Valeria Fabre, M.D.



  • Definition: though a general term for inflammation, cellulitis in this module means a spreading bacterial infection of the skin.
    • Erysipelas: superficial, sharply demarcated--nearly always group A Streptococcus.
    • Cellulitis: deeper (subcutaneous) than erysipelas.
    • Most cases are due to group A Streptococcus, but other streptococci are occasionally implicated, e.g., group G.
    • Purulent cellulitis (often developing around wound or furuncle, abscess, carbuncle):
  • Predisposing conditions: trauma, lymph or venous stasis (prior radiation, mastectomy, saphenous vein harvest), chronic edema, skin disorders (e.g., psoriasis), injection drug use, ulcers, wounds, dermatophytic infections, animal bites, neutropenia, chemotherapy, immunocompromise, immersion injuries.
  • Exam: red, hot, tender skin with edema [Fig 1] + fever and adenopathy.
  • Differential diagnosis: allergic reactions, gout, zoster, erythroderma, insect bite reactions, panniculitis, Lyme disease (erythema migrans), Sweet’s syndrome, pyoderma, fixed drug reaction, dermatitis, thrombophlebitis, necrotizing fasciitis.
    • Orbital cellulitis is potentially serious and merits an ophthalmology consultation and a CT scan to exclude preseptal infection.


  • Usually based upon a clinical diagnosis (appearance and symptoms).
  • Lab:
    • Blood cultures are not routinely indicated due to low yield (positive in < 5%).
      • Blood cultures indicated for extensive cellulitis, special populations (immunosuppressed, severe post-surgical wounds, etc.), and those severely ill.
    • Can prove group A streptococcal infection with ASO and DNAase B by serial titers.
  • Imaging: helpful in some cases.


Terms and General Principles

  • Classification (Based on 2014 IDSA Guidelines for Diagnosis and Management of Skin and Soft Tissue Infections)[2]
  • For infection in which culture information is derived, use results to help guide therapy.
  • Purulent-associated cellulitis: associated with an abscess, carbuncle or furuncle.
    • Severe infection:
      • Patients who have failed I&D plus oral antibiotics
      • Presence of SIRS (≥ 2 of the following: T > 38°C, P > 90, RR > 24, WBC < 4,000 cells/υL or > 12,000 cells/υL) and evidence of end-organ damage
      • Immunocompromised patients
    • Moderate infection:
      • Purulent infection with signs of systemic inflammation
    • Mild infection:
      • Purulent infection requires I&D (without the above)
  • Non-purulent cellulitis: without abscess, necrotizing fasciitis or erysipelas.
    • Severe infection:
      • Failed oral antibiotics
      • Presence of SIRS (≥ 2 of the following: T > 38°C, P > 90, RR > 24, WBC < 4,000 cells/υL or > 12,000 cells/υL) and evidence of end-organ damage
      • Immunocompromised patients
      • Presence of skin sloughing or bullae
      • Hypotension
    • Moderate infection:
      • Typical cellulitis or erysipelas + systemic signs of infection
    • Mild infection:
      • Typical cellulitis or erysipelas
      • No evidence of purulence

Non-purulent Infections

Purulent Infections

  • For all infections, perform thorough I&D.
  • Severe: obtain culture from I&D; use IV abx--may convert to oral when stable/improved.
  • Moderate: obtain culture from I&D. May use IV above or oral selection below based on clinical judgment.
    • Adult:
      • Empiric: IV from the above or oral selection from below.
      • MSSA: IV from above or oral from below
      • MRSA: IV from above or oral below
    • Pediatric:
      • Empiric: IV from above or oral from below.
        • TMP/SMX 8-12 mg/kg/d (based on TMP) PO in two divided doses
      • MSSA: IV from above or oral from below
      • MRSA: IV from above or oral from below.
        • TMP/SMX 8-12 mg/kg/d (based on TMP) PO in two divided doses
  • Mild: no culture required; use oral options from above.
  • Antibiotics can be avoided for small abscesses (< 2cm) in immunocompetent patients who are clinically stable.
  • Studies have shown a benefit in recurrence for those who received antibiotics after I&D, although they also suffered more adverse events related to antibiotics than patients that received a placebo.

