Skin and soft tissue infection

The first branch point: purulent vs non-purulent

The IDSA SSTI guideline organizes management around whether the lesion is purulent. Purulent infections (abscess, furuncle, carbuncle) are typically staphylococcal (mostly MRSA in many US communities) and are treated primarily with incision and drainage (I&D), with antibiotics reserved for severe disease, immunocompromise, or inadequate response. Non-purulent cellulitis and erysipelas are typically streptococcal and respond to a beta-lactam active against streptococci. Adding empiric MRSA coverage to non-purulent cellulitis does not improve outcomes in most trials, but is reasonable with systemic toxicity, IVDU, prior MRSA, or treatment failure.

• Purulent (abscess, furuncle): I&D is the treatment; send culture if severe or for epidemiology.
• Non-purulent cellulitis: beta-lactam (cephalexin, dicloxacillin); adding empiric MRSA cover is reasonable with risk factors.
• Erysipelas: sharply demarcated raised lesion, streptococcal — beta-lactam.
• MRSA risk factors: prior MRSA, IVDU, recent hospitalization, dialysis, household contacts, recurrent SSTI.
• Bilateral 'cellulitis' is almost never cellulitis — look for stasis dermatitis, contact dermatitis, or vascular causes.

Non-purulent cellulitis: streptococcal, beta-lactam-first

Non-purulent cellulitis is an acute spreading infection of the dermis and subcutaneous tissue, usually caused by beta-hemolytic streptococci (Groups A, B, C, G), with Staphylococcus aureus (often MSSA) a less common cause. The classic presentation is unilateral, warm, erythematous, edematous skin with poorly defined margins, often on a lower extremity. Look for and treat the portal of entry (tinea pedis, fissures, ulceration, injection sites). First-line therapy is a beta-lactam active against streptococci — cephalexin or dicloxacillin PO for outpatients; cefazolin or ceftriaxone IV for inpatients. Adding empiric MRSA coverage does not improve outcomes in classic non-purulent cellulitis (three RCTs of TMP-SMX and placebo vs beta-lactam alone found no benefit).

• First-line: cephalexin 500 mg QID or dicloxacillin 500 mg QID × 5–6 days (with clinical response).
• Inpatient IV: cefazolin or ceftriaxone; switch to oral when afebrile and improving.
• Add empiric MRSA cover (TMP-SMX, doxycycline, or clindamycin) if: IVDU, prior MRSA, severe/sepsis, purulence, bite wound, or failure of beta-lactam.
• Mark the border, elevate the limb, treat tinea pedis and any portal of entry.
• Reassess at 48–72 h — if not improving, reconsider diagnosis, antibiotic choice, and need for imaging or source control.

Purulent SSTI & MRSA: drain, then cover

Purulent SSTI (abscess, furuncle, carbuncle) is driven by Staphylococcus aureus — in much of the United States, community-associated MRSA is the dominant strain. Incision and drainage is the cornerstone of therapy; antibiotics are added for severe disease, extensive surrounding cellulitis, immunocompromise, fever, older age, failed I&D, or when source control is incomplete. Empiric oral MRSA coverage is TMP-SMX or doxycycline (plus a beta-lactam if streptococcal coverage is also needed). For inpatient or severe disease, vancomycin is first-line; linezolid or daptomycin are alternatives.

• I&D is the treatment — always; pack the cavity, ensure complete drainage.
• Add antibiotics for: sepsis, rapid progression, extensive cellulitis, immunocompromise, extremes of age, failed I&D, or inadequate source control.
• Oral MRSA cover: TMP-SMX DS BID or doxycycline 100 mg BID (doxycycline lacks some streptococcal activity).
• Clindamycin: active against many MRSA, but check local D-test (inducible resistance); avoid as monotherapy for severe disease.
• Inpatient MRSA cover: vancomycin (AUC-guided), linezolid (avoid >2 weeks), daptomycin (never for pneumonia).

Necrotizing soft tissue infection: a surgical emergency

Necrotizing fasciitis is a rapidly progressive infection of the deep fascia and subcutaneous tissues that causes tissue necrosis and carries high mortality. The single most important principle is that surgical exploration is both diagnostic and therapeutic — and must not wait for definitive imaging or laboratory confirmation. Suspect necrotizing infection when pain is out of proportion to physical findings, when the skin is hard and woody with induration extending beyond visible erythema, when there are bullae, crepitus, or skin necrosis, or when sepsis coexists with a soft tissue complaint. The LRINEC score can support the diagnosis but is not sufficiently sensitive to exclude it.

• Red flags: pain out of proportion, woody/hard induration, bullae, skin necrosis, crepitus, sepsis, rapid progression.
• Surgical exploration is diagnostic — 'hard signs' of necrosis (dishwater fluid, thrombosed vessels, non-contractile muscle) mandate debridement.
• Empiric broad coverage: piperacillin-tazobactam (or carbapenem) + vancomycin + clindamycin (clindamycin for toxin suppression in streptococcal and staphylococcal toxic shock). [VERIFY current empiric regimen]
• Polymicrobial (Type I): post-surgical, diabetic, perineal (Fournier). Monomicrobial (Type II): GAS, often in healthy hosts. Vibrio/Aeromonas: saltwater/freshwater exposure.
• Imaging (CT with contrast) is useful only if it does NOT delay surgery; subcutaneous gas and fascial fluid with enhancement support the diagnosis.

