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

Antibiotics

Stefano Di Bella¹  Carola Mauri²  Francesco Luzzaro²  Luigi Principe³  Alberto Enrico Maraolo⁴ 

[1] Clinical Department of Medical, Surgical and Health Science, Trieste University, 34128 Trieste, Italy;Clinical Microbiology and Virology Unit, “A. Manzoni” Hospital, 23900 Lecco, Italy;Clinical Pathology and Microbiology Unit, “S. Giovanni di Dio” Hospital, 88900 Crotone, Italy;First Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, 80131 Naples, Italy;

关键词: aztreonam;    avibactam;    ceftazidime/avibactam;    Enterobacterales;    Pseudomonas;    Stenotrophomonas;   

DOI  :  10.3390/antibiotics10081012

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown