Macrolides

Question 1

What other drugs are “Mycin” and should not be confused with macrolides?

Answer 1

aminoglycosides and trade name of a tetracycline

Question 2

What macrolide is licensed for food animal general vet use? include formulations and treatment

Answer 2

Tylosin (premix or medicated water)

• swine dysentry and porcine proliferative enteropathy (L. intracellularis)
• reduction in liver abscesses in feedlot cattle
• aid in resp diseases and necrotic enteritis in broilers

Question 3

What are the “respiratory” vet macrolides and their formulations?

Answer 3

Tilmicosin (micotil)

• SC ONLY (Cattle/sheep)
• oral Pulmotil premix and liquid for swine, feedlot cattle and rabbits

Tulathromycin (Draxxin)

• SC in cattle
• IM in swine

Gamithromycin (Zactran)
- SC in cattle

Tuldiprosin (Zuprevo)
- SC in cattle

Question 4

Are these resp/BRD macrolides any different?

Answer 4

all are similar

all about marketing

Question 5

What human drug is often used extra label in small animals?

Answer 5

Azithromycin

- oral tablets and suspensions

Question 6

What 2 macrolides are licensed but not common

Answer 6

tylvalosin (Aivlosin)

• oral premix or water for pigs
• PPE (by L.intracellularis in pigs)

Erythromycin (gallimycin)

• feed premix licensed for poultry (non-specific)
• formerly in IMM tubes
• still recommended as therapy for some things in horses and small animals

Question 7

Name 3 “like macrolides” lincosamides (include formulations and use)

Answer 7

Lincomycin

• oral premix, oral solution, injectable
• licensed for swine, poultry, dogs/cats

Clindamycin (antirobe)

• increase activity compared to lincomycin
• common for skin, dental. bone, anaerobic infections
• resistance emerges quickly

Pirlimycin (Pirsue)
- IMM

Question 8

What drug is a “like macrolide” pleuromutilins?

Answer 8

Tiamulin (Denagard)

• liquid solution or premix
• Tx and prevention of swine dysentry association with brachyspira hyodysenteriae

Question 9

What drug is a “like macrolide” streoptogramins?

Answer 9

Virginiamycin (Stafac)

• feed premix
• “Virax” for cattle
• swine dysentary
• broilers: prevention of necrotic enteritis (C. perfringens)

Question 10

What is the MOA of macrolides and lincosamides?

Answer 10

binds to 50s subunit

• different spot tha phenicols
• incorrect tRNA translation/protein synthesis

Activity pH dependent
- basic amine group decrease bacterial uptake but still clinically effective

Question 11

What is the PK-PD relationship of macrolides and lincosamides?

Answer 11

bacteriostatic
- depends on which macrolide pathogen combo
time dependent
- azithromycin (some concentration dep effect)

Question 12

What is the spectrum of activity of macrolides and lincosamide?

Answer 12

effective
- most gram +, some gram - (BRD and SRD pathogens), some anaerobes (clindamycin esp), helicobacter (azithromycin), some mycoplasma, intracellular pathogens (lawsonia, rhodococcus), spirochetes (brachyspira), chlymydia, taxoplasma (clindamycin)

Less/not effective
- gram - enterics, pseudomonas, enterococcus,

Question 13

What is the mechanism of resistance?

Answer 13

inability to bind to bacterial ribosome
- RNA methylation (erm gene)
- mutations to binding site
effluc pumps
enzymatic inactivaion of drugs
plasma mediated resistance genes (cross resistance)
- happens quickly

Question 14

Which BRD bacteria shows resistance to which macrolides?

Answer 14

mannheimia hemolytica

• tulathromycin, ggamithromycin, tildipirosin, tilmicosin
• beginning of resistance

Question 15

What is the PK of absorption for macrolides and lincosamide?

Answer 15

lots of variation in F between drugs

• special coatings (less irritations)
• food may alter

Question 16

What is the PK of Distribution for macrolides and lincosamide?

Answer 16

high lipophilic drug
low plasma but high Vd
dont use for septicemia (use for resp)

special tissues
- high lung concentrations
CSF: lincomycin and clindamycin

concentrate in leukocyte

• intracellular pathogens
• delivered to site of infection

Question 17

What is the PK of elimination of macrolides and licosamide?

Answer 17

some hepatic metabolism
excretion in bile or urine

long half life (tilmicosin, tullathromycin, gamithromycin, tildopirosin)

once distributed to lung it is slowly eliminated, redistributed back to plasma then eliminated

Question 18

Do macrolides have long withdrawal periods/ are they prohibited in food animal?

Answer 18

not prohibited

- not in edible tissues

Question 19

What are the adverse events of tilmicosin?

Answer 19

cardiovascular toxicity
- SC only in sheep and cattle
FATAL on IV (epinephrine worsens toxicity)
FATAL parenterally in humans, goats, dogs
- CA channel blockage / Ca depletion
tachycardia but neg inotrope
IV CA may be protective

Question 20

What other AE are seen with macrolides and licosamides?

Answer 20

GI

• oral (diarrhea,vomiting)
• irritation/less motility

GI flora

• fatal colitis in horses (erythromycin)
• caution with rodents

injection irritation

• tilmicosin especially (must go SC)
• erythromycin IM very irritating

hyperthermia
- erythromycin with foals

Question 21

What drug interactions should be considered?

Answer 21

some
CYP inhibitors (erythromycin)
- antagonism when used with phenicols
- both bind to 50s
- macrolides dont cause bone marrow toxicity

Question 22

Which antibiotic causes antagonism of macrolides

Answer 22

Phenicols

Question 23

What macrolide has prokinetic capabilities? mechanism?

Answer 23

erythromycin

- motilin recpetor agonist or cholinergic neurons

Question 24

How do macrolides have anti-inflammatory and immunomodulation capabilites? which drug is commonly used for this property?

Answer 24

macrolides inhibit production of proinflammatory cytokines
- decrease neutrophil migration

Tylosin: GI antiinflammatory