Carbapenem-resistant Klebsiella pneumoniae sepsis in corticosteroid receipt mice: tigecycline or colistin monotherapy versus tigecycline/colistin combination

Abstract

This study compared the effect of monotherapy of colistin, tigecycline, and their combination in sepsis model of mice. OXA-48 producing Carbapenem-resistant Klebsiella pneumoniae (CRKP) strain was used in Balb/c mice. The mice were divided into competent and Methylprednisolone acetate (MPA)-treated groups. Each group was sub-divided into (1) colistin or (2) tigecycline monotherapy and (3) colistin/tigecycline combination therapy. After 3 hours of intraperitoneal bacterial inoculation, antimicrobials were administered, and mice were sacrificed at 24 and 48 hours Time-kill curve study demonstrated that colistin sulphate had early bactericidal activity following re-growth. In competent and MPA-treated groups of mice at 24 hours, bacterial counts in liver samples significantly lowered compared to control, however, there were no statistically differences between monotherapy and combination therapy subgroup. Bacterial count in lung samples of competent group was significantly lesser than control for all three antimicrobial subgroups at 24 hours Colistin plus tigecycline combination therapy was not superior against colistin or tigecycline monotherapy.

Keywords:

• Carbapenem-resistant K. pneumoniae
• Experimental sepsis
• Methylprednisolone acetate
• Colistin
• Tigecycline

Acknowledgements

The authors would like to thank Associate Professor Zerrin Aktas from the Department of Microbiology, Faculty of Medicine, Istanbul University, Istanbul, for kindly supplying the strain of carbapenem-resistant K. pneumoniae OXA-48, and Dr. Kemal Deniz, Associate Professor, Department of Pathology for his support.

This study was an oral presentation in ‘The 5th Eurasia Congress of Infectious Diseases’ in Tirana, Albania held during 15th–18th May 2013, and was supported by the Scientific Research Project Unit of Erciyes University (Project no: TSA-11-3615).