Metronidazole

Question 1

What are common indications?

Answer 1

1. Oropharyngeal g-negative anaerobes including:
   - dental infections
   - infected human/animal bites
   -aspiration pneumonia
2. H.pylori (in combination with PPI and amoxicillin or clarithromycin.
3. intrabdominal infection and pelvic inflammatory disease
4. protozoal infections

5.C-diff colitis (If IV treatment is needed)

Question 2

What is the spectrum of activity?

Answer 2

anaerobic bacteria and Protozoa

Question 3

what’s the mechanism of action and why does it only have a spectrum of activity to aerobic bacteria?

Answer 3

In anaerobic bacteria, reduction of metronidazole generates a nitroso free radical.

This binds to DNA, reducing synthesis and causing widespread damage, DNA degradation, and cell death (bactericidal).

As aerobic bacteria are not able to reduce metronidazole in this manner, they are not susceptible to its effects.

Question 4

What is the mechanism of resistance?

Answer 4

Mechanisms include reduced uptake of metronidazole and reduced generation of nitroso free radicals.

Question 5

Who should not be prescribed metronidazole?

Answer 5

Severe liver disease- metabolised by P450 Enzymes do reduced dose

Question 6

What are side effects?

Answer 6

GI upset: nausea and vomiting
metallic taste /Furred tongue

High doses/prolonged course:

neurological adverse effects
peripheral and optic neuropathy
seizures
encephalopathy

Question 7

Why should alcohol be avoided?WHat can concurrent use cause?

Answer 7

inhibits the enzyme acetaldehyde dehydrogenase, which is responsible for clearing the intermediate alcohol metabolite

Causes :
flushing, headache, nausea and vomiting

should be avoided during and 48 hours after treatment stopped

Take with food

Question 8

What are important interactions?

Answer 8

Metronidazole has some inhibitory effect on CYP enzymes reducing metabolism of:
warfarin
(increasing the risk of bleeding) phenytoin
(increasing the risk of toxicity, including impaired cerebellar function).

Taken with CYP inducers (phenytoin, rifampicin):
increase metronidazole metabolism resulting in reduced plasma concentrations and impaired antimicrobial efficacy.

Metronidazole also increases the risk of toxicity with lithium.

Question 9

What are dosages?

Answer 9

Oral-
400mg TDS

IV-
500mg IV 8hrly
For severe infection

Question 10

What are indications for topical;n metronidazole?

Answer 10

BV
Skin infections-rosacea
infected skin ulcer to reduce odour

Question 11

What are monitoring requirements?

Answer 11

Monitor efficacy by reviewing symptoms, signs and inflammatory markers

For treatment exceeding 10days, monitor safety by measuring:
-FBC
-liver enzymes to look for adverse effects