Cellulitis Empiric Therapy 

Updated: Apr 15, 2021
  • Author: Alfred Scott Lea, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Empiric Therapy Regimens

The publication of Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections 2014 - Update by the Infectious Diseases Society of America addresses an array of skin and soft tissue infections (SSTIs), emphasizing the clinical skills needed to properly treat the likely pathogens before and after culture results are available. [1]

The empiric treatment of cellulitis in adults begins with the categorization of patients into one of the following categories:

  • Nonpurulent cellulitis: Includes rapidly spreading superficial cellulitis and erysipelas; typically involves groups A, B, C, and G beta-hemolytic streptococci and, occasionally, methicillin-susceptible Staphylococcus aureus (MSSA). These infections are diagnosed clinically, and cultures are not mandatory since there is usually no reliable and easily accessible source of specimen to culture. [1, 2, 3, 4]

  • Purulent cellulitis: Includes cutaneous abscesses, carbuncles, furuncles, and sebaceous cyst infection typically involving S aureus, both MSSA and methicillin-resistant S aureus (MRSA); culture should be performed when possible to determine the pathogen’s presence and resistance pattern [1, 5, 6, 7, 8]

When treating nonpurulent cellulitis, typically involving beta-hemolytic streptococci and MSSA, it is unlikely that MRSA is a causative pathogen and it's coverage is not necessary. [4]

When treating purulent cellulitis, the initial antibiotic selection should cover MRSA for patients with coexisting penetrating and/or surgical trauma, evidence of MRSA infection elsewhere, known nasal MRSA colonization, and intravenous drug abuse. Coverage should also take into consideration the prevalence of MRSA in the patient’s hospital and community. [1, 6]

Outpatient therapy with oral antibiotics is indicated for healthy individuals who have no evidence of sepsis (qSOFA  ≤ 1 ). [1, 9]

Inpatient therapy with parenteral antibiotics is recommended for patients with sepsis, hemodynamic instability, and/or mental status changes. Additional considerations include poor compliance, failure to absorb or respond to oral antibiotics, rapid  progression of disease, extensive  involvement past a joint of an extremity, extensive involvement of two body regions (ie, thorax and abdomen, etc.), facial involvement, and immune suppression. Parenteral therapy is continued until the patient is stable and improving (usually 1-3 days).{ref 1}

Cellulitis without associated purulent drainage or abscess (nonpurulent cellulitis)

Considerations are as follows:

  •  Limb elevation, tinea pedis eradication, and edema control are important adjuncts to therapy.
  • Use of glucocorticoids can be considered in selected cases to reduce inflammation, but is not routine
  •  Limb cellulitis is usually unilateral. One needs to be sure that the patient does not have a disease that mimics cellulitis (ie, stasis dermatitis, etc). [10, 11, 12]  

Outpatient treatment recommendations are as follows: [1, 4]

Inpatient treatment recommendations are as follows:

* Total duration of therapy is typically 5-7 days. Extend therapy if cellulitis is slow to respond. [13]

** Parenteral antibiotics are given 1-3 days until the patient is stabilized and improving; then, transition to oral antibiotics for the duration of therapy. [1]

Cellulitis with associated purulent drainage or abscess (purulent cellulitis)

Considerations are as follows: [5, 6, 7, 8]

  • If abscess is present, drainage is required. Brdside ultrasond may help localize abscess for drainage.

  • Drainage of abscess without associated cellulitis may be sufficient therapy.

  • Consider antibiotics if cellulitis is present.

  • Gram stain and culture are indicated to determine presence and resistance pattern of pathogen. [1]

Outpatient treatment recommendations (MRSA prevalent) are as follows:

  • Doxycycline or minocycline 200 mg PO followed by 100 mg PO q12h*

  • Trimethoprim-sulfamethoxazole (160 mg/800 mg) 1-2 tabs PO q12h*

  • Linezolid 600 mg PO q12h*§

  • Clindamycin 300-600 mg PO q6-8h*∞

  • Dalbavancin - 1.5 mg/kg x 1, or Oritavancin - 1200 mg IV x 1 (may avoid hospitalization in more severe cases)§

Inpatient treatment recommendations (MRSA prevalent) are as follows:

  • Vancomycin 15 mg/kg IV q12h followed by dosage adjustment based on trough levels maintained between 10 and 20 µg/mL and serial renal function**

  • Daptomycin 4 mg/kg IV q24h (q48h if creatinine clearance [CrCl] < 30 mL/min)** §

  • Linezolid 600 mg IV q12h** §

  • Ceftaroline 600 mg IV q12h (dose reduction required if CrCl ≤50 mL/min)** §

* Total duration of therapy is 7-14 days. Extend therapy if cellulitis is slow to respond. [1, 6]

** Parenteral antibiotics given 1-3 days until patient debrided, stabilized, and improving; then, transition to oral antibiotics for the duration of therapy. [1]

§ Expensive

∞ Requires special sensitivity testing (D test) to exclude hidden (inducible) resistance. [14]

Organism-specific therapy and special circumstances

Once microorganisms are identified based on cultures, treatment is tailored to the patient’s needs. The most common offenders (beta-hemolytic streptococci, MSSA, MRSA) are discussed in Cellulitis Organism-Specific Therapy.

Empiric therapy in patients with 'complicated' cellulitis involving specific clinical situations (ie, marine exposure, fresh water exposure, nonhuman mammalian bites, human bites, diabetic foot wounds, recurrent cellulitis, facial cellulitis/erysipelas/periorbital cellulitis, surgical site infections, immunosuppressive states, and necrotizing cellulitis/Fournier gangrene)  are more difficult and are not treated as 'uncomplicated cellulitis'.

Unusual forms of SSTI (ie, clostridial myonecrosis, pyomyositis, cutaneous anthrax, erysipeloid, glanders, tularemia, plague, and bacillary angiomatosis), are discussed in separate Medscape topics.

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