title: Invitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015 - Results from the SMART global surveillance program.
abstract: The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n=853) and Pseudomonas aeruginosa (n=598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for non-Proteeae Enterobacteriaceae and 93.1% and 68.1% for P. aeruginosa. Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible non-Proteeae Enterobacteriaceae isolates (n=72) and P. aeruginosa (n=191), respectively. Further development of imipenem-relebactam as therapy for lower respiratory tract infections is warranted given relebactam's ability to restore activity to imipenem against non-susceptible non-Proteeae Enterobacteriaceae and P. aeruginosa.
authors.affiliation: International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA. Electronic address: shlob@ihmainc.com.
authors.forename: Sibylle H
authors.initials: SH
authors.lastname: Lob
authors.affiliation: International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA. Electronic address: mhackel@ihmainc.com.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Hackel
authors.affiliation: International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA. Electronic address: kkazmierczak@ihmainc.com.
authors.forename: Krystyna M
authors.initials: KM
authors.lastname: Kazmierczak
authors.affiliation: International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA; Department of Medical Microbiology, College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada. Electronic address: dhoban@dsmanitoba.ca.
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: katherine_young@merck.com.
authors.forename: Katherine
authors.initials: K
authors.lastname: Young
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: mary_motyl@merck.com.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Motyl
authors.affiliation: Department of Medical Microbiology, College of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada. Electronic address: JKarlowsky@dsmanitoba.ca.
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
authors.affiliation: International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL, 60173, USA. Electronic address: dsahm@ihmainc.com.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D014481:United States; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D065093:beta-Lactamase Inhibitors; D015378:Imipenem; C568736:relebactam
keywords: Imipenem; Relebactam; Respiratory; SMART; Surveillance