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Cellulitis

Valeria Fabre, M.D., John G. Bartlett, M.D.

PATHOGENS

CLINICAL

  • Definition: spreading infection of skin.
    • Erysipelas: superficial, sharply demarcated--nearly always group A Streptococcus.
    • Cellulitis: deeper (subcutaneous) than erysipelas. Also usually group A Streptococcus, but other streptococci occasionally implicated, e.g., group G.
    • Purulent cellulitis (often developing around wound or furuncle, abscess, carbunclue): Staphylococcus aureus.
  • 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 + 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.

DIAGNOSIS

  • Usually based upon a clinical diagnosis (appearance and symptoms).
  • Lab:
    • Blood cultures not routinely indicated due to low yield (positive in < 5%).
      • Blood cultures indicated with extensive cellulitis and in special populations (immunosuppressed, severe post-surgical wounds, etc).
      • Consider priority for immunocompromised patients, unusual pathogen suspected, no response to adequate antibiotic therapy.
    • Can prove group A streptococcal infection with ASO and/or DNAase B by serial titers.
  • Imaging: helpful in some cases.

TREATMENT

Terms and General Principles

  • Classification (Based on 2014 IDSA Guidelines for Diagnosis and Management of Skin and Soft Tissue Infections)[1]
  • For infection in which culture information is derived, use results to help guide therapy.
  • Purulent: cellulitis associated with abscess, carbuncle, 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)
      • Immunocompromised patients
    • Moderate infection:
      • Purulent infection with signs of systemic inflammation
    • Mild infection:
      • Purulent infection, requires I&D (without the above)
  • Non-purulent: cellulitis, necrotizing fasciitis, 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)
      • Immunocompromised patients
      • Presence of skin sloughing or bullae
      • Hypotension
      • End organ dysfunction
    • 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

  • All infections, perform thorough I&D.
  • Severe: obtain culture from I&D; use IV abx--may convert to oral when stable/improved.
    • Adult
      • Empiric: to cover MRSA
        • Vancomycin 15 mg/kg IV q 12h
        • Linezolid 600 mg every 12h IV
        • Daptomycin 6-8 mg/kg IV q 24h
        • Telavancin 10 mg/kg IV once daily (infuse over 1 hr)
        • Ceftaroline 600 mg IV q 8-12h (consider only if other options not available)
        • Clindamycin: Not longer an option in most places due to increased resistance among MRSA and MSSA isolates (can be considered if prevalence of resistance < 10%)
      • MSSA:
      • MRSA:
        • See empiric selections above
  • Pediatric
  • Moderate: obtain culture from I&D. May use IV above or oral selection below based on clinical judgement.
    • Adult:
      • Empiric: IV from 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.
  • β-lactam allergy: Vancomycin (above doses)

Adjunctive Therapy

  • Erysipelas: consider prednisone 30mg with taper over 8 days to assist with inflammatory reaction (may want to avoid in diabetes).
  • For infections of limbs, elevate affected site.
  • Treat associated conditions (especially if recurrent infection): Tinea pedis, venous stasis, lymphedema, eczema, trauma sites.

Prevention

  • Prevent edema: diuretics, limb elevation, compression stockings, 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

Drug

Recommendation

Penicillin

Pen G IV or pen V PO, probably the drug of choice for streptococci.

Amoxicillin

Not effective against Staphyloccocus aureus, but good coverage against Group A Strep. Group A Strep is always sensitive to penicillin and amoxicillin. Inexpensive oral medication.

Amoxicillin/clavulanate

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

Ceftriaxone

If the patient is sick enough to be admitted, this drug is a good option if MRSA not suspected.

Cephalexin

Effective against group A Strep and MSSA but not MRSA.

Dicloxacillin

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.

Doxycycline

Along with minocycline, often thought of as an oral alternative to TMP/SMX for community-acquired MRSA, the drug has a reputation as having poor anti-streptococcal activity and should not be relied upon alone for typical cellulitis unless strongly thought to be related to S. aureus.

Moxifloxacin

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

Linezolid

Broad Gram positive activity. Use if MRSA proven/suspect. Oral dosing makes conversion from IV vancomycin attractive. Though now generic in U.S., remains expensive.

Clindamycin

Concern is C. difficile infection.

TMP/SMX

Active vs. >95% community-acquired MRSA, but less active vs. hospital strains. Has relatively poor streptococcal coverage.

FOLLOW UP

  • Symptoms typically dissipate within first few days of antibiotic therapy but 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 antibiotic has achieved bacteriocidal effect.
    • Also consider whether deeper process present, e.g., necrotizing fascitiis.
  • Severe cellulitis may predispose to repeat bouts: "cellulitis begets cellulitis."

OTHER INFORMATION

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

Pathogen Specific Therapy

Basis for recommendation

  1. Infectious Diseases Society of America, et al. "Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update By the Infectious Diseases Society of America." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 59, no. 2, 2014, pp. e10-52.  [PMID:24973422]

    Comment: Foundation for recommendations presented in this module.

