Fluoroquinolones are bactericidal antimicrobials widely used in veterinary medicine. Nalidixic acid, the first antibacterial quinolone developed for clinical use and the precursor to other fluoroquinolones, was discovered in 1962 and approved for clinical use in 1967.1,2 Quinolone carboxylic acid derivatives have a broad spectrum of activity against gram-positive and gram-negative bacteria as well as Mycoplasma organisms.2 Quinolones inhibit bacterial DNA gyrase and deactivate bacterial enzymes necessary for the transcription of DNA. This results in uncoiling of DNA and interference of bacterial DNA synthesis, repair, recombination, and transposition.3–11 The DNA segments become unreadable, and the bacterial cell dies.
Fluoroquinolones are excreted by renal and hepatic routes. Toxic effects of fluoroquinolones in mammalian cells are low compared with toxic effects in bacterial cells because the enzyme analogue to bacterial DNA gyrase in eukaryotes is 100 to 1,000 times less susceptible to gyrase inhibitors.12
Enrofloxacin was approved for use in cats in the United States in 1990 at a dosage of 2.5 mg/kg, PO.a,b Enrofloxacin is also approved in the United States for use in dogs and cattle. Prior to FDA approval, enrofloxacin underwent mandatory toxicologic testing in dogs and cats. Preapproval safety studies conducted in 1989 in dogs and cats revealed the product was safe when administered at a dosage of 25 mg/kg/d for 30 days.a In 1992, the general safety of enrofloxacin in young cats was determined at dosages of 5, 15, and 25 mg/kg; there was no evidence of adverse effects.13 Subsequently, in 1997, a flexible dosing regimen of 5 to 20 mg/kg, PO, once daily or as a divided dose was recommended.14,a Once-daily dosing of enrofloxacin was widely accepted after pharmacologic testing revealed that such use achieved higher peak plasma drug concentrations, increased bactericidal efficacy, decreased risk of bacterial resistance, and provided increased ease of administration.14 After introduction of this flexible dosing regimen, veterinarians reported an increased incidence of vision-related problems that resulted after once-daily oral administration of enrofloxacin. These problems included blindness, partial blindness, and mydriasis.14–19,a In 2 reports15,16 published between 1999 and 2001, investigators suggested a possible link between enrofloxacin administration and vision problems in cats.
In response to the increased incidence of visionrelated problems, the manufacturer enlisted input and expertise from members of the American College of Veterinary Ophthalmologists to determine the best means to objectively investigate this matter. A specific safety study was performed to assess potential effects of enrofloxacin on ocular variables in cats. In June 2000, a postapproval studyc was conducted in which doses of 5, 20, and 50 mg/kg, PO, were administered once daily. In that study, investigators observed dose-related ocular effects attributable to enrofloxacin, with the most severe ocular effects in cats administered 50 mg/kg/d (ie, 2.5 times the high end of the approved dosage range) and with fundic signs that developed within 1 week after onset of administration. No changes were observed in cats administered 5 mg/kg/d (ie, the low end of the approved dosage range). In 2001, the drug label was revised to reflect an FDA-approved dosage for oral administration of 5 mg/kg/d in cats.19
A link between enrofloxacin administration and visual deficits in cats has been established, but little is known concerning the mechanisms by which enrofloxacin causes visual compromise. The proven usefulness of fluoroquinolones in the management of cats with a wide array of diseases ensures their continued, common use in veterinary medicine. The objective of the study reported here was to determine the clinical, funduscopic, electroretinographic, and histologic effects of oral administration of a high dose of enrofloxacin on the retinas of clinically normal cats.
Schirmer tear test
Retinal pigmented epithelium
Photoreceptor outer segment
Photoreceptor inner segment
Outer nuclear layer
Outer plexiform layer
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