2443. Searching for the Optimal Treatment Regimen for Metallo-ß-Lactamase Producing Enterobacteriaceae: Aztreonam plus Ceftazidime-Avibactam vs. Aztreonam plus Meropenem-Vaborbactam
Session: Poster Abstract Session: Treatment of AMR Infections
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • Biagi IDWeek 2018 NDM Poster_EW_Sep 22 MB_Sep 24 MB_Sep 25 MB.pdf (68.1 kB)
  • Background: Pathogens harboring metallo-β-lactamase (MBL) enzymes pose a large threat to public health. Aztreonam (ATM) is not hydrolyzed by MBLs but is inactivated by other β-lactamases, which are often co-harbored in MBL-producers. Ceftazidime/avibactam (CAZ/AVI) and meropenem/vaborbactam (MER/VBR) are novel ß-lactam/ß-lactamase inhibitors (BL/BLI) with potent activity against serine ß-lactamase producing Enterobacteriaceae. Combining ATM with BL/BLI agents may provide activity against Enterobacteriaceae producing serine and MBLs.

    Methods: Two clinical E. coli isolates were used. MICs were determined in triplicate and modal values are reported. Time kill analyses were performed in triplicate at standard inoculum (106). Each agent was tested alone and in combination at either fCmax or ¼, ½, 1, 2, or 4x MIC based on susceptibility. Bactericidal activity was ≥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. Antagonism was ≥2 log10 increase in CFU/mL compared to the most active agent alone.

    Results: Genotypic/phenotypic susceptibilities are in Table 1. Against EC-1, ATM alone at fCmax had no activity. When combined with CAZ/AVI or MER/VBR, respectively, synergy was observed with average log10 decrease in CFU/mL at 24 hours of 3.92 and 5.04 (Figure 1a). Synergy seemed to be driven solely by the addition of the BLI as ATM/CAZ and ATM/MER did not demonstrate synergy (Figure 1a). Against EC-2, ATM alone at 1/4x MIC showed no activity (Figure 1b). Combining ATM with either CAZ/AVI or MER/VBR did not improve the activity or demonstrate synergy (Figure 1b). Interestingly, removing CAZ significantly improved the activity of ATM/AVI.

    Conclusion: There were no significant differences in activity or synergy observed between the combinations of ATM with either CAZ/AVI or MER/VBR against serine- and MBL-producing E. coli. Synergy appears to be driven by the ATM-BLI combinations, with ATM-AVI demonstrating more consistent synergy than ATM-VBR. Further studies including more isolates and combinations are warranted.

     

    EC-1

    (NDM, CMY2/FOX,

    CTX-M-1, TEM)

    EC-2

    (NDM-5, OXA-1)

    ATM

    >256

    0.25

    ATM/AVI

    16

    0.25

    ATM/VBR

    128

    0.25

    CAZ

    >256

    >256

    CAZ/AVI

    >256

    >256

    MER

    64

    256

    MER/VBR

    128

    >256

     

    Mark Biagi, PharmD, University of Illinois at Chicago, College of Pharmacy, Chicago, IL and Eric Wenzler, PharmD, College of Pharmacy, University of Illinois at Chicago, Chicago, IL

    Disclosures:

    M. Biagi, None

    E. Wenzler, Melinta Therapeutics: Speaker's Bureau , Speaker honorarium .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.