Anaerobic antimicrobials

Question 1

Example of an Anaerobic antimicrobial

Answer 1

Metronidazole

Question 2

How does Metronidazole work?

Answer 2

Metronidazole enters bacterial cells by passive diffusion. 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. As aerobic bacteria are not able to reduce metronidazole in this manner, the spectrum of action of metronidazole is restricted to anaerobic bacteria (and protozoa).

Bacterial resistance to metronidazole is generally low but is increasing in prevalence. Mechanisms include reduced uptake of metronidazole and reduced generation of nitroso free radicals.

Question 3

Indications for Metronidazole

Answer 3

Treatment of infections caused by anaerobic bacteria in:
Antibiotic-associated colitis caused by Clostridium difficile, which is a Gram-positive anaerobe.

Oral infections (such as dental abscess) or aspiration pneumonia caused by Gram-negative anaerobes from the mouth.

Surgical and gynaecological infections caused by Gram-negative anaerobes from the colon, for example

Bacteroides fragilis. Also effective for treatment of protozoal infections including trichomonal vaginal infection, amoebic dysentery, giardiasis.

Question 4

Contraindications of Metronidazole

Answer 4

Metronidazole is metabolised by hepatic cytochrome P450 enzymes, so the dose should be reduced in people with severe liver disease. Metronidazole inhibits the enzyme acetaldehyde dehydrogenase, which is responsible for clearing the intermediate alcohol metabolite acetaldehyde from the body. Alcohol should not be drunk while taking metronidazole as the combination can cause a ‘disulfiram-like’ reaction, including flushing, headache, nausea and vomiting.

Question 5

Side effects of Metronidazole

Answer 5

As with many antibiotics, metronidazole can cause gastrointestinal upset (such as nausea and vomiting) and immediate and delayed hypersensitivity reactions (see Penicillins, broad-spectrum).

When used at high doses or for a prolonged course, metronidazole can cause neurological adverse effects including peripheral and optic neuropathy, seizures and encephalopathy.

Question 6

Interactions of Metronidazole

Answer 6

Metronidazole has some inhibitory effect on cytochrome P450 enzymes, reducing metabolism of warfarin (increasing the risk of bleeding) and phenytoin (increasing the risk of toxicity, including impaired cerebellar function). The reverse interaction can occur with cytochrome P450 inducers (e.g. phenytoin, rifampicin) resulting in reduced plasma concentrations and impaired antimicrobial efficacy. Metronidazole also increases the risk of toxicity with lithium.

Question 7

Elimination of Metronidazole

Answer 7

Renal

Question 8

Patient information on Metronidazole

Answer 8

Explain that the aim of treatment is to get rid of infection and improve symptoms. For oral treatment, encourage the patient to complete the prescribed course. Before prescribing, always check with your patient personally or get collateral history to ensure that they have no allergy to metronidazole. Warn the patient not to take alcohol during or for 48 hours after treatment, explaining that if they do they may feel very unwell with nausea, vomiting, flushing and headache. If an allergy develops during treatment, give the patient written and verbal advice not to take this antibiotic in the future and make sure that the allergy is clearly documented in their medical records.