Activity of novel β-lactam/β-lactamase inhibitor combinations against serine carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
Year: 2023
Type: article
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.
DOI: 10.1093/jac/dkad225
Authors: Su Young Lee, Christian M Gill, David P Nicolau, ERACE-PA Global Study Group, Elif Aktas, Wadha Alfouzan, Lori Bourassa, Adrian Brink, Carey-Ann D Burnham, Rafael Canton, Yehuda Carmeli, Marco Falcone, Carlos Kiffer, Anna Marchese, Octavio Martinez, Spyros Pournaras, Michael Satlin, Harald Seifert, Abrar K Thabit, Kenneth S Thomson, Maria Virginia Villegas, Julia Wille, Thais Teles Freitas Rezende, Zuhal Cekin, Gulsah Malkocoglu, Desirae Gijón, Layla Abdullah Tarakmeh, Chun Yat Chu, Christoffel Johannes Opperman, Hafsah Deepa Tootla, Clinton Moodley, Jennifer Coetzee, Sophia Vourli, George Dimopoulos, Dalya M Attallah, Giusy Tiseo, Alessandro Leonildi, Cesira Giordano, Simona Barnini, Francesco Menichetti, Vincenzo Di Pilato, Giulia Codda, Antonio Vena, Daniele Roberto Giacobbe, Lars Westblade, Armando Cardona, Lauren Curtis, Ferric Fang, Gina Thomson
Institutions: West Coast University, Hartford Hospital
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,268
OpenAlex ID: W4387651563