Adjunctive Therapy

  • For infections of limbs, elevate the affected site.
  • Treat associated conditions (especially if recurrent infection):
  • Erysipelas: consider prednisone 30mg with a taper over 8 days to assist with inflammatory reaction (may want to avoid in diabetes).


  • Prevent edema: diuretics, limb elevation, compression stockings, and decongestive therapy.
  • Keep skin hydrated using emollients.
  • Treat dermatophytic infections, especially interdigital spaces on feet.
  • Prevention of recurrent cellulitis, especially with lymphedema (consider if > 3-4 episodes/ year and correction of underlying risk factors have been addressed already):
  • Topical antibiotics are not effective.

For recurrent S. aureus abscesses, consider a) decolonization with twice daily intranasal mupirocin for 5 days, b) daily chlorhexidine washes, c) daily decontamination of personal items such as towels, sheets, and clothes.

Selected Drug Comments




Pen G IV or pen Vk PO is probably the drug of choice for streptococci.


Not effective against Staphylococcus aureus, ex., for the rare isolate that remains penicillin-susceptible, but good coverage against Group A Strep. Group A Strep is always sensitive to penicillin and amoxicillin. Inexpensive oral medication.


Good oral drug for Group A Strep and Staphylococcus aureus (MSSA but not MRSA).


Effective against group A Strep and MSSA but not MRSA.


Also a good choice for covering both group A Strep and methicillin-sensitive Staphylococcus aureus in patients with mild to moderate disease that can be treated with oral antibiotics.


Along with minocycline, often thought of as an oral alternative to TMP/SMX for community-acquired MRSA.


Very convenient for once-daily dosing and effective against Staphylococcus aureus (MSSA and some CA-MRSA), but it may represent abusive prescribing as it has much more spectrum of coverage than typically needed for S. pyogenes and some S. aureus.


It may favor patients with previous vancomycin-associated nephropathy or at high risk for nephrotoxicity. Also, consider for patients who may clear Vanc very quickly and might be challenging to achieve adequate therapeutic levels. Oral dosing makes conversion from IV vancomycin attractive.


Concern is C. difficile infection.


Active vs. >95% community-acquired MRSA, but less active vs. hospital strains.


  • Symptoms typically dissipate within the first few days of antibiotic therapy. Still, they may take longer, especially in limbs with poor circulation or chronic edema, even though the constitutional symptoms may disappear earlier.
  • Cellulitis may appear to worsen the first 24-48+ hrs despite antibiotics. This may be due to toxins and/or bacterial lysis that drive inflammation, even though the antibiotic has achieved a bacteriocidal effect.
  • Severe cellulitis may predispose to repeated bouts: "cellulitis begets cellulitis."


  • S. aureus: including MRSA, leading cause of soft tissue abscesses -- easy to find and to culture.
  • S. pyogenes: a major cause of cellulitis, but very hard to culture in this setting.
    • Always sensitive to penicillin, which is the drug of choice.
  • A most common form of cellulitis afflicts the leg (tibial area) with a breach in the skin, sometimes due to intertrigo.
  • Treatment: always cover streptococci, which is always sensitive to beta-lactams.

Pathogen Specific Therapy

Basis for recommendation

  1. Gottlieb M, DeMott JM, Hallock M, et al. Systemic Antibiotics for the Treatment of Skin and Soft Tissue Abscesses: A Systematic Review and Meta-Analysis. Ann Emerg Med. 2019;73(1):8-16.  [PMID:29530658]

    Comment: This meta-analysis explored the benefit of antibiotics for managing cutaneous abscess post-I&D. Four studies (n=2,406 participants) were identified. There were 89 treatment failures (7.7%) in the antibiotic group and 150 (16.1%) in the placebo group. There was also a decreased incidence of new lesions in the antibiotic group (risk difference -10.0%, 95% CI -12.8% to -7.2%; odds ratio 0.32, 95% CI 0.23 to 0.44) and a mildly increased risk of minor adverse events (risk difference 4.4%, 95% CI 1.0% to 7.8%; odds ratio 1.29, 95% CI 1.06 to 1.58).

