Phenicols

Question 1

What are the two phenicol drugs?

Answer 1

florfenicol

chloramphenicol

Question 2

what are the different label claims/formulations for each drug?

Answer 2

Nuflor (IM,SC - cattle)(swime IM)

• cattle: resp disease, footrot, pinkeye
• swine: resp

Resflor: florfenicol + flunixin (SC)
- cattle: resp + pyrexia

Aquaflor: premix for salmon
- aeromonas and vibrio infections

Osurnia: ear medication with terinafine (antifungal) and betamethasone (steroid)

Chlorseptin (chewable tablets)
- dogs

ChlorPalm 250 (oral)
- dogs and cats

Human generic

• oral tablets and suspensions
• injectable

Question 3

What is the MOA of phenicols?

Answer 3

binds to 50s subunit
- incorrect protein synthesis
inhibits mitochondrial protein synthesis in mammalian bone marrow
- dose dependent
- especialy chloramphenicol
- nbd

Question 4

What is the spectrum of activity of phenicols?

Answer 4

“second line therapy for small animals”

generally effective

• gram + (some MRSA/MRSP)
• gram -
• anaerobes
• some mycoplasma (not clinically)
• some rickettsia & chlamydia

less effective

• gram - enteric often resistant (mostly chloramphenicol)
• pseudomonas
• enterococcus
• rhodococcus, mycobacterium, nocardia
• resistance rapidly emerges

Question 5

What is the mechanism in which bacteria develop resistance to phenicols?

Answer 5

enzymes adding acetyl groups

• prevents binding to 50s
• flor less susceptible

decrease permeability
increase efflux (floR gene in gram - enterics)
mutations to 50s

resistance genes are mobile

Question 6

what is the F of phenicols?

Answer 6

chloramphenicol

• good oral
• lower absorption of palmitate formulations in fasting cats
• inactivated in rumen

Florfenicol

• prolonged absorption afte rIM/SC
• flip flop kinetics (IM is being absorbed slow while elimination is only slightly faster, where IV and IMM are quick elimination)

Question 7

What is the distribution of Phenicols?

Answer 7

moderate/high VD
specific tissues in dogs
- highest in lung and kidney
- lung, spleen, heart, muscles similar to plasma
- good penetration in aqueous and vitreous humor
- can diffuse into CSF, milk, pleural, and peritoneal fluid, cross placenta
- little into prostate unlss unflammed

Question 8

Why should you be cautious about giving phenicols to pregnant animals?

Answer 8

crosses placenta

Question 9

What is the metabolism/elimination of phenicols?

Answer 9

hepatic metabolism and glucuronide conjuction

• poor in cats (longer half life and dosing interval)
• longer t1/2 in younger

primary renal excretion of inactive metabolites

Question 10

What is the PK-PD relationship of phenicols?

Answer 10

bacteriostatic
- ratio of of MBC:MIC is large = not safe to administer cidal concentrations

Time dependent
- reccomended T>MIC for > 50% of dosing interval

combo of time and concentration
- dosing probably doesn’t make a difference other than AE

Question 11

What interactions does phenicols have with other drugs?

Answer 11

may be antagonistic in combo with other drugs

Question 12

What interactions do phenicols have with B-lactams, macrolides, AGs, and fluroquinolones?

Answer 12

B-lactams
- phenicol mediated bacterial protein inhibition decreases B-lactam effect on cell wall synthesis

Macrolides
- both act on 50s

AG
- bacteriocidal AG affect is decrease with phenicol mediated bacterial inhibition

Fluoros
- interferes with lysis of bacteria after FQ interfere with DNA synthesis

Question 13

What is the clinical relevance of these interactions?

Answer 13

NEVER USE IN COMBO

Question 14

What other drug interactions does chloramphenicols have?

Answer 14

hepatic matabolism interactions

• can prolong barbiturate anesthesia
• can inhibit phenobarbital metabolism

Question 15

What other drug interactions do Florfenicols have?

Answer 15

not known for hepatic drug interactions

- b/c used in large and often dont look for them or use combo drugs

Question 16

What are some blood AE that occur with phenicols?

Answer 16

blood dyscrasias (aplastic anemia, pancytopenia)

• dose dependent for both phenicols
• related to total exposure (AUC, dose and duration)
• cats more likely to develop (decreased clearance)

dose independent (idosyncratic)

• few reports in vet med
• only with chloramphenicol

Question 17

Which phenicol drug is banned in food animal?

Answer 17

Chloramphenicol

Question 18

What are some GI adverse events?

Answer 18

CHL: vomit, diarrhea, inappetance
FLOR: change in GI flora = diarrhea in calves
Nuflor label (dont use in scours calves)

Question 19

Why should you not use Nuflor (Florfenicol) in scours calf?

Answer 19

change GI flora = diarrhea

Question 20

What are some things to consider when dosing Chloramphenicol?

Answer 20

Dogs: high dose TID or QID
Cats: high BID

prolonged administration not recommended

• due to AMR and or AE
• limited to 10d
• if no response in 3-5d discontinue

Question 21

Is phenicols an option for MDR pathogens? which drug? (studies)

Answer 21

case:

uterine culture: enterococcus
- Cloramphenicol can be used if there are no other options

Skin culture
- not ideal because skin infections often need long duration treatment

Question 22

Why should you not use phenicols for skin infections?

Answer 22

often need long duration of use (not recommended due to AMR and AE)

Question 23

Should NuFlor be used to treat foot rot or pink eye in cattle?

Answer 23

those conditions are easy to treat and would be a waste of florfenicol
- use something else