5. Fluoroquinolones, Novobiocin, & Rifampin

What is the mechanism of action of the fluoroquinolones?

inhibit DNA gyrase and topoisomerase

Are fluoroquinolones bacteriostatic or bactericidal?

bacteriocidal

What is the spectrum of fluoroquinolones?

Gram positive and negative aerobes

non-fluorinated precursor that only kills some Gram negatives

nalidixic acid

What was the purpose of adding fluorine to nalidixic acid?

added Gram positives to their spectrum

Another chemical addition

True or false: Each chemical addition to fluoroquinolones can broaden or narrow the spectrum. It can cause them to target a specific bug, kill everything, or circumvent resistance.

true

Fluoroquinolones have how many different sites for chemical additions? What is the equation?

four; (10,000 chemical groups)⁴ = 1X10⁸ drugs

What is the most common way for there to be resistance to fluoroquinolones? What does this cause?

point mutations in DNA gyrase genes; fluoroquinolones have a decreased affinity for the gyrase

True or false: There are about 50 different mutations that will lead to a decrease in sensitivity. The first mutation is sensitive, the second mutation is intermediate, and the third mutation is resistant.

true

Certain mutation combinations can lead to ________ resistance. The plasma fluoroquinolone concentration cannot be ________ than the MIC.

insurmountable; greater

What is a less common way that there is resistance to fluoroquinolones?

bacteria make a peptide that sequesters or modifies the fluoroquinolones before reaching DNA gyrase

How can resistance to fluoroquinolones be eliminated?

small chemical changes can eliminate resistance by certain bugs

What is interesting about moxifloxacin?

kill anaerobes but not MRSA

True or false: Each bug may have its own fluoroquinolone.

true

What has the fastest development of resistance to fluoroquinolones?

campylobacter

When are fluoroquinolones most effective?

if the plasma concentration is 5-10 times the MIC

What is the mutation prevention concentration (MPC)?

simply equals the MIC times 5 or 10

What is the MPC for Gram negatives with fluoroquinolone treatment?

times 10

What is the MPC for Gram positives with fluoroquinolone treatment?

times 5

During the dosing interval with fluoroquinolones, what must happen with C_max? Why?

it must exceed the MPC; resistance will develop during treatment

Momentary exposure to an antibiotic can lead to bacterial stasis for up to how long? What is significant about fluoroquinolones?

48 hours; very dramatic

Where are the concentrates in fluoroquinolones in all species?

1. W

2. P

3. B

1. WBCs

2. prostate

3. brain

Fluoroquinolones are well absorbed ________. There is no need to ______/______ dogs or cats.

orally; IV/IM

What is the effect on the oral C_max after 1 hour?

it stays the same

What is the plasma protein binding of fluoroquinolones? What is the V_d?

low; high

How are fluoroquinolones excreted in the urine? Why is this significant?

mostly unchanged; good against UTIs and there are not worries about drug metabolism issues in patients with hepatopathies

What is the special consideration about fluoroquinolones in neonates/juveniles?

it is chondrotoxic

What is specifically affected by fluoroquinolones in neonates/juveniles?

mitochondria in immature articular chondrocytes

Does the chondrotoxicity of fluoroquinolones in neonates/juveniles affect horses or dogs more? Is this reversible or irreversible?

dogs; reversible

What is the special consideration with fluoroquinolones in cats? Is this reversible or irreversible? What is this least likely with?

cause retinopathies; irreversible; pradofloxacin

What is the special consideration with fluoroquinolones in epileptic dogs? How?

exacerbates seizures; GABA-R antagonism

What drug causes the Herxheimer’s reaction in dogs? Specifically dogs with what bacterial infection?

fluoroquinolones; strep canis

What fluoroquinolone is used in a dog with S.canis? What does it do? What does this cause? What is the end result?

enrofloxacin; activates the bacteriophage; lyses S.canis; massive inflammatory response

Fluoroquinolones are never the first choice unless what?

