Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 8 ANTIBACTERIAL DRUGS
● Rarely synergistic or antagonistic in combination
with other antibacterial drugs.
● Fluoroquinolones currently in the veterinary market
are relatively inactive against obligate anaerobic bacteria.
However, newer fluoroquinolones with antianaerobic
activity (such as trovafloxacin) have been
developed and used in human medicine. Similar
drugs may reach the veterinary market in the
future.
There are some differences in antibacterial spectrum
between individual fluoroquinolones. Norfloxacin is
less active than newer fluoroquinolones against Pseudomonas.
Ciprofloxacin has greater activity against
multidrug-resistant Gram-negative bacteria such as
Pseudomonas, various Mycoplasma and intracellular
pathogens such as Brucella and Mycobacterium. Enrofloxacin,
the first ‘veterinary’ fluoroquinolone, has
greater absorption after oral administration than ciprofloxacin
but less antipseudomonal activity.
Clinical applications
Fluoroquinolones are important drugs for treating
serious Gram-negative infections and should not be
used routinely and nonselectively for small animal infections.
Possible indications for use as drug of first choice
include the following.
● Urinary tract infections caused by Pseudomonas
● Bacterial prostatitis in dogs
● Serious Gram-negative systemic infections
● Osteomyelitis caused by Gram-negative aerobes
● Saprophytic Mycobacterium infection in cats
● Deep granulomatous pyoderma
● Serious bacterial respiratory tract infections
● Management of neutropenic, febrile patients on
cancer chemotherapy
● Otitis externa due to Gram-negative infections
(following culture and susceptibility testing).
Pharmacokinetics
Fluoroquinolones are rapidly absorbed after oral administration
in monogastric animals; absorption is complete
(80–100%) for enrofloxacin, less so for ciprofloxacin
(50–70%) and norfloxacin (40%). Administration
with food may delay the time to peak plasma concentration
but does not alter the concentration achieved.
Administration with compounds that contain metal
ions will adversely affect plasma fluoroquinolone
concentrations.
Low protein binding, low ionization and high lipid
solubility result in large volumes of distribution and
good penetration into CSF, bronchial secretions, bone,
cartilage and prostate. Concentrations achieved in respiratory
and genitourinary tract secretions are higher than
plasma concentrations and prostatic concentrations
may be 2–3 times higher than in plasma.
The major metabolite of enrofloxacin is ciprofloxacin
but the amount of ciprofloxacin produced varies between
and within species. Elimination may be renal, hepatic
or both, depending on the drug. Enrofloxacin undergoes
predominantly renal elimination, for difloxacin it is
fecal and marbofloxacin is excreted in both urine and
feces.
The elimination half-life varies with the drug but is
usually sufficiently long (8–12 h) to permit once-daily
dosing. A postantibiotic effect (continued suppression
of bacterial growth following removal of the drug) of a
few minutes to several hours occurs with fluoroquinolones
against most Gram-negative and some Grampositive
bacteria. The duration of the postantibiotic
effect depends on the pathogen, the concentration of the
drug above MIC and the duration of exposure.
Urinary drug concentrations are substantially in
excess of MIC values for virtually all susceptible pathogens,
exceeding plasma concentrations by several
hundred times and remaining high for 24 h after
administration.
Adverse effects
● Adverse effects with fluoroquinolones are uncommon.
Vomiting, inappetence or diarrhea may occur
occasionally. Facial erythema and edema have been
reported rarely, as have tremors and ataxia.
● Seizures have been reported rarely in animals with
CNS disorders, with high doses and with concurrent
use of nonsteroidal anti-inflammatory drugs.
● An apparent species-specific toxicity is acute retinal
degeneration in cats treated with enrofloxacin. Blindness
often results but some cats may regain vision.
The daily and total doses of enrofloxacin administered
and duration of treatment in affected cats seem
highly variable. However, the blindness does appear
to be dose related and doses in cats should not exceed
5 mg/kg/day. It has been postulated that the relatively
open blood–brain barrier of cats combined
with the lipophilic properties of enrofloxacin predispose
cats to accumulating high concentrations of the
drug in the CNS. The risk may be higher in cats with
urinary tract infections and concomitant renal failure
and care should be taken with dosage in geriatric
cats or those with liver or renal impairment. It is not
clear whether other fluoroquinolones can also cause
blindness.
● Fluoroquinolones should not be used in young
animals as they cause erosion of articular cartilage
(in dogs more than cats and large dogs especially).
The mechanism of cartilage damage may be related
to chelation of magnesium in joints. Lesions have
been documented in dogs given five times the recom-
182