In Vitro Activity of Imipenem/Relebactam and Ceftolozane/Tazobactam Against Clinical Isolates of Gram-negative Bacilli With Difficult-to-Treat Resistance and Multidrug-resistant Phenotypes—Study for Monitoring Antimicrobial Resistance Trends, United States 2015–2017

Abstract Background Multidrug-resistant (MDR) bacteria are frequently defined using the criteria established by Magiorakos et al [Clin Microbiol Infect 2012;18:268–81]. Difficult-to-treat resistance (DTR) [Kadri et al, Clin Infect Dis 2018;67:1803–14] is a novel approach to defining resistance in gram-negative bacilli focusing on treatment-limiting resistance to first-line agents (all β-lactams and fluoroquinolones). Methods Clinical and Laboratory Standards Institute–defined broth microdilution minimum inhibitory concentrations (MICs) were determined for imipenem/relebactam, ceftolozane/tazobactam, and comparators against respiratory, intraabdominal, and urinary isolates of Enterobacterales (n = 10 516) and Pseudomonas aeruginosa (n = 2732) collected in 26 US hospitals in 2015–2017. Results Among all Enterobacterales, 1.0% of isolates were DTR and 15.6% were MDR; 8.4% of P. aeruginosa isolates were DTR and 32.4% were MDR. MDR rates for Enterobacterales and DTR and MDR rates for P. aeruginosa were significantly higher (P