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
Gianluca Morroni,
Raffaela Bressan,
Simona Fioriti,
Gloria D’Achille,
Marina Mingoia,
Oscar Cirioni,
Stefano Di Bella,
Aurora Piazza,
Francesco Comandatore,
Carola Mauri,
Roberta Migliavacca,
Francesco Luzzaro,
Luigi Principe,
Cristina Lagatolla
Affiliations
Gianluca Morroni
Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60126 Ancona, Italy
Raffaela Bressan
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
Simona Fioriti
Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60126 Ancona, Italy
Gloria D’Achille
Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60126 Ancona, Italy
Marina Mingoia
Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60126 Ancona, Italy
Oscar Cirioni
Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60126 Ancona, Italy
Stefano Di Bella
Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, 34129 Trieste, Italy
Aurora Piazza
Unit of Microbiology and Clinical Microbiology, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
Francesco Comandatore
Department of Romeo and Enrica Invernizzi Pediatric Research Center, Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, 20157 Milan, Italy
Carola Mauri
Clinical Microbiology and Virology Unit, A. Manzoni Hospital, 23900 Lecco, Italy
Roberta Migliavacca
Unit of Microbiology and Clinical Microbiology, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
Francesco Luzzaro
Clinical Microbiology and Virology Unit, A. Manzoni Hospital, 23900 Lecco, Italy
Luigi Principe
Clinical Pathology and Microbiology Unit, S. Giovanni di Dio Hospital, 88900 Crotone, Italy
Cristina Lagatolla
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
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.
