Fluoroquinolones (and related)
- Antibacterial activity
- Bactericidal provided combination of concentration and time is adequate.
- Gram positive and gram negative
- Aerobes only
- Not especially good against streptococci
- Bacterial resistance
- Resistance does not limit clinical usefulness.
- Resistance is increasing
- Concentrations and doses
- Combination of concentration and time allows dosing flexibility.
- Disbtribution to reserved spaces is fair.
- Toxicity Profile
- Life threatening adverse effects are extremely rare except certain drugs in cats (blindness).
- Neurologic side effects may limit clinical usefulness in some patients.
- enrofloxacin, marbofloxacin, orbifloxacin, pradofloxacin
Beneficial actions and effects
Fluroquinolone antibiotics inhibit binding of DNA gyrase(aka topoisomerase II) to specific portions of DNA (the ligase domain). This prevents uncoiling of bacterial DNA required for duplication. Continued activity of topoisomerase II (other regions of DNA) leads to DNA fragmentation and cell death.
- DNA mechanism precludes plasmid mediated resistance
- excellent activity against nearly all gram negative species
- fair but limited activity against gram positive species
- new drugs have better activity against streptococci (no veterinary examples)
Resistance (by bacteria)
- alteration of target enzyme (DNA gyrase) - not plasmid mediated
- Reduced access through altered Porins (especially Pseudomonas)
A spectrum of adverse effects but relatively consistent between species
- Arthropathy in immature animals
- CNS excitement/siezures/nightmares
- Retinal degneration in cats (pradofloxacin appears to be an exception)
Fluoroquinolones are relatively uniform (consistent across the individual drugs)
- Oral absorption is essentially 100% in most monogastrics. Horses absorb <70% of enrofloxacin, marbofloxacin and orbifloxacin and < 7% of ciprofloxacin (human)
- widely distributed but not concentrated in tissues. Distribution to cns and prostate not especially good.
- Protein binding is relatively low
- Elimination pattern varies by drug. (mostly known for dogs)
- Danofloxacin (cattle and pigs): roughly 60% hepatic, 40% renal unchanged
- Difloxacin (dogs): almost all hepatic, <5% in urine
- Enrofloxain: Primarily renal
- Marbofloxacin: 60% hepatic, 40% renal unchanged
- Orbifloxacin: < 50% renal, higher in Pigs