Susceptibility of OXA-48-producing Enterobacterales to imipenem/relebactam, meropenem/vaborbactam and ceftazidime/avibactam

• Published in: International journal of antimicrobial agents Vol. 60; no. 4; p. 106660
• Main Authors: Bonnin, Rémy A., Bernabeu, Sandrine, Emeraud, Cécile, Creton, Elodie, Vanparis, Océane, Naas, Thierry, Jousset, Agnès B., Dortet, Laurent
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2022
• Subjects: antibiotic resistance genes; beta-lactamase; Carbapenemase; ceftazidime; Ceftolozane/tazobactam; DBO; imipenem; Infectious Disease; meropenem; β-Lactamase; β-Lactamase inhibitor; DBO; Carbapenemase; Ceftolozane/tazobactam; β-Lactamase; β-Lactamase inhibitor
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2022.106660

•Susceptibility of a large collection of OXA-48-like-producing Enterobacterales to relebactam and vaborbactam.•Susceptibility rate was 75.7% to imipenem whereas it was 81.3% for imipenem/relebactam combination.•95.1% of total isolates were susceptible to meropenem/vaborbactam.•Susceptibility was 63.9% for meropenem at standard dosage but increased to 94% at high meropenem exposure.•Ceftazidime/avibactam remains the best therapeutic option with a susceptibility rate of 99.5%. Relebactam and vaborbactam are among the newest β-lactamase inhibitors marketed. They were originally designed to inhibit the Ambler class A carbapenemase KPC. In this study, susceptibility to imipenem/relebactam and meropenem/vaborbactam was determined against a collection of OXA-48-like-producing Enterobacterales (n = 407). The clonality and resistomes of the isolates were determined by whole-genome sequencing. Comparison was performed with other relevant antibiotics such as carbapenems alone, ceftazidime/avibactam and ceftolozane/tazobactam. Addition of relebactam and vaborbactam did not significantly modify the MIC50 and MIC90 values obtained for imipenem and meropenem alone. In contrast, addition of avibactam strongly restored ceftazidime susceptibility. According to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, MIC50/MIC90 values were at 2/4, 2/4, 2/8, 2/8, 32/>32 and 0.5/2 mg/L for imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, ceftazidime and ceftazidime/avibactam, respectively. No differences were observed depending on the species. This study highlights the lack of benefit in vitro for carbapenem/inhibitor combination compared with carbapenem alone against OXA-48-producing isolates as well as the difficulties in comparing molecules since carbapenem/inhibitor combinations were not developed with the same dosage of carbapenem.