Emergence of Resistance to Ceftazidime-Avibactam in a Pseudomonas aeruginosa Isolate Producing Derepressed <i>bla</i> <sub>PDC</sub> in a Hollow-Fiber Infection Model
George L. Drusano, Robert A. Bonomo, Steven Marshall, Laura J. Rojas, Mark D. Adams, María F. Mojica, Barry N. Kreiswirth, Liang Chen, Nino Mtchedlidze, Meredith Bacci, Michael Vicchiarelli, Jürgen B. Bulitta, Arnold Louie
Abstract
-derived cephalosporinase (PDC) β-lactamase. Further experiments in which CAZ and AVI were both administered intermittently with regimens above and below the AUC of 89.3 mg · h/liter resulted in resistance in the lower-exposure groups. Deletion mutants were not identified. Finally, in an experiment in which paired exposures as both continuous and intermittent infusions were performed, the lower value of 25 mg · h/liter by both profiles allowed selection of deletion mutants. Of the five instances in which these mutants were recovered, four had a continuous-infusion profile. Both continuous-infusion administration and low AVI AUC exposures have a role in selection of this mutation.