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Canadian Journal of Infectious Diseases and Medical Microbiology
Volume 2017 (2017), Article ID 3948626, 6 pages
https://doi.org/10.1155/2017/3948626
Research Article

In Vitro Activity of Iclaprim against Methicillin-Resistant Staphylococcus aureus Nonsusceptible to Daptomycin, Linezolid, or Vancomycin: A Pilot Study

1Motif BioSciences, New York, NY, USA
2Rutgers New Jersey Medical School, Trenton, NY, USA
3IHMA Europe Sàrl, Route de I’Ile-au-Bois 1A, 1870 Monthey, Valais, Switzerland
4Department of Bacteriology, University of Glasgow Medical School, Glasgow, UK
5IHMA, Schaumburg, IL, USA

Correspondence should be addressed to David B. Huang; moc.oibfitom@gnauh.divad

Received 31 July 2017; Revised 18 October 2017; Accepted 2 November 2017; Published 17 December 2017

Academic Editor: Paul-Louis Woerther

Copyright © 2017 David B. Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Iclaprim is a bacterial dihydrofolate reductase inhibitor in Phase 3 clinical development for the treatment of acute bacterial skin and skin structure infections and hospital-acquired bacterial pneumonia caused by Gram-positive bacteria. Daptomycin, linezolid, and vancomycin are commonly used antibiotics for these indications. With increased selective pressure to these antibiotics, outbreaks of bacterial resistance to these antibiotics have been reported. This in vitro pilot study evaluated the activity of iclaprim against methicillin-resistant Staphylococcus aureus (MRSA) isolates, which were also not susceptible to daptomycin, linezolid, or vancomycin. Iclaprim had an MIC ≤ 1 µg/ml to the majority of MRSA isolates that were nonsusceptible to daptomycin (5 of 7 (71.4%)), linezolid (26 of 26 (100%)), or vancomycin (19 of 28 (66.7%)). In the analysis of time-kill curves, iclaprim demonstrated ≥ 3 log10 reduction in CFU/mL at 4–8 hours for tested strains and isolates nonsusceptible to daptomycin, linezolid, or vancomycin. Together, these data support the use of iclaprim in serious infections caused by MRSA nonsusceptible to daptomycin, linezolid, or vancomycin.