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Antimicrobial Agents and Chemotherapy, March 1998, p. 624-630, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Susceptibilities of Penicillin- and Erythromycin-Susceptible and -Resistant Pneumococci to HMR 3647 (RU 66647), a New Ketolide, Compared with Susceptibilities to 17 Other Agents

G. A. Pankuch,1 M. A. Visalli,1 M. R. Jacobs,2 and P. C. Appelbaum1,*

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

Received 23 July 1997/Returned for modification 1 December 1997/Accepted 18 December 1997

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 µg/ml for erythromycin-susceptible strains (MICs, <= 0.25 µg/ml) and 0.25 µg/ml for erythromycin-resistant strains (MICs, >= 1.0 µg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 µg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were <= 0.125 µg/ml. The MICs of pristinamycin for all strains were <= 1.0 µg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 µg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at <= 1.0 µg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelba{at}psuhmc.hmc.psu.edu.

Antimicrobial Agents and Chemotherapy, March 1998, p. 624-630, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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