P
R

• potentially fatal malady or antibiogram

• resistant to all other choices

What is the affect of fluoroquinolones on divalent cations? Which one specifically?

chelate them; Mg2+

Since fluoroquinolones chelate divalent cations, what does this mean?

they are poorly absorbed when given with antacids

What enzymes do fluoroquinolones inhibit? Especially which fluoroquinolone? What is the most dramatic effect on?

cP450; enrofloxacin; theophylline

In what species are fluoroquinolones banned? Why?

poultry; leads to fluoroquinolone resistant campylobacter in poultry

What happens if humans take fluoroquinolones?

D
H

• depression

• hallucinations

True or false: You cannot use fluoroquinolones extra-label in food animals.

true

fluoroquinolone that is the oldest and approved in swine, small animals, and cattle

enrofloxacin

Which fluoroquinolone is approved just for bovine?

danofloxacin

Which fluoroquinolones are less retinotoxic?

orbifloxacin and marbofloxacin

Which fluoroquinolone has the best peritoneal distribution?

difloxacin

Which fluoroquinolone in oral suspension is non-retinotoxic in cats? What else is it used for?

pradofloxacin; BRD and SRD (injectable)

What is the method of action of novobiocin?

prevents ATP from binding to DNA gyrase and has no effect on topoisomerase

Is novobiocin bacteriostatic or bacteriocidal?

bacteriostatic

What is the spectrum of novobiocin?

staph aureus

What is the only use for novobiocin?

dry cow mastitis treatment with penicillin

What is significant about the resistance of novobiocin? So what needs to be done?

resistance develops rapidly; use with another antibiotic

What is the mechanism of action of rifampin?

inhibits RNA polymerase

What is the spectrum of rifampin? What is its purpose in humans?

mycobacteria and Gram positive; TB drug

What is significant about the resistance of rifampin? Therefore, what needs to be done?

develops quickly; use with another drug

What can occur in horse with IV use of rifampin?

sweat and hemolysis

What drug class causes immune-mediated hepatitis in dogs on prolonged treatment?

rifampin

Which drug class causes an orange discoloration of body fluids like sweat, urine, and saliva?

rifampin

What is rifampin an inducer of?

microsomal enzymes

What drug class would you use for salmonella DT104?

fluoroquinolones

Which fluoroquinolones are used in BRD?

E
D
P

• endrofloxacin

• danofloxacin

• pradofloxacin

Which fluoroquinolones can be used in feline respiratory disease?

O
M
P

• orbifloxacin

• marbofloxacin

• pradofloxacin

In canines, why might fluoroquinolones be used?

R
O
P
P

• respiratory disease

• ostemyelitis

• peritonitis

• prostatitis

Which fluoroquinolones could be used in canines if necessary?

E
D
O
M

• enrofloxacin

• difloxacin

• orbifloxacin

• marbofloxacin

What fluoroquinolone can be used for equine peritonitis/pleuritis?

difloxacin

Which fluoroquinolones can be used for swine respiratory disease?

E
P

• enrofloxacin

• pradofloxacin

When would you use rifampin in horses? Along with what drug?

rhodococcus equi infection; clarithromycin

When would you use rifampin in the oryx?

M. bovis infection

What is a third reason to use rifampin? With what drug?

deep pyodermas; cephalosporin

When is novobiocin indicated?

chronic S. aureus mastitis that will not clear up during lactation

What does baytril otic contain?

enrofloxacin and silver sulfadiazine

What is the purpose of enrofloxacin in Baytril otic?

provides the antibacterial activity

What is the purpose of the silver sulfadiazine in Baytril otic?

provdes the anti-mycotic activity

True or false: No fluoroquinolones are used in feed.

true

What are the main indications for enrofloxacin? What type of formulation is available for dogs?

cattle and swine respiratory; chewable

What are the main indications for pradofloxacin?

cats and BRD and swine respiratory disease