Docobo-Pérez, F.López-Cerero, L.López-Rojas, R.Egea, P.Domínguez-Herrera, J.Rodríguez-Baño, J.Pascual, A.Pachón, J.2014-04-032014-04-032013-05Docobo-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):2109-130066-4804http://hdl.handle.net/10668/1567Journal Article; Research Support, Non-U.S. Gov't;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.enRatones consanguíneos C57BLCombinación de amoxicilina clavulanato potásicoRecuento de colonias microbianasInfecciones intraabdominalesPruebas de sensibilidad microbianaÁcido penicilánicoMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial AgentsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Colony Count, MicrobialMedical Subject Headings::Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Escherichia::Escherichia coliMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Negative Bacterial Infections::Enterobacteriaceae Infections::Escherichia coli InfectionsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Carbapenems::Thienamycins::ImipenemMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Injections::Injections, IntramuscularMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Injections::Injections, IntraperitonealMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Infection::Intraabdominal InfectionsMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BLMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Microbiological Techniques::Microbial Sensitivity TestsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillanic AcidMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::PiperacillinMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Infection::SepsisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::beta-LactamasesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Clavulanic Acids::Clavulanic Acid::Amoxicillin-Potassium Clavulanate Combinationresearch article23439636open access10.1128/AAC.02190-121098-6596PMC3632932