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.
  • 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 are positive in < 5% positive. Culture often not performed due to low yield.
      • 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 Gr 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

  • 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: clindamycin or vancomycin (above doses)

Adjunctive Therapy

  • Erysipelas: consider prednisone 30mg with taper over 8 days to assist with inflammatory reaction.
  • 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:
  • Topical antibiotics are not effective.

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. Very, very expensive.

Clindamycin

Excellent for S. aureus and most Streptococcus infections. Covers most community-acquired MRSA. 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.
  • 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.

Basis for recommendation

  1. Stevens DL 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 59:e10, 2014  [PMID:24973422]

    Comment: Foundation for recommendations presented in this module.

References

  1. Moran GJ et al: Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 355:666, 2006  [PMID:16914702]

    Comment: 11 Emergency Ward study of skin and soft tissue infection. Of 422, 320 (76%) were caused by MRSA. Most of these were abscesses that responded well to I & D with or without antibiotics.
    Rating: Important

  2. Eriksson BK: Anal colonization of group G beta-hemolytic streptococci in relapsing erysipelas of the lower extremity. Clin Infect Dis 29:1319, 1999  [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.

  3. Sebeny PJ, Riddle MS, Petersen K: Acinetobacter baumannii skin and soft-tissue infection associated with war trauma. Clin Infect Dis 47:444, 2008  [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

  4. Baang J: Antibacterial Treatment for Uncomplicated Skin Infections. N Engl J Med 372:, 2015  [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.

  5. Bailey E, Kroshinsky D: Cellulitis: diagnosis and management. Dermatol Ther 24:229, 2011 Mar-Apr  [PMID:21410612]

    Comment: Dermatology recs for cellulitis.

  6. Swartz MN: Clinical practice. Cellulitis. N Engl J Med 350:904, 2004  [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

  7. Gunderson CG, Martinello RA: A systematic review of bacteremias in cellulitis and erysipelas. J Infect Nov 11  [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

  8. Jeng A et al: The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation. Medicine (Baltimore) 89:217, 2010  [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.

  9. Jenkins TC et al: Skin and soft-tissue infections requiring hospitalization at an academic medical center: opportunities for antimicrobial stewardship. Clin Infect Dis 51:895, 2010  [PMID:20839951]

    Comment: Review of a community hospital experience with 322 patients hospitalized for soft tissue infections -- 66 (20%) had cellulitis 103 (32%) had abscesses and 153 (48%) had other complicating factors like diabetes, IDU, etc. Positive cultures in 150-97% were S. aureus or strep, but broad spectrum antibiotics active vs. GNB were used in 70%. Most had CT or MRI scans with a yield < 1%. This is a humbling review of antibiotic abuse and unnecessary use of expensive imaging. The conclusion -- the need for antibiotic stewardship.
    Rating: Important

  10. Kahloun R et al: Orbital infections: review of 28 cases. Tunis Med 93:673, 2015  [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.

  11. Keller EC, Tomecki KJ, Alraies MC: Distinguishing cellulitis from its mimics. Cleve Clin J Med 79:547, 2012  [PMID:22854433]

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

  12. Khawcharoenporn T, Tice A: Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med 123:942, 2010  [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

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

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

  14. Gabillot-Carré M, Roujeau JC: Acute bacterial skin infections and cellulitis. Curr Opin Infect Dis 20:118, 2007  [PMID:17496568]

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

  15. Levender MM et al: Use of topical antibiotics as prophylaxis in clean dermatologic procedures. J Am Acad Dermatol Aug 5  [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.

  16. McNamara DR et al: A predictive model of recurrent lower extremity cellulitis in a population-based cohort. Arch Intern Med 167:709, 2007  [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

  17. Hook EW et al: Microbiologic evaluation of cutaneous cellulitis in adults. Arch Intern Med 146:295, 1986  [PMID:3947189]

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

  18. Miller LG et al: Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med 372:1093, 2015  [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)

  19. Obaitan I et al: Failure of antibiotics in cellulitis trials: a systematic review and meta-analysis. Am J Emerg Med 34:1645, 2016  [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.

  20. Perl B et al: Cost-effectiveness of blood cultures for adult patients with cellulitis. Clin Infect Dis 29:1483, 1999  [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.

  21. 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 30:206, 1998  [PMID:9730318]

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

  22. Lamagni TL et al: Epidemiology of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 46:2359, 2008  [PMID:18463210]

    Comment: Prospective survey of severe strep infections in 11 countries in Europe. Skin lesions were the most common predisposing cause -- 25% . Cellulitis accounted for 32% and necrotizing fasciitis -- 8%. Fatality rate was 19% and 44% in those with strep toxic shock.
    Rating: Important

  23. Hepburn MJ et al: Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med 164:1669, 2004 Aug 9-23  [PMID:15302637]

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

  24. Stevens DL et al: Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 34:1481, 2002  [PMID:12015695]

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

  25. Stevens DL et al: Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 44:3408, 2000  [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).

  26. 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 51:3298, 2007  [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).

  27. Zimmerman LH et al: Twelve hundred abscesses operatively drained: an antibiotic conundrum? Surgery 146:794, 2009  [PMID:19789040]

    Comment: Review from Detroit with 1,200 abscesses. Most common pathogen: S. aureus accounting for 30% with 80% of the isolates MRSA.

  28. Lamagni TL et al: Predictors of death after severe Streptococcus pyogenes infection. Emerg Infect Dis 15:1304, 2009  [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

  29. Siljander T et al: Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings. Clin Infect Dis 46:855, 2008  [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%.

  30. Liao CH et al: Bacteremia caused by group G Streptococci, taiwan. Emerg Infect Dis 14:837, 2008  [PMID:18439377]

    Comment: Review of 92 cases of Group G strep bacteremia. Cellulitis was the source in 48 cases followed by "primary bacteremia" in 34. Mortality -- 3.3%.
    Rating: Important

  31. 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 16:103, 2003  [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.

  32. Leclerc S et al: Recurrent erysipelas: 47 cases. Dermatology 214:52, 2007  [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.

  33. Walraven CJ 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 Apr 25  [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

  34. van Bijnen EM et al: Evidence-based primary care treatment guidelines for skin infections in Europe: a comparative analysis. Eur J Gen Pract 20:294, 2014  [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.

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Last updated: October 25, 2016