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Fast Facts

A brief refresher with useful tables, figures, and research summaries

Skin and Soft-Tissue Infections

Skin and soft-tissue infections (SSTIs) are common, and they range from mild cellulitis to life-threatening necrotizing soft-tissue infections (NSTIs). Key management considerations include making an accurate diagnosis, assessing for purulence and severity of infection, and choosing antibiotics to target the most likely microbes. In this section, we will cover the diagnosis and treatment of:

Cellulitis

Cellulitis is an infection of the dermis and subcutaneous tissue. Because isolating an organism is difficult, often no specific organism is identified. Most cases are likely caused by group A streptococci and less commonly Staphylococcus aureus. Immunosuppression, water exposure, and small wounds or bites may predispose to rarer microbes. Cellulitis is categorized by the presence or absence of purulence and the severity of the presentation (mild, moderate, or severe infection), which influences choice of antibiotics.

Severity classification:

  • Mild infection is localized.

  • Moderate infection includes systemic symptoms.

  • Severe infection includes failure of oral antibiotics, signs of sepsis, or immunosuppression.

Diagnosis

Diagnosis of cellulitis is mainly based on history and exam. Look for an acutely spreading, poorly demarcated erythema with associated pain, warmth, and swelling, typically unilateral in the lower extremities. Fever is variably present. Aspiration of an abscess when present can yield an organism and antibiotic sensitivities. Routine blood cultures are unnecessary but recommended for patients with severe presentation, malignancy, neutropenia, immunosuppression, immersion injury, or animal bites.

Unfortunately, many conditions mimic cellulitis, and the misdiagnosis rate is high (studies indicate 74% of dermatology-consulted cases and 31% in the emergency department). The following table lists some common conditions that mimic cellulitis and some distinguishing features.

Differential Diagnoses of Cellulitis
Differential Diagnosis Key Distinguishing Features
Stasis dermatitis Bilateral leg involvement; circumferential erythema and swelling; usually no fevers
Contact dermatitis Unusual patterns of distribution; pruritus; no fevers
Inflammatory arthritis Erythema overlies a joint; pain with range of motion
Deep venous thrombosis/ thrombophlebitis Deep pain in calf; linear venous cord; usually no fevers
Hypersensitivity/drug reaction History of medication, allergen, insect bite exposure; erythema doesn’t spread as fast as cellulitis
Pyoderma gangrenosum Nodular, bullous, ulcerated lesions; usually on anterior shin; often associated with inflammatory bowel disease or collagen vascular syndromes
Erythema migrans (Lyme disease) Well-demarcated erythema; annular; usually not painful; slow-growing
Necrotizing fasciitis See necrotizing fasciitis below

Treatment

The treatment of cellulitis varies. In general, severity and suspicion for methicillin-resistant Staphylococcus aureus (MRSA) should guide antibiotic selection. The following figure illustrates recommendations from the Infectious Diseases Society of America (IDSA) for SSTI management. Recommended treatment duration is typically 5 days but may require up to 14 days based on clinical improvement.

IDSA Algorithm for Management of SSTIs
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Abbreviations: C & S, culture and sensitivity; I & D, incision and drainage; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; Rx, treatment; TMP/SMX, trimethoprim-sulfamethoxazole. (Source: 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. Reproduced with permission of the Infectious Disease Society of America.)

Note: Although current guidelines recommend incision and drainage alone for uncomplicated purulent abscesses measuring <2 cm, recent data suggest that even in smaller abscesses, adjunctive antibiotic therapy may lead to a higher cure rate. For larger abscesses, adjunctive antimicrobial therapy is warranted.

MRSA is not likely to cause typical cellulitis, and the IDSA algorithm simplifies the determination of MRSA involvement by indicating that purulence implies MRSA. Consider other risk factors for community-acquired MRSA infection to guide treatment.

Antibiotics for the treatment of MRSA:

  • trimethoprim-sulfamethoxazole

  • doxycycline

  • linezolid

  • clindamycin

  • vancomycin

  • daptomycin

  • ceftaroline

The antibiotics listed above are not ideal for treating methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus. Therefore, use of a beta-lactam (e.g., dicloxacillin, cephalexin) is recommended when possible.

