What is the recommended treatment with Keflex (cefalexin) for a patient with cellulitis of the toe caused by an ingrown toenail?

Prescribing Keflex (Cephalexin) for Toe Cellulitis from Ingrown Toenail

For toe cellulitis from an ingrown toenail, prescribe cephalexin 500 mg orally four times daily for 5 days, extending only if symptoms have not improved within this timeframe. 1

Standard Treatment Regimen

• Cephalexin 500 mg orally every 6 hours (four times daily) is the first-line oral beta-lactam for typical nonpurulent toe cellulitis, providing excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus 1, 2
• Treatment duration is exactly 5 days if clinical improvement occurs (resolution of warmth, tenderness, and improving erythema), with extension only if the infection has not improved within this initial period 1, 2
• Beta-lactam monotherapy succeeds in 96% of typical cellulitis cases, confirming that MRSA coverage is unnecessary in most situations 2

When to Modify This Approach

Add MRSA Coverage If:

• Penetrating trauma is present (the ingrown toenail itself may qualify if it penetrated deeply) 1
• Purulent drainage or exudate is visible 1
• Evidence of MRSA infection elsewhere or known MRSA colonization 1
• Illicit drug use 1

For these scenarios, switch to clindamycin 300-450 mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA), or combine trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin 1, 2

Hospitalize If:

• Systemic inflammatory response syndrome (SIRS) is present (fever, tachycardia, hypotension) 1
• Altered mental status or hemodynamic instability 1
• Concern for deeper infection or necrotizing fasciitis (severe pain out of proportion to exam, rapid progression, "wooden-hard" tissues) 1
• Severe immunocompromise 1

Essential Adjunctive Measures

• Elevate the affected foot above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances 1, 2
• Carefully examine and treat interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, as treating these eradicates colonization and reduces recurrent infection risk 1, 3
• Address the ingrown toenail itself—the cellulitis will not fully resolve without treating the underlying predisposing factor 1

Critical Evidence and Nuances

The 5-day duration is supported by high-quality randomized controlled trial evidence showing equivalence to 10-14 day courses for uncomplicated cellulitis 2. Traditional longer courses increase antibiotic resistance without improving outcomes 2.

A 2017 JAMA trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit in pure cellulitis without abscess, ulcer, or purulent drainage (clinical cure 83.5% vs 85.5%, difference -2.0%, 95% CI -9.7% to 5.7%) 4. This confirms that MRSA coverage is unnecessary for typical nonpurulent cellulitis 4.

However, a 2010 retrospective study from Hawaii (high MRSA prevalence area) found trimethoprim-sulfamethoxazole had higher success rates than cephalexin (91% vs 74%, P<.001), with MRSA recovered in 62% of positive cultures 5. This divergence highlights that in high MRSA-prevalence settings or when purulent drainage is present, MRSA-active therapy may be superior 5.

Common Pitfalls to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone—some inflammation persists even after bacterial eradication 2
• Do not add MRSA coverage for typical nonpurulent toe cellulitis without specific risk factors—this represents overtreatment and increases resistance 2
• Do not use doxycycline as monotherapy—its activity against beta-hemolytic streptococci is unreliable and requires combination with a beta-lactam 2
• Antibiotics alone are insufficient if the ingrown toenail is not addressed—the mechanical trauma and bacterial portal of entry must be eliminated 6

Special Consideration: Diabetic Patients

For diabetic patients with toe cellulitis, broader coverage is recommended, including amoxicillin-clavulanate 875/125 mg twice daily, which provides single-agent coverage for both streptococci and common polymicrobial flora 1, 2. Diabetic foot infections require longer treatment duration (7-14 days) and comprehensive vascular assessment 2.

Reassessment Timeline

Mandatory reassessment at 24-48 hours is critical to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens 2. If no improvement in warmth, tenderness, or erythema occurs, extend treatment and reassess for complications including abscess formation or deeper infection 2.