1958. Comparison of Dalbavancin, Oritavancin and Vancomycin Pharmacodynamics using Clinical Targets against ABSSSI Pathogens
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Comparison of Dalbavancin, Oritavancin and Vancomycin PKPD.pdf (760.7 kB)
  • Background: Oritavancin (ORI) and dalbavancin (DAL) are newer agents for treatment of ABSSSI; however, vancomycin (VANC) is still frequently used. Since ORI and DAL have not been directly compared to each other in clinical trials, Monte Carlo analysis (MCA) was used to assess potential efficacy differences between these drugs and against VANC for methicillin-susceptible (MSSA), resistant (MRSA), and VANC intermediate (VISA) Staphylococcus aureus, and coagulase negative Staplylococcus (CoNS).

    Methods: Multi-compartment pharmacokinetic parameters, current MIC distributions, and clinical pharmacodynamic targets from peer-reviewed literature were used. AUC simulations used population distributions for clearance (a distribution for ORI, derived from CrCl - Cl regressions for DAL and VANC) and volume for: ORI (3 h infusion) 1.2 g single dose; DAL (0.5 h infusion) 1g, then 0.5g 7 days later and a 1.5 g single dose; VANC 1g, 1.5g, and 2g given q12h. Doses of DAL and VANC were adjusted for CrCl (using a distribution of CrCl from our tertiary-care institution). Serum protein binding (PB) values (85% - 90% for ORI and 93% - 97% for DAL) were used to estimate free (f) AUCs for ORI and DAL. Total AUCs were used for VANC. AUC/MIC clinical targets of 1797 (ORI, fAUC/MIC 0-72 h), 1031 and 1489 (DAL , mean 24 h fAUC/MIC 0-120 h for clinical and microbiological targets, respectively), and 400 (VANC, total AUC24/MIC) were used in the MCA.

    Results: Target attainment (TA%) using the clinical targets (DAL 93% PB, ORI 85% PB) were:

    Drug

    Vancomycin

    Dalbavancin

    Oritavancin

    Dose

    1 g q12

    1.5 g q12

    2 g q12

    1 g/0.5 g

    1.5 g

    1.2 g

    MSSA

    86

    97

    99

    85

    96

    99

    MRSA

    85

    97

    99

    85

    96

    99

    CoNS

    49

    74

    94

    90

    95

    100

    TA% for VISA was 0%, 1%, and 8% for VANC, DAL, and ORI, respectively. For DAL, microbiologic success TA% was 10-33% lower than for clinical success. TA% was lower when the higher PB values were used (12-50% for DAL and 1-4% for ORI).

    Conclusion: Single-dose regimens of DAL and ORI achieved good target attainment (>90%) for MSSA, MRSA, and CoNS. Differences in DAL regimens were likely due to the 0-120h AUC calculation that gives a numeric advantage to the higher dose. VANC TA% was highly dependent on the dosage regimen; VANC doses of 1.5g and 2g were needed to achieve target attainment >90% for MSSA/MRSA and CoNS, respectively. Target attainment was poor for all drugs and regimens against VISA.

    Jordan Chiasson, PharmD Candidate and Roger White, PharmD, Medical University of South Carolina, Charleston, SC

    Disclosures:

    J. Chiasson, None

    R. White, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.