Fluroquinolones

Question 1

What are the 6 commonly used FQs and their formulations?

Answer 1

Enrofloxacin (Baytril)
- small animal
- IM solution for dogs
- otic solution
Baytril 100
- food animal
- SC, solution in cattle and swine
- resp disease
- uncomplicated resp disease (better use macrolides, these are important for human medicine)

Danofloxacin (A180) “zoetis version of baytril100”

• SC and solution for cattle
• resp disease claims

Marbofloxacin (zeniquin)

• oral tablets (dogs/cats)
• otic solution

Orbifloxacin (orbax)
- oral tablets (dogs/cats)

Pradofloxacin (Verflox)
- oral tablets (dog), suspension (cats)

Question 2

What is the human (many generics) FQ that is also a metabolite of enrofloxacin?

Answer 2

Ciprofloxacin

Question 3

What is the MOA of FQs?

Answer 3

bacterial DNA inhibition

• toopisomerase 2 (DNA gyrase) binds to dsDNA and supercoils it - cuts and reconnects it (tightly wound DNA is needed for bacteria)
• FQ binds to DNA gyrase (inhibiting reconnection and destroys it)
• FQ also inhibits topoisomerase 4 (relaxes super coils)

Question 4

What is the PK-PD relationship of FQ?

Answer 4

bactericidal concentration dependent

to maximize efficacy
- need an AUC/MIC ratio above 125 can can reach quickly with higher ratio

Question 5

Why is it beneficial to hit em hard and fast with FQs (same as AGs)?

Answer 5

to reach concentration dependent doses

to minimize AMR (chromosomal mutations from pressure) from long term therapy

Question 6

What is the spectrum of activity of FQs?

Answer 6

effective
- some gram + (staph), most gram - (BRD,SRD, enteric pathogens), some anaerobes (PRADO), Pseudomonas (CIPRO), some mycoplasma, chlamydia, rickettsia

less/not effective?
- strep and enterococcus (less), anaerobes (except PRADO)

Question 7

What is FQ the best option for treating?

Answer 7

enteric pathogens

pseudomonas

Question 8

What are the mechanism of resistance used for FQs?

Answer 8

lots of resistance emerged (historical MIC no accurate)

chromosomal mechanism (not transferred)

• mutations in topoisomerase genes
• decrease permeability/efflux

plasmid mediated
- qnr gene: protects DNA gyrase

cross resistance

chromosomal mutations occur with selective pressure
- chronic low dose

Question 9

What bacteria is there lots of resistance in and what is emerging?

Answer 9

staph and pseudomonas (lots)

Mannheimia (rising)

Question 10

What are FQ warning statements about resistance?

Answer 10

dont use in feedlot - mass medication
use susceptibility test
dont use extra label (illegal in US)

Question 11

What is the PK of absorption with FQs?

Answer 11

good oral F

chelation with divalent cation = decrease F

Question 12

is compounded FQ effective?

Answer 12

oral
- generally yes (stable)
- use flavouring agents
exception = chelation

enrofloxacin chelated
orbifloxacin chelated
- greatly reduces F

Question 13

What is the PK of distribution?

Answer 13

lipophilic and low protein binding = high distribution to tissues

• tissue greater than plasma (but comparable)
• prostate and CSF as well

uptake into phagocytic cells
- antimicrobial activity persists (good for intracellular pathogens

Question 14

What is the PK of elimination for FQs?

Answer 14

hepatic metabolism

• ENRO metabolized to CIPRO in dogs, cats, horses
• comparable activity

excreted

• renal (filtration and tubular secretion)
• some biliary

T1/2 between 4-10h
- SID

Question 15

Will FQ be a good antibiotic to treat pleuropneumonia in horses?

Answer 15

no due to its ineffectiveness to treat streptococcus and anaerobes
- exception PRADO

use in combo

Question 16

What is the mechanism behind streptococcal shock syndrome and necrotising fasciitis (an AE of FQ)?

Answer 16

strep canis infected with bacteriophage (transfer of genetic material)

• enrofloxacin causes bacteriophage damage (SOS response in gene transfer)
• encode toxin = shock
• exacerbated by concurrent NSAID or steroid use

Question 17

what should you treat strep canis with instead of FQ and why?

Answer 17

streptococcal shock syndrome

treat with B-lactam

Question 18

What other AE can occur with FQ?

Answer 18

Arthropathies

• chronic high dose can cause articular cartilage lesions (juv dogs, large breed, foals)
• due to chelation of Mg

Retinopathy in cats

• feline ABCG2 transporter gene (blood retina barrier to pump drugs away)
• accumulation of NEOR/CIPRO at retina = degen or atrophy
• high doses
• not with PRADO less with MARBO/ORBI

Bone marrow suppression
- in dogs with extremem doses

GI
- mild irritation

Neuro

• seizures in dogs, cats, horses
• IV injection slow in horses
• Baytril = enro hullucinations in people

Question 19

What do FQ label claim about administration during growth periods?

Answer 19

dont use during rapid growth phase in dogs

• can be up to 18m in giant breeds
• 2-8m in small

Question 20

What drug interactions should be considered with FQ?

Answer 20

CYP enzyme inhibtion (ENRO/CIPRO)
- pgyp substrates

enrofloxacin + theophyline = increase theophyline concentrations