Abstract Background The occurrences of S. maltophilia and B. cepacia infections, mainly pneumonia, have increased continuously in the last few years. We evaluated the in vitro activities of aztreonam-avibactam (ATM-AVI) and comparators against S. maltophilia and B. cepacia causing pneumonia in United States medical centers.Table 1.Antimicrobial activity of selected antimicrobials against S. maltophilia and B. cepacia from patients with pneumonia.a CLSI (2025) breakpoints for Enterobacterales were applied for comparison for comparison.b Based on CLSI (2025) breakpoints for S. maltophilia.Aztreonam-avibactam MIC distributions for S. maltophilia and B. cepacia from patients with pneumonia Methods 958 clinical isolates, including 830 S. maltophilia and 128 B. cepacia, were consecutively collected from patients with pneumonia in 65 United States (US) medical centers in 2022-2024. Isolates were susceptibility tested by CLSI M07 broth microdilution. CLSI breakpoints were applied for S. maltophilia when available. Enterobacterales breakpoints were applied to B. cepacia and susceptible S/resistant breakpoints of ≤ 4/≥ 16 mg/L were applied for ATM-AVI against both organisms for comparison.Activity of aztreonam-avibactam and comparators against S. maltophilia resistant subsets.* % inhibited at ≤4 mg/L. ** % inhibited at ≤2 mg/L.Abbreviations: TMP-SMX, trimethoprim-sulfamethoxazole, NS, nonsusceptible. Results The most active agents against S. maltophilia were trimethoprim-sulfamethoxazole (TMP-SMX; 97.2% S), minocycline (92.6% S) and ATM-AVI (92.2% inhibited at ≤ 4 mg/L; Table 1 and Figure 1). ATM-AVI retained potent activity against isolates non-S (NS) to other agents commonly used to treat S. maltophilia infections (Figure 2). Levofloxacin showed moderate activity (81.2%S), tigecycline inhibited 90.0% of isolates at ≤ 2 mg/L (42.5% at ≤0.5 mg/L), and both ceftazidime and colistin exhibited limited activity against S. maltophilia. The most active agents against B. cepacia were ceftazidime-avibactam (CAZ-AVI; 97.7% inhibited at ≤ 8 mg/L), meropenem-vaborbactam (MEM-VAB; 96.1% inhibited at ≤ 4 mg/L) and TMP-SMX (82.8% inhibited at ≤ 2 mg/L); ATM-AVI inhibited 64.1% at ≤ 4 mg/L and 89.8% at ≤ 8 mg/L. CAZ-AVI and MEM-VAB were active against 91.4% of B. cepacia isolates with ceftazidime MIC 4 mg/L. Conclusion ATM-AVI exhibited potent activity and broad coverage against S. maltophilia from US hospitals and its activity was not adversely affected by resistance to other agents. The β-lactamase inhibitor combinations CAZ-AVI and MEM-VAB were the most active agents against B. cepacia based on CLSI breakpoints published for Enterobacterales. Appropriate assessment of breakpoints for these organisms is urgently needed to provide better guidance of antimicrobial therapy for infections caused by S. maltophilia and B. cepacia. Disclosures Helio Sader, United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Marisa Winkler, MD, PhD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support
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Helio SaderMarisa Winkler
JMI Laboratories
Rodrigo E. Mendes
JMI Laboratories
Dmitri Debabov
AbbVie (United States)
Open Forum Infectious Diseases
AbbVie (United States)
JMI Laboratories
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Winkler et al. (Thu,) studied this question.
synapsesocial.com/papers/6966f2fb13bf7a6f02c00744 — DOI: https://doi.org/10.1093/ofid/ofaf695.1508