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Review
. 2021 Aug 20;10(8):1012.
doi: 10.3390/antibiotics10081012.

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

Carola Mauri  1 , Alberto Enrico Maraolo  2 , Stefano Di Bella  3 , Francesco Luzzaro  1 , Luigi Principe  4
Affiliations
Review

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

Carola Mauri et al. Antibiotics (Basel). .

Abstract

Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials.

Keywords: Enterobacterales; Pseudomonas; Stenotrophomonas; antibiotic combination; avibactam; aztreonam; ceftazidime/avibactam; last resource antibiotic; metallo-β-lactamase; old antibiotic.

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Conflict of interest statement

All the authors declare no conflict of interest.

Figures

Figure 1
Figure 1
β-lactam antibiotic targets of MBL enzymatic activity.
Figure 2
Figure 2
Literature search strategy.
Figure 3
Figure 3
Forest plot of the 30-day mortality odds ratio between CZA plus ATM and other regimens against infections by MBL-producing strains. ATM, aztreonam; CZA, ceftazidime/avibactam; OAA, other active agent.
See this image and copyright information in PMC

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