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

M L Monogue; L M Abbo; R Rosa; J F Camargo; O Martinez; R A Bonomo; D P Nicolau

doi:10.1128/AAC.00486-17

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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

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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

M L Monogue, L M Abbo, R Rosa, J F Camargo, O Martinez, R A Bonomo and D P Nicolau

Antimicrobial agents and chemotherapy, Vol.61(7)

2017-07

DOI: https://doi.org/10.1128/AAC.00486-17

PMCID: PMC5487677

PMID: 28416558

Abstract

Azabicyclo Compounds - pharmacology

Klebsiella Infections - drug therapy

Klebsiella pneumoniae - drug effects

Ceftazidime - pharmacology

Aztreonam - therapeutic use

Aztreonam - pharmacology

beta-Lactamase Inhibitors - pharmacology

Microbial Sensitivity Tests

Anti-Bacterial Agents - therapeutic use

Animals

beta-Lactamase Inhibitors - therapeutic use

Enterobacteriaceae - drug effects

Azabicyclo Compounds - therapeutic use

Female

Anti-Bacterial Agents - pharmacology

Mice

Ceftazidime - therapeutic use

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 , ceftazidime-avibactam previously demonstrated activity against NDM-positive Herein, we observed synergy with ceftazidime-avibactam and aztreonam against an MDR harboring NDM. , humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log CFU bacterial reduction; therefore, no synergy was observed.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.23 Antibiotics & Antimicrobials; 1.23.146 Antibiotic Resistance
Web Of Science research areas: Microbiology; Pharmacology & Pharmacy
ESI research areas: Pharmacology & Toxicology

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Title: 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
Creators: M L Monogue - Center for Anti-infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA
L M Abbo - Division of Infectious Diseases, Jackson Health System, Miami, Florida, USA
R Rosa - Division of Infectious Diseases, Jackson Health System, Miami, Florida, USA
J F Camargo - Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
O Martinez - Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA
R A Bonomo - Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio
D P Nicolau - Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA
Publication Details: Antimicrobial agents and chemotherapy, Vol.61(7)
Publisher: United States
Grant note: R01 AI100560 / NIAID NIH HHS R01 AI072219 / NIAID NIH HHS R01 AI063517 / NIAID NIH HHS I01 BX001974 / BLRD VA
Academic Unit: Miller School of Medicine; UMMG Department of Pathology; UMMG Dept of Medicine - Infectious Diseases
Language: English
Resource Type: Journal article
PMID: 28416558
PMCID: PMC5487677
Record Identifier: 991031576564602976