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Antimicrobial Agents and Chemotherapy, November 1998, p. 2956-2960, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activities of New Fluoroquinolones against Fluoroquinolone-Resistant Pathogens of the Lower Respiratory Tract

Laura J. V. Piddock,1,* M. Johnson,2 V. Ricci,1 and S. L. Hill2

Antimicrobial Agents Research Group, Department of Infection,1 and Respiratory Research Laboratory,2 University of Birmingham, Birmingham, United Kingdom

Received 9 April 1998/Returned for modification 8 July 1998/Accepted 25 August 1998

The activities of six new fluoroquinolones (moxifloxacin, grepafloxacin, gatifloxacin, trovafloxacin, clinafloxacin, and levofloxacin) compared with those of sparfloxacin and ciprofloxacin with or without reserpine (20 µg/ml) were determined for 19 Streptococcus pneumoniae isolates, 5 Haemophilus sp. isolates, and 10 Pseudomonas aeruginosa isolates with decreased susceptibility to ciprofloxacin from patients with clinically confirmed lower respiratory tract infections. Based upon the MICs at which 50% of isolates were inhibited (MIC50s) and MIC90s, the most active agent was clinafloxacin, followed by (in order of decreasing activity) trovafloxacin, moxifloxacin, gatifloxacin, sparfloxacin, and grepafloxacin. Except for clinafloxacin (and gatifloxacin and trovafloxacin for H. influenzae), none of the new agents had improved activities compared with that of ciprofloxacin for P. aeruginosa and H. influenzae. A variable reserpine effect was observed for ciprofloxacin and S. pneumoniae; however, for 9 of 19 (47%) isolates the MIC of ciprofloxacin was decreased by at least fourfold, suggesting the presence of an efflux pump contributing to the resistance phenotype. The laboratory parC (Ser79) mutant strain of S. pneumoniae required eightfold more ciprofloxacin for inhibition than the wild-type strain, but there was no change in the MIC of sparfloxacin and only a 1-dilution increase in the MICs of the other agents. For efflux pump mutant S. pneumoniae the activities of all the newer agents, except for levofloxacin, were reduced. Except for clinafloxacin, all second-step laboratory mutants required at least 2 µg of all fluoroquinolones per ml for inhibition.

* Corresponding author. Mailing address: Antimicrobial Agents Research Group, Department of Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom. Phone: 44-21-414-6969. Fax: 44-21-414-6966. E-mail: l.j.v.piddock{at}bham.ac.uk.

Antimicrobial Agents and Chemotherapy, November 1998, p. 2956-2960, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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