in vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam Against Resistant Gram-Negative Bacilli [PublishAheadOfPrint]

Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empiric therapy as mechanistic-based (i.e., molecular) rapid diagnostics are adopted. Here, we determined the MICs of the novel β-lactam/β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 283 multidrug resistant isolates of Gram-negative bacilli. For isolates harboring bla_KPC (n=111), 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 bla_CTX-M (n=48), the MIC₅₀/MIC₉₀ of ceftolozane-tazobactam was 0.5/16 μg/ml (83% susceptible). For isolates harboring bla_CMY-2 (n=17), the MIC₅₀/MIC₉₀ of ceftolozane-tazobactam was 4/8 μg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae, and is an encouraging addition to the present antibiotic repertoire.

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