What's the next step for a patient with cellulitis of the leg, on Keflex (cephalexin) for 7-10 days, with no improvement?

Management of Cellulitis Not Responding to Cephalexin

For a patient with cellulitis of the leg who has not improved after 7-10 days of Keflex (cephalexin), the next step should be switching to an antibiotic with coverage for methicillin-resistant Staphylococcus aureus (MRSA), such as clindamycin or trimethoprim-sulfamethoxazole.

Assessment of Treatment Failure

• Failure to respond to cephalexin after 7-10 days indicates possible resistance or a deeper infection than initially recognized 1
• Consider the possibility of MRSA as a causative organism, which would not respond to cephalexin 1
• Assess for underlying conditions that may contribute to poor response, such as diabetes, chronic venous insufficiency, or lymphedema 2

Antibiotic Options After Cephalexin Failure

• Clindamycin is an effective option for suspected MRSA infections in patients who can be managed as outpatients 1
• Trimethoprim-sulfamethoxazole is another appropriate choice for coverage of potential MRSA 1
• For more severe cases that can still be managed as outpatients, linezolid may be considered 1
• If there are signs of systemic illness or rapid progression, hospitalization for intravenous antibiotics (such as vancomycin) is warranted 2

Duration of New Antibiotic Therapy

• For complicated infections or those that failed initial therapy, extend treatment to 7-14 days based on clinical response 1
• Monitor for clinical improvement within 24-48 hours of initiating the new antibiotic regimen 1

Evidence for MRSA Coverage

• While adding trimethoprim-sulfamethoxazole to cephalexin did not significantly improve outcomes in uncomplicated cellulitis in the per-protocol analysis of one study, the modified intention-to-treat analysis showed a potential benefit 3
• For patients who have failed first-line therapy with a beta-lactam like cephalexin, coverage for MRSA becomes more important 1

Adjunctive Measures

• Elevate the affected leg to promote drainage of edema and inflammatory substances 2
• Address any underlying conditions that may predispose to infection or poor response 2
• Consider systemic corticosteroids in selected non-diabetic adult patients to hasten resolution 2

When to Consider Hospitalization

• If there is no improvement within 24-48 hours after switching antibiotics 1
• If there are signs of systemic illness, rapid progression, or suspicion of deeper infection 2
• If the patient has significant comorbidities that may complicate outpatient management 2

Common Pitfalls to Avoid

• Not addressing underlying conditions that contribute to recurrent infections or poor response 1
• Inadequate follow-up within 24-48 hours when using new antibiotics 1
• Overlooking deeper or more serious infections in patients with poor response to initial therapy 1
• Continuing the same antibiotic despite clear evidence of treatment failure 2