1833. In Vitro activity of Fosfomycin (ZTI-01, Fosfomycin for Injection) Against Contemporary Gram-negative and Gram-positive Isolates- a Comparison of Inter-Method Testing
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
  • IDWeek16 Fosfomycin 1833.pdf (492.3 kB)
  • Background: ZTI-01 (FOS) is an epoxide antibiotic with a novel MOA active against Gram-negative (GN) and –positive (GP) organisms, including MDR organisms. The IV formulation is in clinical development in the US for the treatment of complicated urinary tract infections.. FOS susceptibility (S) testing is unique in that only agar dilution (AD) is recommended as the reference method by both CLSI and EUCAST.

    Methods: A total of 354 GN and GP from USA medical centers (2014) were selected. A subset of 106 isolates were MIC tested against FOS by AD +/- 25 µg/mL glucose-6-phosphate [G-6-P], Etest® and disk diffusion. Additionally all isolates were tested by broth microdilution (BMD) +/- 25 µg/mL G-6-P.

    Results: The overall FOS MIC50/90 (n=106) was 8/64 µg/mL by reference AD. FOS was active against Escherichia coli (n=17; MIC50/90, 0.5/1 µg/mL) and Enterococci (n=21; MIC50/90, 32/64 µg/mL). Staphylococcus aureus MICs ranged from 1-16 µg/mL (n=9), Enterobacter spp. from 8-16 µg/mL (n=12), Klebsiella spp. from 4-32 µg/mL (n=9), Proteus and Providencia spp. from ≤0.12-64 µg/mL (n=11), and 6 Serratia marscescens from 4-16 µg/mL. A total of 55/106 (51.9%) Etest® MIC values were +/- one-dilution of the reference AD MIC value. Enterobacteriaceae (EB) Etest® MICs were generally higher than AD reference method. BMD (no G-6-P) MICs were generally higher (60/106 [56.6%] ≥ 2 dilutions) than AD. Only E. faecalis and E. coli have CLSI MIC and disk diameter breakpoint criteria. All 17 E. coli were categorized as S by disk and MIC. However, two E. faecalis were falsely resistant by disk (major error).The significant effect of G-6-P was shown in broth when 354 isolates were tested in the presence of 25 µg/mL G-6-P. A total of 146/230 (63.5%) of EB showed MIC values ≤ 2 dilutions lower when tested with G-6-P.

    Conclusion: FOS was highly active against all organisms tested. FOS MICs (reference AD) are lower than Etest® for some organisms. G-6-P lowers MICs in broth and in agar but appears to be more pronounced for select organism groups. BMD MIC values in the presence of G-6-P correlate within +/- one dilution with reference AD a majority of the time, but differ by > 1 dilution depending on organism group. AD is the recommended reference method, with ETest® MICs typically >1-dilution of the reference value.

    Robert K. Flamm, Ph.D.1, Paul R. Rhomberg, BS1, Holly K. Huynh, BS1, Helio S. Sader, MD, PhD1 and E. J. Ellis-Grosse, PhD2, (1)JMI Laboratories, Inc., North Liberty, IA, (2)Zavante Therapeutics, Inc, San Diego, CA


    R. K. Flamm, Zavante Therapeutics, Inc.: Research Contractor , Research grant

    P. R. Rhomberg, Zavante Therapeutics, Inc.: Research Contractor , Research grant

    H. K. Huynh, Zavante Therapeutics, Inc.: Research Contractor , Research grant

    H. S. Sader, Zavante Therapeutics, Inc.: Research Contractor , Research grant

    E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee , Salary

    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.