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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 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.
![[Image]](content_item_media_uploads/Management-of-SSTIs_qmkxin.jpg)
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.
![[Image]](content_item_media_uploads/nejmra1600673_f1_i0kwno.jpg)
(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.
![[Image]](content_item_media_uploads/nejmra1600673-7_gekgao.jpg)
(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
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.
![[Image]](content_item_thumbnails/nejmoa1917197_f2.jpg)
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.
![[Image]](content_item_thumbnails/6956.jpg)
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.
![[Image]](content_item_thumbnails/6694.jpg)
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.
![[Image]](content_item_thumbnails/nejmoa1403789_f2.jpg)
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.
![[Image]](content_item_thumbnails/ciu778.jpg)
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.
![[Image]](content_item_thumbnails/ciu304.jpg)
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.
![[Image]](content_item_thumbnails/nejmoa1310480_t2.jpg)
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.
![[Image]](content_item_thumbnails/cit122.jpg)
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).
![[Image]](content_item_thumbnails/6697.jpg)
Reviews
The best overviews of the literature on this topic
Stevens DL and Bryant AE. N Engl J Med 2017.
![[Image]](content_item_thumbnails/nejmra1600673_t1.jpg)
Singer AJ and Talan DA. N Engl J Med 2014.
![[Image]](content_item_thumbnails/nejmra1212788_f2.jpg)
Guidelines
The current guidelines from the major specialty associations in the field
Rybak MJ et al. Am J Health Syst Pharm 2020.
![[Image]](content_item_thumbnails/54145.jpg)
Stevens DL et al. Clin Infect Dis 2014.
IDSA guidelines on the diagnosis and management of various SSTIs
![[Image]](content_item_thumbnails/6703.jpg)
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
![[Image]](content_item_thumbnails/ciq146.jpg)
Additional Resources
Videos, cases, and other links for more interactive learning
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.
![[Image]](content_item_thumbnails/6707.jpg)
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.
![[Image]](content_item_thumbnails/nejmclde0708359_f1.jpg)