50S RIBOSOMAL INHIBITORS: Macrolides, Lincosamides, Pleuromutilins, Phenicols

1st Gen Natural (S. erythreus) that deals with gram + aerobes, selected anaerobes, and atypical pathogens

Erythromycin

TX for Rhodococcus equi pneumonia in foals (with rifampin).

Erythromycin

Azithromycin

Clarithromycin

GI irritation, vomiting & diarrhea.

Poor CNS entry. Soluble powder in poultry.

Erythromycin

Mycoplasma & Gram(+) aerobes in livestock.

• Swine dysentery & mycoplasma pneumonia.

• Bovine respiratory disease & liver abscesses (F. necrophorum).

Tylosin

Feed/water additives & injection.

FATAL HAZARD: Causes fatal enterocolitis in horses!

Tylosin

Bovine & Ovine Respiratory Disease (BRD/SRD) caused

by Mannheimia haemolytica & Pasteurella multocida.

Tilmicosin

(Pulmotil / Micotil)

Long tissue persistence allows single SC dose.

HUMAN LETHALITY HAZARD: Fatal cardiotoxicity! NEVER give IV!

Tilmicosin

(Pulmotil / Micotil)

Single-dose SC treatment/control of Bovine & Swine

Respiratory Disease complex (BRD/SRD).

Rapid lung accumulation, multi-day tissue

persistence. Labeled for cattle & swine.

Tulathromycin

Gamithromycin

Tildipirosin

Off-label companion animal & foal therapy.

• R. equi in foals (with rifampin). Feline respiratory infections.

Azithromycin

Clarithromycin

Enhanced acid stability & tissue/CNS penetration vs. erythromycin.

Contraindicated in adult horses.

Azithromycin

Clarithromycin

Gram(+) spectrum + activity against Toxoplasma gondii & Isospora spp. (Spiramycin).

Agricultural feed additives and specialty veterinary formulations.

Spiramycin

Josamycin / Kitasamycin

Natural (S. lincolnensis)

• Swine: Dysentery, mycoplasma pneumonia, erysipelas, streptococci.

• Ruminants: Intramammary infusion for mastitis.

• Small Animals: Abscesses, skin/wound infections, osteomyelitis.

Lincomycin

High lipid solubility & Vd.

WARNING: No systemic formulation labeled for ruminants!

Lincomycin

• Small Animal: Staphylococcal osteomyelitis, deep pyoderma, periodontal disease, wound infections.

• Active against Toxoplasma gondii.

Clindamycin

Superior potency & oral bioavail vs. lincomycin.

Can cause esophageal irritation in cats (follow pill with water).

Clindamycin

Lincosamide + Aminocyclitol ; Synergistic water-soluble powder/injection for livestock & poultry.

• Poultry: Mycoplasmal air sacculitis, CRD (M. gallisepticum + E. coli), necrotic enteritis (C. perfringens).

• Livestock: Enteric/respiratory infections.

Lincomycin + Spectinomycin

• Swine: Swine dysentery (Brachyspira), mycoplasma pneumonia, proliferative enteropathy (Lawsonia).

• Feed/water additive or IM injection.

Lipophilic weak base; rapid oral absorption in monogastrics; hepatic metabolism &

biliary excretion. Concentrates in milk.

Tiamulin

(Denagard)

FATAL IONOPHORE INTERACTION:

Inactivates hepatic P450 metabolism of

ionophores (monensin, salinomycin, narasin),

causing severe muscle necrosis, ataxia,

paralysis, and death!

Tiamulin

(Denagard)

Swine mycoplasmal pneumonia, swine dysentery, and spirochetal enteropathy. Extensive tissue volume of distribution; rapid oral absorption in swine.

Same severe ionophore interaction risk. Strictly observe separation intervals in feed.

Valnemulin

Broad spectrum: Gram(+), Gram(-), anaerobes, Rickettsia.

Reserved for non-food animal severe infections (CNS/ocular).

Chloramphenicol

High Vd; 50% of plasma conc reaches CNS & ocular fluids.

Hepatic glucuronidation. Long t1⁄2 in cats (5.1h) due to glucuronyl transferase deficiency.

Chloramphenicol

STRICTLY PROHIBITED IN FOOD

ANIMALS! Causes human fatal idiosyncratic

aplastic anemia (not dose-dependent).

Dose-related marrow suppression in pets.

Chloramphenicol

Fluorinated derivative.

• Bovine Respiratory Disease (BRD): M. haemolytica, P. multocida, Histophilus somni.

