TY - JOUR
T1 - In vitro activity of imipenem-relebactam and ceftolozane-tazobactam against resistant gram-negative bacilli
AU - Schmidt-Malan, Suzannah M.
AU - Mishra, Avisya J.
AU - Mushtaq, Ammara
AU - Brinkman, Cassandra L.
AU - Patela, Robin
N1 - Funding Information:
We acknowledge Kerryl E. Greenwood-Quaintance, M.S., Melissa J. Karau, Audrey N. Schuetz, Peggy C. Kohner, Nicolynn C. Cole, and Scott A. Cunningham for technical advice. We thank Mayo Clinic Clinical Bacteriology Lab, Donna J. Hata from Mayo Clinic in Jacksonville, FL, James R. Johnson from the VA Medical Center in Minneapolis, MN, Hennepin County Medical Center in Minneapolis, MN, Mary K. Hayden and Karen Lolans from Rush University Medical Center, and Paul C. Schreckenberger from Loyola, both in Chicago, IL, Patricia J. Simner with the Canadian Antimicrobial Resistance Alliance and the CANWARD study, George G. Zhanel and Daryl J. Hoban from the University of Manitoba, Partha Pratim De, Sanjay Ryan Menon, and Shawn Vasoo from Tan Tock Seng Hospital, and Koh Tse Hsien from Singapore General Hospital in Singapore for isolates included in this study.
Funding Information:
Research reported in this publication was supported by Merck & Co.
Publisher Copyright:
Copyright © 2018 American Society for Microbiology. All Rights Reserved.
PY - 2018/8
Y1 - 2018/8
N2 - 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 blaKPC (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 blaCTX-M (n 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 g/ml (83% susceptible). For isolates harboring blaCMY-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.
AB - 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 blaKPC (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 blaCTX-M (n 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 g/ml (83% susceptible). For isolates harboring blaCMY-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.
KW - Antimicrobial resistance
KW - Gram-negative bacilli
UR - http://www.scopus.com/inward/record.url?scp=85052017885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052017885&partnerID=8YFLogxK
U2 - 10.1128/AAC.00533-18
DO - 10.1128/AAC.00533-18
M3 - Article
C2 - 29760145
AN - SCOPUS:85052017885
VL - 62
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 8
M1 - e00533-18
ER -