Medical Studies

DNA Gyrase in Mitochondria Affected by Quinolones

Incorporation of labeled deoxynucleoside triphosphates into mtDNA by isolated rat liver mitochondria has been shown previously to reflect DNA replication. We have used this system to seek evidence for a mtDNA gyrase. Coumermycin, novobiocin, nalidixic acid, and oxolinic acid are known to be inhibitors of Escherichia coli gyrase, to inhibit E. coli DNA replication, to abolish colicin E1 replication, and to depress the supercoiling of phage lambda DNA, the last two via inhibition of the DNA gyrase.

— Frank J. Castora, Melvin V. Simpson, Department of Biochemistry, State University of New York,

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Quinolone Induced Mitochondrial DNA Damage

The loss in mtDNA was associated with a delayed loss in mitochondrial function. Here, we report that the 4-quinolone drug ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concentrations that deplete cells of mtDNA. The IC50 values for ciprofloxacin varied from 40 to 80 micrograms/ml depending on the cell line tested. Cytotoxicity required continuous exposure of cells to drug for 2-4 days, which corresponded to approximately three or four cell doublings. Shorter times of drug exposure did not cause significant cytotoxicity.

— JW Lawrence, DC Claire, V Weissig, TC Rowe, Department of Pharmacology and Therapeutics, University of Florida College of Medicine

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Safety results of Levofloxacin in pediatric patients

Of the 712 [pediatric] subjects evaluable for safety, 275 (52%) levofloxacin-treated subjects experienced one or more adverse event... Serious adverse events were reported in 33 (6%) levofloxacin-treated subjects...Two serious adverse events in levofloxacin-treated subjects resulted in fatal outcomes.

— John Bradley, M.D., Children’s Hospital and Health Center, San Diego, CA

A Study to Compare the Efficacy and Safety of Levofloxacin in the Treatment of Children With Community-Acquired Pneumonia in the Hospital or Outpatient Setting Source: http://download.veritasmedicine.com/PDF/CR002392_CSR.pdf

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Only appropriate in children for anthrax

The risk-benefit assessment indicates that levofloxacin is only appropriate in pediatric patients for treatment of inhalational anthrax (post-exposure).

— Ortho McNeil

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Long term changes after single dose

We observed ultrastructural changes in rat tendons several months after a single oral dose of a fluoroquinolone. I have no doubt what we found in rats corresponds to the clinical symptoms observed in patients during [fluoroquinolone] treatment.

— Dr. Ralf Stahlmann

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Possibly higher rates of neurotoxicity with levofloxacin

"Thus, this trend may reflect... a previously unrecognized tendency toward greater neurotoxicity with levofloxacin."

— JS Cohen, MD

Cohen JS (December 2001). "Peripheral Neuropathy Associated with Fluoroquinolones" (PDF). Ann Pharmacother 35 (12): 1540–7. doi:10.1345/aph.1Z429. PMID 11793615. http://fqvictims.org/fqvictims/News/neuropathy/Neuropathy.pdf

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Spontaneous Achilles tendon rupture

We report two cases of tendon rupture associated with ciprofloxacin. One patient had a complete rupture of an Achilles tendon 6 months after taking the medication. The other case involved a partial rupture of the subscapularis tendon. Both ruptures occurred with minimal mechanical stress on the tendons, suggesting that the fluoroquinolone increased the susceptibility to rupture...

— J. Michael Casparian, MD, Michael Luchi, MD, Department of Medicine, University of Kansas

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Quinolone tendon rupture warning

Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested. Damage of weight bearing joints was observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative articular changes of the knee joint.

— Schering-Plough Corporation

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Inappropriate use of fluoroquinolones

Of 100 total patients, 81 received an FQ for an inappropriate indication. Of these cases, 43 (53%) were judged inappropriate because another agent was considered first line, 27 (33%) because there was no evidence of infection based on the documented evaluation, and 11 (14%) because of inability to assess the need for antimicrobial therapy. Although the prevalence of inappropriate use was similar across various clinical scenarios, there was a borderline significant association between the hospital in which the ED was located and inappropriate FQ use.

— Ebbing Lautenbach, MD, MPH; Lori A. Larosa, PharmD; Nishaminy Kasbekar, PharmD; Helen P. Peng, PharmD; Richard J. Maniglia, MD; Neil O. Fishman, MD

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Reproductive damage from quinolones

A significant decrease in both epididymal sperm count and sperm motility besides abnormal spermatozoa rate were observed in enrofloxacin group compared to controls... These results suggested that a fixed 150 mg/kg dose of enrofloxacin would lead disruption of spermatogenesis in the testes causing deterioration of motility and content of sperms as well as morphological abnormalities.

— Aral F, Karaçal F, Baba F

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