulfate combined with atomization: a case report. , 2021, Annals of palliative medicine.

[7]  T. Velkov,et al.  Rescuing the Last-Line Polymyxins: Achievements and Challenges , 2021, Pharmacological Reviews.

[8]  Haibo Zhang,et al.  Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study , 2021, Journal of Translational Medicine.

[9]  Á. Soriano,et al.  Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins. , 2020, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[10]  Dumessa Edessa,et al.  Polymyxin-induced nephrotoxicity and its predictors: a systematic review and meta-analysis of studies conducted using RIFLE criteria of acute kidney injury. , 2020, Pharmacological research.

[11]  C. Milikowski,et al.  Polymyxin B‐induced skin hyperpigmentation , 2020, Transplant infectious disease : an official journal of the Transplantation Society.

[12]  A. Earl,et al.  Adaptive evolution of virulence and persistence in carbapenem-resistant Klebsiella pneumoniae , 2020, Nature Medicine.

[13]  Y. Doi,et al.  Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019) , 2020, Emerging microbes & infections.

[14]  Ziyan Shen,et al.  Predictors of mortality in patients infected with carbapenem-resistant Acinetobacter baumannii: A systematic review and meta-analysis. , 2019, American journal of infection control.

[15]  B. Levin,et al.  Antibiotic Killing of Diversely Generated Populations of Nonreplicating Bacteria , 2018, Antimicrobial Agents and Chemotherapy.

[16]  Andrew Lee,et al.  A Review of the Clinical Pharmacokinetics of Polymyxin B , 2019, Antibiotics.

[17]  Thomas B. Clarke,et al.  Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane , 2018, eLife.

[18]  E. Mao,et al.  Polymyxin B-induced skin hyperpigmentation: a rare case report and literature review , 2018, BMC pharmacology & toxicology.

[19]  Man Huang,et al.  High-dose tigecycline for the treatment of nosocomial carbapenem-resistant Klebsiella pneumoniae bloodstream infections , 2018, Medicine.

[20]  D. Falci,et al.  Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B , 2017, Antimicrobial Agents and Chemotherapy.

[21]  K. Porter,et al.  Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia , 2017, Journal of intensive care medicine.

[22]  D. van Duin,et al.  The global epidemiology of carbapenemase-producing Enterobacteriaceae , 2017, Virulence.

[23]  André Reis,et al.  Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients , 2017, Pathogens and global health.

[24]  D. Burgess,et al.  Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin , 2017, Antimicrobial Agents and Chemotherapy.

[25]  M. Falagas,et al.  Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis. , 2017, International journal of antimicrobial agents.

[26]  Yefei Zhu,et al.  Tigecycline Therapy for Nosocomial Pneumonia due to Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Who Received Inappropriate Initial Antibiotic Treatment: A Retrospective Case Study , 2016, BioMed research international.

[27]  J. Osorio,et al.  Risk Factors for Acute Kidney Injury in Patients Treated with Polymyxin B: Experience from 139 Cases at a Tertiary University Hospital in Colombia , 2016 .

[28]  J. Li,et al.  Polymyxins: a new hope in combating Gram-negative superbugs? , 2016, Future medicinal chemistry.

[29]  A. Trifi,et al.  Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series , 2016, Chemotherapy.

[30]  A. Levin,et al.  Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B , 2016, Antimicrobial Agents and Chemotherapy.

[31]  D. Calfee,et al.  Clinical Outcomes Associated with Polymyxin B Dose in Patients with Bloodstream Infections Due to Carbapenem-Resistant Gram-Negative Rods , 2015, Antimicrobial Agents and Chemotherapy.

[32]  A. Ellrodt,et al.  Sepsis and septic shock. , 1986, Emergency medicine clinics of North America.