Affiliation:
1. The Anti-Infective Research Laboratory and Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center,1
2. College of Pharmacy and Allied Health Professions,2 and
3. Division of Infectious Diseases, Department of Internal Medicine, School of Medicine,3 Wayne State University, and
4. Department of Veterans Affairs Medical Center,4 Detroit, Michigan
Abstract
ABSTRACT
The incidence of ciprofloxacin resistance in
Streptococcus pneumoniae
is low but steadily increasing, which raises concerns regarding the clinical impact of potential cross-resistance with newer fluoroquinolones. To investigate this problem, we utilized an in vitro pharmacodynamic model and compared the activities of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin to that of ciprofloxacin against two laboratory-derived, ciprofloxacin-resistant derivatives of
S. pneumoniae
(strains R919 and R921). Ciprofloxacin resistance in these strains involved the activity of a multidrug efflux pump and possibly, for R919, a mutation resulting in an amino acid substitution in GyrA. Gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin achieved 99.9% killing of both R919 and R921 in ≤28 h. With respect to levofloxacin, significant regrowth of both mutants was observed at 48 h (
P
< 0.05). For gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin, regrowth was minimal at 48 h, with each maintaining 99.9% killing against both mutants. No killing of either R919 or R921 was observed with exposure to ciprofloxacin. During model experiments, resistance to gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin did not develop but the MICs of ciprofloxacin and levofloxacin increased 1 to 2 dilutions for both R919 and R921. Although specific area under the concentration-time curve from 0 to 24 h (AUC
0–24
)/MIC and maximum concentration of drug in serum (
C
max
)/MIC ratios have not been defined for the fluoroquinolones with respect to gram-positive organisms, our study revealed that significant regrowth and/or resistance was associated with AUC
0–24
/MIC ratios of ≤31.7 and
C
max
/MIC ratios of ≤3.1. It is evident that the newer fluoroquinolones tested possess improved activity against
S. pneumoniae
, including strains for which ciprofloxacin MICs were elevated.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
40 articles.
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