RT Journal Article
T1 Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model.
A1 Docobo-Pérez, F.
A1 López-Cerero, L.
A1 López-Rojas, R.
A1 Egea, P.
A1 Domínguez-Herrera, J.
A1 Rodríguez-Baño, J.
A1 Pascual, A.
A1 Pachón, J.
K1 Ratones consanguíneos C57BL
K1 Combinación de amoxicilina clavulanato potásico
K1 Recuento de colonias microbianas
K1 Infecciones intraabdominales
K1 Pruebas de sensibilidad microbiana
K1 Ácido penicilánico
AB Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P < 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (-1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: -0.73, -1.89, and -1.62 log10 CFU/g (P < 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P < 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.
PB American Society for Microbiology
SN 0066-4804
YR 2013
FD 2013-05
LK http://hdl.handle.net/10668/1567
UL http://hdl.handle.net/10668/1567
LA en
NO Docobo-Pérez F, López-Cerero L, López-Rojas R, Egea P, Domínguez-Herrera J, Rodríguez-Baño J, et al. Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model. Antimicrob. Agents Chemother. 2013; 57(5):2109-13
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Mar 14, 2025