Activity of novel β-lactam/β-lactamase inhibitor combinations against serine carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
Author:
Lee Su Young1ORCID, Gill Christian M2ORCID, Nicolau David P23ORCID, Aktas Elif, Alfouzan Wadha, Bourassa Lori, Brink Adrian, Burnham Carey-Ann D, Canton Rafael, Carmeli Yehuda, Falcone Marco, Kiffer Carlos, Marchese Anna, Martinez Octavio, Pournaras Spyros, Satlin Michael, Seifert Harald, Thabit Abrar K, Thomson Kenneth S, Villegas Maria Virginia, Wille Julia, Rezende Thais Teles Freitas, Cekin Zuhal, Malkocoglu Gulsah, Gijón Desirae, Tarakmeh Layla Abdullah, Chu Chun Yat, Opperman Christoffel Johannes, Tootla Hafsah Deepa, Moodley Clinton, Coetzee Jennifer, Vourli Sophia, Dimopoulos George, Attallah Dalya M, Tiseo Giusy, Leonildi Alessandro, Giordano Cesira, Barnini Simona, Menichetti Francesco, Di Pilato Vincenzo, Codda Giulia, Vena Antonio, Giacobbe Daniele Roberto, Westblade Lars, Cardona Armando, Curtis Lauren, Fang Ferric, Thomson Gina,
Affiliation:
1. School of Pharmacy, West Coast University , 590 N. Vermont Ave, Los Angeles, CA 90004 , USA 2. Center for Anti-Infective Research & Development, Hartford Hospital , 80 Seymour Street, Hartford, CT 06102 , USA 3. Division of Infectious Diseases, Hartford Hospital , Hartford, CT , USA
Abstract
Abstract
Background
Antimicrobial resistance in Pseudomonas aeruginosa is complex and multifaceted. While the novel β-lactamase inhibitors (BLIs) avibactam, relebactam and vaborbactam inhibit serine-based β-lactamases, the comparative potency of the novel β-lactam (BL)/BLI combinations against serine carbapenemase-producing P. aeruginosa is unknown.
Objectives
To compare the in vitro activity of ceftazidime/avibactam, ceftazidime, imipenem/relebactam, imipenem, meropenem/vaborbactam and meropenem against serine β-lactamase-producing P. aeruginosa.
Methods
Carbapenem-resistant P. aeruginosa were collated through the Enhancing Rational Antimicrobials against Carbapenem-resistant P. aeruginosa (ERACE-PA) Global Surveillance. Isolates positive for serine-based carbapenemases were assessed. MICs were determined by broth microdilution to each novel BL/BLI and BL alone.
Results
GES was the most common carbapenemase identified (n = 59) followed by KPC (n = 8). Ceftazidime/avibactam had MIC50/MIC90 values of 4/8 mg/L and 91% of isolates were susceptible. Conversely, ceftazidime alone was active against only 3% of isolates. The MIC50/MIC90 of imipenem/relebactam were 16/>16 mg/L and 13% of all isolates were defined as susceptible. Of the KPC-producing isolates, 38% were susceptible to imipenem/relebactam, compared with 0% to imipenem. The meropenem/vaborbactam MIC50/MIC90 were >16/>16 mg/L, and 6% of isolates were susceptible, which was similar to meropenem alone (MIC50/90, >8/>8 mg/L; 3% susceptible) suggesting the addition of vaborbactam cannot overcome co-expressed, non-enzymatic resistance mechanisms.
Conclusions
Among the novel BL/BLIs, ceftazidime/avibactam displayed better in vitro activity and thus is a rational treatment option for serine carbapenemase-harbouring P. aeruginosa. While imipenem/relebactam displayed some activity, particularly against isolates with blaKPC, meropenem/vaborbactam exhibited poor activity, with MICs similar to meropenem alone.
Funder
Center for Anti-Infective Research
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)
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