References

  1. DMID 07-0051 Team, et al. "A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses." The New England Journal of Medicine, vol. 376, no. 26, 2017, pp. 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 patietns with S. aureus infections, patients on the abx groups had a higher cure rate and less likey to have a recurrent infection at 1 month. Adverse events were common in the abx groups.
    Rating: Important

  2. Camargo, Carlos A., et al. "Failure of Antibiotics in Cellulitis Trials: a Systematic Review and Meta-analysis." The American Journal of Emergency Medicine, vol. 34, no. 8, 2016, pp. 1645-52.  [PMID:27344098]

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

  3. Abroug, Nesrine, et al. "Orbital Infections: Review of 28 Cases." La Tunisie Medicale, vol. 93, no. 11, 2015, pp. 673-7.  [PMID:27126422]

    Comment: A retrospective review of 28 cases of orbital infections, including 15 (54%) with cellulitis and abscesses accounted for 68%. S. aureus with the most common pathogen and 93% had a good outcome.

  4. DMID 07-0051 Team, et al. "Clindamycin Versus Trimethoprim-sulfamethoxazole for Uncomplicated Skin Infections." The New England Journal of Medicine, vol. 372, no. 12, 2015, pp. 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. Outcome of the 2 groups were similar (cure rates of 90% vs 88%; P=0.8)

  5. Baang, Jihoon. "Antibacterial Treatment for Uncomplicated Skin Infections." The New England Journal of Medicine, vol. 372, no. 25, 2015, p. 2459.  [PMID:26083211]

    Comment: Letter to editor noted 30% in each group had abscesses that may only need drainage without antibiotics. Authors respond that this query was not addressed so their trial could not answer it.

  6. APRES study team, et al. "Evidence-based Primary Care Treatment Guidelines for Skin Infections in Europe: a Comparative Analysis." The European Journal of General Practice, vol. 20, no. 4, 2014, pp. 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), oxacillin (1); duration was 7-14 days, usually 10 days.

  7. Alraies, M Chadi, et al. "Distinguishing Cellulitis From Its Mimics." Cleveland Clinic Journal of Medicine, vol. 79, no. 8, 2012, pp. 547-52.  [PMID:22854433]

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

  8. Gunderson, Craig G., and Richard A. Martinello. "A Systematic Review of Bacteremias in Cellulitis and Erysipelas." The Journal of Infection, 2011,  [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%. Conclusion is that these results show most cellulitis cases are caused by Group A strep.
    Rating: Important

  9. Davis, Scott A., et al. "Use of Topical Antibiotics as Prophylaxis in Clean Dermatologic Procedures." Journal of the American Academy of Dermatology, 2011,  [PMID:21821310]

    Comment: Clean dermatologic surgery database was reviewed for use of topical antibiotics. Topical antibiotics were used in 8 million of 212 million cases (5%), which the authors considered inappropriate use. Note that this reiew was selected because of the useless but sometimes common practice of using topical antibiotics on clean wounds.

  10. Alexander, Donald P., et al. "Diagnostic and Therapeutic Evaluation of Community-acquired Methicillin-resistant Staphylococcus Aureus (MRSA) Skin and Soft Tissue Infections in the Emergency Department." The Journal of Emergency Medicine, 2011,  [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 that of many other reports for the past 4 years. TMP/SMX or clindamycin are usually "preferred."
    Rating: Important

  11. Khawcharoenporn, Thana, and Alan Tice. "Empiric Outpatient Therapy With Trimethoprim-sulfamethoxazole, Cephalexin, or Clindamycin for Cellulitis." The American Journal of Medicine, vol. 123, no. 10, 2010, pp. 942-50.  [PMID:20920697]

    Comment: Evaluation of treatment of cellulitis in 405 patients. 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 value of TMP/SMX for CA-MRSA infections.
    Rating: Important

  12. Beheshti, Manie, et al. "The Role of Beta-hemolytic Streptococci in Causing Diffuse, Nonculturable Cellulitis: a Prospective Investigation." Medicine, vol. 89, no. 4, 2010, pp. 217-26.  [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. Note that cellulitis with no pus and negative cultures is usually caused by Group A Strep.

