Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?
Steven H. Marshall,Andrea M. Hujer,Andrea M. Hujer,Laura J. Rojas,Laura J. Rojas,Krisztina M. Papp-Wallace,Romney M. Humphries,Brad Spellberg,Kristine M. Hujer,Kristine M. Hujer,Emma K. Marshall,Susan D. Rudin,Susan D. Rudin,Federico Perez,Federico Perez,Brigid Wilson,Ronald B. Wasserman,Linda Chikowski,David L. Paterson,Alejandro J. Vila,David van Duin,Barry N. Kreiswirth,Henry F. Chambers,Vance G. Fowler,Michael R. Jacobs,Mark Pulse,William J. Weiss,Robert A. Bonomo +27 more
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TLDR
In vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated, and the data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteria.Abstract:
Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log10-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log10-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.read more
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Mechanistic Insights to Combating NDM- and CTX-M-Coproducing Klebsiella pneumoniae by Targeting Cell Wall Synthesis and Outer Membrane Integrity
Nicholas M. Smith,Katie Rose Boissonneault,Liang Cheng,Vidmantas Petraitis,Ruta Petraitiene,Xun Tao,Jieqiang Zhou,Yinzhi Lang,Povilas Kavaliauskas,Zackery P Bulman,Patricia N. Holden,Raymond Cha,Jürgen B. Bulitta,Barry N. Kreiswirth,Thomas J. Walsh,Brian T. Tsuji +15 more
TL;DR: The combination of aztreonam and ceftazidime-avibactam with and without polymyxin B against a clinical Klebsiella pneumoniae isolate producing NDM-1 and CTX-M by use of the hollow fiber infection model (HFIM) improved bacterial killing effects, reduced lung inflammation, suppressed resistance amplification, and limited virulence changes.
Journal ArticleDOI
A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-β-Lactamase Producing Enterobacterales
Zhou Liu,Xiu-ju Hang,Tao Yang,Wenwen Chu,Zhen Gong,Yanyan Liu,Yuanyuan Dai,Min Yang,Jiabin Li,Qiang Zhou +9 more
TL;DR: In this paper , a disk stacking plus micro-elution (DSE) method was used to detect the synergistic effect between aztreonam and ceftazidime/avibactam (CZA) against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).
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Emergence of NDM-producing Pseudomonas aeruginosa among hospitalized patients and impact on antimicrobial therapy during the coronavirus disease 2019 (COVID-19) pandemic.
Journal ArticleDOI
A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-β-Lactamase Producing Enterobacterales
TL;DR: In this article , a disk stacking plus micro-elution (DSE) method was used to detect the synergistic effect between aztreonam (ATM) and ceftazidime/avibactam (CZA) against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).
Book ChapterDOI
Bacteremia in Neutropenic Patients
TL;DR: Neutropenic patients are predisposed to polymicrobial infections that may cause substantial morbidity and mortality and the use of prophylactic antibiotics can lead to breakthrough MDR bacteria limiting antimicrobial options for therapy.
References
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Journal Article
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Jesse T. Jacob,Eili Y. Klein,Ramanan Laxminarayan,Zintars G. Beldavs,Ruth Lynfield,Alexander J. Kallen,Philip Ricks,Jonathan R. Edwards,Arjun Srinivasan,Scott K. Fridkin,J. Kamile Rasheed,David Lonsway,Sandie Bulens,Rosa Herrera,L. Clifford McDonald,Jean B. Patel,Brandi Limbago,Michael Bell,Denise M. Cardo +18 more
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Journal ArticleDOI
Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Second-generation β-Lactam/β-Lactamase Inhibitor Combinations.
David van Duin,Robert A. Bonomo +1 more
TL;DR: Ceftolozane/tazobactam and ceftazidime/avibactam are 2 new second-generation cephalosporin/β-lactamase inhibitor combinations and may prove useful in the treatment of MDR GNB infections.
Journal ArticleDOI
New Delhi Metallo-β-Lactamase-Producing Carbapenem-Resistant Escherichia coli Associated With Exposure to Duodenoscopes
Lauren Epstein,Jennifer C. Hunter,M. Allison Arwady,M. Allison Arwady,Victoria Tsai,Linda Stein,Marguerite Gribogiannis,Mabel Frias,Alice Guh,Alison S. Laufer,Stephanie R. Black,Massimo Pacilli,Heather Moulton-Meissner,J. Kamile Rasheed,Johannetsy J. Avillan,Brandon Kitchel,Brandi Limbago,Duncan MacCannell,David Lonsway,Judith Noble-Wang,Judith Conway,Craig Conover,Michael O. Vernon,Alexander J. Kallen +23 more
TL;DR: Exposure to duodenoscopes with bacterial contamination was associated with apparent transmission of NDM-producing E coli among patients at 1 hospital and facilities should be aware of the potential for transmission of bacteria including antimicrobial-resistant organisms via this route.
Journal ArticleDOI
New β-Lactamase Inhibitors: a Therapeutic Renaissance in an MDR World
TL;DR: This “renaissance” of β-lactamase inhibitors offers new hope in a world plagued by multidrug-resistant (MDR) Gram-negative bacteria.
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