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

Imran Kosar; Gokcen Dinc; Esma Eren; Yusuf Aykemat; Mesut Kilic; Huseyin Kilic; Mehmet Doganay

doi:10.14744/nci.2020.14238

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

North Clin Istanb. 2021 Mar 10;8(2):113-118. doi: 10.14744/nci.2020.14238. eCollection 2021.

Authors

Imran Kosar¹, Gokcen Dinc^{1

2}, Esma Eren³, Yusuf Aykemat⁴, Mesut Kilic⁵, Huseyin Kilic¹, Mehmet Doganay⁶

Affiliations

¹ Department of Medical Microbiology, Erciyes University Faculty of Medicine, Kayseri, Turkey.
² Department of Molecular Microbiology, Erciyes University Genome and Stem Cell Centre, Kayseri, Turkey.
³ Department of Infectious Diseases and Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri, Turkey.
⁴ Faculty of Health Science, Nuh Naci Yazgan University, Kayseri, Turkey.
⁵ Department of Internal Medicine, Kayseri City Hospital, Kayseri, Turkey.
⁶ Department of Infectious Diseases and Clinical Microbiology, Lokman Hekim University Faculty of Medicine, Ankara, Turkey.

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. 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, 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 48^th 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.

Keywords: Colistin resistance; Klebsiella pneumoniae; experimental sepsis.