1988. High doses of ertapenem (1g/12h) administered subcutaneously optimize the ertapemem exposure in patients with bone in joint infections (BJI): a Monte Carlo simulation stud
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Poster_Erta_IDweek2016.pdf (369.5 kB)
  • Background: Ertapenem could be used for the treatement of BJI, but high doses (1g/12h) seem to be more appropriate that the standard dose of 1g/day. The subcutaneous (SC) route of administration is convenient in ambulatory care setting but, to date, no PK data supporting the use of high doses of ertapenem subcutaneously are available.

    Methods: This was a retrospective analysis of data prospectively collected in patients with BJI who received ertapemem (1g/ day or 1g/12h) administered as a SC or intravenous (IV) 30-min infusion, from August 2010 to March 2014. An ertapenem plasma concentration profile was determined on at least one occasion in each patient, and typically included trough, peak, and 6h post-dose levels measured by HPLC. Population PK analysis was performed by using the NPAG algorithm implemented in the Pmetrics program. Then, 1000-patient Monte Carlo simulations were performed based on the final model to investigate the influence of ertapenem route of administration (SC or IV), dosage (1g once or twice daily), and renal function on the probability of target attainment (PTA), considering an efficacy target defined as a percentage of time during which ertapemen free plasma concentration remain above the MIC (fT>MIC) of 40%.

    Results: Forty-six PK profiles (13 with IV and 33 with SC ertapenem) with a total of 133 concentrations from 31 subjects (21 males and 10 females; mean age, 58 ± 16 years) were available for the analysis. A two-compartment model, with linear SC absorption and linear elimination best fit the data. Creatinine clearance (CCR) was found to significantly influence ertapenem plasma clearance. Both population and individual predictions correlated well with observed concentrations (R2 = 0.77 and 0.95, respectively), with little mean prediction error (-0.40 and -1.94 mg/L, respectively) and root mean squared error (18.1 and 8.3 mg/L, respectively). Simulations showed that twice daily dosing, SC administration and renal impairment were associated with increased in fT>MIC and higher PTA. As an example, for a MIC of 1 mg/L, the PTA in patients with CCR of 100 ml/min were 100%, 100%, 91.8%, and 70.1% for the regimens SC/q12, IV/q12, SC/q24, IV/q24, respectively.

    Conclusion: Our study suggests that the subcutaneous administration of ertapenem at the dose of 1g/12h may optimize the ertapemem exposure in patients with BJI.

    Tristan Ferry, MD, PhD1, Sylvain Goutelle, DPharm, PhD2, Marie-Claude Gagnieu, DPharm2, Frederic Laurent, DPharm, PhD3, Christian Chidiac, MD, PhD4, Florent Valour, MD, PhD5 and Lyon bone and Joint Infection, (1)Inserm 1111, UCBL1, Hospices Civils de Lyon, Lyon, France, (2)Hospices Civils de Lyon, Lyon, France, (3)Laboratory of Bacteriology, Regional Reference Center for Bji, Hospices Civils de Lyon, Lyon, France, (4)Inserm U1111, UCBL1, Hospices Civils de Lyon, Lyon, France, (5)ID Department, Regional Reference Center for Bji, Hospices Civils de Lyon, Lyon, France

    Disclosures:

    T. Ferry, None

    S. Goutelle, None

    M. C. Gagnieu, None

    F. Laurent, None

    C. Chidiac, None

    F. Valour, None

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