Efficacy of aztreonam/avibactam against Stenotrophomonas maltophilia alone and in combination with tigecycline

Abstract

Background and Aims: Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen that threatens human and public health because of its widespread intrinsic and acquired antibiotic resistance. These bacteria become resistant to aztreonam by degrading it using the beta-lactamases. The aim of this study was to evaluate the effect of aztreonam/avibactam on aztreonam resistance in clinical strains of S. maltophilia and to assess the synergistic potential of aztreonam in combination with tigecycline. Methods: Minimum Inhibitory Concentrations (MICs) of aztreonam, aztreonam/avibactam, tigecycline, and doxycycline were determined using broth microdilution in sixty-six S. maltophilia isolates. Additionally, six isolates with the most common MICs of aztreonam/avibactam against the strains, 2 μg/ml and 4 μg/ml were selected from among the sixty-six tested strains, and the effectiveness of the combination of aztreonam/avibactam with tigecycline was determined using both the checkerboard test and the time-dependent killing method. Results: Aztreonam/avibactam restored aztreonam activity in 96.9% of resistant S. maltophilia isolates. Half of the isolates were susceptible to tigecycline, whereas all were susceptible to doxycycline. The combination of aztreonam/avibactam with tigecycline was found to have an additive effect against all isolates in the checkerboard experiment in which the activity of aztreonam/avibactam in combination with tigecycline was investigated against six isolates. In the time-dependent killing experiment, the combination exerted a synergistic effect against two isolates. Conclusion: Aztreonam/avibactam appears to be an important alternative for reversing aztreonam resistance in S. maltophilia. Additionally, tetracyclines, such as tigecycline and doxycycline, are highly effective against these bacteria. To confirm these promising findings, further in vitro, in vivo, and clinical studies are required.

Keywords

• Stenotrophomonas maltophilia
• Aztreonam/avibactam
• Tigecycline
• Combination

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