James A Karlowsky1,2, Sibylle H Lob1, Janet Raddatz3, Daryl D DePestel3, Katherine Young3,4, Mary R Motyl3,4, Daniel F Sahm1. 1. Department of Scientific Affairs, IHMA, Schaumburg, Illinois, USA. 2. Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 3. US Medical Affairs, Merck & Co., Inc., Kenilworth, New Jersey, USA. 4. Clinical Microbiology and Virology, Merck & Co., Inc., Kenilworth, New Jersey, USA.
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 < .05) in isolates collected in intensive care units (ICUs) than in non-ICUs and in respiratory tract isolates than in intraabdominal or urinary tract isolates. In addition, 82.4% of DTR and 92.1% of MDR Enterobacterales and 62.2% of DTR and 82.2% of MDR P. aeruginosa were imipenem/relebactam-susceptible, and 1.5% of DTR and 65.8% of MDR Enterobacterales and 67.5% of DTR and 84.0% of MDR P. aeruginosa were ceftolozane/tazobactam-susceptible. CONCLUSIONS: MDR phenotypes defined using the Magiorakos criteria may overcall treatment-limiting resistance in gram-negative bacilli. In the US, DTR Enterobacterales were infrequent, while MDR Enterobacterales isolates and DTR and MDR P. aeruginosa were common. Imipenem/relebactam (Enterobacterales, P. aeruginosa) and ceftolozane/tazobactam (P. aeruginosa) retained in vitro activity against most DTR and MDR isolates.
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 < .05) in isolates collected in intensive care units (ICUs) than in non-ICUs and in respiratory tract isolates than in intraabdominal or urinary tract isolates. In addition, 82.4% of DTR and 92.1% of MDR Enterobacterales and 62.2% of DTR and 82.2% of MDR P. aeruginosa were imipenem/relebactam-susceptible, and 1.5% of DTR and 65.8% of MDR Enterobacterales and 67.5% of DTR and 84.0% of MDR P. aeruginosa were ceftolozane/tazobactam-susceptible. CONCLUSIONS: MDR phenotypes defined using the Magiorakos criteria may overcall treatment-limiting resistance in gram-negative bacilli. In the US, DTR Enterobacterales were infrequent, while MDR Enterobacterales isolates and DTR and MDR P. aeruginosa were common. Imipenem/relebactam (Enterobacterales, P. aeruginosa) and ceftolozane/tazobactam (P. aeruginosa) retained in vitro activity against most DTR and MDR isolates.
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