What are the appropriate antibiotics for treating cellulitis?

From the Guidelines

Cellulitis treatment with two antibiotics is recommended in certain situations, such as moderate to severe infection, particularly when there's concern for MRSA or polymicrobial infection, and the most recent evidence suggests using vancomycin plus piperacillin-tazobactam or cefepime as a reasonable empiric regimen 1.

Key Considerations

• The choice of antibiotics should cover the most common causative organisms, including Staphylococcus aureus and Streptococcus species.
• Combination therapy with two antibiotics may be necessary in certain situations, such as:
  • Moderate to severe cellulitis
  • Concern for MRSA or polymicrobial infection
  • Patients with diabetes, immunocompromised status, or severe infection
• The most recent evidence from 2021 suggests that a shorter course of antibiotic therapy, typically 5-7 days, may be adequate for uncomplicated cellulitis 1.

Recommended Antibiotic Regimens

• For moderate to severe cellulitis, a common dual antibiotic regimen includes:
  • Vancomycin 15-20 mg/kg IV every 12 hours
  • Piperacillin-tazobactam 4.5g IV every 6-8 hours or cefepime 2g IV every 8-12 hours
• For patients with concern for MRSA or polymicrobial infection, alternative regimens may include:
  • Clindamycin plus a fluoroquinolone
  • Trimethoprim-sulfamethoxazole plus amoxicillin-clavulanate

Essential Components of Treatment

• Elevation of the affected area
• Pain management
• Monitoring for improvement (decreased redness, swelling, and pain)
• Reassessment and possible adjustment of the antibiotic regimen if no improvement occurs within 48-72 hours

Supporting Evidence

• The 2014 IDSA guideline recommends considering extending treatment if the infection has not improved after 5 days 1.
• The 2019 NICE guideline recommends a course of 5 to 7 days 1.
• Recent studies, such as the DANCE RCT, suggest that a shorter course of antibiotic therapy may be adequate for uncomplicated cellulitis 1.

From the FDA Drug Label

The two trials were similar in design but differed in patient characteristics, including history of diabetes and peripheral vascular disease. There were a total of 534 adult patients treated with daptomycin for injection and 558 treated with comparator in the two trials. Patients could switch to oral therapy after a minimum of 4 days of IV treatment if clinical improvement was demonstrated. The efficacy endpoints in both trials were the clinical success rates in the intent-to-treat (ITT) population and in the clinically evaluable (CE) population.

The treatment of cellulitis with two antibiotics is not directly supported by the provided drug label. However, the label does mention the use of daptomycin in combination with other antibiotics for the treatment of complicated skin and skin structure infections (cSSSI), which may include cellulitis.

• Key points:
  • Daptomycin was compared to vancomycin or an anti-staphylococcal semi-synthetic penicillin in two randomized trials.
  • Clinical success rates were similar between daptomycin and comparator groups.
  • The label does not provide information on the use of two antibiotics in combination for the treatment of cellulitis specifically. 2

From the Research

Cellulitis Treatment with Two Antibiotics

• The use of two antibiotics, such as cephalexin plus trimethoprim-sulfamethoxazole, for the treatment of cellulitis has been studied in several clinical trials 3, 4.
• A randomized clinical trial published in JAMA in 2017 found that the use of cephalexin plus trimethoprim-sulfamethoxazole did not result in higher rates of clinical resolution of cellulitis compared to cephalexin alone 3.
• Another study published in The Annals of Pharmacotherapy in 2007 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 4.

Route and Duration of Antibiotic Therapy

• The route and duration of antibiotic therapy for cellulitis have also been studied, with some studies suggesting that oral antibiotics may be as effective as intravenous antibiotics 5, 6.
• A systematic review and meta-analysis published in The Journal of Infection in 2020 found no evidence of difference in clinical response rates for antibiotic route or duration 6.
• Another systematic review and meta-analysis published in JAMA Dermatology in 2019 found that there was no evidence to support the superiority of any one antibiotic over another, and that antibiotics with activity against methicillin-resistant Staphylococcus aureus did not add an advantage 7.

Clinical Implications

• The available evidence suggests that the choice of antibiotic and route of administration for cellulitis should be based on individual patient factors, such as the severity of the infection and the presence of comorbidities 3, 5, 6, 4, 7.
• Further research is needed to determine the most effective and cost-effective treatment strategies for cellulitis, including the use of two antibiotics and the optimal route and duration of therapy 3, 6, 7.