Co-Trimoxazole

Co-Trimoxazole - Sulphamethoxazole and trimethoprim are used in combination because of their synergistic activity. Increasing resistance to sulphonamides and the high incidence of sulphonamide-related side-effects have diminished the value of co-trimoxazole.Trimethoprim alone is now preferred for urinary tract infections and exacerbations of chronic bronchitis. However, high-dose co-trimoxazole is the preferred treatment for Pneumocystis carinii pneumonia (PCP). It has certain theoretical advantages over pentamidine: pentamidine accumulates slowly in the lung parenchyma and improvement may occur more slowly; co-trimoxazole has a broad spectrum of activity and may treat any bacterial co-pathogens. Pneumonia caused by Pneumocystis carinii (now renamed Pneumocystis jirovecii) occurs in immunosuppressed patients; it is a common cause
of pneumonia in AIDS. High-dose co-trimoxazole with corticosteroid therapy is the treatment of choice for moderate to severe infections. Co-trimoxazole prophylaxis should be considered for severely immunocompromised patients.

Uses:
Pneumocystis carinii pneumonia

Contraindications:
Pregnancy
Severe renal/hepatic failure
Blood disorders
Porphyria

Administration
• Can infuse undiluted solution via central line (unlicensed)
• Pneumocystis carinii pneumonia

60 mg/kg 12 hourly IV for 14 days followed orally for a further 7 days. Some units reduce the dose from day 3 to 45 mg/kg 12 hourly as this appears to reduce side effects but maintain efficacy. IV infusion: dilute every 1 ml (96 mg) in 25 ml glucose 5% or sodium chloride 0.9%, given over 1.5–2 h. If fluid restriction necessary, dilute in half the amount of glucose 5%
Adjuvant corticosteroid has been shown to improve survival. The steroid should be started at the same time as the co-trimoxazole and should be withdrawn before the antibiotic treatment is complete. Oral prednisolone 50–80 mg daily or IV hydrocortisone 100 mg 6 hourly or IV dexamethasone 8 mg 6 hourly or IV methylprednisolone 1 g for 5 days, then dose reduced to complete 21 days of treatment.

• PCP prophylaxis
Oral: 960 mg daily or 960 mg on alternate days (3 times a week) or 480 mg daily to improve tolerance

• In renal impairment
CC 15–30 ml/min:reduce dose to 50% after day 3 for PCP treatment
CC <15 ml/min: reduce dose to 50%; should only be given with renal replacement therapy.

Note: 
treatment should be stopped if rashes or serious blood disorders develop. A fall in white cell count should be treated with folic/folinic acid and a dose reduction to 75%.

How not to use co-trimoxazole:
Concurrent use of co-trimoxazole and pentamidine is not of benefit and may increase the incidence of serious side-effects.

Adverse effects:
Nausea, vomiting and diarrhoea (including pseudomembranous colitis)
Rashes (including Stevens–Johnson syndrome)
Blood disorders (includes leucopenia, thrombocytopenia, anaemia)
Fluid overload (due to large volumes required)

Cautions:
Elderly
Renal impairment (rashes and blood disorders increase, may cause further
deterioration in renal function)

Renal replacement therapy:
CVVH dialysed, dose as in CC 15–30 ml/min, i.e. 60 mg/kg twice daily for 3 days then 30 mg/kg twice daily (for PCP) or 50% of normal dose. HD dialysed, dose as in CC <15 ml/min, i.e. 30 mg/kg twice daily (PCP) or 50% of dose. PD not dialysed, dose as for HD.