Treatment Guideline Chart
Cellulitis is a spreading bacterial skin infection that infects deeply involving the subcutaneous tissues.
It typically occurs in areas where the skin integrity has been compromised.
It may also result from blood-borne spread of infection to the skin and subcutaneous tissues.
It is commonly caused by beta-hemolytic streptococci and Staphylococcus aureus.
Erysipelas is a type of cellulitis with margins that are sharply demarcated, involves the epidermis and superficial lymphatics.
Onset of symptoms is acute whereas cellulitis has an indolent course.
It is more commonly caused by beta-hemolytic streptococci.

Cellulitis_erysipelas Treatment

Principles of Therapy

Choice of Route of Administration for Empiric Treatment

Oral Antibiotics

  • If lymphadenopathy, fever and other constitutional signs are not present [eg White blood cell (WBC) <15,000], then may typically treat patient with oral antibiotics on an outpatient basis
    • Given for uncomplicated cellulitis
  • If symptoms do not improve or if disease progresses significantly within the first 24-48 hours, parenteral therapy may be needed

Parenteral Antibiotics

  • Should be considered in the presence of the following:
    • Presence of signs of toxicity (fever >100.5°F/38°C, tachycardia, hypotension)
    • Rapid progression of erythema
    • Unresponsive/intolerant to oral antibiotic therapy with significant disease progression after 2 days of initiation
    • Presence of indwelling medical device (eg prosthesis, stents)
  • Considered in patients with complicated cellulitis and comorbidities [eg diabetes mellitus (DM), peripheral vascular diseases]
  • Consider switching to oral therapy after 48 hours if possible

Choice of Antibiotic

  • Tailored according to known pathogen, comorbid condition (eg DM), and special situations like water (salt or freshwater) exposure or animal bites
    • Treatment should also address underlying predisposing conditions
  • Empiric therapy may be started pending culture results
    • For patients with purulent cellulitis, treatment is directed towards Methicillin-resistant S aureus (MRSA) since it is the dominant pathogen in this type of cellulitis; therapy for beta-hemolytic streptococci is likely not needed
    • For patients with nonpurulent cellulitis, treatment is directed towards Methicillin-sensitive S aureus (MSSA) and beta-hemolytic streptococci
      • Empiric therapy for MRSA may be needed if patient has signs of systemic infection, is unresponsive to initial therapy, has recurrent infection, has a previous episode of or is at high risk for MRSA infection, or with indwelling medical device in close proximity to the location of the lesion
  • Increased use of biocides (eg antiseptics and disinfectants) during the COVID-19 pandemic has led to the emergence of antimicrobial-resistant organisms 
    • Empiric antimicrobial stewardship should be guided by the local resistance patterns of pathogens 
    • Recent studies show the potential use of antimicrobial fatty acids in developing antibacterial agents to reduce antibiotic resistance


Aminopenicillin/Beta-lactamase Inhibitors

  • Eg Amoxicillin/clavulanic acid, Ampicillin 
  • Recommended 1st-line therapy for patients with cellulitis or erysipelas near the eyes or nose
  • Considered 2nd-line alternative for patients with severe infection
  • Effective and especially useful in the presence of bone or joint infection

Cephalosporins - 1st Generation

  • Eg Cefadroxil, Cefalexin, Cefazolin 
  • Usually sufficient for mild nonpurulent uncomplicated cellulitis and treatment option for erysipelas
  • Active against streptococci and MSSA
  • Cefalexin may be used in patients with erysipelas with beta-lactam allergy

Cephalosporins - 2nd and 3rd Generation (Parenteral)

  • Eg Ceftriaxone, Cefuroxime 
  • Treatment alternative for patients with moderate nonpurulent cellulitis or severe infection
  • Usually used empirically in DM patients who have early mild cellulitis
  • Active against streptococci and MSSA
  • Aminoglycosides may be added if needed

Cephalosporins - Other Generations

  • Eg Ceftaroline, Ceftobiprole
  • May be considered for patients with MRSA infections


  • Used in patients allergic to Penicillin and cephalosporins
  • Alternative therapy for patients with nonpurulent or purulent cellulitis caused by MSSA or MRSA infection or severe infection


  • Used for nonpurulent cellulitis and moderate purulent cellulitis
  • Treatment option for patients with erysipelas with beta-lactam allergy
  • Has very good activity against community-acquired MRSA but not to streptococci

