Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema, and edema. Fever may occur, and regional lymph nodes may enlarge in more serious infections. Diagnosis is by appearance; cultures may help, but treatment, with antibiotics, should not be delayed pending those results. Prognosis is excellent with timely treatment.
(See also Overview of Bacterial Skin Infections.)
Etiology of Cellulitis
The most common causes of cellulitis are
- Streptococcus pyogenes
- Staphylococcus aureus
Cellulitis is most often caused by group A beta-hemolytic streptococci (eg, Streptococcus pyogenes) or Staphylococcus aureus. The skin barrier is usually compromised. Streptococci cause diffuse, rapidly spreading infection because enzymes produced by the organism (streptokinase, DNase, hyaluronidase) break down cellular components that would otherwise contain and localize the inflammation. Staphylococcal cellulitis is typically more localized and usually occurs in open wounds or cutaneous abscesses.
Methicillin-resistant S. aureus (MRSA-USA300) has become the predominant community strain of MRSA in the US (community-associated MRSA [CA-MRSA]; 1). If S. aureus is suspected, MRSA infection should now be considered the most probable etiology. Patients who are exposed to MRSA in a hospital or nursing facility may have a MRSA strain that has a different pattern of resistance from that of MRSA-USA300.
Less common causes of cellulitis are group B streptococci (eg, S. agalactiae) in older patients with diabetes; gram-negative bacilli (eg, Haemophilus influenzae) in children; and Pseudomonas aeruginosa in patients with diabetes or neutropenia, hot tub or spa users, and hospitalized patients. Animal bites may result in cellulitis and are often polymicrobial; Pasteurella multocida is often the cause in cat bites, and Pasteurella or Capnocytophaga species are typically responsible in dog bites. Immersion injuries in fresh water may result in cellulitis caused by Aeromonas hydrophila; immersion injuries in warm salt water may result in cellulitis caused by Vibrio vulnificus.
Immunocompromised patients may become infected by opportunistic organisms, including gram-negative bacteria (such as Proteus, Serratia, Enterobacter, or Citrobacter), anaerobic bacteria, and Helicobacter and Fusarium species. Mycobacteria may rarely cause cellulitis.
Risk factors include skin abnormalities (eg, trauma, ulceration, fungal infection, other skin barrier compromise due to preexisting skin disease), which are common in patients with chronic venous insufficiency or lymphedema. Scars from saphenous vein removal for cardiac or vascular surgery are common sites for recurrent cellulitis, especially if tinea pedis is present. Frequently, no predisposing condition or site of entry is evident.
- 1. Lakhundi S, Zhang K: Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology. Clin Microbiol Rev 31:e00020-18, 2018. doi: 10.1128/CMR.00020-18
Symptoms and Signs of Cellulitis
Infection is most common in the lower extremities. Cellulitis is typically unilateral; stasis dermatitis closely mimics cellulitis but is usually bilateral.
The major findings are local erythema and tenderness and, in more severe infections, often lymphangitis and regional lymphadenopathy. The skin is hot, red, and edematous, often with surface appearance resembling the skin of an orange (peau d’orange). The borders are usually indistinct, except in erysipelas (a type of cellulitis with sharply demarcated margins). Petechiae are common; large areas of ecchymosis are rare. Vesicles and bullae may develop and rupture, occasionally with necrosis of the involved skin. Cellulitis may mimic deep venous thrombosis but can often be differentiated by one or more features (see Table: Differentiating Cellulitis and Deep Venous Thrombosis).
Differentiating Cellulitis and Deep Venous Thrombosis
Deep Venous Thrombosis
Normal or cool
Normal or cyanotic
Lymphangitis and regional lymphadenopathy
Most cellulitis is nonpurulent. However, cellulitis sometimes is accompanied by one or more pustules, furuncles, or abscesses with or without purulent drainage or exudate and is referred to as purulent.
Fever, chills, tachycardia, headache, hypotension, and delirium (usually indicating severe infection) may precede cutaneous findings by several hours, but many patients do not appear ill. Leukocytosis is common. Cellulitis with rapid spread of infection, rapidly increasing pain, hypotension, delirium, or skin sloughing, particularly with bullae and fevers, suggests life-threatening infection.
