What are the recommended antibiotics for cellulitis of the lower extremities?

From the Guidelines

For cellulitis of the lower extremities, the recommended first-line antibiotic treatment is a 5- to 6-day course of antibiotics active against streptococci, such as cephalexin 500 mg orally four times daily. This recommendation is based on the most recent and highest quality study available, which suggests that a short course of antibiotics is effective for nonpurulent cellulitis 1. Alternatively, dicloxacillin 500 mg orally four times daily, clindamycin 300-450 mg orally three times daily, or amoxicillin-clavulanate 875/125 mg twice daily can be used for the same duration. For patients with beta-lactam allergies, clindamycin or trimethoprim-sulfamethoxazole plus doxycycline 100 mg twice daily are appropriate alternatives.

Key Considerations

• More severe cases may require intravenous antibiotics such as cefazolin 1-2 g every 8 hours or vancomycin 15-20 mg/kg every 12 hours.
• These antibiotics target the most common causative organisms in cellulitis, primarily Streptococcus and Staphylococcus species.
• In addition to antibiotics, patients should elevate the affected limb to reduce swelling, apply warm compresses, and monitor for signs of worsening infection such as increasing redness, warmth, pain, or fever.
• If MRSA is suspected based on risk factors or previous cultures, consider adding coverage with trimethoprim-sulfamethoxazole or doxycycline, as recommended by the 2014 IDSA guideline 1.

Patient Monitoring

• Patients should see improvement within 48-72 hours; if not, reassessment and possibly broader antibiotic coverage may be needed.
• The 2019 National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5 to 7 days, but the most recent study suggests that a 5- to 6-day course may be sufficient 1.

From the FDA Drug Label

Complicated Skin and Skin Structure Infections Adult patients with clinically documented complicated skin and skin structure infections were enrolled in a randomized, multi-center, double-blind, double-dummy trial comparing study medications administered IV followed by medications given orally for a total of 10 to 21 days of treatment. The cure rates in clinically evaluable patients were 90% in linezolid-treated patients and 85% in oxacillin-treated patients Diabetic Foot Infections Adult diabetic patients with clinically documented complicated skin and skin structure infections ("diabetic foot infections") were enrolled in a randomized (2:1 ratio), multi-center, open-label trial comparing study medications administered IV or orally for a total of 14 to 28 days of treatment The cure rates in the ITT population, were 68. 5% (165/241) in linezolid-treated patients and 64% (77/120) in comparator-treated patients

Cellulitis of the lower extremities can be treated with antibiotics such as Linezolid.

• The cure rates for complicated skin and skin structure infections, including those of the lower extremities, were 90% in linezolid-treated patients and 85% in oxacillin-treated patients 2.
• For diabetic foot infections, which can include cellulitis of the lower extremities, the cure rates were 68.5% in linezolid-treated patients and 64% in comparator-treated patients 2.
• It is essential to note that these studies did not specifically focus on cellulitis of the lower extremities but rather on complicated skin and skin structure infections and diabetic foot infections, which can include cellulitis.
• The choice of antibiotic should be based on the causative pathogen and its susceptibility pattern, as well as clinical judgment and local epidemiology.

From the Research

Cellulitis of the Lower Extremities and Antibiotic Treatment

• Cellulitis is an infection of the deep dermis and subcutaneous tissue, commonly affecting the lower extremities, and is a significant global health burden 3.
• The majority of cases of cellulitis are nonculturable, but when organisms are identified, most are due to β-hemolytic Streptococcus and Staphylococcus aureus 3.
• Treatment of primary and recurrent cellulitis should initially cover Streptococcus and methicillin-sensitive S. aureus, with expansion for methicillin-resistant S. aureus (MRSA) in cases of cellulitis associated with specific risk factors 3.

Antibiotic Regimens for Lower Limb Cellulitis

• There is variation in the treatment of lower limb cellulitis (LLC) with no agreement on the most effective antibiotic regimen 4.
• Many patients with cellulitis fail to respond to first-line antibiotics, which can negatively affect patient care and result in unnecessary hospital admissions 4.
• A systematic review found that all included studies showed no significant differences between the clinical response to different antibiotic type, administration route, treatment duration, or dose 4.

Empiric Antibiotic Strategies for Cellulitis

• The rise in community-onset methicillin-resistant Staphylococcus aureus (MRSA) infections potentially complicates the empiric management of cellulitis 5.
• A decision analysis found that cephalexin was the most cost-effective option for outpatient empiric therapy of cellulitis, while clindamycin became a more cost-effective therapy at high likelihoods of MRSA infection 5.
• Trimethoprim/sulfamethoxazole (TMP/SMX) was unlikely to be cost-effective for treatment of simple cellulitis 5.

Specific Antibiotic Options

• Trimethoprim-sulfamethoxazole has been shown to have a higher treatment success rate than cephalexin for empiric therapy of cellulitis 6.
• Clindamycin has been found to have higher success rates than cephalexin in patients with culture-confirmed MRSA infections, moderately severe cellulitis, and obesity 6.
• Penicillin, amoxicillin, and cephalexin are sufficient for targeted coverage of β-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus in non-purulent, uncomplicated cases of cellulitis 7.