  13. Duckworth, Georgia, et al. "Predictors of Death After Severe Streptococcus Pyogenes Infection." Emerging Infectious Diseases, vol. 15, no. 8, 2009, pp. 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 (34%).
    Rating: Important

  14. Jussila, Tapio, et al. "Acute Bacterial, Nonnecrotizing Cellulitis in Finland: Microbiological Findings." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 46, no. 6, 2008, pp. 855-61.  [PMID:18260753]

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

  15. Petersen, Kyle, et al. "Acinetobacter Baumannii Skin and Soft-tissue Infection Associated With War Trauma." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 47, no. 4, 2008, pp. 444-9.  [PMID:18611157]

    Comment: Authors describe 8 patients with A. baumannii infections associated with war wounds. The presentation was cellulitis with "peau d'orange" appearance, with vesicles and progressed to necrosis with bullae.
    Rating: Important

  16. Menon, Anupama, and Jörg J. Ruhe. "Tetracyclines as an Oral Treatment Option for Patients With Community Onset Skin and Soft Tissue Infections Caused By Methicillin-resistant Staphylococcus Aureus." Antimicrobial Agents and Chemotherapy, vol. 51, no. 9, 2007, pp. 3298-303.  [PMID:17576834]

    Comment: 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 a beta-lactam (OR 3.9, p=0.02).

  17. Gabillot-Carré, Marion, and Jean-Claude Roujeau. "Acute Bacterial Skin Infections and Cellulitis." Current Opinion in Infectious Diseases, vol. 20, no. 2, 2007, pp. 118-23.  [PMID:17496568]

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

  18. Baddour, Larry M., et al. "A Predictive Model of Recurrent Lower Extremity Cellulitis in a Population-based Cohort." Archives of Internal Medicine, vol. 167, no. 7, 2007, pp. 709-15.  [PMID:17420430]

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

  19. Chosidow, O, et al. "Recurrent Erysipelas: 47 Cases." Dermatology (Basel, Switzerland), vol. 214, no. 1, 2007, pp. 52-7.  [PMID:17191048]

    Comment: Review of recurrent erysipelas in 47 patients. 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 2 years.

  20. Swartz, Morton N.. "Clinical Practice. Cellulitis." The New England Journal of Medicine, vol. 350, no. 9, 2004, pp. 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. Cove, Jonathan H., and E Anne Eady. "Staphylococcal Resistance Revisited: Community-acquired Methicillin Resistant Staphylococcus Aureus--an Emerging Problem for the Management of Skin and Soft Tissue Infections." Current Opinion in Infectious Diseases, vol. 16, no. 2, 2003, pp. 103-24.  [PMID:12734443]

    Comment: Review of emerging problem of community-acquired MRSA. Though most often identified in children, sporadic and outbreak cases 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. Batts, Donald H., et al. "Linezolid Versus Vancomycin for the Treatment of Methicillin-resistant Staphylococcus Aureus Infections." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 34, no. 11, 2002, pp. 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. Bruss, J B., et al. "Randomized Comparison of Linezolid (PNU-100766) Versus Oxacillin-dicloxacillin for Treatment of Complicated Skin and Soft Tissue Infections." Antimicrobial Agents and Chemotherapy, vol. 44, no. 12, 2000, pp. 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, B K.. "Anal Colonization of Group G Beta-hemolytic Streptococci in Relapsing Erysipelas of the Lower Extremity." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 29, no. 5, 1999, pp. 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. Gottehrer, N P., et al. "Cost-effectiveness of Blood Cultures for Adult Patients With Cellulitis." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 29, no. 6, 1999, pp. 1483-8.  [PMID:10585800]

    Comment: Retrospective review of 757 patients admitted with community acquired cellulitis over a 41 month period 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, P I., and K Sjöbeck. "Relapse of Erysipelas Following Treatment With Prednisolone or Placebo in Addition to Antibiotics: a 1-year Follow-up." Scandinavian Journal of Infectious Diseases, vol. 30, no. 2, 1998, pp. 206-7.  [PMID:9730318]

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

  27. Klempner, M S., and B Styrt. "Prevention of Recurrent Staphylococcal Skin Infections With Low-dose Oral Clindamycin Therapy." JAMA : the Journal of the American Medical Association, vol. 260, no. 18, 1988, pp. 2682-5.  [PMID:3184334]

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

  28. Coyle, M B., et al. "Microbiologic Evaluation of Cutaneous Cellulitis in Adults." Archives of Internal Medicine, vol. 146, no. 2, 1986, pp. 295-7.  [PMID:3947189]

    Comment: Microbiology studies in 50 patients hospitalized with cellulitis showed pathogen in blood - 5, needle aspirate - 5, and punch biopsy - 10.

  29. Dooley, David P., et al. "Comparison of Short-course (5 Days) and Standard (10 Days) Treatment for Uncomplicated Cellulitis." Archives of Internal Medicine, vol. 164, no. 15, 2004 Aug 9-23, pp. 1669-74.  [PMID:15302637]

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

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Last updated: January 1, 2019

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TY - ELEC T1 - Cellulitis ID - 540106 A1 - Bartlett,John,M.D. AU - Fabre,Valeria,M.D. Y1 - 2019/01/01/ BT - Johns Hopkins ABX Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540106/all/Cellulitis PB - The Johns Hopkins University DB - Johns Hopkins Guide DP - Unbound Medicine ER -