RIFAMYCINS:

• These are group of structurally similar, complex macrocyclic antibiotics produced by Streptomyces mediterranei.
• They are effective against gram +ve organism with no/negligible activity against gram -ve bacteria.
• They are particularly effective against mycobacteria and therefore used to treat tuberculosis, leprosy and mycobacterium avium complex in human patients.
• They also possess antiviral activity

Rifampicin:

• It is semi-synthetic rifamycin derived from rifamycin B.

Mechanism of action:

Inhibits the bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase

This halts the initiation of mRNA transcription

Prevention of translation of polypeptides

• Inhibits only prokaryotic DNA primed RNA polymerase
• In normal concentration they doesnot inhibit mammalian enzyme

Antimicrobial spectrum:

• It has high activity against gram +ve bacteria and mycobacteria
• Susceptible organism includes Staphylococcus, Haemophilus, Neisseria, Chlamydia and Mycobacterium species.
• It is also used in treatment of clostridium and bacteroides species infection.
• It has also some activity against gram -ve bacteria like Brucella
• Enterobacteriaceae, Actinobacter & Pseudomonas species are intrinsically resistant to rifampicin

Bacterial resistance:

• Bacterial resistance develops quickly when used as sole antibitotic
• Resistance is due to alteration in DNA dependent RNA polymerase
• Combination of rifampicin with erythromycin, β-lactam antibiotics and aminoglycosides decrease resistance.

Pharmacokinetics:

• It is relatively well absorbed (40-70%) from GI tract after oral administration
• Peak plasma concentration occurs within 2-4 hours after oral administration
• Absorption from IM site is rapid
• Rapidly distributed to body tissues and fluids
• It can also penetrate abscess and caseous material
• 75-80% of rifampicin are bound to plasma protein
• Metabolized by liver to active metabolites
• Primarily excreted in bile and less in urine
• Elimination half-lives in dogs=8 hrs, horses= 6.8 hrs, sheep= 3.5 hrs.

Side effects/Adverse effects:

• Hepatoxicity
• IV administration may produce CNS depression, sweating, hemolysis and anorexia
• Nausea, vomiting, anorexia, abdominal cramps and diarrhoea
• Orange-red discolouration of urine
• Hypersensitivity

Contraindications and precautions:

• Contraindicated in patients with hypersensitivity to rifampicin
• It should be used cautiously in patients with hepatic dysfunction
• It should be used cautiously in pregnant animals.

Drug interactions:

• It can enhance elimination half-live of digitalis, corticosteroids, oral anticoagulants, ketoconazole, propanolol, quinidine, barbiturates, verapamil

Clinical uses:

• It is used in combination with erythromycin for treatment of pneumonic infections in foals, caused by Rhodococcus equi.
• It is combined with amphotericin B to treat CNS fungal infection
• In humans, it is primarily used in tuberculosis

Dose:

For R. equi and other

Foals: 5mg/kg, PO, 2 times daily

Dogs & cats: 10-20 mg/kg, PO, 1-2 times daily

Birds: 10-20 mg/kg, PO, 2 times daily

For CNS fungal infection

Dogs & cats: 10-20 mg/kg, PO, 3 times daily in combination with amphotericin B