In VitroActivity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program).
Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, includingKlebsiella pneumoniaecarbapenemase (KPC), and is currently in clinical development in combination with imipenem-cilastatin. Using Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution methodology, we evaluated thein vitroactivities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against Gram-negative ESKAPE pathogens (includingKlebsiella pneumoniae,n= 689;Acinetobacter baumannii,n= 72;Pseudomonas aeruginosa,n= 845; andEnterobacterspp.,n= 399) submitted by 21 clinical laboratories in the United States in 2015 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 μg/ml in combination with doubling dilutions of imipenem. Imipenem-relebactam MICs were interpreted using CLSI imipenem breakpoints. The respective rates of susceptibility to imipenem-relebactam and imipenem were 94.2% (796/845) and 70.3% (594/845) forP. aeruginosa, 99.0% (682/689) and 96.1% (662/689) forK. pneumoniae, and 100% (399/399) and 98.0% (391/399) forEnterobacterspp. Relebactam restored imipenem susceptibility to 80.5% (202/251), 74.1% (20/27), and 100% (8/8) of isolates of imipenem-nonsusceptibleP. aeruginosa,K. pneumoniae, andEnterobacterspp. Relebactam did not increase the number of isolates ofAcinetobacterspp. susceptible to imipenem, and the rates of resistance to all of the agents tested against this pathogen were >30%. Further development of imipenem-relebactam is warranted given the demonstrated ability of relebactam to restore the activity of imipenem against current clinical isolates ofEnterobacteriaceaeandP. aeruginosathat are nonsusceptible to carbapenems and its potential as a therapy for treating patients with antimicrobial-resistant Gram-negative infections.
International Health Management Associates, Inc., Schaumburg, Illinois, USA shlob@ihmainc.com.
Sibylle H
SH
Lob
International Health Management Associates, Inc., Schaumburg, Illinois, USA.
Meredith A
MA
Hackel
International Health Management Associates, Inc., Schaumburg, Illinois, USA.
Krystyna M
KM
Kazmierczak
Merck & Co., Inc., Kenilworth, New Jersey, USA.
Katherine
K
Young
Merck & Co., Inc., Kenilworth, New Jersey, USA.
Mary R
MR
Motyl
Department of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
James A
JA
Karlowsky
International Health Management Associates, Inc., Schaumburg, Illinois, USA.
Daniel F
DF
Sahm
D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D015378:Imipenem / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D015378:Imipenem; C568736:relebactam
ESKAPE pathogens; SMART; imipenem; relebactam; surveillance