Efficacy of beta-lactam and inhibitor combinations in a diffusion chamber model in rabbits

Using a diffusion chamber in rabbits, we evaluated therapy with the combina tion of ceftriaxone plus the beta-lactamase inhibitor tazobactam in compari son with ceftriaxone alone, One sensitive and one resistant strain of Esche richia coli, Enterobacter cloacae and Klebsiella pneumoniae were inoculated into one of the six diffusion chambers, implanted in the same animal. In o rder to simulate pharmacokinetics in humans, both substances were administe red in decreasing doses. Ceftriaxone was given 0, 2, 4 and 6 h after infect ion in dosages of 45, 35, 25 and 15 mg/kg of body weight, while tazobactam was administered either in one dose at 0 h, or divided into two doses at 0 and 1 h or 0 and 4 h, or divided into three doses at 0, 1 and 4 h after inf ection. The ratio of ceftriaxone:tazobactam was fixed at 8:1. Ceftriaxone, in combination with tazobactam, given in one dose immediately after infecti on showed a significant reduction in bacterial count. All other combination s of ceftriaxone and tazobactam did not differ from ceftriaxone in monother apy. Co-administration of the beta-lactamase inhibitor tazobactam significa ntly enhanced the activity of ceftriaxone against all three tested species.