1422. Comparative Monte Carlo Analysis of Aztreonam-avibactam vs Ceftazidime-avibactam against Carbapenem-resistant Gram-negative Pathogens
Session: Poster Abstract Session: PK/PD Studies
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • ASmith IDWeek2018 Poster.pdf (226.2 kB)
  • Background: The new β-lactamase inhibitor, avibactam (AVI), has recently been combined with ceftazidime (CAZ) as CAZ-AVI. AVI is also in Phase 3 clinical trials combined with aztreonam as ATM-AVI. Both drug combinations have similar in vitro activity against some organisms, but ATM-AVI is more potent against metallo-β-lactamase (MBL) producing organisms. However, against P. aeruginosa (PA), CAZ-AVI is more potent. Since these compounds have similar pharmacokinetic (PK)/pharmacodynamic (PD) profiles, and there is a need for drugs for the treatment of resistant microorganisms, a Monte Carlo Analysis (MCA) was used to assess their potential efficacy against carbapenem-resistant pathogens.

    Methods: MCA (n=10,000) was performed for ATM-AVI and CAZ-AVI using PK parameters, CrCl vs. Cl regression, PD targets, and recent MICs from peer-reviewed literature against five carbapenem-resistant (CR) organisms: P. aeruginosa (CR-PA), E. cloacae (CR-EC), K. pneumoniae (CR-KP), Enterobacteriaceae (CR-ENT), and MBL producing Enterobacteriaceae (MBL-ENT). Only MIC studies that directly evaluated both combinations were utilized. Our institution’s inpatient CrCl distribution (range: 10-120 ml/min) was used to assess drug clearance. The ATM-AVI regimen was 1.5g q6h with a 3 h infusion and adjusted for renal function) and the CAZ-AVI regimen was 2g q8h with a 2h infusion and adjusted for renal function). PD targets (%fT>MIC) for ATM-AVI were 40% and 60% and for CAZ-AVI were 40% and 70%.

    Results: Target attainment (TA%) for each regimen and organism was:

    Drug

    ATM-AVI

    CAZ-AVI

    Regimen

    1.5 g q6h (3 hr infusion)

    2 g q 8h (2 hour infusion)

    fT>MIC (% of interval)

    40%

    60%

    40%

    70%

    CR-PA

    48

    43

    93

    87

    CR-EC

    100

    100

    100

    100

    CR-KP

    100

    100

    100

    100

    CR-ENT

    100

    100

    96

    96

    MBL-ENT

    100

    99

    2

    2

    Conclusion: Both ATM-AVI and CAZ-AVI displayed very high TA% (>95%) for CR-EC, CR-KP, and CR-ENT at both PD targets. However, TA% for MBL-ENT was very low for CAZ-AVI and ≥99% for ATM-AVI. Against CR-PA, CAZ-AVI was had much higher TA% than ATM-AVI (87 – 93% vs. 43 – 48%). These differences suggest different roles for each drug combination in clinical practice.

    Aaron Smith, PharmD Candidate, College of Pharmacy, Medical University of South Carolina, Charleston, SC and Roger White, PharmD, Medical University of South Carolina, Charleston, SC

    Disclosures:

    A. Smith, None

    R. White, None

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