  2. Stevens DL, Bisno AL, Chambers HF, 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;59(2):e10-52.  [PMID:24973422]

    Comment: Foundation for recommendations presented in this module.


  1. Cross ELA, Jordan H, Godfrey R, et al. Route and duration of antibiotic therapy in acute cellulitis: A systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment. J Infect. 2020;81(4):521-531.  [PMID:32745638]

    Comment: Meta-analysis could not find any evidence to support a difference between shorter or longer durations of therapy although there were only 2 trials that had the same drug as a comparator.

  2. Webb E, Neeman T, Bowden FJ, et al. Compression Therapy to Prevent Recurrent Cellulitis of the Leg. N Engl J Med. 2020;383(7):630-639.  [PMID:32786188]

    Comment: A small trial showed that regular use lowered risk by about 80% in analysis with up to three years of follow-up.

  3. Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555.  [PMID:28657870]

    Comment: Adults and children with a single skin abscess 5 cm in diameter or smaller were randomly assigned to receive oral clindamycin, TMP-SMX, or placebo in addition to incision and drainage. In patients with S. aureus infections, patients in the abx groups had a higher cure rate and were less likely to have a recurrent infection at 1 month. Adverse events were common in the abx groups.
    Rating: Important

  4. Obaitan I, Dwyer R, Lipworth AD, et al. Failure of antibiotics in cellulitis trials: a systematic review and meta-analysis. Am J Emerg Med. 2016;34(8):1645-52.  [PMID:27344098]

    Comment: According to the literature review, cellulitis failure rates vary widely (6-37%). The author speculates that this reflects many cases that mimic cellulitis.

  5. Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372(12):1093-103.  [PMID:25785967]

    Comment: Comparative trial of 524 patients with cellulitis, cutaneous abscess or both using TMP/SMX vs clindamycin x 10 days. Abscesses were drained. Outcomes of the two groups were similar (cure rates of 90% vs. 88%; P=0.8).

  6. Baang J. Antibacterial Treatment for Uncomplicated Skin Infections. N Engl J Med. 2015;372(25):2459.  [PMID:26083211]

    Comment: The letter to the editor noted 30% of each group had abscesses that may only need drainage without antibiotics. The authors respond that this query was not addressed, so their trial could not answer it.

  7. van Bijnen EM, Paget J, den Heijer CD, et al. Evidence-based primary care treatment guidelines for skin infections in Europe: a comparative analysis. Eur J Gen Pract. 2014;20(4):294-300.  [PMID:24456348]

    Comment: Review of 13 guidelines for skin infections from 9 European countries. Conditions included erysipelas, folliculitis, cellulitis, impetigo and furuncle. All recommended beta-lactam agents, mainly those with limited spectrum. Seven also recommended topical fusidic acid. The beta-lactam recommended for adults varied, including penicillin (2), flucloxacillin (4), and oxacillin (1); the duration was 7-14 days, usually 10 days.

  8. Gunderson CG, Martinello RA. A systematic review of bacteremias in cellulitis and erysipelas. J Infect. 2012;64(2):148-55.  [PMID:22101078]

    Comment: Literature review of patients hospitalized with cultures were positive in 4.6% of 607 cases, of which Group A strep accounted for 65%, S. aureus for 14% and Gram negative bacilli 11%. The conclusion is that these results show most cellulitis cases are caused by Group A strep.
    Rating: Important

  9. Keller EC, Tomecki KJ, Alraies MC. Distinguishing cellulitis from its mimics. Cleve Clin J Med. 2012;79(8):547-52.  [PMID:22854433]

    Comment: The skin conditions that mimic cellulitis include stasis dermatitis, contact dermatitis, lymphedema, eosinophilic cellulitis, and papular urticaria.

