In vivo Anti-pseudomonal Activity of Ceftobiprole (original) (raw)

Abstract

Background: Ceftobiprole medocaril (BPR), the prodrug of ceftobiprole, is an investigational broad-spectrum cephalosporin with anti-MRSA and Gram-negative activity. The efficacy of this agent against P. aeruginosa was examined in two murine infection models. Methods: The neutropenic mouse thigh model was used to evaluate the BPR efficacy. Mice were made neutropenic with 2 ip injections of cyclophosphamide given 96 and 24 h prior to infection (150 and 100 mg/kg respectively). Animals were subsequently infected intramuscularly 5 x 105 CFU of P. aeruginosa OC4351, and dosed subcutaneously (sc) 1 and 3 h post-infection with ceftobiprole (BPR), Ceftazidime (CAZ), or Meropenem/cilastatin (MEM) (1:1ratio ). The bacterial load of the thigh muscle was determined 24-h post-infection. Efficacy was also evaluated in a lethal systemic infection model. Mice (n=24 in 3 experiments) were infected i.p. with P. aeruginosa OC4351 and dosed sc 1 and 3 h post-infection with BPR or CAZ. . The percent sur...

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