Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae

Objective: Klebsiella pneumoniae, a Gram-negative pathogen, especially which produces carbapenemase, is seen as a major threat to public health due to rapid plasmid-mediated spread of resistance and limited therapeutic options available for treatment. Although colistin has been recognized as a last resort antimicrobial for multidrug-resistant K. pneumoniae infections, these isolates have developed resistance to colistin as a result of its intensive use. The aim of this study was to evaluate the efficacy of double-carbapenem treatment of colistin-resistant K. pneumoniae experimental sepsis in mice.Methods: In the study, 8-10-week-old Balb-c mice were divided as control groups (positive and negative) and treatment groups (colistin, ertapenemmeropenem, and ertapenemmeropenemcolistin). Sepsis was developed in mice by an intraperitoneal injection of colistin resistant K. pneumoniae. Antibiotics were given intraperitoneally 3 h after bacterial inoculation. Mice in each subgroup were sacrificed with overdose anesthetic at the end of 24-48 h and cultures were made from the heart, lung, liver, and spleen. Furthermore, homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was evaluated in lung and liver at different time points.Results: When the quantitative bacterial loads in the lung and liver tissues are evaluated, no statistically significant difference was observed between different antibiotic treatments (p>0.05). All three treatment options were not effective, especially in 24 h. Only the decrease in bacterial load at the 48th h of the group treated with ertapenem meropenem colistin was found significant (p<0.05) compared to the 24 h.Conclusion: In the light of these data, it was understood that double-carbapenem application was not sufficient in the treatment of experimental sepsis in mice with colistin-resistant K. pneumoniae. Furthermore, ertapenem meropenem colistin combined therapy was not found to be superior to colistin monotherapy or double-carbapenem therapy.

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