In Vitro Activity of β-Lactam Antimicrobial Agents in Combination with Aztreonam Tested Against Metallob-β-Lactamase-Producing Pseudomonas aeruginosa and Acinetobacter baumannii

Abstract

We evaluate the antimicrobial interactions between aztreonam and selected beta-lactams when tested against metallo-β-lactamase (MβL)-producing clinical strains. Ten Pseudomonsa aeruginosa strains, including nine MβL-producers (IMP- 1, -2, -13, -16, VIM-1, -2, -7, SPM-1 and GIM-1) and five Acinetobacter baumannii strains, including three MβL-producers (IMP-1 and -2) were tested using time kill/bactericidal activity methods. Aztreonam at 4, 8 and 16 mg/L was combined with four other β-lactam antimicrobials (cefepime, ceftazidime, meropenem and piperacillin/tazobactam or ampicillin/sulbactam), each tested at the recognized susceptible breakpoint concentration. Enhanced activity (synergism or additive effect) was observed with four P. aeruginosa strains (IMP-16, VIM-2, SPM-1 and GIM-1 containing strains) and four A. baumannii strains, while antagonism was observed with two P. aeruginosa (IMP-16 and SPM-1-producing strains) and one A. baumannii (non-MβL) strain. All other strains showed indifferent interaction (variation of ± 1 log₁₀ CFU/ml) with any combination evaluated.

Keywords:

• Metallo-β-lactamases
• carbapanem-resistance
• aztreonam
• Pseudomonas aeruginosa
• Acinetobacter baumanni