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P1157 Searching for Optimal Treatment Regimens For P1157 Searching for optimal treatment regimens for Stenotrophomonas maltophilia resistant to levofloxacin and/or sulfamethoxazole-trimethoprim: aztreonam in combination with avibactam or vaborbactam Mark Biagi*1, Samah Qasmieh1, Denise Lamm1, Kevin Meyer1, Tiffany Wu1, Eric Wenzler1 1 Pharmacy Practice, University of Illinois at Chicago, Chicago, United States Background: Current preferred treatment options for Stenotrophomonas maltophilia include sulfamethoxazole- trimethoprim and levofloxacin but their use may be compromised by increasing reports of resistance, toxicities, and drug interactions. Among the β-lactams, only aztreonam is able to evade S. maltophilia’s L1 metallo-β- lactamase-mediated hydrolysis but it remains prone to hydrolysis by the L2 serine β-lactamase, effectively rendering all β-lactams ineffective. Combining aztreonam with a β-lactamase inhibitor with activity against L2 may restore aztreonam’s activity and offer clinicians a novel treatment option. Materials/methods: MICs for 37 clinical S. maltophilia isolates resistant to levofloxacin and/or sulfamethoxazole- trimethoprim were tested in triplicate via broth microdilution method according to CLSI guidelines. Modal MICs are reported. Susceptibility interpretations were based on CLSI breakpoints for levofloxacin and sulfamethoxazole- trimethoprim against S. maltophilia and against Pseudomonas aeruginosa for aztreonam-based regimens. Time kill analyses were performed in triplicate for 5 isolates at standard inoculum (106) for aztreonam, aztreonam/avibactam, and aztreonam/vaborbactam at either fCmax or ¼, ½, 1, 2, or 4x MIC. Bactericidal activity was considered a ≥3 log10 reduction in CFU/mL from the starting inoculum. Synergy was ≥2 log10 reduction in CFU/mL compared to the most active agent alone. Results: Susceptibilities are summarized in Table 1. 97% (36/37) of isolates were resistant to aztreonam. Aztreonam susceptibility was restored in 35/36 and 4/36 aztreonam-resistant isolates following the addition of avibactam and vaborbactam, respectively. In time kill analyses, aztreonam alone demonstrated no activity while bactericidality was observed for aztreonam/avibactam against 3/5 isolates at 4x MIC. Aztreonam/vaborbactam was bactericidal against just 1/5 isolates at fCmax. Conclusions: The addition of avibactam restored aztreonam susceptibility in 31 more isolates than the addition of vaborbactam. Until the combination of aztreonam-avibactam is commercially available, aztreonam combined with ceftazidime-avibactam may be the optimal alternative treatment option for S. maltophilia isolates resistant to currently preferred agents. Future studies evaluating this combination against multi-drug resistant S. maltophilia are warranted. MIC50 MIC90 MIC Range % Susceptible Aztreonam >128 >128 8->128 2.7 Aztreonam/avibactam 2 4 0.5-16 97.3 Aztreonam/vaborbactam 64 >128 2->128 13.5 Levofloxacin 8 >16 1->16 32.4 Sulfamethoxazole-trimethoprim 8/152 >8/152 0.03/0.57->8/152 32.4 29TH ECCMID 13-16 APRIL 2019 AMSTERDAM, NETHERLANDS POWERED BY M-ANAGE.COM .
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