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

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 log₁₀ CFU bacterial reduction; therefore, no in vivo synergy was observed.