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Antimicrobial Agents and Chemotherapy, November 2000, p. 2962-2968, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Activities of Clinafloxacin, Gatifloxacin, Gemifloxacin, and Trovafloxacin against Recent Clinical Isolates of Levofloxacin-Resistant Streptococcus pneumoniae

J. H. Jorgensen,1,* L. M. Weigel,2 J. M. Swenson,2 C. G. Whitney,3 M. J. Ferraro,4 and F. C. Tenover2

Department of Pathology, The University of Texas Health Science Center, San Antonio, Texas 782291; Hospital Infections Program2 and Division of Bacterial and Mycotic Diseases,3 Centers for Disease Control and Prevention, Atlanta, Georgia 30333; and The Massachusetts General Hospital, Boston, Massachusetts 021144

Received 19 May 2000/Returned for modification 8 July 2000/Accepted 2 August 2000

The activities of two investigational fluoroquinolones and three fluoroquinolones that are currently marketed were determined for 182 clinical isolates of Streptococcus pneumoniae. The collection included 57 pneumococcal isolates resistant to levofloxacin (MIC >=  8 µg/ml) recovered from patients in North America and Europe. All isolates were tested with clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, and trovafloxacin by the National Committee for Clinical Laboratory Standards broth microdilution and disk diffusion susceptibility test methods. Gemifloxacin demonstrated the greatest activity on a per gram basis, followed by clinafloxacin, trovafloxacin, gatifloxacin, and levofloxacin. Scatterplots of the MICs and disk diffusion zone sizes revealed a well-defined separation of levofloxacin-resistant and -susceptible strains when the isolates were tested against clinafloxacin and gatifloxacin. DNA sequence analyses of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE from 21 of the levofloxacin-resistant strains identified eight different patterns of amino acid changes. Mutations among the four loci had the least effect on the MICs of gemifloxacin and clinafloxacin, while the MICs of gatifloxacin and trovafloxacin increased by up to six doubling dilutions. These data indicate that the newer fluoroquinolones have greater activities than levofloxacin against pneumococci with mutations in the DNA gyrase or topoisomerase IV genes. Depending upon pharmacokinetics and safety, the greater potency of these agents could provide improved clinical efficacy against levofloxacin-resistant pneumococcal strains.

* Corresponding author. Mailing address: Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229-390. Phone: (210) 567-4088. Fax: (210) 567-2367. E-mail: jorgensen{at}uthscsa.edu.

Antimicrobial Agents and Chemotherapy, November 2000, p. 2962-2968, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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