Skin & Soft Tissue Infections

  • Cellulitis of dental origin

  • Diabetic foot infections

  • Severely immunocompromised patients (e.g. neutropenia, immunosuppressive therapy)

  • Surgical site infections

  • Recent history of fresh/salt water exposure

  • Recent hot tub use

  • Cellulitis associated with fish and seafood processing

Treatment Criteria and Considerations

  • The diagnosis of cellulitis is largely clinical, and the initial treatment is usually empirical.

  • Misdiagnosis is not uncommon, so the clinician should be alert to the possibility of cellulitis “mimics”, such as: venous stasis dermatitis, DVT/thrombophlebitis, hematomas, and gout.

  • Cellulitis of the extremities is almost always unilateral.

    • “Bilateral cellulitis” is extremely unlikely; first consider an alternate non-infectious diagnosis

  • Evaluate all patients for predisposing features (e.g. tinea pedis, dermatoses, lymphedema, venous stasis, wounds) as the source of cellulitis, especially in the setting of recurrent cellulitis.
    • If possible, treat predisposing factors to prevent recurrent cellulitis.
    • May consider MRSA decolonization in patients with recurrent MRSA infections.

  • Non-pharmacologic interventions (such as elevation and compression of the affected limb, if appropriate) are adjunctive, but essential, components of cellulitis management:
    • Affected upper extremities should be elevated higher than the shoulder.
    • Affected lower extremities should be elevated higher than the hip joint.

  • Marking the outline of the erythema and/or daily photographs may assist in the assessment.

  • Assessment of clinical response in the first 48 hours should be limited to improvement of: pain, fever, and the patient’s overall condition

    • During the first 48 hours, a mild progression of erythema is expected and “acceptable”.
  • Review and adjust therapy as needed if microbiology results become available.

  • There is no evidence to support that IV therapy is superior to PO therapy in the management of uncomplicated cellulitis*.

  • There is no evidence to support a minimum duration of IV therapy for the management of uncomplicated cellulitis*.

  • Patients meeting the following suggested criteria can generally have their therapy converted from IV to PO:

    • The patient is afebrile for at least 24 hours.
    • Clinical improvement (such as: overall clinical improvement, decreased pain).
    • There are no complicating factors (e.g. deeper tissue involvement, undrained abscess, insufficient perfusion to the affected area).
    • The patient can tolerate oral medications that will achieve adequate tissue levels.

*Uncomplicated cellulitis: cellulitis WITHOUT periorbital involvement, severe sepsis, extensive bullous skin changes, undrained abscesses, deep tissue involvement, necrotizing fasciitis, or infected prosthetic material.

  • In patients with uncomplicated cellulitis who show improvement after 72 hours of therapy, a duration of therapy of 5 days is just as effective as 10 days.

  • In cellulitis, a relatively small number of bacteria cause a disproportionately large amount of inflammation.

  • Greater than 5 days of therapy is rarely required if the patient responds within the first 72 hours of therapy.

  • Follow-up is essential to re-assure patients (and prescribers) that any residual redness is only due to inflammation.

*Uncomplicated cellulitis: cellulitis WITHOUT periorbital involvement, severe sepsis, extensive bullous skin changes, undrained abscesses, deep tissue involvement, necrotizing fasciitis, or infected prosthetic material.

  • MRSA is most often associated with PURULENT skin and soft tissue infections. It has been common practice to prescribe anti-MRSA therapy for all cases of mild to moderate cellulitis in patients with a history of MRSA.

  • However, only mild to moderate PURULENT cellulitis requires empiric anti-MRSA therapy, even in the setting of prior MRSA infection.

  • Empiric coverage of MRSA is NOT required in mild to moderate NON-purulent cellulitis.

  • Risk Factors for MRSA include:

    • History of MRSA infection or colonization
    • Household contact with a MRSA colonized individual
    • IV drug use
    • Homelessness
    • Incarcerated persons
    • Recent travel to or residing in an MRSA endemic region or community

