What is the recommended treatment regimen for a patient with a skin infection using Keflex (Cephalexin), considering potential allergies and impaired renal function?

Cephalexin for Skin Infections: Treatment Regimen and Key Considerations

For uncomplicated skin and soft tissue infections, cephalexin 500 mg every 6 hours (or 500 mg every 12 hours for improved compliance) is the recommended first-line treatment, but must be avoided entirely in patients with a history of anaphylactic penicillin allergy due to 16.45% cross-reactivity risk. 1, 2

Standard Dosing Regimen

Adult Dosing

• Standard dose: 250 mg every 6 hours for mild infections 3
• Preferred dose for skin infections: 500 mg every 12 hours for streptococcal pharyngitis, skin and skin structure infections 3
• Alternative: 500 mg four times daily for more severe infections 2
• Duration: 5-10 days (5 days is as effective as 10 days if clinical improvement is observed) 2
• Maximum daily dose: 4 grams; if higher doses needed, consider parenteral cephalosporins 3

Pediatric Dosing

• Standard dose: 25-50 mg/kg/day divided into doses 3
• For skin infections: Total daily dose may be divided every 12 hours in patients over 1 year 3
• Severe infections: Dosage may be doubled 3

Critical Allergy Considerations

Patients with Penicillin Allergy History

DO NOT use cephalexin in patients with anaphylactic penicillin allergy history - the cross-reactivity rate is 16.45% (95% CI: 11.07-23.75) because cephalexin shares an identical R1 side chain with aminopenicillins (amoxicillin/ampicillin). 4, 1

Management Algorithm for Penicillin-Allergic Patients:

If anaphylaxis, angioedema, or severe IgE-mediated reaction to penicillin:

• First choice: Select a different cephalosporin with dissimilar R1 side chain (cefazolin, ceftriaxone, cefepime) - can be given directly without testing 1
• Second choice: Consider penicillin delabeling (penicillin skin testing followed by oral amoxicillin challenge) to remove the allergy label entirely 1
• Never: Give cephalexin without extensive testing 1

If distant (>10 years) or mild reaction (maculopapular rash, urticaria without systemic symptoms):

• Direct oral challenge with cephalexin may be considered without prior testing 4
• Reaction rate to cephalosporins in unverified penicillin allergy is <5% 1

If patient anxiety or discomfort about direct challenge:

• Negative skin testing may alleviate fears, though cephalexin skin testing has "no clear utility" 1
• Stepwise skin testing: epicutaneous 200 mg/mL, then intradermal 2.0 mg/mL and 20 mg/mL 1

Patients with Cephalosporin Allergy History

If history of urticaria to cephalexin:

• Can receive amoxicillin without prior testing 1
• Penicillin skin testing not recommended unless the cephalosporin reaction was anaphylaxis 1

If anaphylaxis to another cephalosporin:

• Cephalosporin skin testing required before parenteral administration 4
• Direct challenge acceptable if R1 side chains are dissimilar and reaction was nonanaphylactic 4

Renal Impairment Dosing

Cephalexin must be dose-adjusted in markedly impaired renal function - careful clinical observation and laboratory monitoring required, as safe dosage may be lower than standard recommendations. 3

• The FDA label emphasizes caution but does not provide specific dose adjustments 3
• Monitor closely for adverse effects and consider reducing frequency or dose 3
• Drug is substantially excreted by kidney; elderly patients at higher risk due to decreased renal function 3

When NOT to Use Cephalexin

Absolute Contraindications:

• MRSA suspected or confirmed - cephalexin has no activity; use trimethoprim-sulfamethoxazole, doxycycline, clindamycin, or linezolid instead 2
• Necrotizing infections - require combination therapy with clindamycin plus piperacillin-tazobactam or ceftriaxone plus metronidazole 2
• Animal or human bites - require amoxicillin-clavulanate for anaerobic coverage 2
• Moderate-to-severe diabetic infections - require broader spectrum coverage 2
• Surgical site infections involving intestinal/genitourinary tract or axilla/perineum - require anaerobic coverage 2

Clinical Indications Where Cephalexin IS Appropriate:

• Mild, uncomplicated skin and soft tissue infections caused by susceptible Staphylococcus aureus and Streptococcus pyogenes 2
• Non-purulent infections (cellulitis) when MRSA not suspected 2
• Purulent infections when local MRSA prevalence is low 2
• Mild diabetic wound infections 2
• Incisional surgical site infections after surgery of trunk or extremities 2

Important Drug Interactions and Monitoring

Metformin Interaction:

• Cephalexin increases metformin Cmax by 34% and AUC by 24%, decreases renal clearance by 14% 3
• Careful monitoring and dose adjustment of metformin recommended when co-administered 3

Probenecid Interaction:

• Probenecid inhibits renal excretion of cephalexin 3

Monitoring Requirements:

• Prothrombin time in patients at risk (renal/hepatic impairment, poor nutritional state, protracted antimicrobial therapy, on anticoagulants) 3
• Administer exogenous vitamin K as indicated 3
• Monitor for Clostridioides difficile infection - can occur up to 2+ months after last dose 3

Common Pitfalls to Avoid

1. Assuming all first-generation cephalosporins have equal cross-reactivity with penicillins - cefazolin has unique side chain with very low cross-reactivity (0.8%), while cephalexin shares R1 side chain with aminopenicillins (16.45% cross-reactivity) 4, 1

2. Using cephalexin empirically in areas with high MRSA prevalence - treatment failure rate will be unacceptably high 2

3. Failing to remove penicillin allergy label after successful delabeling - document across all platforms, provide written documentation to patient, modify medical alert bracelets 4

4. Prescribing inadequate duration - while 5 days may be sufficient if clinical improvement observed, β-hemolytic streptococcal infections require at least 10 days 3

5. Not adjusting dose in elderly patients with decreased renal function - risk of toxic reactions is greater 3

Efficacy Data

Clinical studies demonstrate 90-97% satisfactory response rates for skin and soft tissue infections treated with cephalexin. 5, 6 Cephalexin is equivalent to dicloxacillin in efficacy but offers more convenient twice-daily dosing and better tolerability. 2, 6