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Antibiotic Dosing in CKD Pregnancy: Avoid in 1st trimester (folate antagonism — neural tube defect risk) and at term (neonatal folate deficiency). Use only if essential in 2nd trimester with folate supplementation.

Trimethoprim (CKD Considerations)

Brand names: Monotrim

Adult dose

Dose: 200 mg twice daily (treatment); 100 mg at night (prophylaxis)
Route: Oral
Frequency: Twice daily (treatment); once nightly (prophylaxis)
Max: 400 mg/day
Dihydrofolate reductase inhibitor. Active for uncomplicated UTI. Reduce dose by 50% if eGFR 15-30. Avoid if eGFR <15. CRITICAL: trimethoprim competitively blocks tubular secretion of creatinine — serum creatinine rises without true GFR change. This is not AKI.

Paediatric dose

Dose: 4 mg/kg
Route: Oral
Frequency: Twice daily
Max: 200 mg BD
Prophylaxis for recurrent UTI: 2 mg/kg once nightly (max 100 mg). BNFc for age-specific dosing. Not for infants under 6 weeks.

Dose adjustments

Renal

eGFR 15-30: halve the dose and double the interval. eGFR <15: avoid (folate antagonism and metabolite accumulation). Monitor potassium — trimethoprim blocks distal tubular potassium secretion (ENaC) causing hyperkalaemia, especially with ACEi/ARB.

Hepatic

Caution in severe hepatic impairment

Paediatric weight-based calculator

Prophylaxis for recurrent UTI: 2 mg/kg once nightly (max 100 mg). BNFc for age-specific dosing. Not for infants under 6 weeks.

Clinical pearls

  • Creatinine rise artefact: trimethoprim blocks OAT3-mediated tubular secretion of creatinine. Serum creatinine rises 10-20% within 24-48 hours of starting — this does NOT reflect a fall in GFR. eGFR equations based on creatinine will appear worse. Cystatin C-based eGFR is unaffected. Stop trimethoprim and recheck creatinine to distinguish from true AKI.
  • Hyperkalaemia mechanism: trimethoprim acts like amiloride on ENaC in the collecting duct — blocks sodium reabsorption and potassium secretion. In CKD patients already on ACEi/ARB/finerenone, combination can cause dangerous hyperkalaemia.
  • High-dose trimethoprim (20 mg/kg/day): used for Pneumocystis jirovecii pneumonia (PCP) treatment — typically combined with dapsone or as part of co-trimoxazole. The dose-related toxicities (hyperkalaemia, creatinine rise, folate deficiency) are more pronounced.
  • Resistance: E. coli trimethoprim resistance is now >30% in many UK areas (Public Health England). Local antibiogram should guide empiric treatment for complicated UTI.
  • Folate supplementation: for women of childbearing age on long-term trimethoprim prophylaxis, ensure adequate folate intake (folic acid 400 mcg daily) to prevent neural tube defect risk if pregnancy occurs.

Contraindications

  • Severe renal impairment (eGFR <15)
  • Blood dyscrasias
  • Megaloblastic anaemia due to folate deficiency
  • Hypersensitivity

Side effects

  • Hyperkalaemia (blocks renal K+ excretion — significant in CKD patients on ACEi/ARB/MRA)
  • Hyponatraemia (blocks Na+ reabsorption similarly to amiloride)
  • Rash
  • Nausea
  • Folate deficiency with prolonged use
  • Thrombocytopenia

Interactions

  • ACEi/ARBs/potassium-sparing diuretics — severe hyperkalaemia (additive potassium retention); monitor K+ closely in CKD
  • Warfarin — increases INR (inhibits warfarin metabolism + vitamin K-dependent clotting factors via folate)
  • Methotrexate — additive antifolate toxicity; avoid
  • Phenytoin — trimethoprim increases phenytoin levels

Monitoring

  • Potassium (check within 1 week of starting in CKD patients on ACEi/ARB)
  • Creatinine (interpret cautiously — artefact expected)
  • FBC (prolonged use — folate deficiency)
  • Urinary culture and sensitivity

Reference: BNFc; BNF 90; BNFc; NICE NG109 (UTI Adults); MHRA guidance; PHE Antimicrobial Resistance Reports; SPC Monotrim. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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