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      Evaluation of in vitro activity of iclaprim in combination with other antimicrobials against pulmonary pathogens: a pilot study

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          Abstract

          In this pilot study, the in vitro antimicrobial activity of iclaprim, a diaminopyrimidine, tested in combination with other antimicrobials against recent and common Gram-positive and Gram-negative respiratory pathogens, was examined by the checkerboard method. The range of minimal inhibitory concentrations (MICs) for iclaprim against all bacteria tested in the study was 0.03 to >128 µg ml −1. Iclaprim exhibited synergy with sulfamethoxazole against 11 of the 16 bacterial strains tested, with mean fractional inhibitory concentration index (FICI) values of 0.2–0.5. Synergy with sulfamethoxazole was demonstrated against all Gram-positive bacteria and selected Gram-negative bacteria. Neither synergy nor antagonism was observed for combinations of iclaprim with ampicillin, meropenem, tetracycline, levofloxacin, aztreonam, piperacillin/tazobactam, colistin, cefepime or gentamicin against any of the bacterial strains tested. The significant reduction in the MIC values observed with the combination of iclaprim and sulfamethoxazole demonstrates that this regimen could be effective against common Gram-positive and selected Gram-negative respiratory bacteria.

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          Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria.

          Iclaprim, a new selective dihydrofolate inhibitor was synthesized based on rational drug design. Iclaprim's interaction with a resistant Staphylococcus aureus dihydrofolate reductase (DHFR) is outlined in comparison to trimethoprim (TMP). This compound is active against methicillin, TMP and vancomycin resistant strains. Arpida Ltd. is developing Iclaprim for serious hospital infections from Gram-positive pathogens and respiratory tract infections.
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            Potency and bactericidal activity of iclaprim against recent clinical gram-positive isolates.

            The in vitro activity of iclaprim, a novel diaminopyrimidine derivative, was evaluated against 5,937 recent gram-positive clinical isolates collected in the United States and Europe. Iclaprim demonstrated potent activity against Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), beta-hemolytic Streptococcus spp., and Enterococcus faecalis strains tested. In addition, iclaprim exhibited bactericidal activity against all S. aureus strains tested, including MRSA.
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              A Phase II Randomized, Double-blind, Multicenter Study to Evaluate Efficacy and Safety of Intravenous Iclaprim Versus Vancomycin for the Treatment of Nosocomial Pneumonia Suspected or Confirmed to be Due to Gram-positive Pathogens.

              The primary objective of this Phase II study was to compare the clinical cure rates of 2 iclaprim dosages versus vancomycin in the treatment of patients with nosocomial pneumonia suspected or confirmed to be caused by gram-positive pathogens.
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                Author and article information

                Journal
                Access Microbiol
                Access Microbiol
                acmi
                acmi
                Access Microbiology
                Microbiology Society
                2516-8290
                2019
                20 May 2019
                20 May 2019
                : 1
                : 3
                : e000027
                Affiliations
                [1 ] Motif BioSciences , New York, USA
                [2 ] Rutgers New Jersey Medical School , Trenton, New Jersey, USA
                [3 ] IHMA , Rte De I’lle-au-Bois, Switzerland
                Author notes
                *Correspondence: David B. Huang, david.huang@ 123456motifbio.com
                Author information
                https://orcid.org/0000-0001-8228-7911
                Article
                000027
                10.1099/acmi.0.000027
                7471776
                b67c67f4-cb29-494d-86ee-22dd708eaded
                © 2019 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License.

                History
                : 06 March 2019
                : 23 April 2019
                Categories
                Short Communication
                Custom metadata
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                iclaprim,synergy,pneumonia,in vitro
                iclaprim, synergy, pneumonia, in vitro

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