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Infectious Diseases - Skin and Soft-Tissue Infections - Fast Facts | NEJM Resident 360

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

• Necrotizing Soft-Tissue Infections

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 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 Diagnosis 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

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 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).

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., Streptococcus pyogenes, Staphylococcus, Clostridium, 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

(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

(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

• penicillin and clindamycin (can inhibit toxin production) for Streptococcus and Clostridium 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.

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