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dc.creatorDocobo Pérez, Fernando
dc.creatorLópez Cerero, Lorena
dc.creatorLópez-Rojas, Rafael
dc.creatorEgea, P.
dc.creatorDomínguez-Herrera, J.
dc.creatorRodríguez-Baño, Jesús
dc.creatorPascual Hernández, Álvaro
dc.creatorPachón Díaz, Jerónimo
dc.description.abstractEscherichia 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 -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 log10 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. Escheries
dc.publisherAmerican Society for Microbiologyes
dc.relation.ispartofAntimicrobial Agents and Chemotherapy,57(5), 2109–2113es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.subjectCombinación de amoxicilinaes
dc.subjectÁcido penicilánicoes
dc.subjectPruebas de sensibilidad microbianaes
dc.subjectInfecciones intraabdominaleses
dc.subjectRatones consanguíneos C57BLes
dc.subjectRecuento de colonias microbianas clavulanato potásicoes
dc.subjectEscherichia colies
dc.titleInoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum -Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Modeles
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Microbiologíaes

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