AMINOCOUMARINS:
- These are class of antibiotics which contain core structure of 3-amino-4,7- dihydroxycoumarin ring.
- They act by inhibition of DNA gyrase
- These class of antibiotics include novobiocin, coumermycin and clorobiocin.
Novobiocin:
- It is narrow spectrum antibiotic obtained from actinomycetes Streptomyces niveus and spheroids.
Mechanism of action:
Novobiocin binds to 2B subunit of DNA gyrase
Novobiocin competes with ATP for binding to 2B subunit of bacterial DNA gyrase
Inhibition of ATP-dependent DNA supercoiling
Inhibition of cell wall synthesis
Antimicrobial spectrum:
- It is mostly active against gram +ve bacteria
- Some gram -ve bacteria like some species of Haemophilus, Proteus, Neisseria and Brucella are also susceptible
- Staphylococcus aureus and Streptococcal pneumonia are gram +ve bacteria sensitive to novobiocin.
- Many species of bacteria (ex: Staphylococci) can develop resistance to novobiocin.
Pharmacokinetics:
- It is well absorbed only with peak plasma levels reaching 1-4 hours.
- Presence of food in G.I tract can decrease peak concentration of drug.
- It is not well distributed in body tissues and fluids with minimal amount in synovial, pleural, cerebrospinal fluid and brain
- Approximately 90% drugs are plasma protein bound
- It is mainly excreted in bile and faeces.
Side effects/Adverse effects:
- GI disturbances (nausea, vomiting & diarrhoea)
- Blood dyscrasias (leucopenia, pancytopenia, anemia, agranulocytosis and thrombocytopenia)
- Fever, rashes and hypersensitivity.
Clinical uses:
- It is mostly used in combination with penicillin G in treatment of mastitis.
- In treatment of MRSA infection
- As feed additive in poultry ration
Dose:
Dogs: 10-20 mg/kg, PO, 2-3 times daily