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antibiotics (Subject) / Macrolides (Lesson)
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- structure macrocyclic lactone ring attached to sugar molecules -> lipophilic -> positive charge (due to nitrogen atoms, that absorb protons from the environment) -> high intracellular concentrations + broad distribution in tissues
- Mechanism, Mode of action Mechanism: 50S ribosome subunit inhibition -> inhibited protein synthesis Mode: bacteristatic (bactericidal in lung)
- Resistance not so common - decreased permeability - degrading enzymes - modified binding sites (50S)
- microbial spectrum primarily Gram+ Gram-: - anaerobic - Fastidious - Bordetella - Campylobacter - Brachyspira hyodysenteriae - Mycoplasma IC organisms: - Lawsonia intracellularis - Borrelia - Rhodococcus equi - Chlamydophila
- absorption PO: - variable - eg. erythromycin given as capsule - eg. tylosin given with feed IM, SC: - very good - very irritating
- Distribution excellent - penetration of special barriers (BBB not appropriate) -> used in bone infections, not in prostatitis because E. coli is resistant - high IC-concentrations (esp. azalides and trimamilides) - high concentrations especially in the lung -> used in respiratory tract infections accumulation of azalides and triamilides: because of ion-traps -> extremely long half-lifes
- metabolism lipophilic -> extensive liver-metabolism can inhibit CYP-450 (mainly erythromycin)
- excretion 90% via bile -> not appropriate for UTI treatment
- active substances macrolides: 1 nitrogen atom - erythromycin - clarithromycin - spiramycin - tylosin - tylvalosin - tilmicosin - tildipirosin azalides: 2 nitrogen atoms - azithromycin - gamithromycin triamilides: 3 nitrogen atoms - tulatrohmycin
- side effects - dysbacteriosis: especially in herbivore-rodents and horses (shouldn't be treated with macrolides -> only in serious infections, eg. Rhodococcus equi + foals aren't sensitive) - tissue irritation at site of injection -> injection only in large animals, PO-adm. in small animals - GIT disturbances: vomiting, diarrhea
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- Erythromycin - old, obsolete - small animals: Campylobacter infections - large animals: respiratory tract infections, diamond skin disease in Su - horses: R. equii
- Azithromycin, Clarithromycin - replaced erythromycin completely - used in small animals (PO) - excellent absorption and distribution, long half-life, high lung-concentrations - very safe, only side-effect can be vomiting - Indications: Gr+ (dermatitis, mastitis etc.) fastidious (respiratory infections) Mycoplasma, Campylobacter, R. equi Borrelia (if Doxy can't be used)
- Spiramycin - small animals: oral cavity infections (anaerobes) - large animals: very infrequent use, sometimes mastitis & metritis
- Tylosin - frequent resistance - small animals: antibiotic responsive diarrhea - FIRST CHOICE - Su: Lawsonia intracellularis (formerly Brachyspira, but resistant nowadays) - large animals: respiratory infections (Mycoplasma, fastidious) necrotic enteritis (if Penicillin and Amoxicillin don't work)
- Tylvalosin Tylosin-derivate only given PO pigs, poultry: - Brachyspira hyodysenteriae - Lawsonia intracellularis - Mycoplasma (+++) - Fastidious (+)
- Tylmicosin - most toxic macrolide (cardiotoxic for horses, goats and humans) - Ru: SC (not IM or IV) - Su: PO (not IM or IV) - excellent pharmacokinetics, accumulated in lungs -> respiratory infections - Mycoplasma + - Fastidious ++
- Tulathromycin, Gamithromycin - adm.: injection - species: pigs, ruminants - excellent distribution, very high lung concentration -> respiratory infections - Mycoplasma +++ - Fastidious +++
- Tildipirosin - adm.: injection - species: pigs, ruminants - excellent distribution, longest DOA - Mycoplasma: NO action - Fastidious: +++
- Azithromycin dose dog, cat: PO 10 mg/kg BID horse: PO 10 mg/kg SID