Glycopeptide Antibacterials

  • Eg Dalbavancin, Oritavancin, Telavancin
  • Lipoglycopeptide antibacterials with properties similar to Vancomycin that may be considered for complicated cellulitis caused by gram-positive organisms including MRSA


  • Eg Clarithromycin, Erythromycin, Roxithromycin
  • May be used if patient is allergic to Penicillin
  • Macrolide resistance among Group A Streptococci has increased and has become a concern in some countries
  • Erythromycin is the main macrolide used unless Erythromycin resistance is widespread in the community
  • Alternative therapy for patients with cellulitis or erysipelas near the eyes or nose
  • Also used for prophylactic treatment against recurrent cellulitis
  • Studies showed that the efficacy of Roxithromycin for erysipelas was comparable to that of Benzylpenicillin


  • Eg Linezolid, Tidezolid
  • May be used in patients allergic to Penicillin and for complicated cellulitis and erysipelas, or MRSA infections

Penicillins (Beta-lactamase Resistant)

  • Eg Dicloxacillin, Flucloxacillin, Nafcillin, Oxacillin
  • Recommended therapy for patients with erysipelas, moderate nonpurulent and purulent cellulitis, and MRSA infection
  • Recommended antibiotics against mild nonpurulent cellulitis caused by group A Streptococcus or S aureus
    • Some authorities recommend antistaphylococcal penicillin alone while others advocate antistaphylococcal penicillin + Penicillin or Amoxicillin
    • Combination may increase adverse effects
  • Recommended for initial treatment of neonates with moderate to severe cellulitis
  • Also recommended for recurrent cellulitis

Penicillin G (Intravenous [IV])

  • Used for erysipelas and moderate nonpurulent uncomplicated cellulitis
  • Treatment option for patients with recurrent cellulitis
  • Usually sufficient for uncomplicated cellulitis of an extremity caused by streptococci


  • Eg Ciprofloxacin, Delafloxacin, Levofloxacin, Moxifloxacin, Ofloxacin
  • Those that have enhanced activity against Gram-positive bacteria have been shown to be effective
  • Used for cellulitis caused by Vibrio vulnificus
  • Used in combination with other antibiotics for MRSA and other Gram-positive or Gram-negative organisms and anaerobes


  • Alternative to Vancomycin for patients with cellulitis caused by gram-positive organisms including MRSA
  • Used for cellulitis caused by Vibrio vulnificus


  • Eg Doxycycline, Minocycline, Omadacycline, Tigecycline
  • May be considered for moderate-severe purulent cellulitis, MSSA, and MRSA infections
  • May be used in patients allergic to Penicillin
  • Tigecycline may be used for treatment of complicated skin infections
    • Clinical efficacy is comparable with standard treatment


  • Treatment option for patients allergic to Penicillin
  • Combination with Ampicillin/sulbactam, Piperacillin/tazobactam, Ticarcillin/clavulanate, or Ceftriaxone/Ciprofloxacin/Levofloxacin plus Metronidazole is recommended for patients with purulent cellulitis caused by MRSA infection and other Gram-positive or Gram-negative organisms and anaerobes
  • Combination with Cefotaxime or Gentamicin is recommended as 1st-line parenteral treatment for neonates with MRSA infections
  • Also used for patients with penetrating trauma, nasal colonization with MRSA, and intravenous drug use
  • Daptomycin is an alternative option if Vancomycin is unavailable

Length of Therapy

Uncomplicated/Purulent/Nonpurulent Cellulitis and Erysipelas

  • Patient may be treated with antibiotics for 5 to 14 days depending on clinical response

Complicated Cellulitis

  • It is typically recommended that once erythema, warmth and edema have subsided significantly, patient may be treated for an additional 10 days with oral antibiotics
  • Patients with peripheral vascular disease, chronic venous stasis, diabetes mellitus or alcoholic cirrhosis may take 1-2 weeks to improve and often require 3-4 weeks of treatment

Adjunct Therapy


  • Eg Prednisolone, Prednisone
  • Studies showed that when used in combination with antibiotics, healing time of lesions are reduced
  • Should be considered in nondiabetic patients

Non-Pharmacological Therapy

  • Immobilization and elevation of affected limb
    • Effects: May help to decrease swelling and pain especially if used early in the course of treatment, and may also shorten time to recovery
  • Dressings
    • Cool sterile saline dressing may be applied
    • Effects: Remove purulent exudate from ulcers or infected abrasions, may help decrease local pain
  • Compression stockings
    • May help with edema
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