Aztreonam plus Clavulanate, Tazobactam, or Avibactam for Treatment of Infections Caused by Metallo-β-Lactamase-Producing Gram-Negative Bacteria.

Abstract

Metallo-β-lactamase (MBL)-producing Gram-negative bacteria are often extremely resistant, leading to a real therapeutic dead end. Here, we evaluated the in vitro and in vivo efficacy of aztreonam in combination with ceftazidime-avibactam, ceftolozane-tazobactam, or amoxicillin-clavulanate for the treatment of infections caused by MBL-producing Enterobacteriaceae, MBL-producing Pseudomonas aeruginosa, and extremely drug-resistant Stenotrophomonas maltophilia First, we report two clinical cases, namely, a urinary tract infection caused by an NDM-5-producing Escherichia coli isolate and a pulmonary infection caused by a S. maltophilia isolate efficiently treated with the association of aztreonam-ceftazidime-avibactam and aztreonam-amoxicillin-clavulanate, respectively. Then, a total of 50 MBL-producing Enterobacteriaceae isolates, 3 MBL-producing P. aeruginosa isolates, and 5 extremely drug-resistant S. maltophilia isolates were used to test aztreonam susceptibility in combination with ceftolozane-tazobactam, ceftazidime-avibactam, or amoxicillin-clavulanate. The Etest strip superposition method was used to determine the MICs of the aztreonam/inhibitor combinations. According to CLSI breakpoints, aztreonam susceptibility was fully restored for 86%, 20%, and 50% of the MBL-producing Enterobacteriaceae isolates when combined with ceftazidime-avibactam, ceftolozane-tazobactam, and amoxicillin-clavulanate, respectively. In P. aeruginosa, the aztreonam-ceftazidime-avibactam combination was the most potent, even though the reduction in MICs was at most 2-fold. With the 5 S. maltophilia isolates, aztreonam-ceftazidime-avibactam and aztreonam-amoxicillin-clavulanate were found to be equal (100% susceptibility). Overall, aztreonam-ceftazidime-avibactam was the most potent combination to treat infections caused by MBL producers compared with aztreonam-amoxicillin-clavulanate and aztreonam-ceftolozane-tazobactam. However, in many cases aztreonam-amoxicillin-clavulanate was found to be as efficient as aztreonam-ceftazidime-avibactam, offering the main advantage to be markedly cheaper. We also confirmed the validity of Etest superpositions as a very simple method to determine MICs of aztreonam combinations.

• Authors: Cécile Emeraud, Lelia Escaut, Athénaïs Boucly, Nicolas Fortineau, Rémy A Bonnin, Thierry Naas, Laurent Dortet
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 63 Issue 5 (05 2019) ISSN: 1098-6596 [Electronic] United States
• PMID: 30858212 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Microbiology.

Chemical References

• Anti-Bacterial Agents
• Azabicyclo Compounds
• Clavulanic Acid
• avibactam
• beta-Lactamases
• Aztreonam
• Tazobactam

Topics

• Aged
• Anti-Bacterial Agents (therapeutic use)
• Azabicyclo Compounds (therapeutic use)
• Aztreonam (therapeutic use)
• Clavulanic Acid (therapeutic use)
• Gram-Negative Bacteria (drug effects, enzymology)
• Humans
• Male
• Microbial Sensitivity Tests
• Tazobactam (therapeutic use)
• beta-Lactamases (metabolism)