<i>In Vitro</i> Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli

Abstract

Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel β-lactam-β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring <i>bla</i>_KPC (<i>n</i> = 110), the addition of relebactam to imipenem lowered the MIC₅₀/MIC₉₀ from 16/>128 μg/ml for imipenem alone to 0.25/1 μg/ml. For isolates harboring <i>bla</i>_CTX-M (<i>n</i> = 48), the MIC₅₀/MIC₉₀ of ceftolozane-tazobactam were 0.5/16 μg/ml (83% susceptible). For isolates harboring <i>bla</i>_CMY-2 (<i>n</i> = 17), the MIC₅₀/MIC₉₀ of ceftolozane-tazobactam were 4/8 μg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) <i>Enterobacteriaceae</i> and is an encouraging addition to the present antibiotic repertoire.