Cellulitis/Erysipelas

PATHOGENS

• Streptococcus species usually group A (S. pyogenes, for most cases).
• Other Streptococcus groups: B, C, G (especially group G).
• Staphylococcus aureus: MRSA now dominates both in and out of the hospital.
• Dog/cat bite: Pasteurella multocida, Capnocytophaga canimorsus
  
• Salt water exposure: Vibrio vulnificus
  
• Fresh or brackish water exposure: Aeromonas hydrophobia, Plesiomonas shigelloides
• Neutropenia: P. aeruginosa, other GNB.
• Human bite: Eikenella corrodens, anaerobes, S. aureus.
• Occasional causes (see individual pathogen modules): other Vibrio spp. (saltwater exposure), other Aeromonas spp. (freshwater exposure), S. pneumoniae, H. influenzae, Legionella spp., Helicobacter cinaedi (immunocompromised), Erysipelothrix rhusiopathiae (meat/fish exposure), Staphylococcus epidermidis (immunocompromised patients), Group B streptococci (infants), fungal.

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 also Group G in recent reports.
• Predisposing conditions: trauma, lymph stasis (prior radiation, mastectomy, saphenous vein harvest), injection drug use, ulcers, wounds, dermatophytic infections.
• Exam: red, hot, tender skin with edema + fever and adenopathy.
• Differential diagnosis: allergy, gout, zoster, erythroderma, insect bite, panniculitis, Lyme disease (erythema migrans), Sweet’s syndrome, pyoderma, fixed drug reaction, thrombophlebitis, necrotizing fasciitis.

DIAGNOSIS

• Usually clinical diagnosis based on appearance and symptoms.
• Lab: blood cultures are positive in < 5% positive. Culture often not performed due to low yield. Can prove Gr A streptococcal infection with ASO and/or DNAase B serial titers.
  • Blood cultures indicated with extensive cellulitis and in special populations. Consider for immunocompromised patients, unusual pathogen suspected, no response to adequate antibiotic therapy.
• Imaging helpful in some cases: ultrasound (to differentiate DVT), CT (if suspect necrotizing fasciitis or pyomyositis).

TREATMENT

FOLLOW UP

• Symptoms typically dissipate within first few days of antibiotic therapy but may take longer 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 abx have achieved bacteriocidal effect.
• Severe cellulitis may predispose to repeat bouts; "cellulitis begets cellulitis."

OTHER INFORMATION

• S. aureus including MRSA now the leading cause of soft tissue abscesses -- easy to find and to culture.
• S. pyogenes: major cause of cellulitis, but very hard to culture.
• Gr A strep is 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

• Stevens DL et al: Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 41:1373, 2005 Nov. 15  [PMID:16231249]

  Comment: Foundation for recommendations presented in this module.
  Rating: Basis for recommendation
  

References

1. Levender MM et al: Use of topical antibiotics as prophylaxis in clean dermatologic procedures. J Am Acad Dermatol 2011 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.
   

2. 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 2011 April 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
   

3. Gunderson CG, Martinello RA: A systematic review of bacteremias in cellulitis and erysipelas. J Infect 2011 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
   

4. 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.
   

5. 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
   

6. 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 Oct. 15  [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
   

7. 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
   

8. 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.
   

9. Sebeny PJ, Riddle MS, Petersen K: Acinetobacter baumannii skin and soft-tissue infection associated with war trauma. Clin Infect Dis 47:444, 2008 Aug. 15  [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
   

10. 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
    

11. 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
    

12. Siljander T et al: Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings. Clin Infect Dis 46:855, 2008 March 15  [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%.
    

13. 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.
    

14. 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).
    

15. 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.
    

16. McNamara DR et al: A predictive model of recurrent lower extremity cellulitis in a population-based cohort. Arch Intern Med 167:709, 2007 April 9  [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. Moran GJ et al: Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 355:666, 2006 Aug. 17  [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
    

18. Swartz MN: Clinical practice. Cellulitis. N Engl J Med 350:904, 2004 Feb. 26  [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
    

19. 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.
    

20. Laube S, Farrell AM: Bacterial skin infections in the elderly: diagnosis and treatment. Drugs Aging 19:331, 2002   [PMID:12093320]

    Comment: Cutaneous infections are very common in the elderly. Cellulitis and infected ulcers are the most commonly diagnoses.
    

21. Stevens DL et al: Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 34:1481, 2002 June 1  [PMID:12015695]

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

22. 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).
    

23. 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.
    

24. 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.
    

25. 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.
    

26. Bisno AL, Stevens DL: Streptococcal infections of skin and soft tissues. N Engl J Med 334:240, 1996 Jan. 25  [PMID:8532002]

    Comment: Practice guidelines from IDSA used for these recommendations, but updated for MRSA. Classic review of streptococcal skin infections, especially erysipelas that is most common in infants, children and elderly, nearly always group A strep and usually involves legs or butterfly area of face.
    

27. Klempner MS, Styrt B: Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy. JAMA 260:2682, 1988 Nov. 11  [PMID:3184334]

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

28. 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.
    

29. 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.