Other treatment considerations:

  • Symptoms should improve within 48 hours with appropriate antibiotics; consider other diagnoses if symptoms do not improve.

  • Cellulitis involving the face or neck can reflect more-dangerous processes and requires careful consideration.

  • Animal and human bites result in polymicrobial infection with anaerobes; consider oral amoxicillin-clavulanate, intravenous ampicillin-sulbactam, or doxycycline (excellent against Pasteurella multocida).

See NEJM Journal Watch for information on telavancin and oritavancin.

Necrotizing Soft-Tissue Infections

Necrotizing soft-tissue infections (NSTIs) are rare but serious infections that are associated with increased morbidity and mortality if not recognized and treated immediately. Various predisposing factors lead to subcategories of NSTIs, including necrotizing fasciitis (NF) type I (polymicrobial) and type II (monomicrobial; e.g., due to Streptococcus pyogenes, Staphylococcus, Clostridioides, and Vibrio species). Specific syndromes associated with NSTIs include Ludwig angina, Lemierre syndrome, Fournier gangrene, and gas gangrene.

The following figure illustrates the pathogenesis of NSTIs.

Evolution of Necrotizing Fasciitis or Myonecrosis
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(Source: Necrotizing Soft-Tissue Infections. N Engl J Med 2017.)

Diagnosis

Diagnosis of NSTI is clinical and challenging due to inaccurate clinical signs and pitfalls that can delay diagnosis.

Factors that distinguish NSTI from cellulitis include the following:

  • recent surgery

  • pain out of proportion to clinical signs

  • hypotension

  • skin necrosis

  • hemorrhagic bullae

The LRINEC score is one prediction tool for diagnosing NSTI. CT or MRI can show gas in tissue or abnormal enhancement. Maintain a high level of clinical suspicion and involve surgeons early.

Algorithm for the Diagnosis of Necrotizing Infections
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(Source: Necrotizing Soft-Tissue Infections. N Engl J Med 2017.)

Treatment

Surgical debridement is the cornerstone of treatment and can lead to a definite diagnosis and identification of the infecting organism. Reinspection and repeat debridement are usually necessary. Start broad-spectrum antibiotics early for possible polymicrobial infection.

IDSA recommends:

  • empiric therapy:

    • vancomycin or linezolid AND

    • piperacillin-tazobactam or a carbapenem or ceftriaxone-metronidazole

  • clindamycin or linezolid (can inhibit toxin production) for Streptococcus and Clostridioides species

Other adjunctive therapies include intravenous immunoglobulin (to neutralize exotoxins) and hyperbaric oxygen. The evidence of efficacy is mixed for these treatments; therefore they are not recommended by the IDSA.

Research

Landmark clinical trials and other important studies

Research

Compression Therapy to Prevent Recurrent Cellulitis of the Leg

Webb E et al. N Engl J Med 2020.

In this single-center, randomized trial, patients who used knee-high compression stockings that were fitted by a professional technician had significantly lower incidence of recurrent cellulitis than patients receiving conservative treatment.

Read the NEJM Journal Watch Summary

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A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses

Daum RS et al. N Engl J Med 2017.

In this prospective, multicenter, double-blind trial, outpatient adults and children with skin abscess <5 cm were randomly assigned to receive clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo for 10 days after abscess incision and drainage. Individuals treated with antibiotics had better short-term outcomes than those who received placebo.

Read the NEJM Journal Watch Summary

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Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess

Talan DA. N Engl J Med 2016.

In this randomized, controlled trial comparing trimethoprim-sulfamethoxazole to placebo in patients with a drained, uncomplicated skin abscess, trimethoprim-sulfamethoxazole was found to have a higher cure rate than placebo.

Read the NEJM Journal Watch Summary

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Clindamycin versus Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Infections

Miller LG et al. for the DMID 07-0051 Team. N Engl J Med 2015.

