Comparison of the Efficacy of Colistin and Meropenem Monotherapy with Meropenem/Ertapenem Combination in an Experimental Sepsis Model of Carbapenemase-producing Klebsiella pneumoniae

Abstract

Introduction: To investigate the efficacy of double carbapenem therapy (ertapenem + meropenem combination) in an experimental sepsis model in rats with Klebsiella pneumoniae (K. pneumoniae), which is carbapenem-resistant and colistin susceptible, and compare it with colistin and meropenem monotherapy. Materials and Methods: K. pneumoniae isolate that is known to carry the blaOXA-48 and blaNDM carbapenemase genes was used, and 1-2×108 colony forming unit/ml was inoculated intraperitoneally to 40 rats (20 males/20 females), and a sepsis model was created. The rats were divided into four equal groups: control, colistin, meropenem, and meropenem + ertapenem combination. The rats were followed for 24 h for signs of sepsis and mortality. Euthanasia was then performed, and blood cultures were taken. Results: After 24 h, none of the rats in the control or treatment groups died. K. pneumoniae growth was observed in all rats in the control, five in the colistin, seven in the meropenem, and five in the meropenem + ertapenem combination groups. A statistically significant difference was found between the control group and the colistin and meropenem + ertapenem combination groups (p=0.033 and p=0.033, respectively). No statistically significant difference was found between the control group and the meropenem monotherapy group (p=0.215). The numbers of non-growth blood cultures were comparable between the colistin group and the meropenem + ertapenem combination group, and no statistically significant difference was found between the two groups (p=1). The mean time of growth signals (minutes) were compared between the treatment groups: colistin, 642.6 ± 116.4; meropenem, 582.6 ± 107.7; and meropenem + ertapenem combination, 701.2 ± 70.4 min. Conclusion: Meropenem + ertapenem combination treatment was comparable to colistin monotherapy, and the mean time of growth signals of blood cultures were longer than those in the colistin and meropenem monotherapy groups.

Keywords

• klebsiella pneumoniae
• double carbapenem therapy
• experimental rat sepsis model