Evaluating the antibacterial activity of ceftazidime/avibactam and aztreonam combinations against multidrug-resistant Stenotrophomonas maltophilia complex isolates in a hollow fibre infection model.

OBJECTIVES

Stenotrophomonas maltophilia is a multidrug-resistant Gram-negative pathogen causing serious infections in vulnerable populations, including individuals with cystic fibrosis and immunocompromised patients. We evaluated the activity of aztreonam (ATM) and ceftazidime/avibactam (CZA) against S. maltophilia complex (Smc) isolates.

METHODS

Interactions between ATM and CZA were evaluated using static concentration time-kill assays across 11 Smc isolates. A mechanism-based pharmacokinetic/pharmacodynamic model was developed to characterize bacterial killing dynamics and guide regimen selection. Selected regimens were then evaluated in the hollow fibre infection model under clinically relevant drug exposures. Emergence of resistance was assessed via population analysis profiles, and scanning electron microscopy visualized antibiotic-induced morphological changes.

RESULTS

Clinically relevant ATM + CZA exposures produced 31-74% reduction in area under the log-transformed bacterial count versus time curve across all Smc isolates in static concentration time-kill assays. In the hollow fibre infection model, ATM + CZA achieved ≥3-log10 CFU/mL reduction at 24 hours from an initial ∼7.5-log10 CFU/mL inoculum. This effect was sustained over 168 hours against GG6 strain. Against the non-GG6 strain, both continuous-infusion and standard-dosing regimens showed ∼2-log10 regrowth after 72 hours, but overall suppressed resistant subpopulations more effectively than trimethoprim/sulfamethoxazole.

CONCLUSIONS

Smc infections remain challenging because of intrinsic resistance mechanisms. These findings demonstrate the therapeutic potential of ATM + CZA, and support further evaluation using murine pneumonia and bacteraemia models of S. maltophilia.