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 1.5x1099. Mimoz O, Leotard S, Jacolot A, Padoin C, Louchahi K, Petitjean O, Nordmann P.. Efficacies of imipenem, meropenem, cefepime, and ceftazidime in rats with experimental pneumonia due to a carbapenem-hydrolyzing beta-lactamase-producing strain of Enterobacter cloacae. Antimicrob Agents Chemother 2000; 44: 885-890. colony-forming units per milliliter (CFU/mL) to 2.0x1010 10. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113.CFU/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 2.0x1010 10. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113.CFU/mL inoculums were treated with single meropenem dose (30mg/kg) after one hour and those which received 1.0x1010 10. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113.CFU/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 x1099. Mimoz O, Leotard S, Jacolot A, Padoin C, Louchahi K, Petitjean O, Nordmann P.. Efficacies of imipenem, meropenem, cefepime, and ceftazidime in rats with experimental pneumonia due to a carbapenem-hydrolyzing beta-lactamase-producing strain of Enterobacter cloacae. Antimicrob Agents Chemother 2000; 44: 885-890. and 6.0x1099. Mimoz O, Leotard S, Jacolot A, Padoin C, Louchahi K, Petitjean O, Nordmann P.. Efficacies of imipenem, meropenem, cefepime, and ceftazidime in rats with experimental pneumonia due to a carbapenem-hydrolyzing beta-lactamase-producing strain of Enterobacter cloacae. Antimicrob Agents Chemother 2000; 44: 885-890. CFU/mL were not lethal within 24 hours. Inoculums of 1.0x1010 10. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113.CFU/mL were lethal in 80% and solutions with 2.0x101010. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113. CFU/mL were lethal in 100% of animals. ESBL lethal sepsis (1.0x101010. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113.CFU/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 104 4. Endimiani A, Hujer KM, Hujer AM, Pulse ME, Weiss WJ, Bonomo RA.. Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2011; 55: 82-85.CFU/mL or less for treated animals compared to more than 1055. Giacometti A, Cirioni O, Ghiselli R, Mocchegiani F, Paggi AM, Orlando F, Kamysz W, Kasprzykowski F, Mackiewicz Z, Scalise G, Saba V.. Therapeutic efficacy of intraperitoneal polymyxin B and polymyxin-like peptides alone or combined with levofloxacin in rat models of septic shock. J Antimicrob Chemother 2002; 49: 193-196. for untreated animals (p=0.001).
CONCLUSION:
Inoculums of 1.0x101010. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012; 56: 2108-2113.CFU/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.
Klebsiella pneumoniae; Sepsis; Models, animal
