Activity of novel β-lactam/β-lactamase inhibitor combinations against serine carbapenemase-producing carbapenem-resistant <i>Pseudomonas aeruginosa</i>
Su Young Lee, Christian M Gill, David P. Nicolau, ERACE-PA Global Study Group, Elif Aktaş, Wadha Alfouzan, Lori Bourassa, Adrian Brink, Carey‐Ann D. Burnham, Rafael Cantón, Yehuda Carmeli, Marco Falcone, Carlos Roberto Veiga Kiffer, Anna Marchese, Octavio Martínez, Spyros Pournaras, Michael J. Satlin, Harald Seifert, Abrar K. Thabit, Kenneth S. Thomson, María Virginia Villegas, Julia Wille, Thais Teles Freitas Rezende, Zuhal Kalaycı Çekin, Gülşah Malkoçoğlu, Desirae Gijón, Layla Abdullah Tarakmeh, Chun Yat Chu, Christoffel J. Opperman, Hafsah Deepa Tootla, Clinton Moodley, Jennifer Coetzee, Sophia Vourli, George Dimopoulos, Dalya Attallah, Giusy Tiseo, Alessandro Leonildi, Cesira Giordano, Simona Barnini, Francesco Menichetti, Vincenzo Di Pilato, Giulia Codda, Antonio Vena, Daniele Roberto Giacobbe, Lars F. Westblade, Armando Cardona, Lauren M. Curtis, Ferric C. Fang, Gina K. Thomson
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.