Greater Glasgow and Clyde Medicines

Co-trimoxazole: Reintroduction to GGC Acute Infection Management Guidelines for Adults

Key messages:

• Co-trimoxazole has been included for use more widely in the latest infection management guidelines due to increasing resistance to alternative antibiotics.
• Dosage adjustment is required in renal impairment (details below).
• Co-trimoxazole may exacerbate hyperkalaemia and increase creatinine.
• Co-trimoxazole has been associated with rare but serious skin and blood adverse effects. These are more common with higher doses and more prolonged courses than recommended here (details below).

Co-trimoxazole overview

Co-trimoxazole is a combination of sulfamethoxazole and trimethoprim, previous brand name Septrin®. They are used in combination due to their synergistic action against bacterial folic acid synthesis. Organisms that are reported as sensitive to trimethoprim on microbiology results will also be sensitive to co-trimoxazole. Co-trimoxazole is available in tablet, liquid and injection form. Co-trimoxazole must be avoided in patients who have a previous allergy to co-trimoxazole, Septrin®, sulfamethoxazole or trimethoprim.

Place within GGC acute infection management guidelines

Co-trimoxazole has been included more widely in the updated adult infection management guidelines (IMG) due to increasing resistance in Gram negative organisms to co-amoxiclav and temocillin. Co-trimoxazole is now included for the following indications in the updated IMG:

In the IV to oral switch (IVOST) guidance it is also first line following IV therapy for urinary sepsis/pyelonephritis, HAP and SBP (if not receiving co-trimoxazole prophylaxis).

Dosage

The standard dose of co-trimoxazole in the infection management guidance, for the indications above, is 960mg 12 hourly (IV or oral depending on the indication and the severity of infection, see guideline for more details). Please note that higher doses are advised for treatment of Pneumocystis jirovecii infections.

Renal Impairment: Dosage adjustments are required in patients with renal impairment.

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Monitor for hyperkalaemia and transient rises in serum creatinine in patients with renal impairment.

IV Administration

Co-trimoxazole can be given by IV infusion. Details are included within the adult Medusa monograph or the Summary of Product Characteristics (SPC), including information for patients with a fluid restriction or prescribed lower/higher doses. IV co-trimoxazole may cause extravasation, administer via a large peripheral vein or central venous access device.

Adverse Effects

• Most common include headache, GI disturbances, rash and hyperkalaemia.
• Rise in serum creatinine levels, which may be due to competitive inhibition of tubular secretion of creatinine.
• Very rarely associated with more severe skin reactions such as photosensitivity, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP). If symptoms suggestive of these are present then co-trimoxazole should be discontinued.
• Blood disorders including leucopenia, thrombocytopenia, megaloblastic anaemia, neutropenia and eosinophilia, have also been reported on rare occasions and co-trimoxazole should be discontinued immediately if these develop. Serious adverse effects are more common with high doses (e.g. dose used for Pneumocystis jirovecii infections) or prolonged courses, when FBC should be monitored. 

Please remember to report any suspected adverse reactions via the Yellow Card Scheme.

Interactions

There are a number of important co-trimoxazole interactions to be aware of including interactions with warfarin, methotrexate, phenytoin, drugs that can increase potassium and drugs that can cause myelosuppression. For a full list, please refer to the BNF or SPC via eMC.

For full prescribing information on co-trimoxazole, please refer to the BNF or SPC via eMC.

Originally published 11/01/2021, updated 28/06/2022. Medicines Update blogs are correct at the time of publication.