Antimicrobial Therapy: Macrolides, lincosamides, and related Flashcards
Macrolides
For this group we are lumping several closely related groups: macrolides, azalides, triamilides and others
Chemically similar compounds and as the name suffests are large molecules
These drugs are primarily Bacteriostatic and work by binding to the 50s bacterial ribosomes
They tend to have a time dependent action
Macrolides:
Absorption
many of these drugs are well absorbed PO
Macrolides:
Distribution
- Weak bases
- Lipophilic and penetrate tissues well
- concentrate in tissues and some in white blood cells
- Most have excellent penetration into lungs
- However are not the best choices for CNS or prostate
Macrolides:
Metabolism
pirmarily hepatic metabolism and biliary excretion
Only small amounts eliminated in urine
Macrolides:
Effects
- GI effects:
- erythromycin commonly causes vomiting in dogs
- Diarrhea and nausea common overall
- Horses and other non-ruminant herbivores are susceptible to GI flora alterations and overgrowth — leading to severe illness and +/- death
- SOme macrolides and CYP inhibtors
- erythromycin, clarithromycin
- Many also have anti-inflammatory/immunomodulatory effects independent of antimicrobial effects
- May result in decreased inflammation associated damage
- Azithromycin for COVID
- Tylosin for anitbiotic responsive diarrhea in dogs
Macrolides:
Spectrum
- Primarily Gram postive, but have some activity against some selected gram negative such as Pasteurella and Manheimia
- Also agianst Mycoplasma, Chlamidiophila, Rhodococus, +/- bordetella and some anaerobes
- Some activity agaisnt Leptosporosis (not best choice)
- May have activity against Enterococcus (inconsistent)
- No activity agaist Pseudomonas
Macrolides:
Resistance
Decreased penetration of drug through bacterial cell wall
Altered ribosomal target
Hydrolysis / degradation
Cross resistance with macrolides and lincosamides common
Erythromycin is the class representative on C&S
Erythromycin
- Originally isolated from “Streptomyces erythreus”
- Class repesentative on C&S
- Intramammary products approved (Rarely used)
- Injectable approved for use in cattle respiratory disease
- Oral tablets available, EXPENSIVE
- essentially no longer used
- Direct effects on GI motility – dose dependent and contributes to vomiting
- Topical and ophthalmic ointments
Clirathromycin
- Modified Erythromycin
- Oral tablets, suspension
- twice daily admin in foals, dogs, cats
- Better oral tolerability, enhanced activity, longer half-life compared with erythromycin
- good penetration into lungs, prostate, and aqueous humor
- Poor penetration into CNS
- Most people consider the treatment of choice for Rhodococcus equii pneumonia in foals
- Used occasionally in dogs and cats, but azithromycin more common
- respiratory and dermatology
- Potential adverse effects;
- Nausea, anorexia, diarrhea, CYP drug interactions
Azithromycin
- Long half-life, high tissue, bronchial secretion and leukocyte concentrations result in prolonged effects
- in humans, 5 days of dosing provides 10+ days of drug exposure
- Higer than expected rate of resistance development in humans
- Ideal dosing in dogs and cats not well defined
- once daily?
- Once daily for 7d followed by EOD
- EOD
- High concentrations in lungs, bronchial secretions
- not first choice for prostatitis or CNS
- Poor overall penetration inot aqueous humor
- Most common Adverse effects:
- nausea, vomiting, diarrhea
- Cardiac arrhythmias reported on people, QT prolongation.
- This has not been reported in animals, but is a precaustion in predisposed animals or those receiving antiarrhythmic dugs
Tylosin
- Originally isolated for Streptomyces fradiae
- Similar spectrum/adverse effects to other macrolides
- Approved for cattle and swine
- Occasionally used extralabel in dogs for colitis
- antibiotic responsive diarrhea
- Anti-inflammatory effects can occur independent of antimicrobial effects
Tilmicosin:
Cattle
SQ administration ONLY
Labeled for respiratory disease and foot rot
Fatal if administered IV, Irritating if IM
Prolonged residues in dairy cattle
Tilmicosin:
Swine
PO admin ONLY
Fatal if injected
Tilmicosin:
Goats
can be fatal
Tilmicosin:
Sheep
SQ labeled for respiratory disease and foot rot
Tilmicosin
Bovine and sheep respiratory disease
Single SQ dose, not for use in lactating dairy cattle,
Withdrawal Times:
42 days cattle
28 days sheep
Accidental injection in humans can be fatal
cardiovascular toxicity
Low exposure is less likely to be life threatening, but cautious use is needed
New Macrolides:
Tulathromycin
Bovine and swine respiratory disease, single SQ injection,
not for use in lactating dairy cattle
Withdrawal times:
18 days cattle
5 days swine
New macrolides:
Tildipirosin
Bovine respiratory disease
Single SQ dose
Not for use in lactating dairy cattle
21 day withdrawal times
New Macrolides:
Gamithromycin
Bovine respiratory diesease
SIngle SQ dose
Not for use in lactating dairy cattle
35 day withdrawal time
Lincosamide:
Systemic Administration
Clindamycin
Lincomycin
Lincosamide:
Intramammary Admins
Pirlimycin
Licosamides
Similar in mechanism and spectrum as macrolides,
Chemically distinct
Bacteriostatic, T>MIC
Weak bases, lipid soluble
Avoid use in Horses and other non-ruminant herbivores
Lincomycin
- Originally isolated for Streptomyces lincolnensis
- Approved for use in swine, chickens
- mycoplasma, Erysipelothrix, Brachyspira, Lawsonia, Streptococcus, Staphylococcus, and Leptospira (not first choice)
- NOT enterococcus
- Approved in dogs too
- Oral bioavailability is fair, reduced with feeding
- ELDU in cattle
Clindamycin
- Chemical Derivative of lincomycin
- Better anearobic spectrum than lincomycin,
- Approved for use in dogs and cats
- liquid tastes awful
- Cautious use of capsules in cats, Esophageal stricture risk
- Is available as injection, but almost never used
- Remember there may be cross resistance to macrolides
- Most common usees include dental, abscess/wounds, dermatology, respiratory
- Has been used for Toxoplasma in cats and Neospora in dogs
Clindamycin:
Absorption
Oral bioavailability better than lincomycin and not affected by food
Clindamycin:
Distribution
Distributes into most tissues well including lungs
CNS, Prostate, Eye may achieve effective concentrations for highly susceptible bacteria, but not best choice
Clinidamycin:
Metabolism
Primarily hepatic metabolism
Clindamycin:
Elimination
Small amounts eliminated in urine
May be effective for UTI
