Evaluation of the antimicrobial and antibiofilm activities of aztreonam-avibactam against the Burkholderia cepacia complex

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Abstract Beta-lactamase production by Burkholderia cepacia complex (Bcc) leads to beta-lactam resistance and worsens patient prognosis. This study describes the activity of aztreonam, a monobactam, in combination with avibactam, a beta-lactamase inhibitor, against Bcc isolates. Broth microdilution and time-kill assays were conducted for planktonic cells. Additionally, broth microdilution was repeated using media supplemented with 5% and 10% bovine serum albumin to evaluate its impact on MICs. The effects of aztreonam/avibactam on biofilm formation and the metabolic activity of mature biofilms were determined in all biofilm-positive isolates. Additionally, the biofilm matrix of selected strains was analyzed in terms of viable bacterial count, total protein content, and extracellular DNA (eDNA) concentration, and the biofilm architecture was visualized using scanning electron microscopy (SEM). All the strains were determined to be resistant to aztreonam, and the MIC 50 and MIC 90 of aztreonam/avibactam were found to be 4/4 mg/L and 8/4 mg/L, respectively. Aztreonam/avibactam exhibited activity against planktonic form of Bcc, and decreased the aztreonam MIC values. Serum albumin activity was insignificant at low doses but affected the MIC more at high doses. Moderate to strong biofilm formation was observed in 25 of the 29 isolates, and aztreonam/avibactam showed strain- and concentration-dependent activity against Bcc biofilm formation and mature biofilms. The combination also reduced biofilm matrix components such as total protein and eDNA, and some strain-specific effects were observed at sub-inhibitory concentrations. These findings support the potential use of aztreonam/avibactam as a therapeutic option against Bcc infections by targeting both planktonic bacteria and key components of biofilm matrix.

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