Published on in Vol 5, No 3 (2022): Jul-Sep

Preprints (earlier versions) of this paper are available at https://preprints.jmir.org/preprint/37888, first published .
From the Cochrane Library: Interventions for Cellulitis and Erysipelas

From the Cochrane Library: Interventions for Cellulitis and Erysipelas

From the Cochrane Library: Interventions for Cellulitis and Erysipelas

Research Letter

1University of Colorado School of Medicine, Aurora, CO, United States

2Dermatology Service, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, United States

*these authors contributed equally

Corresponding Author:

Ani Oganesyan, BA

University of Colorado School of Medicine

13001 E 17th Pl

Aurora, CO, 80045

United States

Phone: 1 8184416860

Email: ani.oganesyan@cuanschutz.edu



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].

Table 1. Current Infectious Diseases Society of America guidelines for the management of nonpurulent cellulitis and erysipelas.a
Disease entity and antibioticDosage, adultsDosage, childrenComment
MSSAb SSTIc

Nafcillin or oxacillin1-2 g every 4 h IVd100-150 mg/kg/d in 4 divided dosesInactive against MRSAe

Cefazolin1 g every 8 h IV50 mg/kg/d in 3 divided dosesFor penicillin-allergic patients, except those with immediate hypersensitivity reactions; more convenient than nafcillin with less bone marrow suppression

Clindamycin600 mg every 8 h IV or 300-450 mg 4 times daily by mouth25-40 mg/kg/d in 3 divided doses IV or 25-30 mg/kg/d in 3 divided doses by mouthBacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in MRSA

Dicloxacillin500 mg 4 times daily by mouth25–50 mg/kg/d in 4 divided doses by mouthOral agent of choice for methicillin-susceptible strains in adults; rarely used in pediatrics

Cephalexin500 mg 4 times daily by mouth25-50 mg/kg/d 4 divided doses by mouthFor penicillin-allergic patients except those with immediate hypersensitivity reactions; the availability of a suspension and requirement for less frequent dosing

Doxycycline, minocycline100 mg twice daily by mouthNot recommended for age <8 yBacteriostatic; limited recent clinical experience

Trimethoprim-sulfamethoxazole1-2 double-strength tablets twice daily by mouth8-12 mg/kg (based on trimethoprim component) in either 4 divided doses IV or 2 divided doses by mouthBactericidal; efficacy poorly documented
MRSA SSTI

Vancomycin30 mg/kg/d in 2 divided doses IV40 mg/kg/d in 4 divided doses IVFor penicillin-allergic patients; parenteral drug of choice for treatment of infections caused by MRSA

Linezolid600 mg every 12 h IV or 600 mg twice daily by mouth10 mg/kg every 12 h IV or by mouth for children <12 yBacteriostatic; limited clinical experience; no cross-resistance with other antibiotic classes; costly

Clindamycin600 mg every 8 h IV or 300-450 mg 4 times daily by mouth25-40 mg/kg/d in 3 divided doses IV or 30-40 mg/kg/d in 3 divided doses by mouthBacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in MRSA; important option for pediatrics

Daptomycin4 mg/kg every 24 h IVN/AfBactericidal; possible myopathy

Ceftaroline600 mg twice daily IVN/ABactericidal

Doxycycline, minocycline100 mg twice daily by mouthNot recommended for age <8 yBacteriostatic; limited recent clinical experience

Trimethoprim-sulfamethoxazole1-2 double-strength tablets twice daily by mouth8–12 mg/kg/d (based on trimethoprim component) in either 4 divided doses IV or 2 divided doses by mouthBactericidal; limited published efficacy data
Streptococcal skin infectionsPenicillin: 2-4 million units every 4-6 h IV; Clindamycin: 600-900 mg every 8 h IV; Nafcillin: 1-2 g every 4-6 h IV; Cefazolin: 1 g every 8 h IV; Penicillin: VK 250-500 mg every 6 h by mouth; Cephalexin 500 mg every 6 h by mouthPenicillin: 60,000-100,000 units/kg/dose every 6 h; 10-13 mg/kg dose every 8 h IV; 50 mg/kg/dose every 6 h; 33 mg/kg/dose every 8 h IVN/A

aRecommendation according to the Infectious Diseases Society of America. Doses listed are not appropriate for neonates. Infection due to Staphylococcus and Streptococcus species. Duration of therapy is 7 days depending on the clinical response.

bMSSA: methicillin-susceptible Staphylococcus aureus.

cSSTI: skin and soft tissue infection.

dIV: intravenous.

eMRSA: methicillin-resistant Staphylococcus aureus.

fN/A: not applicable.

Table 2. Treatment comparison with respective results, risk ratio, and CI.a
ComparisonMeasurementResultsRRb (95% CI)Studies, nPatients, n
Macrolides/streptogramins vs penicillin antibioticsSymptoms rated by participant or medical practitionerMacrolides/streptogramins were superior0.84 (0.73-0.97)252488
Oral macrolide vs IVc penicillinSymptoms rated by participant or medical practitionerOral therapy was superior0.85 (0.73-0.98)3419
Penicillin vs cephalosporinSymptoms rated by participant or medical practitionerNo difference in treatment effect0.99 (0.68-1.43)388
Cephalosporin vs cephalosporindSymptoms rated by participant or medical practitionerNo difference in treatment effect1.00 (0.94-1.06)6538

aPrimary 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).

bRR: relative risk.

cIV: intravenous.

dAggregate 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.

Conflicts of Interest

RD is a Joint Coordinating Editor for Cochrane Skin, a dermatology section editor for UpToDate, a Social Media Editor for the Journal of the American Academy of Dermatology (JAAD), a Podcast Editor for the Journal of Investigative Dermatology (JID), Editor-in-Chief of JMIR Dermatology, and a coordinating editor representative on Cochrane Council. TS is an editorial board member-at-large for JMIR Dermatology.

Editorial Notice

The views expressed in this paper are those of the author(s) and in no way represent the Cochrane Library or Wiley.

This article is based on a Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2010, Issue 6, DOI: 10.1002/14651858.CD004299 (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review.

  1. Kilburn SA, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev 2010 Jun 16(6):CD004299. [CrossRef] [Medline]
  2. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis 2014 Jul 15;59(2):147-159. [CrossRef] [Medline]
  3. Chen L, Silverman N, Wu A, Shinder R. Intravenous steroids with antibiotics on admission for children with orbital cellulitis. Ophthalmic Plast Reconstr Surg 2018;34(3):205-208. [CrossRef] [Medline]
  4. Solomon M, Barzilai A, Elphasy H, Trau H, Baum S. Corticosteroid therapy in combination with antibiotics for erysipelas. Isr Med Assoc J 2018 Mar;20(3):137-140 [FREE Full text] [Medline]
  5. Bystritsky RJ. Cellulitis. Infect Dis Clin North Am 2021 Mar;35(1):49-60. [CrossRef] [Medline]


SSTI: skin and soft tissue infection


Edited by R Alhusayen; submitted 10.03.22; peer-reviewed by C Sibbald, V Long; comments to author 17.07.22; revised version received 18.07.22; accepted 20.07.22; published 29.07.22

Copyright

©Ani Oganesyan, Torunn Sivesind, Robert Dellavalle. Originally published in JMIR Dermatology (http://derma.jmir.org), 29.07.2022.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology Research, is properly cited. The complete bibliographic information, a link to the original publication on http://derma.jmir.org, as well as this copyright and license information must be included.