Abstract
To use a pre-clinical pharmacokinetic infection model to assess the antibacterial effect of ceftolozane/tazobactam alone or in combination with fosfomycin or tobramycin against Pseudomonas aeruginosa strains with MICs at or higher than the clinical breakpoint (MIC ≥ 4 mg/L). An in vitro model was used to assess changes in bacterial load and population profiles after exposure to mean human serum concentrations of ceftolozane/tazobactam associated with doses of 2 g/1 g q8h, fosfomycin concentrations associated with doses of 8 g q8h or tobramycin at doses of 7 mg/kg q24 h over 168 h. Simulations of ceftolozane/tazobactam at 2 g/1 g q8h alone produced 3.5-4.5 log reductions in count by 6 h post drug exposure for strains with MIC ≤32 mg/L. The antibacterial effect over the first 24 h was related to ceftolozane/tazobactam MIC. There was subsequent regrowth with most strains to bacterial densities of >106 CFU/mL. Addition of either fosfomycin or tobramycin resulted in suppression of regrowth and in the case of tobramycin more rapid initial bacterial killing up to 6 h. These effects could not be related to either fosfomycin or tobramycin MICs. Changes in population profiles were noted with ceftolozane/tazobactam alone often after 96 h exposure but such changes were suppressed by fosfomycin and almost abolished by the addition of tobramycin. The addition of either fosfomycin or tobramycin to ceftolozane/tazobactam at simulated human clinically observed concentrations reduced P. aeruginosa bacterial loads and the risk of resistance to ceftolozane/tazobactam when strains had ceftolozane/tazobactam MIC values at or above the clinical breakpoint.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.