  10. Walraven CJ, Lingenfelter E, Rollo J, et al. Diagnostic and therapeutic evaluation of community-acquired methicillin-resistant Staphylococcus Aureus (MRSA) skin and soft tissue infections in the emergency department. J Emerg Med. 2012;42(4):392-9.  [PMID:21524884]

    Comment: Evaluation of sensitivity tests of 58 community-acquired MRSA isolates from soft tissue infections in an emergency room in Salt Lake City -- 51 (98%) were sensitive to TMP/SMX -- 50 (80%) sensitive to tetracycline -- 47 (81%) sensitive to clindamycin. Note that this sensitivity pattern is similar to many other reports for the past 4 years. TMP/SMX or clindamycin are usually "preferred."
    Rating: Important

  11. Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med. 2010;123(10):942-50.  [PMID:20920697]

    Comment: Evaluation of treatment of cellulitis in 405 patients. The success rate was 91% with TMP/SMX vs. 74% (P=< 0.001). Factors associated with treatment failure were: antibiotic inactive in vitro (OR=4.2) and cellulitis severity (OR=3.7). This report is testimony to the need to treat with antibiotics and the value of TMP/SMX for CA-MRSA infections.
    Rating: Important

  12. Jeng A, Beheshti M, Li J, et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation. Medicine (Baltimore). 2010;89(4):217-226.  [PMID:20616661]

    Comment: This is a report of 179 patients with diffuse, non-culturable cellulitis using serology (ALSO and DNase B), which was positive in 73%. A separate analysis of 73 showed 71 (97%) responded to a β-lactam. Group A Strep usually causes cellulitis with no pus and negative cultures.

  13. Lamagni TL, Neal S, Keshishian C, et al. Predictors of death after severe Streptococcus pyogenes infection. Emerg Infect Dis. 2009;15(8):1304-7.  [PMID:19751599]

    Comment: Review of 3,566 serious streptococcal infections in England 2003-04. Cellulitis was the most common (30%), and necrotizing fasciitis was the most commonly fatal.
    Rating: Important

  14. Siljander T, Karppelin M, Vähäkuopus S, et al. Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings. Clin Infect Dis. 2008;46(6):855-61.  [PMID:18260753]

    Comment: Review of 90 cases and 90 controls. The most common pathogen was Group G strep -- 26 (29%) cases. Also, in the throat of 7% of cases, 13% of household contacts and no controls. Group A strep was found in 7%. Recurrent infection in 7%.

  15. Sebeny PJ, Riddle MS, Petersen K. Acinetobacter baumannii skin and soft-tissue infection associated with war trauma. Clin Infect Dis. 2008;47(4):444-9.  [PMID:18611157]

    Comment: The authors describe eight patients with A. baumannii infections associated with war wounds. The presentation was cellulitis with a "peau d’orange" appearance, with vesicles and progressed to necrosis with bullae.
    Rating: Important

  16. Ruhe JJ, Menon A. Tetracyclines as an oral treatment option for patients with community onset skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2007;51(9):3298-303.  [PMID:17576834]

    Comment: A retrospective review of 282 patients with MRSA soft tissue infections showed doxycycline in 90 patients and was active vs. the MRSA in 95%. Doxycycline was significantly better than beta-lactam (OR 3.9, p=0.02).

  17. Gabillot-Carré M, Roujeau JC. Acute bacterial skin infections and cellulitis. Curr Opin Infect Dis. 2007;20(2):118-23.  [PMID:17496568]

    Comment: Leg erysipelas/cellulitis is common - 1/1000 persons/year. Group A strep is still the most common, and foot intertrigo is a common risk.

  18. McNamara DR, Tleyjeh IM, Berbari EF, et al. A predictive model of recurrent lower extremity cellulitis in a population-based cohort. Arch Intern Med. 2007;167(7):709-15.  [PMID:17420430]

    Comment: Mayo Clinic review of cellulitis in a population-based cohort. There were 209 cases of cellulitis, and 35 (17%) recurred within 2 years. The most common findings in the cellulitis group are tibial involvement, malignancy and dermatitis. These risks correlate with the risk of recurrence.
    Rating: Important

  19. Leclerc S, Teixeira A, Mahé E, et al. Recurrent erysipelas: 47 cases. Dermatology. 2007;214(1):52-7.  [PMID:17191048]

    Comment: Review of recurrent erysipelas in 47 patients. The average was 4.1 recurrences, most had cutaneous disruption (81%) usually due to intertrigo (60%). Antibiotic prophylaxis was given to 68% - no recurrences were noted in 72% at two years.

