Antibiotics: Metronidazole

Question 1

Indications of metronidazole?

Answer 1

Antibiotic-associated colitis (caused by Gram-positive anaerobic C.diff)

Oral infections or aspiration pneumonia (caused by Gram-negative anaerobes)

Surgical and gynaecological infections (caused by Gram-negative anaerobes from the colon)

Protozoal infections (e.g. trichomonal vaginal infection)

Question 2

Spectrum of activity of metronidazole?

Answer 2

Anaerobic bacteria and protoza.

Question 3

MOA of metronidazole?

Answer 3

Enters bacterial cells by passive diffusion .

In anaerobic bacteria:
- reduction of metronidazole generates a nitroso free radical.
→ This binds to DNA
→ reduces synthesis and causes widespread damage, DNA degradation and cell death (bactericidal).​

Question 4

Adverse effects of metronidazole?

Answer 4

GI upset:
- nausea
- vomiting

Immediate and delayed hypersensitivity reactions

Neurological adverse effects (at high dose)
- peripheral and optic neuropathy
- seizures
- encephalopathy

Question 5

Warnings of metronidazole?

Answer 5

Metronidazole is metabolised by hepatic cytochrome P450 enzymes.
→ so reduce dose in pts with SEVERE LIVER DISEASE

Metronidazole INHIBITS acetaldehyde dehydrogenase.
→ so should not be drunk with alcohol

Question 6

Interactions of metronidazole?

Answer 6

Metronidazole has inhibitory effect on CYP enzymes:
→ reduces metabolism of warfarin (increases risk of bleeding)
→reduces metabolism. of phenytoin (increasing risk of toxicity -impaired cerebellar function)

Reverse interaction can occur with CYP inducers (e.g. phenytoin, rifampicin):
→ results in reduced plasma conc and impaired antimicrobial efficacy.

Increases risk of lithium toxicity.

Question 7

Monitoring of metronidazole?

Answer 7

Check infection resolves by:
- symptoms/signs improved
- blood markers e.g. falling CRP

For tx lasting >10days, monitor adverse effects by measuring:
- FBC
- LFTS

Question 8

Pt education of metronidazole?

Answer 8

Aims to get rid of infection and improve symptoms.

Check for metronidazole allergy.

If allergy develops during treatment, give pt written and verbal advice NOT to take this abx class in future and make sure that the type of reaction (including its nature) is clearly documented in pt’s medical records.

Warn pt NOT to drink alcohol during or for 48 hours after tx.
→can lead to n+v, flushing, and headache.