Abstract

Iclaprim is a diaminopyrimidine, which inhibits bacterial dihydrofolate reductase, and it is highly active against Gram-positive pathogens including emerging drug-resistant pathogens. In vitro activity of iclaprim and comparators against 2814 Gram-positive clinical isolates from the United States, Asia Pacific, Latin American and Europe collected between 2012 and 2014 were tested. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. MIC50/MIC90 for all S. aureus, methicillin susceptible S. aureus, methicillin resistant S. aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae were 0.06/0.12, 0.06/0.12, 0.06/0.5, 0.06/0.25, and 0.06/2μg/mL, respectively. Iclaprim was 8 to 32-fold more potent than trimethoprim, the only FDA approved dihydrofolate reductase inhibitor, against all Gram-positive isolates including resistant phenotypes. The MIC90 of iclaprim was also lower than most of the comparators including linezolid and vancomycin against Gram-positive pathogens. Iclaprim demonstrated potent activity against a contemporary collection (2012–2014) of Gram-positive clinical isolates from the United States, Asia Pacific, Latin America and Europe.

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