  20. Swartz MN. Clinical practice. Cellulitis. N Engl J Med. 2004;350(9):904-12.  [PMID:14985488]

    Comment: Group A Strep: lymphedema, early post-op wound infections, perianal cellulitis; Crepitant cellulitis: Clostridia and other anaerobes; Bites: Human - anaerobes, Eikenella, S. aureus, cats/dogs - Pasteurella; Diabetic foot: GNB and anaerobes; Blood cultures: Usually Group A strep.
    Rating: Important

  21. Eady EA, Cove JH. Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus--an emerging problem for the management of skin and soft tissue infections. Curr Opin Infect Dis. 2003;16(2):103-24.  [PMID:12734443]

    Comment: Review of the emerging problem of community-acquired MRSA. Though most often identified in children, sporadic and outbreak cases are seen in adults (IDU, HIV, sports teams). Routine management of suspected staphylococcal skin and soft-tissue infection as MSSA may need to change in the next few years.

  22. Stevens DL, Herr D, Lampiris H, et al. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis. 2002;34(11):1481-90.  [PMID:12015695]

    Comment: Randomized trial of linezolid vs. vancomycin for soft tissue infections involving MRSA. Clinical cure rates were 73% in both groups.

  23. Stevens DL, Smith LG, Bruss JB, et al. Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother. 2000;44(12):3408-13.  [PMID:11083648]

    Comment: Randomized trial of oxacillin - dicloxacillin vs. linezolid for 826 patients hospitalized with complicated skin and soft tissue infections. Cure rates were 70% for linezolid and 65% for oxacillin - dicloxacillin (p=0.1).

  24. Eriksson BK. Anal colonization of group G beta-hemolytic streptococci in relapsing erysipelas of the lower extremity. Clin Infect Dis. 1999;29(5):1319-20.  [PMID:10524984]

    Comment: Anal colonization with Group G and possibly Group A and other Beta-hemolytic streptococci may be the reservoir for the pathogen in recurrent erysipelas. In recurrent cases, it may be worth educating patients about this possible source of infection.

  25. Perl B, Gottehrer NP, Raveh D, et al. Cost-effectiveness of blood cultures for adult patients with cellulitis. Clin Infect Dis. 1999;29(6):1483-8.  [PMID:10585800]

    Comment: A retrospective review of 757 patients admitted with community-acquired cellulitis over 41 months shows that the yield of blood cultures is very low (2%), has a marginal impact on clinical management and is not cost-effective for most patients with cellulitis.

  26. Bergkvist PI, Sjöbeck K. Relapse of erysipelas following treatment with prednisolone or placebo in addition to antibiotics: a 1-year follow-up. Scand J Infect Dis. 1998;30(2):206-7.  [PMID:9730318]

    Comment: Placebo-controlled trial of antibiotic with or without prednisolone for erysipelas. Steroid treatment hastened response.

  27. Klempner MS, Styrt B. Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy. JAMA. 1988;260(18):2682-5.  [PMID:3184334]

    Comment: A controlled trial showed the benefit of prophylactic clindamycin (150mg/d) to prevent recurrent S. aureus skin infections.

  28. Hook EW, Hooton TM, Horton CA, et al. Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med. 1986;146(2):295-7.  [PMID:3947189]

    Comment: Microbiology studies in 50 patients hospitalized with cellulitis showed pathogen in blood in 5 (10%), by needle aspirate in 5 but with higher yield by skin punch biopsy - 10 (20%), but the latter is rarely performed.

  29. 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(15):1669-74.  [PMID:15302637]

    Comment: A randomized trial for 5 vs. 10 days of treatment showed uncomplicated cellulitis could be treated for 5 days.


Cellulitis with bullae

Descriptive text is not available for this image

Cellulitis developing after an immunization (for smallpox with vaccinia!). There is spreading erythema and swelling as well as bulla.

Source: CDC/A. W. Mathies, MD

Cellulitis of the leg

Descriptive text is not available for this image

Typical cellulitis of the left leg with line drawn at time of evaluation. Despite effective antibitoics, erythema may extend somewhat in the first day or two but not reflect lack of therapeutic effect.

Source: John Campbell

Wikimedia Commons

Last updated: January 13, 2023