This randomized, controlled trial compared clindamycin and trimethoprim-sulfamethoxazole for the treatment of uncomplicated skin infections (cellulitis or small abscess) in children and adults. Outcomes did not differ between the two antibiotics.

Read the NEJM Journal Watch Summary

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Single-Dose Oritavancin versus 7-10 Days of Vancomycin in the Treatment of Gram-Positive Acute Bacterial Skin and Skin Structure Infections: The SOLO II Noninferiority Study

Corey GR et al. for the SOLO II Investigators. Clin Infect Dis 2015.

In this randomized, controlled trial, one dose of oritavancin was noninferior to 7-10 days of vancomycin in acute bacterial SSTI. Efficacy extended across subgroups, including patients with MRSA. Adverse effects were uncommon. Oritavancin has the potential to advance outpatient parenteral therapy and improve adherence.

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Effectiveness of Clindamycin and Intravenous Immunoglobulin, and Risk of Disease in Contacts, in Invasive Group A Streptococcal Infections

Carapetis JR et al. Clin Infect Dis 2014.

In this prospective surveillance study, patients with severe group A streptococcal infections who received treatment with clindamycin and concurrent IVIG had improved outcomes.

Read the NEJM Journal Watch Summary

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Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection

Boucher HW et al. N Engl J Med 2014.

In the DISCOVER 1 and 2 randomized, controlled trials, once-weekly intravenous dalbavancin, a lipoglycopeptide antibiotic agent that is active against gram-positive pathogens, was not inferior to twice-daily intravenous vancomycin followed by oral linezolid for the treatment of SSTIs.

Read the NEJM Journal Watch Summary

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Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial

Pallin DJ et al. Clin Infect Dis 2013.

In this randomized, controlled trial, the addition of trimethoprim-sulfamethoxazole to cephalexin in 153 patients diagnosed with uncomplicated cellulitis without abscess did not improve 30-day cure rate (85% vs. 82%) or subgroup outcomes (progression to abscess, adverse effects, and development of Clostridioides difficile). Of note, the study had many exclusion criteria, including diabetes, underlying peripheral vascular disease, renal insufficiency, hospitalization, purulence, and immunosuppression.

The findings were replicated in a larger 2017 trial with 500 patients.

Read the NEJM Journal Watch Summary

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The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) Score: A Tool for Distinguishing Necrotizing Fasciitis from Other Soft Tissue Infections

Wong CH et al. Crit Care Med 2004.

The data from this retrospective study was used to develop the LRINEC score to predict presence of necrotizing fasciitis. The score includes C-reactive protein, leukocyte, creatinine, glucose, hemoglobin, and sodium levels. The score should be used as an adjunct to clinical presentation and imaging and not as a sole diagnostic tool. If the LRINEC score is low but clinical suspicion is high, you should treat for necrotizing fasciitis (i.e., emergency surgical debridement).

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Reviews

The best overviews of the literature on this topic

Reviews

Necrotizing Soft-Tissue Infections

Stevens DL and Bryant AE. N Engl J Med 2017.

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Guidelines

The current guidelines from the major specialty associations in the field

Guidelines

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Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America

Stevens DL et al. Clin Infect Dis 2014.

IDSA guidelines on the diagnosis and management of various SSTIs

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Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children

Liu C et al. Clin Infect Dis 2011.

IDSA guidelines on treatment of various MRSA infections, including soft-tissue infections, osteomyelitis, meningitis, sepsis, and pneumonia

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Additional Resources

Videos, cases, and other links for more interactive learning

Additional Resources

Clinical Decisions: Skin Abscess

Wilbur MB et al. N Engl J Med 2016.

In this Clinical Decisions case, two experts present differing views on how best to manage a patient with a skin abscess after incision and drainage.

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Clinical Decisions: Management of Skin and Soft-Tissue Infection

Hammond SP and Baden LR. N Engl J Med 2008.

In this Clinical Decisions case, three experts present differing views on how best to manage a patient with a skin abscess.

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