In Vitro Discordance with In Vivo Activity: Humanized Exposures of Ceftazidime-Avibactam, Aztreonam, and Tigecycline Alone and in Combination against New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae in a Murine Lung Infection Model

Abstract

The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)-producing bacteria remains clinically challenging given the multidrug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro , ceftazidime-avibactam previously demonstrated in vivo activity against NDM-positive Enterobacteriaceae . Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In vivo , humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log ₁₀ CFU bacterial reduction; therefore, no in vivo synergy was observed.