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Clinical Therapeutics

Is Ceftazidime/Avibactam an Option for Serious Infections Due to Extended-Spectrum-β-Lactamase- and AmpC-Producing Enterobacterales?: a Systematic Review and Meta-analysis

Burcu Isler, Yukiko Ezure, Jose Luis García-Fogeda Romero, Patrick Harris, Adam G. Stewart, David L. Paterson
Burcu Isler
aUniversity of Queensland, Faculty of Medicine, UQ Center for Clinical Research, Brisbane, Australia
dInfectious Diseases Unit, Royal Brisbane and Women’s Hospital, Brisbane, Australia
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  • ORCID record for Burcu Isler
Yukiko Ezure
aUniversity of Queensland, Faculty of Medicine, UQ Center for Clinical Research, Brisbane, Australia
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Jose Luis García-Fogeda Romero
bHospital Universitario Clínico San Cecilio, Granada, Spain
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Patrick Harris
aUniversity of Queensland, Faculty of Medicine, UQ Center for Clinical Research, Brisbane, Australia
cCentral Microbiology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia
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Adam G. Stewart
aUniversity of Queensland, Faculty of Medicine, UQ Center for Clinical Research, Brisbane, Australia
dInfectious Diseases Unit, Royal Brisbane and Women’s Hospital, Brisbane, Australia
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David L. Paterson
aUniversity of Queensland, Faculty of Medicine, UQ Center for Clinical Research, Brisbane, Australia
dInfectious Diseases Unit, Royal Brisbane and Women’s Hospital, Brisbane, Australia
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DOI: 10.1128/AAC.01052-20
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ABSTRACT

Carbapenem-sparing regimens are needed for the treatment of infections caused by extended-spectrum-β-lactamase (ESBL)- and AmpC-producing members of the Enterobacterales. We sought to compare the clinical efficacy of ceftazidime/avibactam and carbapenems against ESBL- and AmpC-producing Enterobacterales species. A systematic review and meta-analysis of randomized controlled trials comparing ceftazidime/avibactam with carbapenems for the treatment of ESBL- and AmpC-producing Enterobacterales was conducted. Five randomized controlled trials (RCTs) with ESBL- and AmpC-specific outcome data were compiled. Of the 246 patients infected with an ESBL-producing microorganism in the ceftazidime/avibactam arm, 224 (91%) had a clinical response at test of cure (TOC), versus 240 of 271 (89%) patients in the carbapenem arm (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97 to 1.08; P = 0.45; I2 = 0%). Clinical response rates for AmpC producers in the ceftazidime/avibactam and carbapenem arms were 32/40 (80%) and 37/42 (88%), respectively (RR, 0.91; 95% CI, 0.76 to 1.10; P = 0.35; I2 = 0%). Microbiological response and mortality rates were not reported specifically for ESBL/AmpC producers. Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species, and the data are too limited to provide any conclusive recommendations for the AmpC producers. Care should be taken before extrapolating this to severe infections, given that the representation of this population in the reviewed studies was negligible. Ceftazidime/avibactam is a costly drug active against carbapenem-resistant microorganisms and should be used judiciously to preserve its activity against them.

FOOTNOTES

    • Received 26 May 2020.
    • Returned for modification 13 July 2020.
    • Accepted 17 September 2020.
    • Accepted manuscript posted online 12 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Is Ceftazidime/Avibactam an Option for Serious Infections Due to Extended-Spectrum-β-Lactamase- and AmpC-Producing Enterobacterales?: a Systematic Review and Meta-analysis
Burcu Isler, Yukiko Ezure, Jose Luis García-Fogeda Romero, Patrick Harris, Adam G. Stewart, David L. Paterson
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01052-20; DOI: 10.1128/AAC.01052-20

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Is Ceftazidime/Avibactam an Option for Serious Infections Due to Extended-Spectrum-β-Lactamase- and AmpC-Producing Enterobacterales?: a Systematic Review and Meta-analysis
Burcu Isler, Yukiko Ezure, Jose Luis García-Fogeda Romero, Patrick Harris, Adam G. Stewart, David L. Paterson
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01052-20; DOI: 10.1128/AAC.01052-20
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KEYWORDS

AmpC
ESBL
carbapenem sparing
ceftazidime/avibactam

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