1989. In Vitro Activity of Telavancin (TLV) and Other Agents Against Methicillin Resistant Staphylococcus aureus (MRSA) isolates from a Community Hospital in Mid Michigan Area
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Tran IDSA 2016 Poster_Final.pdf (1.1 MB)
  • Background:

    Although vancomycin (VAN) has been the standard of care for treatment of serious MRSA infections, there is increasing need for more potent and effective antibiotics.  Telavancin (TLV) is one  such option and was reintroduced with an additional  indication and susceptibility testing methodology. In this study, we evaluated the in vitro activity of TLV, VAN, daptomycin (DAP), linezolid (LNZ), and ceftaroline (CFT), against MRSA isolates.

    Methods:

    In 2015, 103 unique clinical MRSA isolates (blood, sputum, skin) were collected.  Minimum inhibitory concentrations (MICs) of TLV, VAN, DAP, LNZ, and CFT were determined using TREK panels (Thermo Fisher Scientific, OH) as well as E-test strips (bioMerieux, Durham,NC ) following manufacturers guidelines. In addition, time kill experiments were performed. Briefly, MICs of 2 randomly chosen MRSA blood isolates were determined by microbroth dilution according to CLSI guidelines. Time kill experiments were performed for the antibiotics at 100 % clinical peak levels for VAN, DAP, LNZ and CFT. TLV experiments were done at 50% of peak level in order to limit the DMSO concentration of the sample well.  Pooled normal human serum was mixed 50% (v/v) with CAMHB for the timekill experiments to help simulate free drug concentrations seen in patients. TLV experiments were performed in Cation Adjusted Mueller-Hinton broth (CAMHB) with 0.002% Polysorbate-80 and DAP experiments were performed in CAMHB with calcium adjusted to 50 mg/L.

    Results:

    The MIC90 was 0.03 µg/mL and 0.06 µg/mL (TLV), 0.5 µg/mL and 1.0 µg/mL (VAN), 0.25 µg/mL and 0.75 µg/mL (DAP), 1.0 µg/mL and 2.0 µg/mL (LNZ) for TREK panels and E-tests, respectively. CFT MIC90 was 0.38 µg/mL using E-test.  Timekill studies for both isolates showed that only TLV and DAP exhibited a > 1 log cfu/mL decrease at 2h against the MRSA blood isolates tested (Figure).  Each agent, except LNZ, exhibited bactericidal activity (> 3 log cfu/mL decrease) by 6h in this model and no re-growth was seen by 24hrs.

    Conclusion:

    In this study, TLV, tested at 50% the levels of the comparator agents, was still the most potent agent against clinical isolates of MRSA and was observed to be rapidly bactericidal, exhibiting a rapid and prolonged decrease in bacterial colony counts in time-kill investigations.

    Figure: Time Kill Curves for TLV and comparator antibiotics against MRSA blood isolate #78

    Maryann P. Tran, MD, Apoorv Kalra, MD, Daniel Havlichek, MD, FIDSA, Gary Stein, PharmD and Amy Scharmen, BS, Michigan State University, East Lansing, MI

    Disclosures:

    M. P. Tran, None

    A. Kalra, None

    D. Havlichek, None

    G. Stein, None

    A. Scharmen, 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.