Diagnosis of Cellulitis
- Sometimes blood cultures
- Sometime tissue cultures
Diagnosis of cellulitis is by examination. Contact dermatitis and stasis dermatitis are often misdiagnosed as cellulitis, thus leading to overtreatment. Contact dermatitis can often be differentiated by the presence of itching, limitation of lesions to the site of contact, absence of systemic signs, and sometimes unilateral location. Stasis dermatitis can sometimes be differentiated by features of dermatitis itself (eg, scaling, eczematous findings, lichenification), evidence of venous stasis, and bilateral location. Other disorders to consider include cutaneous T-cell lymphoma, nummular dermatitis, and tinea infection.
Skin and wound cultures (when wounds are present) are generally not indicated in cellulitis because they rarely identify the infecting organism. Blood cultures are useful in immunocompromised patients and patients who have signs of systemic infection (eg, fever and elevated white blood cell count) to detect or rule out bacteremia. Culture of involved tissue may be required in immunocompromised patients if they are not responding to empiric therapy or if blood cultures do not isolate an organism, as well as for patients with cellulitis at the site of certain injuries (eg, animal bite wounds, penetrating injuries). Abscess should be ruled out based on clinical findings, although bedside ultrasonography may be useful.
Prognosis of Cellulitis
Most cellulitis resolves quickly with antibiotic therapy. Local abscesses occasionally form, requiring incision and drainage. Serious but rare complications include severe necrotizing subcutaneous infection and bacteremia with metastatic foci of infection.
Recurrences in the same area are common, sometimes causing serious damage to the lymphatics, chronic lymphatic obstruction, and lymphedema.
Treatment of Cellulitis
Antibiotics are the treatment of choice, and selection is based on the presence or absence of purulence and other risk factors for serious and/or resistant infection (1). Treatments are usually not given for a fixed interval but are continued until there is satisfactory clinical response—but typically for not less than 1 week.
Immobilization and elevation of the affected area help reduce edema; cool, wet dressings relieve local discomfort.
Nonpurulent, uncomplicated cellulitis
For most patients with nonpurulent cellulitis, empiric therapy effective against both group A streptococci and S. aureus is used. Oral therapy is usually adequate for mild infections, typically with dicloxacillin 250 mg or cephalexin 500 mg 4 times a day. Oral levofloxacin 500 mg once a day or moxifloxacin 400 mg once a day works well for patients who are unlikely to adhere to multiple daily dosing schedules; however, bacteria resistant to fluoroquinolones are becoming more prevalent. In patients allergic to penicillin, oral clindamycin 300 to 450 mg 3 times a day or an oral macrolide (clarithromycin 250 to 500 mg 2 times a day or azithromycin 500 mg on 1st day, then 250 mg once a day) are alternatives.
A patient with mild cellulitis caused by mammalian bites can be treated as an outpatient with amoxicillin/clavulanate 875 mg orally every 12 hours. If penicillin allergic, use clindamycin 300 to 450 mg 3 times a day plus either an oral fluoroquinolone (eg, ciprofloxacin 500 mg every 12 hours) or trimethoprim/sulfamethoxazole one double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) orally 2 times a day.
Cellulitis that develops after exposure to brackish or salt water should be treated with doxycycline 100 mg orally 2 times a day plus either ceftazidime 1 g IV every 8 hours or a fluoroquinolone (oral or parenteral depending on clinical circumstances). Cellulitis caused by exposure to fresh water should be treated with ceftazidime, cefepime 2 g IV every 12 hours, or a fluoroquinolone. Likely infecting organisms tend to be similar in brackish and fresh water (eg, Vibrio species, Aeromonas species, Shewanella species, Erysipelothrix rhusiopathiae, Mycobacterium marinum, Streptococcus iniae).
Recurrent cellulitis can occur in patients with risk factors such as tinea pedis, obesity, venous insufficiency, edema, and atopic dermatitis. These disorders should be identified and treated to decrease the likelihood of recurrent cellulitis. Prophylactic antibiotics such as benzathine penicillin 1.2 million units IM monthly or penicillin V or erythromycin 250 mg orally 4 times a day for 1 week/month may be considered for patients who have 3 to 4 episodes of cellulitis per year despite treatment of predispositions. If these regimens prove unsuccessful, tissue culture may be required.
