Antibiotics: Trimethoprim

Question 1

Indications of trimethoprim?

Answer 1

Acute lower UTI

Prophylaxis of recurrent UTI

An option for the tx of:​
- Acne​
- Respiratory tract infections ​
- Prostatitis

Question 2

Spectrum of activity of trimethoprim?

Answer 2

Broad spectrum

Works against Gram-positive and Gram-negative bacteria, but INCREASINGLY limited by resistance.

Combining trimethoprim with sulfonamide EXTENDS the spectrum.

Question 3

MOA of trimethoprim?

Answer 3

Inhibits bacterials folate synthesis -BACTERIOSTASIS (slowing bacterial growth)

Widespread bacterial resistance.

Sulfonamide inhibits bacterials folate synthesis too in a different pathway, so combining both drugs causes more complete inhibition of folate synthesis.

Question 4

Adverse effects of trimethoprim?

Answer 4

GI upset:​
- Nausea ​
- Diarrhoea​
- Sore mouth​

Skin rash​

Severe hypersensitivity reactions including:​
- Anaphylaxis​
- Drug fever ​
- Erythema multiforme

Can impair haematopoiesis:
- megaloblastic anaemia
- leucopenia
- thrombocytopenia

Hyperkalaemia
Elevation of plasma creatinine conc

Question 5

Warnings of trimethoprim?

Answer 5

Contraindicated in:
- first trimester of pregnancy (as it’s a folate antagonist, associated with fetal abnormalities)

Use with caution in:
- folate deficiency pts

Reduce dose in renal impairment.

Neonates, elderly, HIV infection pts are susceptible to adverse effects.

Question 6

Interactions of trimethoprim?

Answer 6

Trimethoprim + Potassium-elevating drugs = hyperkalaemia

Trimethoprim + folate antagonists or drugs thats increase folate metabolism = increase risk of adverse haematological effect

Enhances anticoagulant effect of warfarin by killing normal gut flora that synthesis vitamin K.

Question 7

Monitoring of trimethoprim?

Answer 7

For acute infection:​
- improvement in signs/symptoms e.g. reduction in dysuria​, pyrexia
- Investigations (e.g. fall in CRP/ESR, sterile urine on repeat culture in selected cases)

For long-term tx:
- FBC (for early detection and tx of haematological disorders e.g. replacing folate and/or stopping the abx)

Question 8

Pt education of trimethoprim?

Answer 8

Aims to get rid of infection and improve symptoms.

For prophylaxis, mention it is a long-term tx.

Check for trimethoprim or septrin allergy.

Seek medical advice if they develop a rash or unexpected symptoms.

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.

Question 9

Examples of trimethoprim?

Answer 9

trimethoprim
co-trimoxazole