Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Enterobacter cloacae is a multidrug-resistant Gram-negative bacterium causing significant morbidity and mortality in intensive care units.
• Colistin is a last-resort antibiotic for multidrug-resistant infections, but its use is limited by toxicity at higher concentrations.
• Developing strategies to overcome colistin resistance and reduce its side effects is crucial for treating resistant bacterial infections.

Purpose of the Study:

• To investigate the synergistic effects of combining colistin with chloramphenicol against colistin-resistant Enterobacter cloacae strains.
• To evaluate the efficacy and safety of this combination therapy in vitro.
• To explore a potential alternative treatment for infections caused by multidrug-resistant Enterobacter cloacae.

Main Methods:

• Colistin-resistant Enterobacter cloacae strains were generated through serial propagation in subinhibitory colistin concentrations.
• Bacterial identification and antibiotic resistance profiling were performed using MALDI-TOF MS, VITEK 2, MicroScan, disk diffusion, and automated systems.
• Synergistic effects of colistin-chloramphenicol combinations were assessed using the broth microdilution checkerboard method.

Main Results:

• Generated colistin-resistant Enterobacter cloacae strains exhibited intrinsic resistance to various antibiotics, including penicillin, cephalosporins, and monobactams.
• The combination of colistin and chloramphenicol demonstrated synergistic activity, effectively inhibiting both induced and clinical colistin-resistant Enterobacter cloacae strains.
• The effective concentrations of the colistin-chloramphenicol combination showed no observable cytotoxic effects.

Conclusions:

• The combination of colistin and chloramphenicol presents a promising therapeutic strategy for treating infections caused by colistin-resistant Enterobacter cloacae.
• This combination may allow for reduced colistin dosages, thereby mitigating its associated toxicities.
• Further research is warranted to validate the clinical efficacy and safety of this novel therapeutic approach.