Experimental model for treatment of extended spectrum betalactamase producing-Klebsiella pneumoniae

BACKGROUND:

Animal models are useful to evaluate the efficacy of antimicrobials in experimental sepsis.

AIM:

To elucidate the steps of producing an experimental model for the treatment of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sepsis

METHODS:

Several ESBL inoculums ranging from 1.5x10⁹ colony-forming units per milliliter (CFU/mL) to 2.0x10¹⁰CFU/mL were administered by peritoneal injection in adults Wistar rats. Outcomes and microbiological data of quantitative peritoneal and blood cultures were observed in untreated animals. Animals which received 2.0x10¹⁰CFU/mL inoculums were treated with single meropenem dose (30mg/kg) after one hour and those which received 1.0x10¹⁰CFU/mL inoculums were treated immediately with three doses of meropenem 50 mg/kg. Outcomes were observed for 24 hours after inoculation.

RESULTS:

Solutions with 1.5 x10⁹ and 6.0x10⁹ CFU/mL were not lethal within 24 hours. Inoculums of 1.0x10¹⁰CFU/mL were lethal in 80% and solutions with 2.0x10¹⁰ CFU/mL were lethal in 100% of animals. ESBL lethal sepsis (1.0x10¹⁰CFU/mL) was treated immediately with 50 mg/kg of meropenem every eight hours for 24 hours and presented 40% mortality compared with 80% mortality of the control group (p=0.033). Quantitative cultures of peritoneal fluid presented 10⁴CFU/mL or less for treated animals compared to more than 10⁵ for untreated animals (p=0.001).

CONCLUSION:

Inoculums of 1.0x10¹⁰CFU/mL achieved the best results to study a model of lethal sepsis and this model of treatment of carbapenem-susceptible Enterobacteriaceae can serve as control to further evaluation of treatment of carbapenemase-producing Enterobacteriaceae models.