Evaluation of the post-antibiotic effect in vivo for the combination of a β-lactam antibiotic and a β-lactamase inhibitor: ceftazidime-avibactam in neutropenic mouse thigh and lung infections

The post-antibiotic effect (PAE) of ceftazidime-avibactam in vivo was evaluated using models of thigh- and lung-infection with Pseudomonas aeruginosa in neutropenic mice. In thigh-infected mice, the PAE was negative (-2.18 to -0.11 h) for three of four strains: caused by a 'burst' of rapid bacterial growth after the drug concentrations had fallen below their pre-specified target values. With lung infection, PAE was positive, and longer for target drug concentrations in ELF (>2 h) than plasma (1.69-1.88 h). The time to the start of regrowth was quantified as a new parameter, PAE(R), which was positive (0.35-1.00 h) in both thigh- and lung-infected mice. In the context that measurements of the PAE of beta-lactam/beta-lactamase inhibitor combinations in vivo have not previously been reported, it is noted that the negative values were consistent with previous measurements of the PAE of ceftazidime-avibactam in vitro and of ceftazidime alone in vivo.

Automated summary

The post-antibiotic effect (PAE) of ceftazidime-avibactam in vivo was evaluated in thigh- and lung-infection models with Pseudomonas aeruginosa in neutropenic mice. PAE was negative for most strains in thigh infection due to rapid bacterial growth after drug concentrations fell below target values, while positive and longer in lung infection.