Cefixime Dosing in CKD Patients with UTI
For adults with chronic kidney disease and uncomplicated UTI, cefixime 400 mg daily can be used without dose adjustment when creatinine clearance is ≥60 mL/min; reduce to 260 mg daily (13 mL of 200 mg/5 mL suspension) for CrCl 21-59 mL/min, or 175 mg daily (8.6 mL of 100 mg/5 mL suspension) for CrCl ≤20 mL/min or dialysis patients. 1
Renal Dose Adjustment Algorithm
The FDA-approved dosing adjustments for cefixime are straightforward and based on creatinine clearance 1:
- CrCl ≥60 mL/min: Full dose of 400 mg daily (normal dosing) 1
- CrCl 21-59 mL/min: 260 mg daily (13 mL of 200 mg/5 mL suspension or 6.5 mL of 200 mg/5 mL suspension) 1
- CrCl ≤20 mL/min: 175 mg daily (8.6 mL of 100 mg/5 mL suspension or 4.4 mL of 200 mg/5 mL suspension) 1
- Hemodialysis or peritoneal dialysis: Same as CrCl ≤20 mL/min (175 mg daily), as dialysis does not significantly remove the drug 1
Pharmacokinetic Rationale
The half-life of cefixime increases substantially in renal impairment 2, 3:
- In normal renal function, the elimination half-life is approximately 3.7 hours 2
- In severe renal failure (CrCl <20 mL/min), the half-life extends to 12-14 hours 2
- Peak serum concentrations are slightly increased and occur later in patients with renal impairment 2, 3
- Renal clearance decreases proportionally with declining creatinine clearance 2
Clinical Efficacy Considerations
Important caveat: While cefixime is appropriate for uncomplicated UTI in CKD patients, current European guidelines do not list it as a first-line agent for pyelonephritis 4. For uncomplicated pyelonephritis, fluoroquinolones (ciprofloxacin 500-750 mg twice daily or levofloxacin 750 mg daily) and other oral cephalosporins (cefpodoxime 200 mg twice daily or ceftibuten 400 mg daily) are preferred 4.
For uncomplicated cystitis in CKD patients, cefixime demonstrates 5, 6:
- 100% clinical efficacy rate in acute uncomplicated cystitis when caused by sensitive organisms 6
- 63% efficacy in complicated UTIs, with 79% bacteriological eradication 6
- Good activity against enterobacteriaceae, superior to conventional oral cephalosporins 5
Administration Recommendations
- Divide the daily dose into two administrations (e.g., 200 mg twice daily for normal dosing) rather than once daily to reduce gastrointestinal adverse effects 5
- Can be administered without regard to food 1
- Use the oral suspension formulation for precise dose adjustments in renal impairment 1
- After reconstitution, suspension remains stable for 14 days at room temperature or refrigerated 1
Safety Profile in Renal Impairment
Cefixime has minimal nephrotoxicity 5:
- Gastrointestinal adverse effects (3.1% incidence) are the most common side effects, including lower abdominal symptoms 6
- No significant accumulation of antibacterially active metabolites occurs in uremic patients 2
- Generally well-tolerated in patients with varying degrees of renal dysfunction 5, 3
When to Consider Alternatives
Consider alternative antibiotics in CKD patients when 4, 5:
- Pyelonephritis is suspected (use fluoroquinolones or parenteral cephalosporins like cefepime or ceftriaxone) 4
- Complicated UTI with gram-positive or non-fermenting organisms is present (perform sensitivity testing first) 5
- Local resistance patterns show >10% fluoroquinolone resistance, making empiric therapy selection more complex 4