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Preheating colistimethate sodium enhances its efficacy against multi/extensively drug-resistant Gram-negative bacilli
Daqian Tang1,2, Lijie Zhang1, Yazhe Duan1
1Department of Organ Transplantation, Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Abstract:
This study aimed to evaluate the efficacy and preliminary safety of preheated colistimethate sodium (CMS) in reducing the load of multidrug-resistant and extensively drug-resistant (MDR/XDR) Gram-negative bacilli in preservation fluid (PF) under simulated static cold storage (SCS) conditions in vitro. CMS was preheated at 37-60 °C for 5 ~ 30 min. The antibacterial effects of preheated CMS were evaluated against five MDR/XDR strains: carbapenem-resistant Pseudomonas aeruginosa (CRPA), Klebsiella pneumoniae (CRKP), Escherichia coli (CREC), Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA). Bacterial counts were assessed after 3 h of SCS, and the average inhibition rate (AIR) was calculated. The safety experiment was performed to evaluate the nephrotoxicity of preheated CMS under hypothermic condition. Preheating CMS at 60 °C for 15 ~ 30 min significantly reduced bacterial loads of CRPA, CRKP, CREC, and CRAB, with average inhibition rates (AIR) up to 100%, 96.91%, 98.36%, and 85.06%, respectively. At 37 °C, extended heating (30 min) was required for partial efficacy against CRKP and CRAB, while CREC remained largely unaffected. MRSA showed no susceptibility to preheated CMS. Preheated CMS did not cause significant morphological alterations or reduction in HK-2 cell viability within 3 ~ 6 h of SCS. Thermal pretreatment of CMS at 60 °C represents a novel, practical, and safe strategy for PF decontamination, providing rapid bactericidal activity against frequently encountered MDR/XDR Gram-negative bacilli during the SCS process.
Insights
Preheating colistimethate sodium (CMS) to 60°C effectively reduces multidrug-resistant Gram-negative bacilli in preservation fluid during cold storage. This thermal pretreatment offers a safe and practical method for decontamination, enhancing organ preservation.
Area of Science:
- Microbiology
- Pharmacology
- Biotechnology
Background:
- Multidrug-resistant and extensively drug-resistant (MDR/XDR) Gram-negative bacilli pose a significant threat in healthcare settings.
- Preservation fluids (PF) used in organ transplantation can become contaminated with these resistant bacteria during static cold storage (SCS).
- Effective decontamination strategies are crucial to prevent infectious complications associated with contaminated organs.
Purpose of the Study:
- To evaluate the efficacy of preheated colistimethate sodium (CMS) in reducing MDR/XDR Gram-negative bacilli loads in PF under simulated SCS conditions.
- To assess the preliminary safety of preheated CMS, specifically its nephrotoxicity, under hypothermic conditions.
- To determine optimal preheating parameters (temperature and duration) for CMS activity.
Main Methods:
- CMS was preheated at temperatures ranging from 37°C to 60°C for 5 to 30 minutes.
- Antibacterial effects were tested against carbapenem-resistant Pseudomonas aeruginosa (CRPA), Klebsiella pneumoniae (CRKP), Escherichia coli (CREC), Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA).
- Bacterial counts were assessed after 3 hours of SCS, and average inhibition rates (AIR) were calculated. Nephrotoxicity was evaluated using HK-2 cells.
Main Results:
- Preheating CMS at 60°C for 15-30 minutes achieved significant bacterial load reduction, with AIRs up to 100% for CRPA, 96.91% for CRKP, 98.36% for CREC, and 85.06% for CRAB.
- Lower temperatures (37°C) required longer heating times for partial efficacy, and CREC remained largely unaffected.
- MRSA showed no susceptibility to preheated CMS. Preheated CMS exhibited no significant nephrotoxicity to HK-2 cells within 3-6 hours of SCS.
Conclusions:
- Thermal pretreatment of CMS at 60°C is a novel, practical, and safe strategy for PF decontamination.
- This method provides rapid bactericidal activity against common MDR/XDR Gram-negative bacilli encountered during SCS.
- Preheated CMS shows potential for improving the safety of organ preservation by reducing bacterial contamination.
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