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Antimicrobial Agents and Chemotherapy, April 1999, p. 930-936, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

In Vitro Activities of Two Ketolides, HMR 3647 and HMR 3004, against Gram-Positive Bacteria

Kumthorn Malathum, Teresa M. Coque, Kavindra V. Singh, and Barbara E. Murray*

Center for the Study of Emerging and Re-Emerging Pathogens and Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas 77030

Received 10 July 1998/Returned for modification 27 October 1998/Accepted 25 January 1999

The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (Ems), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 µg/ml; range, 0.03 to 0.06 µg/ml; MIC50 [erythromycin], 0.25 µg/ml; range, 0.25 to 0.5 µg/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of >64 µg/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC <=  0.5 µg/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 µg/ml were 0.015 µg/ml. E. faecalis strains that had erythromycin MICs of 128 to >512 µg/ml showed HMR 3647 MICs in the range of 0.03 to 16 µg/ml and HMR 3004 MICs in the range of 0.03 to 64 µg/ml. In the group of E. faecium strains for which MICs of erythromycin were >= 512 µg/ml, MICs of both ketolides were in the range of 1 to 64 µg/ml, with almost all isolates showing ketolide MICs of <= 16 µg/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.

* Corresponding author. Mailing address: Division of Infectious Diseases, The University of Texas Medical School at Houston, 6431 Fannin St., 1.728 JFB, Houston, TX 77030. Phone: (713) 500-6767. Fax: (713) 500-6766. E-mail: infdis{at}heart.med.uth.tmc.edu.

Antimicrobial Agents and Chemotherapy, April 1999, p. 930-936, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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