Activities of three investigational fluoroquinolones (BAY y 3118, DU-6859a, and clinafloxacin) against Neisseria gonorrhoeae isolates with diminished susceptibilities to ciprofloxacin and ofloxacin

Carlyn, Cynthia J.; Doyle, Laura J.; Knapp, C C; Ludwig, Margaret D.; Washington, John A.

doi:10.1128/aac.39.7.1606

Cited by 15 publications

(3 citation statements)

References 15 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies with quinolone-resistant clinical isolates of several bacterial species also show that C8-modified fluoroquinolones have superior activity (16,(33)(34)(35). Thus the principles discussed in the present work probably apply to most bacterial species that are sensitive to fluoroquinolones.…”

Section: Discussionmentioning

confidence: 62%

DNA topoisomerase targets of the fluoroquinolones: A strategy for avoiding bacterial resistance

Zhao¹,

Chen²,

Domagala³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

187

153

View full text Add to dashboard Cite

Fluoroquinolones are antibacterial agents that attack DNA gyrase and topoisomerase IV on chromosomal DNA. The existence of two f luoroquinolone targets and stepwise accumulation of resistance suggested that new quinolones could be found that would require cells to obtain two topoisomerase mutations to display resistance. For wild-type cells to become resistant, the two mutations must be acquired concomitantly. That is expected to occur infrequently. To identify such compounds, f luoroquinolones were tested for the ability to kill a moderately resistant gyrase mutant. Compounds containing a C8-methoxyl group were particularly lethal, and incubation of wild-type cultures on agar containing C8-methoxyl f luoroquinolones produced no resistant mutant, whereas thousands arose during comparable treatment with control compounds lacking the C8 substituent. When the test strain contained a preexisting topoisomerase IV mutation, which by itself conferred no resistance, equally high numbers of resistant mutants were obtained for C8-methoxyl and control compounds. Thus C8-methoxyl f luoroquinolones required two mutations for expression of resistance. Although highly lethal, C8-methoxyl f luoroquinolones were not more effective than C8-H controls at blocking bacterial growth. Consequently, quinolone action involves two events, which we envision as formation of drug-enzyme-DNA complexes followed by release of lethal double-strand DNA breaks. Release of DNA breaks, which must occur less frequently than complex formation, is probably the process stimulated by the C8-methoxyl group. Understanding this stimulation should provide insight into intracellular quinolone action and contribute to development of f luoroquinolones that prevent selection of resistant bacteria.

show abstract

Section: Discussionmentioning

confidence: 62%

DNA topoisomerase targets of the fluoroquinolones: A strategy for avoiding bacterial resistance

Zhao¹,

Chen²,

Domagala³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

187

153

View full text Add to dashboard Cite

show abstract

“…More importantly clinical isolates of QRNG have been reported to have MICs of ceftriaxone that were four-to-eight-fold higher than cipro¯ox-acin susceptible isolates. These ® ndings suggest that QRNG might promote development of resistance to structurally unrelated cephalosporins during continued exposure to¯uoroquinolones 14 . However, as auxotyping and DNA ampli® cation could not be carried out in the present study, no further comment on the above ® ndings can be made.…”

Section: Discussionmentioning

confidence: 93%

High incidence of treatment failure of Neisseria gonorrhoeae isolates to ciprofloxacin in male gonococcal urethritis in Delhi

et al. 2002

View full text Add to dashboard Cite

Several treatment failures and widespread antimicrobial resistance to ciprofloxacin have been documented, subsequent to its initial recommendation in 1989 as a single dose alternative therapy for gonorrhoea. Still, it continues to be part of various treatment schedules in National STD control guidelines including India. This prompted us to study the current status of this drug in the treatment of gonorrhoea. Thirty-five male patients with gonococcal urethritis were included in the study. The susceptibility to penicillin, tetracycline, ciprofloxacin and ceftriaxone was determined by Kirby-Bauer disc diffusion method and minimum inhibitory concentration (MIC) of ciprofloxacin by agar plate dilution method. The clinical and bacteriological response was assessed on day 5 after treatment with single dose ciprofloxacin, 500 mg. The sensitivity pattern of Neisseria gonorrhoeae was observed to be: ceftriaxone 100%, azithromycin 100%, tetracycline 65.7%, penicillin 40% and ciprofloxacin 5.7% by disc diffusion method. The MIC for ciprofloxacin was below 0.06 microg/mL (sensitive) in one (2.5%) isolate only. On the fifth day a large number of treatment failures (88.5%) were seen with ciprofloxacin while none was noted one week after re-treatment with ceftriaxone. The location of endemic quinolone-resistant N. gonorrhoeae (QRNG) in New Delhi has increased alarmingly, resulting in an extremely high proportion of therapeutic failures, and thus requiring appropriate alterations in the presently recommended treatment regimens.

show abstract

“…All isolates were sus- ceptible to both drugs. It should be noted, however, that N. gonorrhoeae isolates with decreased susceptibilities to ciprofloxacin have higher clinafloxacin MICs (2). The susceptibilities of anaerobes to clinafloxacin were compared to cefoxitin (Table 2).…”

mentioning

confidence: 99%

In Vitro Activities of Clinafloxacin against Contemporary Clinical Bacterial Isolates from 10 North American Centers

Fuchs

Barry

Brown

1998

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Clinafloxacin was more active than ciprofloxacin against 4,213 aerobic and facultative anaerobic bacterial isolates from 10 medical centers, as tested by broth microdilution and disk diffusion methods. The percentage of 201 anaerobes susceptible to clinafloxacin by broth microdilution was comparable to cefoxitin. Our data support the proposed disk diffusion interpretive criteria for aerobic bacteria with 5-μg clinafloxacin disks.

show abstract

Activities of three investigational fluoroquinolones (BAY y 3118, DU-6859a, and clinafloxacin) against Neisseria gonorrhoeae isolates with diminished susceptibilities to ciprofloxacin and ofloxacin

Cited by 15 publications

References 15 publications

DNA topoisomerase targets of the fluoroquinolones: A strategy for avoiding bacterial resistance

DNA topoisomerase targets of the fluoroquinolones: A strategy for avoiding bacterial resistance

High incidence of treatment failure of Neisseria gonorrhoeae isolates to ciprofloxacin in male gonococcal urethritis in Delhi

In Vitro Activities of Clinafloxacin against Contemporary Clinical Bacterial Isolates from 10 North American Centers

Contact Info

Product

Resources

About