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Antimicrobial Agents and Chemotherapy, November 2000, p. 2962-2968, Vol. 44, No. 11
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
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
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.
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