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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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