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  • Title: Activity of cefiderocol and synergy of novel β-lactam-β-lactamase inhibitor-based combinations against metallo-β-lactamase-producing gram-negative bacilli: insights from a two-year study (2019-2020).
    Author: Boattini M, Comini S, Bianco G, Iannaccone M, Casale R, Cavallo R, Costa C.
    Journal: J Chemother; 2023 May; 35(3):198-204. PubMed ID: 35731718.
    Abstract:
    This study was aimed at analyzing the prevalence of metallo-β-lactamase-producing Gram-negative bacilli (MBL-GNB) and evaluating both in vitro activity of cefiderocol and synergy of novel β-lactam-β-lactamase inhibitor-based combinations. Carbapenemase-producing Enterobacterales and meropenem-non-susceptible P. aeruginosa clinical strains were collected (2019-2020) and prevalence of MBL-producers investigated. Activity of cefiderocol was evaluated and synergistic effects of cefiderocol in combination with ceftazidime/avibactam vs aztreonam plus ceftazidime/avibactam vs meropenem/vaborbactam plus aztreonam were compared. Among carbapenemase-producing Enterobacterales, 87% (n = 307) produced KPC, 11.6% (n = 41) produced MBL, and 1.4% (n = 5) produced OXA-48-like. Among MBL-producing Enterobacterales, 78.1% (n = 32) and 21.9% (n = 9) were VIM- and NDM-producers, respectively. Among meropenem-non-susceptible P. aeruginosa, 1.9% (n = 8) produced VIM-type MBL. Cefiderocol resistance rate in VIM-producing Enterobacterales, VIM-producing P. aeruginosa, and NDM-producing Enterobacterales, was 6.2%, 12.5%, and 88.9%, respectively. Among MBL-producers tested, cefiderocol in combination with ceftazidime/avibactam showed a synergy rate of 20%, while for both aztreonam plus ceftazidime/avibactam and meropenem/vaborbactam plus aztreonam was 40%. Prevalence of MBL-producing Enterobacterales was remarkable. VIM-producing isolates were almost all susceptible to cefiderocol, while NDM-producers were often resistant. Meropenem/vaborbactam in combination with aztreonam showed similar synergistic activity to ceftazidime/avibactam plus aztreonam but the addition of aztreonam reduced MICs below the resistance breakpoint only for meropenem/vaborbactam.
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