Novobiocin
Synonyms and keywords: Novobiocin sodium; Streptonivicin

# Overview
Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym forS. spheroides, a member of the order Actinobacteria. Other aminocoumarin antibiotics include clorobiocin and coumermycin A1. Novobiocin was first reported in the middle of 1950s (called then streptonivicin).

# Category
Aminocoumarin

# US Brand Names
ALBAMYCIN (DISCONTINUED)

# Prescribing Information

### Contraindications
- Hypersensitivity to novobiocin

### Precautions
- Leukopenia or blood dyscrasias
- Liver dysfunction

### Adverse Reactions
- Myocarditis
- Skin eruption and fever are the most frequent hypersensitivity phenomena. The incidence of the RASH is in about 12% of treated patients with an onset between the 6th and 12th day of treatment. The rash may appear erythematous, maculopapular, scarlatiniform, or urticarial.
- YELLOW DISCOLORATION of the skin and plasma is the result of a circulating lipochrome pigment that is a degradation product of novobiocin.
- The hemorrhagic nature of cutaneous lesions may indicate that novobiocin has a coumarin-like effect.
- Hematology finding
- Jaundice
- Immune hypersensitivity reaction
- Eye / vision finding
- Respiratory finding

### Teratogenicity/Effects in Pregnancy
- Fetal risk cannot be ruled out.
- Clinical Management

### Breastfeeding
- Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.
- Clinical Management

### Dosage and Administration
Oral route
- The usual oral adult dose is 250 milligrams every 6 hours or 500 milligrams every 12 hours for treating serious infections due to susceptible S aureus or Proteus URINARY TRACT INFECTIONS when other less toxic antibiotics are contraindicated or ineffective.
- Up to 500 milligrams every 6 hours or 1 gram every 12 hours of novobiocin may be administered orally for resistant or severe infections.
- Dosage adjustment in renal failure is not indicated because less than 3% of a dose of novobiocin is eliminated in the urine.
- Dosage adjustment or discontinuation of novobiocin might be indicated if hepatic dysfunction develops.
Oral route
- The usual daily, oral pediatric dose of novobiocin is 15 milligrams of novobiocin/kilogram body weight for moderate to acute infections, administered in divided doses every 6 to 12 hours.
- Up to 30 to 45 milligrams of novobiocin/kilogram body weight may be administered orally in divided doses every 6 to 12 hours for resistant or severe infections.
- Use of novobiocin should be avoided in newborn and young infants because of the possibility of inducing hyperbilirubinemia.

### Therapeutic Uses
Excellent in-vitro activity against virtually all of the 103 strains of methicillin-resistant Staphylococcus aureus in one study.
Used in combination with rifampin in the treatment of methicillin-resistant Staphylococcus aureus.
- Adult:
- For treatment of susceptible urinary tract infections caused by Proteus species.
- Novobiocin plus acidification of the urine was more effective than novobiocin therapy alone in eradicating gram-negative bacilli in the urine of patients with chronic bacteriuria.
- Inadequate in treatment of gonococcal urethritis.

# Mechanism of Action
The molecular basis of action of novobiocin, and other related drugs clorobiocin and coumermycin A1 has been examined. Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved in energy tranduction. Novobiocin as well as the other aminocoumarin antibiotics act as competitive inhibitors of the ATPase reaction catalysed by GyrB. The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a different site on the enzyme. The GyrA subunit is involved in the DNA nicking and ligation activity.

# Structure
Novobiocin is an aromatic ether compound. Novobiocin may be divided up into three entities; a benzoic acid derivative, a coumarin residue, and the sugar novobiose.. X-ray crytallographic studies have found that the drug-receptor complex of Novobiocin and DNA Gyrase shows that ATP and Novobiocin have overlapping binding sites on the gyrase molecule. The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase activity.

## Structure Activity Relationship
In structure activity relationship experiments it was found that removal of the carbamoyl group located on the novobiose sugar lead to a dramatic decrease in inhibitory activity of novobiocin. 

# Clinical Use
Novobiocin was licenced for clinical use under the tradename Albamycin (Pharmacia And Upjohn) in the 1960s. Its efficacy has been demonstrated in
preclinical and clinical trials. It has since been withdrawn from the market. Novobiocin is effective antistaphylococcal agent used in the treatment of MRSA. It is also active against Staphylococcus epidermidis and may be used to differentiate from the other coagulase-negative Staphylococcus saprophyticus, which is resistant to novobiocin, in culture.