Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant .

OBJECTIVE

, 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 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 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 . 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 48 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 . Furthermore, ertapenem + meropenem + colistin combined therapy was not found to be superior to colistin monotherapy or double-carbapenem therapy.