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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):2109-13AA

Abstract

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.

Authors+Show Affiliations

Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23439636

Citation

Docobo-Pérez, F, 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." Antimicrobial Agents and Chemotherapy, vol. 57, no. 5, 2013, pp. 2109-13.
Docobo-Pérez F, López-Cerero L, López-Rojas R, 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.
Docobo-Pérez, F., López-Cerero, L., López-Rojas, R., Egea, P., Domínguez-Herrera, J., Rodríguez-Baño, J., ... Pachón, J. (2013). 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. Antimicrobial Agents and Chemotherapy, 57(5), pp. 2109-13. doi:10.1128/AAC.02190-12.
Docobo-Pérez F, 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. PubMed PMID: 23439636.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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. AU - Docobo-Pérez,F, AU - López-Cerero,L, AU - López-Rojas,R, AU - Egea,P, AU - Domínguez-Herrera,J, AU - Rodríguez-Baño,J, AU - Pascual,A, AU - Pachón,J, Y1 - 2013/02/25/ PY - 2013/2/27/entrez PY - 2013/2/27/pubmed PY - 2013/10/25/medline SP - 2109 EP - 13 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 57 IS - 5 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/23439636/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_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&amp;pmid=23439636 DB - PRIME DP - Unbound Medicine ER -