Ceftolozane-Tazobactam against Pseudomonas aeruginosa Cystic Fibrosis Clinical Isolates in the Hollow-Fiber Infection Model: Challenges Imposed by Hypermutability and Heteroresistance
Jessica R. Tait, Marina Harper, Sara Cortés-Lara, Kate E. Rogers, Carla López-Causapé, Thomas R. Smallman, Yinzhi Lang, Wee Leng Lee, Jieqiang Zhou, Jürgen B. Bulitta, Roger L. Nation, John D. Boyce, Antonio Oliver, Cornelia B. Landersdorfer
Abstract
were identified following CW41 exposure to ceftolozane-tazobactam at 167 to 215 h. Mechanism-based modeling well described total and resistant bacterial counts. The findings highlight the impact of heteroresistance and baseline mutations on the effect of ceftolozane-tazobactam and limitations of MIC to predict bacterial outcomes. The resistance amplification in two of three isolates supports current guidelines that ceftolozane-tazobactam should be utilized together with another antibiotic against P. aeruginosa in CF.