What is the recommended dosage of Keflex (cefalexin) for an obese patient with impaired renal function and an infection?

High-Dose Cephalexin for Infection in Obese Patients

For obese patients with normal renal function, standard-dose cephalexin 500 mg orally every 6 hours is appropriate—weight-based dosing has no pharmacokinetic basis and provides no additional benefit. 1, 2

Pharmacokinetic Rationale Against Weight-Based Dosing

• Cephalexin is a hydrophilic (water-soluble) antibiotic that does not penetrate adipose tissue regardless of IV or oral dose, making weight-based dosing pharmacokinetically irrational in obese patients 2
• Adipose tissue is not a valid target tissue for most infections, as it does not become infected in typical bacterial infections requiring cephalexin 2
• Higher doses result in proportionately higher serum concentrations but do not increase adipose tissue concentrations 2
• Cephalexin displays time-dependent killing kinetics, meaning that as long as serum/tissue concentrations remain above the minimum inhibitory concentration (MIC), there is no enhanced bacterial killing with higher concentrations 2

Standard Dosing Recommendations

• The FDA-approved adult dosage for cephalexin ranges from 1 to 4 grams daily in divided doses, with the usual adult dose being 250 mg every 6 hours 1
• For more severe infections or those caused by less susceptible organisms, 500 mg every 6 hours (2 grams daily) may be administered 1
• The Infectious Diseases Society of America recommends cephalexin 500 mg orally every 6 hours for typical nonpurulent cellulitis in adults with normal renal function 3

Renal Dosing Adjustments (Critical for Obese Patients)

• Patients with creatinine clearance less than 30 mL/min require dose reduction proportional to reduced renal function 4
• Cephalexin is 70-100% renally excreted unchanged within 6-8 hours after each dose, making renal function the primary determinant of dosing adjustments—not body weight 4
• Obese patients often have impaired renal function that may not be reflected in serum creatinine alone; calculate actual creatinine clearance before dosing 1

Treatment Duration

• The Infectious Diseases Society of America recommends treating for 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe 3
• For urinary tract infections (cystitis), therapy should be continued for 7 to 14 days 1

Common Pitfalls to Avoid

• Do not reflexively increase cephalexin doses based solely on body weight in obese patients without considering pharmacokinetic principles 2
• Do not assume "more must be better"—this approach lacks comparative study support and violates antibiotic stewardship principles 2
• Do not overlook renal function assessment in obese patients, as they may have reduced creatinine clearance despite normal serum creatinine 1, 4
• Avoid using cephalexin for infections requiring MRSA coverage (purulent cellulitis, penetrating trauma, injection drug use) without adding appropriate MRSA-active therapy 3

When Higher Doses Are Appropriate

• For severe infections or those caused by less susceptible organisms, doses up to 4 grams daily in divided doses may be needed, but this decision should be based on infection severity and pathogen susceptibility—not patient weight 1
• If daily doses greater than 4 grams are required, parenteral cephalosporins in appropriate doses should be considered instead 1

Antibiotic Stewardship Considerations

• Unnecessary high-dose antibiotics expose patients to potential adverse effects including Clostridioides difficile infection without providing additional benefit 2
• There is no dose-dependent or duration-of-exposure effect on resistance with standard pre-operative or therapeutic dosing 2
• Well-designed pharmacokinetic studies in obese patients demonstrate no incremental benefit from high doses in achieving therapeutic tissue concentrations 2