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 | Zendy

Marguerite L. Monogue | Zendy; Lilian M. Abbo | Zendy; Rossana Rosa | Zendy; José F. Camargo | Zendy; Octavio Martínez | Zendy; Robert A. Bonomo | Zendy; David P. Nicolau | Zendy

Open Access

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

Author(s) -

Marguerite L. Monogue,

Lilian M. Abbo,

Rossana Rosa,

José F. Camargo,

Octavio Martínez,

Robert A. Bonomo,

David P. Nicolau

Publication year - 2017

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.00486-17

Subject(s) - ceftazidime/avibactam , klebsiella pneumoniae , aztreonam , tigecycline , ceftazidime , microbiology and biotechnology , avibactam , in vivo , enterobacteriaceae , in vitro , biology , medicine , bacteria , antibiotics , antibiotic resistance , escherichia coli , pseudomonas aeruginosa , imipenem , biochemistry , genetics , gene

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 resistancein vitro , ceftazidime-avibactam previously demonstratedin vivo activity against NDM-positiveEnterobacteriaceae . Herein, we observedin vitro synergy with ceftazidime-avibactam and aztreonam against an MDRKlebsiella pneumoniae harboring NDM.In vivo , humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10 CFU bacterial reduction; therefore, noin vivo synergy was observed.

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