[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
Inoculum effect on the efficacy of amoxicillin/clavulanate, piperacillin/tazobactam, and imipenem in an experimental ESBL- and non-ESBL-producing Escherichia coli murine sepsis model [PublishAheadOfPrint]

Docobo-Perez, F., Lopez-Cerero, L., Lopez-Rojas, R., Egea, P., Dominguez-Herrera, J., Rodriguez-Bano, J., Pascual, A., Pachon, J.

Escherichia coli are commonly involved in infections with a heavy bacterial burden. Piperacillin/tazobactam and carbapenems are among the empiric recommended treatments for health care?associated complicated intra-abdominal infections. In contrast to amoxicillin/clavulanate, both have a reduced in vitro activity in the presence of high bacterial concentration of ESBL-producing and not- producing E. coli. Our goal was to compare the efficacy of these antimicrobials against different bacterial concentrations of two clinical ESBL-producing and ESBL-not-producing E. coli strains in a murine sepsis model. An experimental sepsis model, using (~5.5 [LI] or ~7.5 Log<SUB>10</SUB> CFU/g [HI]) two E. coli strains (ATCC 25922 [non-ESBL-producer] and Ec1062 [CTX-M-14]) susceptible to the three antimicrobials was performed. Doses of amoxicillin/clavulanate (50/12.5 mg/kg/i.m.), piperacillin/tazobactam (25/3.125 mg/kg/i.p.), and imipenem (30 mg/kg/i.m.) were used. Piperacillin/tazobactam and imipenem reduced bacterial spleen concentrations (-2.53 and -2.14 Log<SUB>10</SUB> CFU/g, P<0.05, respectively) against the ATCC 25922 strain in the HI versus LI groups, while amoxicillin/clavulanate maintained its efficacy (-1.01 Log<SUB>10</SUB> CFU/g, p=NS). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI relative to the LI groups: -0.73, -1.89, and -1.62 Log<SUB>10</SUB> 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 (fT<SUB>MIC</SUB> using the MIC obtained with HI of the ATCC 25922 strain) improved its efficacy, -1.67 Log<SUB>10</SUB> CFU/g (P<0.05). These results suggest that amoxicillin/clavulanate could be an alternative treatment to imipenem in infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin/tazobactam.