Additional Information

  1. Stevens, D., Bisne, A., Chambers, H., Everett, E., Dellinger, P., Goldstein, E. … Wade, J. (2014). Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clinical Infectious Disease,41 (15, November), 1373-1406
  2. Blondel-Hill and Fryters. Bugs & Drugs 2.0. Accessed online 06-2020.
  3. Hopkins ABX Guide. Accessed online 06-2020
  4. INESSS. Optimal Usage Guide: Cellulitis in Adults. October 2017. Accessed online 06-2020.
  5. Bystritsky R & Chambers H. In the Clinic ® - Cellulitis and Soft Tissue Infections. Annals of Internal Medicine. 2018. doi:10.7326/AITC201802060
  6. SHS+UHN Antimicrobial Stewardship Program. Skin and Skin Structure Infections (SSSIs). Accessed online 06-2020.
  7. SHS+UHN Antimicrobial Stewardship Program. Management of Uncomplicated Skin and Skin Structure Infections (Non-Purulent and Purulent). Accessed online 06-2020.
  8. Raff A & Kroshinsky D. Cellulitis: A Review. JAMA. 2016;316(3):325-337. doi:10.1001/jama.2016.8825
  9. McCreary EK, Heim ME, Schulz LT et al. Top 10 Myths Regarding the Diagnosis and Treatment of Cellulitis. The Journal of Emergency Medicine. 2017; 53 (4): 485–492
  10. Public Health Ontario. Evidence Brief: Duration of Antibiotic Treatment for Uncomplicated Cellulitis in Long-Term Care Residents. October 2018.
  11. Hepburn MJ, Dooley DP, Skidmore PJ et al. Comparison of Short-Course (5 Days) and Standard (10 Days) Treatment for Uncomplicated Cellulitis. Arch Intern Med. 2004;164:1669-1674
  12. Prokocimer P, De Anda C, Fang E, et al. Tedizolid Phosphate vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections: The ESTABLISH-1 Randomized Trial. JAMA. 2013;309(6):559-569
  13. Moran GJ, Fang E, Corey GR, et al. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 2014;14: 696–705
  14. Cranendonk DR, Opmeer BC, Van Agtmael MA, et al. Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial. Clinical Microbiology and Infection. 2019; DOI:https://doi.org/10.1016/j.cmi.2019.09.019
  15. Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med 2017;376:2545-55. DOI: 10.1056/NEJMoa1607033
  16. Conway J & Friedman B. Adjuvant Antibiotic Therapy After Incision and Drainage of Cutaneous Abscesses. Academic Emergency Medicine. 2020; 27: 427–428
  17. Lake JG, Miller LG, Fritz SA. Antibiotic Duration, but Not Abscess Size, Impacts Clinical Cure of Limited Skin and Soft Tissue Infection After Incision and Drainage. Clinical Infectious Diseases. 2019; DOI: 10.1093/cid/ciz1129
  18. Wang W, Chen W, Liu Y, et al. Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis. BMJ Open. 2018; 8: e020991. doi:10.1136/bmjopen-2017-020991
  19. Hurley HJ, Knepper BC, Price CS, et al. Avoidable Antibiotic Exposure for Uncomplicated Skin and Soft Tissue Infections in the Ambulatory Care Setting. Am J Med. 2013; 126(12): 1099–1106. doi:10.1016/j.amjmed.2013.08.016
  20. Collazos J, de la Fuente B, Garcia A, Goomez H, Menendez C, Enriquez H, et al. (2018) Cellulitis in adult patients: A large, multicenter, observational, prospective study of 606 episodes and analysis of the factors related to the response to treatment. PLoS ONE 13(9): e0204036. https://doi.org/10.1371/journal.pone.0204036
  21. Sutton JD, Carico R, Burk M, et al. Inpatient Management of Uncomplicated Skin and Soft Tissue Infections in 34 Veterans Affairs Medical Centers: A Medication Use Evaluation. Open Forum Infectious Diseases. 2020. DOI: 10.1093/ofid/ofz554
  22. Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016 March 3; 374(9): 823–832. doi:10.1056/NEJMoa1507476
  23. Talan DA, Moran GJ, Krishnadasan A, et al. Subgroup Analysis of Antibiotic Treatment for Skin Abscesses. Ann Emerg Med. 2018 January ; 71(1): 21–30. doi:10.1016/j.annemergmed.2017.07.483
  24. Ihm C, Sutton JD, Timbrook TT, Spivak ES. Treatment Duration and Associated Outcomes for Skin and Soft Tissue Infections in Patients With Obesity or Heart Failure. Open Forum Infectious Diseases. 2019. DOI: 10.1093/ofid/ofz217
  25. Landry DL, Eltonsy S, et al. Continuous cefazolin infusion versus cefazolin plus probenecid for the ambulatory treatment of uncomplicated cellulitis: A retrospective cohort study. Official Journal of the Association of Medical Microbiology and Infectious Disease Canada. 2018. doi:10.3138/jammi.2018-0039
  26. AHRQ Safety Program for Improving Antibiotic Use. Best Practices in the Diagnosis and Treatment of Cellulitis and Skin and Soft Tissue Infections. November 2019
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