In vitro activity of imipenem-relebactam and ceftolozane-tazobactam against resistant gram-negative bacilli

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 -lactam–-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 bla_KPC (n 110), the addition of relebactam to imipenem lowered the MIC₅₀/MIC₉₀ from 16/ 128 g/ml for imipenem alone to 0.25/1 g/ml. For isolates harboring bla_CTX-M (n 48), the MIC₅₀/MIC₉₀ of ceftolozane-tazobactam were 0.5/16 g/ml (83% susceptible). For isolates harboring bla_CMY-2 (n 17), the MIC₅₀/MIC₉₀ of ceftolozane-tazobactam were 4/8 g/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.