Diabetic foot infection: probe, culture, cover broadly

Diabetic foot infection ranges from mild cellulitis to limb-threatening infection with osteomyelitis and deep space abscess. The most important early steps are: probe the ulcer to bone (probe-to-bone test), assess perfusion, evaluate for osteomyelitis (plain films, MRI), and obtain deep tissue cultures (preferably after debridement) before starting broad empiric therapy. Mild infection is often streptococcal or staphylococcal; moderate-to-severe infection is polymicrobial (aerobes and anaerobes) and requires broad coverage with a focus on source control (debridement, offloading, revascularization). Always involve podiatry, vascular surgery, and ID.

• Probe-to-bone: a positive test predicts osteomyelitis in high-risk patients; correlate with imaging and cultures.
• Mild infection: cephalexin or dicloxacillin (add MRSA cover if risk factors).
• Moderate-to-severe: ampicillin-sulbactam, piperacillin-tazobactam, or a carbapenem; add MRSA and (sometimes) Pseudomonas coverage in severe or chronic infection.
• Obtain deep tissue or bone cultures after debridement; avoid superficial swabs.
• Image with plain radiographs first; MRI is most sensitive for osteomyelitis and deep abscess.
• Multidisciplinary care: podiatry, vascular surgery (for revascularization), ID, and endocrinology.

Bite wounds and special exposures

Bite wounds and environmental exposures shape the empiric antibiotic choice. Cat and dog bites inoculate Pasteurella multocida, anaerobes, and oral streptococci; first-line is amoxicillin-clavulanate. Human bites add Eikenella corrodens and require the same. Seawater exposure raises concern for Vibrio vulnificus; freshwater for Aeromonas. Puncture wounds (through shoes) risk Pseudomonas osteomyelitis. Consider rabies for animal bites in endemic areas, and tetanus for all contaminated wounds. Surgical assessment is essential for bites involving joints, tendons, or deep structures of the hand.

• Dog/cat/human bites: amoxicillin-clavulanate (Pasteurella, anaerobes, Eikenella); doxycycline or TMP-SMX + metronidazole in penicillin-allergic.
• Seawater exposure: add coverage for Vibrio (doxycycline + ceftazidime for severe infection). [VERIFY]
• Freshwater: add coverage for Aeromonas (fluoroquinolone or TMP-SMX).
• Puncture through shoes: cover Pseudomonas (fluoroquinolone); assess for osteomyelitis.
• Update tetanus and assess rabies risk for all animal bites.

Recurrent SSTI and decolonization

Recurrent SSTI (especially MRSA) is common in households and among close contacts. After treating the acute infection, address modifiable risk factors: nasal colonization, skin hygiene, fomites, and any underlying portal of entry (injection drug use, tinea, eczema). Decolonization regimens combine nasal mupirocin with chlorhexidine body washes, though evidence is mixed and benefit is often temporary. Educate households about personal hygiene, not sharing personal items, and cleaning high-touch surfaces.

• Address modifiable risk factors: IVDU, tinea, eczema, obesity, diabetes, chronic wounds.
• MRSA decolonization: nasal mupirocin × 5–10 days + chlorhexidine body washes; benefit is often temporary and evidence is mixed. [VERIFY current guideline]
• Household hygiene: clean high-touch surfaces, do not share razors/towels, cover draining wounds.
• Consider decolonization for: ≥ 2 documented MRSA infections in a year, or household outbreaks.

Guidelines

• IDSA Guideline on the Diagnosis and Management of Skin and Soft Tissue InfectionsStevens DL, et al. Clin Infect Dis. 2014;59(2):e10–e52 [VERIFY — 2024 update pending]The foundational US SSTI guideline — purulent vs non-purulent, severity, empiric therapy.

Reviews

• LRINEC — Laboratory Risk Indicator for Necrotizing FasciitisWong CH, et al. Crit Care Med. 2004 [VERIFY; external validation shows lower sensitivity]Bedside score to support necrotizing infection diagnosis — never overrides clinical judgment.

Key trials

• Cephalexin plus TMP-SMX vs cephalexin alone for uncomplicated cellulitisBrindle R, et al. (3 RCTs). [VERIFY — identify trials and citations]Adding empiric MRSA cover to a beta-lactam did not improve outcomes in non-purulent cellulitis.
• Trimethoprim-sulfamethoxazole vs placebo for uncomplicated abscess (I&D)Talan DA, et al. N Engl J Med. 2016;374:823–832 [VERIFY]TMP-SMX modestly improved outcomes after I&D in some patients (larger abscesses); I&D remains primary.
• Placebo vs TMP-SMX after drainage of small abscessesChen AE, et al. (pediatric trial). [VERIFY]Small uncomplicated abscesses do well with I&D alone; antibiotics add little.