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Antimicrobial Agents and Chemotherapy, November 2009, p. 4949-4952, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00845-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Three New Dihydrofolate Reductase Inhibitors against Clinical Isolates of Gram-Positive Bacteria{triangledown}

Karen E. Bowker,1* Patrick Caspers,2 Bérengère Gaucher,2 and Alasdair P. MacGowan1

BCARE, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom,1 Basilea Pharmaceutica AG, Grenzacherstrasse 487, CH-4058 Basel, Switzerland2

Received 23 June 2009/ Returned for modification 3 August 2009/ Accepted 27 August 2009

BAL0030543, BAL0030544, and BAL0030545 are dihydrophthalazine inhibitors with in vitro potency against gram-positive pathogens. The MIC50s for methicillin (meticillin)-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, hetero-vancomycin-resistant Staphylococcus aureus, and vancomycin-resistant Staphylococcus aureus (VISA) range from 0.015 to 0.25 µg/ml (MIC90s ≤ 0.5 µg/ml). MIC50s for beta-hemolytic streptococci range from 0.03 to 0.06 µg/ml, MIC50s for Streptococcus pneumoniae range from 0.06 to 0.12 µg/ml, MIC50s for Listeria monocytogenes range from 0.015 to 0.06 µg/ml, and MIC50s for Streptococcus mitis are ≤0.015 µg/ml. These three dihydrophthalazine antifolates have improved potency compared to that of trimethoprim and activity against gram-positive pathogens resistant to other drug classes.

(This work was presented in part at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008 [1].)

* Corresponding author. Mailing address: BCARE, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom. Phone: 44 (0) 117 323 5654. Fax: 44 (0) 117 959 3217. E-mail: karen.bowker{at}nbt.nhs.uk

{triangledown} Published ahead of print on 8 September 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4949-4952, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00845-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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