• Swine respiratory disease.

Florfenicol

(Nuflor)

Lacks p-nitro group. Highly lipophilic.

Note: Milk interferes with oral absorption!

Long elimination t1⁄2 in cattle (18.3h).

Florfenicol

(Nuflor)

Approved for food animals (no idiosyncratic

aplastic anemia). FloR gene-mediated efflux

resistance occurs. Adverse: transient

diarrhea, inappetence.

Florfenicol

(Nuflor)

Broad-spectrum bacteriostatic phenicol.

Respiratory, GIT, and topical hoof/wound infections in livestock.

Hepatic metabolism; excreted in urine and bile.

Hepatic metabolism; excreted in urine and

bile.

Lacks nitro group; lower risk of idiosyncratic

aplastic anemia, but dose-dependent bone

marrow suppression remains possible.

Thiamphenicol

ELDU in cats.

With rifampin for R. equi. Do NOT use in adult horses!

Erythromycin

BRD & liver abscesses.

Swine dysentery / mycoplasma.

ELDU in pets. American Foulbrood. Fatal in horses!

Tylosin

BRD / SRD treatment. Single dose.

FATAL HUMAN IV/SELF-INJECTION HAZARD!

Tilmicosin

Single-dose BRD/SRD therapy.

Tulathromycin

BRD treatment & control.

Gamithromycin
Tildipirosin

Off-label. Intracellulars. Combined with rifampin in foals.

Azithromycin

Off-label. High oral bioavail. Do NOT use in adult horses.

Clarithromycin

Swine dysentery. Pet pyoderma/wounds. No systemic ruminant use.

Lincomycin

ELDU. Osteomyelitis, pyoderma, periodontal, toxoplasmosis.

Clindamycin

Labeled BRD / SRD treatment. Milk interferes with PO absorption.

Florfenicol

50S peptidyl-transferase

Mycoplasma, Brachyspira, anaerobes

Swine dysentery, ileitis, mycoplasmal pneumonia

Lethal interaction with ionophore anticoccidials

Pleuromutilins

50S subunit

Gram(+), Mycoplasma, atypical intracellulars

Livestock BRD/SRD, foal R. equi pneumonia

Tilmicosin human lethality; horse enterocolitis

Macrolides

50S subunit

Gram(+), anaerobes, Mycoplasma

Small animal osteomyelitis, pyoderma, mastitis

Fatal enterocolitis in herbivores/horses

Lincosamides

50S subunit

Broad-spectrum: Gram(+), Gram(-), anaerobes

Livestock BRD (___); pet CNS/eye (___ + food animal prohibition)

Livestock BRD (Florfenicol); pet CNS/eye (Chloramphenicol + food animal prohibition)

NEVER ADMINISTER IV. Intravenous injection of this medicine in cattle, sheep, or any animal induces acute, lethal cardiotoxicity.

TILMICOSIN

HUMAN FATALITY RISK: Accidental human self-injection has caused fatal myocardial depression and cardiac arrest. Handle syringes with extreme caution. Emergency medical attention is required immediately upon accidental exposure.

TILMICOSIN

inhibits cytochrome P450 metabolic degradation of ionophores (monensin, salinomycin, narasin, maduramicin).

• Concurrent or closely spaced administration in poultry or swine leads to toxic ionophore accumulation, resulting in severe muscle necrosis, inappetence, locomotor ataxia, paralysis, and death. Always verify feed additive history and observe required separation intervals.

TIAMULIN

used ONLY in foals for R. equi; strictly contraindicated in adult horses.

Macrolides (Erythromycin, Azithromycin, Clarithromycin)

Horses, Rabbits, Guinea Pigs & Rodents: Systemic oral or parenteral administration of - - - - severely disrupts normal cecal/colonic anaerobic microflora.

• Triggers rapid overgrowth of Clostridium difficile / Clostridium perfringens, producing fatal hemorrhagic enterocolitis.

Tylosin, Lincomycin, Clindamycin, or Tiamulin

STRICTLY PROHIBITED IN FOOD ANIMALS: Human dietary exposure to __ residues can trigger rare, unpredictable, and fatal idiosyncratic aplastic anemia (not dose-dependent). Zero tolerance in food animals.

Cats lack glucuronyl transferase, leading to prolonged elimination half-life (t1⁄2 = 5.1h) and risk of dose-dependent bone marrow suppression.

chloramphenicol

lacks the p-nitro group responsible for aplastic anemia and is safely approved for livestock.

Florfenicol