From the Cochrane Library: Interventions for Cellulitis and Erysipelas

Cellulitis and erysipelas are types of skin and soft tissue infections (SSTIs) that occur when bacteria, commonly group A beta-hemolytic Streptococcus and Staphylococcus, enter through breaks in the skin. Cellulitis infects the dermis and subcutaneous fat, while erysipelas is a more superficial variant, affecting the superficial dermal lymphatics and adjacent tissues. Untreated, these conditions may result in life-threatening conditions including sepsis, gangrene, or necrotizing fasciitis [1]. Due to the potential risks associated with these conditions, evidence-based research to inform up-to-date treatment guidelines is critical; Table 1 provides guidelines for reference.

Cellulitis and erysipelas are types of skin and soft tissue infections (SSTIs) that occur when bacteria, commonly group A beta-hemolytic Streptococcus and Staphylococcus, enter through breaks in the skin. Cellulitis infects the dermis and subcutaneous fat, while erysipelas is a more superficial variant, affecting the superficial dermal lymphatics and adjacent tissues. Untreated, these conditions may result in life-threatening conditions including sepsis, gangrene, or necrotizing fasciitis [1]. Due to the potential risks associated with these conditions, evidence-based research to inform up-to-date treatment guidelines is critical; Table 1 provides guidelines for reference.
A 2010 Cochrane Review [1], "Interventions for Cellulitis and Erysipelas," assessed 25 randomized controlled trials comparing treatments for primary skin infections, involving a total of 2488 participants. Specifically, the included trials each compared two or more interventions (eg, antibiotics, such as penicillin, macrolides/streptogramins, or cephalosporins, and steroids), routes of administration, and therapy durations. The objective of the review was to assess the efficacy of interventions for nonsurgically acquired SSTIs. This letter will address the limitations of the original review and provide updates based on recent studies.
Macrolides and streptogramins proved superior to penicillin antibiotics in eliminating or reducing cellulitis symptoms (N=2488). Trials comparing oral macrolides against intravenous penicillin found the former to be superior (n=419). No significant differences were found in studies comparing penicillin to cephalosporins (n=88) or among cephalosporin generations (n=538). These comparisons are summarized in Table 2.
Notably, the review [1] highlights a lack of evidence regarding the incorporation of corticosteroids into the antibiotic therapy regimen, whereas subsequent studies have suggested a benefit. The Infectious Disease Society of America states that systemic corticosteroids should be considered in nondiabetic adults to hasten the clinical improvement of cellulitis [2]. A 2018 study [3] assessing corticosteroids (0.5 mg/kg prednisone for 2-3 days) as an add-on therapy to antibiotics for patients hospitalized with erysipelas found that adding steroids resulted in quicker recovery rates and return to full function, with less risk of recurrence [4]. A study of 43 children admitted to the hospital for orbital cellulitis reported a 3-day decrease in length of stay for those treated with adjunctive intravenous dexamethasone (0.3 mg/kg/d every 6 hours for 3 days) compared to those treated with antibiotic monotherapy [3].
Notably, the review [1] did not examine the effectiveness of prophylaxis for cellulitis recurrence; the annual recurrence rate is approximately 8% to 20%. In patients with frequent cellulitis recurrence (3-4 episodes annually), erythromycin, intramuscular penicillin, and oral penicillin VK have been posited as appropriate prophylactic options. A 2021 meta-analysis assessing the use of erythromycin and penicillin found a 69% decreased risk of recurrent cellulitis versus placebo and improved recurrence interval. Penicillin was preferred over erythromycin due to its superior tolerability and cost [5].  Primary outcomes included symptoms rated by participant or medical practitioner (eg, duration and intensity of fever, pain, redness of the affected area, swelling of the skin surface and subcutaneous tissue, blister formation), proportion symptom-free (cure), and at a time specified by the study authors), the proportion with severe complications (eg, severe sepsis, multi-organ failure, or death), and quality of life scores (ie, generic and disease-specific items and return to normal activity). b RR: relative risk. c IV: intravenous. d Aggregate data from studies evaluating the following cephalosporins: ceftriaxone, cefdinir, cefonicid, cefditoren, cefadroxil, and cefuroxime.
The review reported insufficient data to determine the ideal duration of therapy. International recommendations for treatment duration in SSTIs are inconsistent (5-14 days) [2]-however, this is largely based on expert opinion, with few randomized controlled trials evaluating this parameter. Future research should address this limitation to maximize patient benefit while reducing the effects of prolonged exposure.