MRSA and purulent or complicated cellulitis
Purulent cellulitis, regarded as high risk, should include coverage for MRSA. Coverage for MRSA should also be initiated in patients with the following:
- Penetrating trauma
- Surgical wounds
- Recent hospitalization or nursing home exposure
- IV drug use
- Proximity of infection to an implanted medical device such as a prosthetic joint
- Previous MRSA infection
- Known nasal colonization with MRSA
- High-risk symptoms for serious infection
High-risk symptoms for serious (eg, deeper, invasive, systemic) infection include the following:
- Pain disproportionate to physical findings
- Cutaneous hemorrhage
- Skin sloughing
- Skin anesthesia
- Rapid progression
- Tissue gas
- Symptoms of systemic toxicity (fever or hypothermia, tachycardia, hypotension, delirium)
For suspected MRSA without high-risk symptoms, empiric outpatient treatment is reasonable using double-strength trimethoprim/sulfamethoxazole (160 mg trimethoprim/800 mg sulfamethoxazole) orally 2 times a day, clindamycin 300 to 450 mg orally 3 times a day (however, resistance to clindamycin is becoming more prevalent), doxycycline 100 mg orally 2 times a day, or linezolid 600 mg orally 2 times a day.
Patients who have more serious infections, with high-risk symptoms with suspected or confirmed MRSA, or who have failed oral therapy are hospitalized and given the following:
- Vancomycin 15 mg/kg IV every 12 hours is the drug of choice (see also Antibiotic resistance).
- Linezolid 600 mg IV every 12 hours for 10 to 14 days, usually for highly resistant MRSA
- Daptomycin 4 to 6 mg/kg IV once/day
- Teicoplanin 6 mg/kg IV every 12 hours for 2 doses, followed by 3 or 6 mg/kg IV or IM once a day (mechanism of action similar to that of vancomycin; commonly used outside the US to treat MRSA)
Four other drugs are now available for severe acute bacterial skin and skin structure infection (ABSSSI) with S. aureus (including MRSA). These drugs should be used only for cellulitis that is complex or unresponsive to other antibiotic regimens:
- Oritavancin 1200 mg IV once, administered over 3 hours
- Dalbavancin 1500 mg IV once, or 1000 mg IV once, then 500 mg IV 1 week after the first dose infused over 30 minutes
- Tedizolid 200 mg orally or IV once/day for 6 days
- Delafloxacin 300 mg IV every 12 hours or 450 mg orally every 12 hours for 5 to 14 days
Cellulitis in a patient with neutropenia requires empiric vancomycin in addition to antipseudomonal antibiotics (eg, tobramycin 1.5 mg/kg IV every 8 hours and piperacillin 3 g IV every 4 hours) until blood culture results are available. Tissue culture should be strongly considered for identification of the causative organism because of the increased risk of fungal infection. Culture should be considered for immunocompromised patients if they are not responding to empiric therapy or if blood cultures do not isolate an organism and for patients with cellulitis at the site of certain injuries (eg, animal bite wounds, penetrating injuries).
- 1. Brindle R, Williams OM, Barton E, Featherstone P: Assessment of antibiotic treatment of cellulitis and erysipelas: A systematic review and meta-analysis. JAMA Dermatol 155(9):1033–1040, 2019. doi: 10.1001/jamadermatol.2019.0884
Key Points about Cellulitis
- The most common pathogens causing cellulitis overall are S. pyogenes and S. aureus.
- Methicillin-resistant S. aureus (MRSA) should be considered in the presence of certain risk factors (eg, purulent cellulitis, penetrating trauma, wound infection, nasal colonization), particularly if there is a known outbreak or local prevalence is high.
- Differentiate leg cellulitis from deep vein thrombosis by the presence of skin warmth, redness, peau d'orange quality, and lymphadenopathy.
- Tissue culture may be required for immunocompromised patients if they are not responding to empiric therapy or if blood cultures do not isolate an organism and for patients with cellulitis at the site of certain injuries (eg, animal bite wounds, penetrating injuries).
- Direct antibiotic therapy against the most likely pathogens in specific clinical situations.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|dicloxacillin||No US brand name|
|levofloxacin||IQUIX, LEVAQUIN, QUIXIN|