Cefixime Dosing in Renal Impairment Based on Serum Creatinine
For trauma patients with impaired renal function, cefixime dosing should be adjusted based on creatinine clearance, with the standard 400 mg daily dose maintained for creatinine clearance ≥60 mL/min, reduced to 260 mg daily (13 mL of 200 mg/5 mL suspension) for creatinine clearance 21-59 mL/min, and further reduced to 176 mg daily (8.6 mL of 100 mg/5 mL suspension) for creatinine clearance ≤20 mL/min or patients on dialysis. 1
Direct Serum Creatinine-Based Approach
While the FDA label provides dosing based on creatinine clearance, serum creatinine alone significantly underestimates renal dysfunction, particularly in elderly patients, those with low muscle mass, and trauma patients with sarcopenia. 2 The relationship between serum creatinine and actual glomerular filtration rate is unreliable without calculating creatinine clearance. 2
Critical Caveat for Trauma Patients
In trauma patients, you must calculate creatinine clearance rather than relying on serum creatinine values alone, as these patients often have altered muscle mass, volume status changes, and acute kidney injury that make serum creatinine an inaccurate marker of renal function. 2, 3
Practical Dosing Algorithm
Step 1: Calculate Creatinine Clearance
- Use the Cockcroft-Gault equation or measured 24-hour urine collection 2
- Do not use serum creatinine thresholds alone 2
Step 2: Apply FDA-Approved Dosing Adjustments
For CrCl ≥60 mL/min:
- Standard dose: 400 mg once daily (capsule or 20 mL of 100 mg/5 mL suspension or 10 mL of 200 mg/5 mL suspension) 1
For CrCl 21-59 mL/min:
- Reduced dose: 260 mg once daily (13 mL of 200 mg/5 mL suspension preferred) 1
- This represents approximately 65% of the standard dose 1
For CrCl ≤20 mL/min or dialysis patients:
- Further reduced dose: 176 mg once daily (8.6 mL of 100 mg/5 mL suspension or 4.4 mL of 200 mg/5 mL suspension) 1
- This represents approximately 44% of the standard dose 1
- Neither hemodialysis nor peritoneal dialysis removes significant amounts of cefixime, so no supplemental dosing is needed post-dialysis 1, 4
Pharmacokinetic Rationale
The elimination half-life of cefixime increases dramatically with declining renal function: from 3.7 hours in normal subjects to 12-14 hours in patients with CrCl <20 mL/min. 5, 6 This prolonged half-life necessitates dose reduction to prevent drug accumulation. 5, 4
Approximately 40% of cefixime is cleared renally unchanged, with the remaining 60% cleared hepatically. 6 The renal clearance correlates linearly with creatinine clearance, making dose adjustment essential in renal impairment. 5, 4
Monitoring Recommendations
- Reassess renal function every 2-3 days during therapy, as renal function may change during the course of treatment, particularly in trauma patients. 3
- Evaluate clinical response within 48-72 hours to determine efficacy. 3
- Urinary concentrations remain above MIC for most urinary pathogens for up to 24 hours even in severe renal insufficiency, making once-daily dosing appropriate. 4
Common Pitfalls to Avoid
Do not use serum creatinine values alone without calculating creatinine clearance - this is the most critical error, as a "normal" creatinine of 1.1 mg/dL may represent significant renal impairment in elderly or low-muscle-mass patients 2
Do not give supplemental doses after dialysis - cefixime is not significantly removed by hemodialysis or peritoneal dialysis 1, 4
Do not substitute tablets/capsules for suspension in otitis media - suspension achieves higher peak levels 1
Do not forget that trauma patients may have acute kidney injury superimposed on chronic kidney disease - use the most recent creatinine clearance calculation 2