Comparative in vitro activity of aztreonam–avibactam and aztreonam plus ceftazidime–avibactam against Stenotrophomonas maltophilia complex

Authors

• Ashlan J. Kunz Coyne, University of KentuckyFollow
• Rachel Gray, University of Kentucky
• Pavani Gonnabathula, University of Kentucky
• Elizabeth S. May, University of Kentucky
• Pranita A. Tamma, University of Pennsylvania
• Alex Do, University of Kentucky

Abstract

Members of the Stenotrophomonas maltophilia complex are intrinsically multidrug-resistant pathogens that disproportionately affect critically ill patients. Aztreonam–avibactam (ATM–AVI), FDA approved in 2025, combines aztreonam (ATM; stable to L1 β-lactamase) with avibactam (AVI; an L2 β-lactamase inhibitor). Aztreonam plus ceftazidime–avibactam (ATM–CZA) has been used as a surrogate for ATM–AVI, but direct comparisons between the two regimens are lacking. Twenty-three clinical S. maltophilia complex isolates underwent broth microdilution (BMD) testing for ATM, ceftazidime, ATM–AVI, and ATM–CZA, with gradient diffusion performed in parallel for ATM–AVI and ATM–CZA. Static 24-h time-kill assays at humanized steady-state Cmax concentrations evaluated bactericidal activity (≥3-log₁₀ reduction). Semi-mechanistic pharmacodynamic modeling characterized growth kill dynamics by resistance determinants (blaL1, blaL2, smeABC). ATM–CZA and ATM–AVI MIC_50/90 values for BMD were 1/2 and 2/4 mg/L, respectively. Both regimens were bactericidal against most isolates, with a mean paired difference of 0.09 log₁₀ colony-forming units (CFU)/mL (P = 0.83). Isolate-level variation was evident: ATM–AVI sustained killing, whereas ATM–CZA permitted regrowth for MD17639, −4.86 vs 0.13 log₁₀ CFU/mL, P = 0.019; MD17061, −2.61 vs 0.64 log₁₀ CFU/mL, P < 0.001). Conversely, ATM–CZA achieved greater reductions in MD17662 (−3.84 vs −1.95; P = 0.026), MD17047 (−4.27 vs −2.64; P = 0.021), and UK4 (−3.47 vs −1.58; P = 0.017). Modeling predicted ATM–AVI benefit in blaL2 and ATM–CZA benefit against blaL1 or smeABC dominant isolates, and diminished activity of both when mechanisms coexisted. ATM–AVI and ATM–CZA show comparable in vitro activity against S. maltophilia complex. Isolate-level heterogeneity warrants further study of genotype–phenotype relationships.

Document Type

Article

Publication Date

2026

Notes/Citation Information

Copyright © 2026 Kunz Coyne et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Digital Object Identifier (DOI)

https://doi.org/10.1128/aac.01456-25

Funding Information

PhRMA Foundation

Repository Citation

Coyne, Ashlan J. Kunz; Gray, Rachel; Gonnabathula, Pavani; May, Elizabeth S.; Tamma, Pranita A.; and Do, Alex, "Comparative in vitro activity of aztreonam–avibactam and aztreonam plus ceftazidime–avibactam against Stenotrophomonas maltophilia complex" (2026). Pharmacy Practice and Science Faculty Publications. 86.
https://uknowledge.uky.edu/pps_facpub/86