Revista ABCd (São Paulo). 01 Sep, 2014

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

Paula Virginia Michelon TOLEDO
Felipe Francisco TUON
Larissa BAIL
Francine MANENTE
Polliane ARRUDA
DOI: 10.1590/S0102-67202014000300002


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


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


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.


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).


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.

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