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Antimicrobial Agents and Chemotherapy, July 2000, p. 1894-1899, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antipneumococcal Activity of ABT-773 Compared to Those of 10 Other Agents

Todd A. Davies,1 Lois M. Ednie,1 Dianne M. Hoellman,1 Glenn A. Pankuch,1 Michael R. Jacobs,2 and Peter C. Appelbaum1,*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,1 and Department of Pathology, Case Western Reserve University, Cleveland, Ohio 441062

Received 9 March 2000/Returned for modification 11 April 2000/Accepted 27 April 2000

MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC50s) and MIC90s were 0.016 to 0.03 and 0.125 µg/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing mefE (MIC50, 0.06 µg/ml; MIC90, 0.125 µg/ml). Activities of pristinamycin (MIC90, 0.5 µg/ml) and vancomycin (MIC90, 0.25 µg/ml) were unaffected by macrolide or penicillin resistance, while beta -lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 µg/ml, while macrolide and azalide MICs were all >= 16.0 µg/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 µg/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or beta -lactams, including against ermB-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psghs.edu.

Antimicrobial Agents and Chemotherapy, July 2000, p. 1894-1899, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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