Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections

Antibiotics

Stefano Di Bella¹  Carola Mauri²  Francesco Luzzaro²  Luigi Principe³  Simona Fioriti⁴  Oscar Cirioni⁴  Gianluca Morroni⁴  Gloria D’Achille⁴  Marina Mingoia⁴  Cristina Lagatolla⁵  Raffaela Bressan⁵  Francesco Comandatore⁶  Aurora Piazza⁷  Roberta Migliavacca⁷ 

[1] Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, 34129 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;Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60126 Ancona, Italy;Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;Department of Romeo and Enrica Invernizzi Pediatric Research Center, Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, 20157 Milan, Italy;Unit of Microbiology and Clinical Microbiology, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;

关键词: aztreonam;    β-lactamases inhibitors;    synergism;    MBLs;    ESBL;    complicated infection;   

DOI  :  10.3390/antibiotics10111341

来源: DOAJ

【 摘 要 】

Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six Enterobacterales and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time–kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. E. meningoseptica and C. indologenes were not inhibited by any ATM–BLI combination. ATM–BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.

【 授权许可】

Unknown