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

Abstract

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. pneumoniaeinfections, 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, ertapenem+meropenem, and ertapenem+meropenem+colistin). 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