Quinolones and Fluoroquinolones Flashcards
Quinolones MOA
Inhibition of bacterial DNA gyrase and or topoisomerase IV leads to inhibition of DNA supercoiling and replication
How to fluoroquinolones enter the cell?
Via porins = accumulate rapidly
Fluoroquinolone efficacy
Concentration dependent
-Cmax:MIC
-AUC:MIC; AUIC
Has a post-antibiotic effect been demonstrated for enrofloxacin?
Yes
PK properties of fluoroquinolones
Good oral absorption
Large volume of distribution
Good intracellular drug penetration
Extended elimination half-lives
How do fluoroquinolones accumulate in infected tissue?
Rapidly accumulate in macrophages and neutrophils > more infected tissue over healthy tissue
Biotransformation of enrofloxacin
In many species, enrofloxacin is metabolized to for ciprofloxacin
What should you know about off label use of fluoroquinolones in vet med?
Off-label use in food-producing animals is illegal
Common fluoroquinolones
Enrofloxacin
Ciprofloxacin (people)
Orbifloxacin
Marbofloxacin
Difloxacin
Danofloxacin
Pradofloaxacin
Fluoroquinolone Empiric activity
Good activity: Gram - aerobes inlcuding E. coli, Salmonella, Brucella, Leptospira, Pasteurella, Mycoplasma, Rickettsia
Moderate activity: Gram + aerobes (strep, R equi)
Resistant: MOST anaerobic bacteria
Fluoroquinolone Contraindications
Cats: retinal degeneration w/ enrofloxacin (reduced ABCG2 efflux transporter leads to drug accumulation + photosensitization)
Immature animals: arthropathies and cartilage erosions in young cats, dogs, horses
Neurotoxic effects/GABA receptor inhibition
Horses: enterocolitis
Categories of fluoroquinolone resistance
Target modification
Decreased permeability
Efflux
Target protection
-Can all be done simultaneously = high level of resistance
Are fluoroquinolones bacteriocidal or bacteriostatic?
-static at MIC
-cidal at 2-4x MIC
Dose calculations
Yes
