1. IV infusion by syringe pump over 30 minutes.
2. Preterm infants less than one month of age: 7.5 mg/kg/dose 12 hourly.
3. All other infants: 7.5 mg/kg/dose 8 hourly.
4. Loading dose of 15 mg/kg is optional.

Indications

1. Suspected/proven anaerobic infection, especially Bacteroides fragilis.
2. Necrotising enterocolitis.
3. Peritonitis.

Contraindications and Precautions

1. Known hypersensitivity to metronidazole.
2. Infants with biliary tract obstruction.
3. Caution in preterm infants especially extreme immaturity.
4. Caution in infants with jaundice, liver dysfunction and biliary tract disease.

Clinical Pharmacology

Metronidazole is active against a wide range of anaerobic micro-organisms, including Bacteroides species, Fusobacteria, Clostridia, Eubacteria and anaerobic cocci. Also active against Gardnerella vaginalis, Trichomonas, Entamoeba histolytica, Giardia lamblia and Balantidium coli. The precise mode of action is not clear. Active metabolites of metronidazole appear to bind to DNA and disrupt protein synthesis.

Readily absorbed after oral administration. Slower and more variable absorption from the rectum. Diffuses throughout the body and readily penetrates CSF and cerebral abscesses. High apparent distribution volume similar to that of total body water. Low binding (20%) to human plasma protein. Elimination mainly by hepatic biotransformation, resulting from side chain oxidation, hydroxylation or conjugation of the parent compound. The major metabolites are active. Elimination half-life remains unchanged in renal failure. Rapidly removed from the plasma by dialysis.

Possible Adverse Effects

1. Venous irritation, soft tissue injury at IV injection site.
2. Gastrointestinal disturbance (nausea, vomiting)
3. Peripheral neuropathy, encephalopathy (usually during intensive and/or prolonged therapy).
4. Neutropenia (moderate, reversible).
5. Hypersensitivity reactions rare (urticaria, skin eruptions, anaphylaxis).

Special Considerations

1. Lengthen dosing interval if extreme immaturity, severe jaundice, and/or hepatic dysfunction.
2. Neonates receiving phenobarbitone metabolise metronidazole at a much greater rate than normal, reducing half life by approximately 50-75%.
3. Darkening of the urine, due to metronidazole metabolites, has been reported.
4. Serum levels should be measured if toxicity suspected (toxic levels greater than 300 umol/L).
5. Is considered safe by National Women’s paediatricians, that mothers receiving metronidazole breast feed their babies.