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.)
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 in the US (community-associated MRSA [CA-MRSA]). 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 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; Pasteurella multocida is the cause in cat bites, and Capnocytophaga sp is responsible in dog bites. Immersion injuries in fresh water may result in cellulitis caused by Aeromonas hydrophila; in warm salt water, by Vibrio vulnificus (see Gram-Negative Bacilli).
Immunocompromised patients may become infected by opportunistic organisms, including gram-negative bacteria (such as Proteus,Serratia,Enterobacter, or Citrobacter—see Gram-Negative Bacilli), anaerobic bacteria, and Helicobacter (see Helicobacter pylori Infection) and Fusarium spp (see Miscellaneous Opportunistic Fungi). 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.
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).
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 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) 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.
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.
Antibiotics are the treatment of choice, and selection is based on the presence or absence of purulence. For most patients with nonpurulent cellulitis, empiric therapy effective against both group A streptococci and S. aureus is used. Oral therapy is usually adequate with dicloxacillin 250 mg or cephalexin 500 mg qid for mild infections. Levofloxacin 500 mg po once/day or moxifloxacin 400 mg po once/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, clindamycin 300 to 450 mg po tid or a macrolide (clarithromycin 250 to 500 mg po bid or azithromycin 500 mg po on 1st day, then 250 mg po once/day) are alternatives.
Purulent cellulitis, regarded as high risk, should include coverage for MRSA. Coverage for MRSA should also be initiated in patients with the following:
High-risk symptoms include the following:
Double-strength trimethoprim/sulfamethoxazole (160 mg trimethoprim/800 mg sulfamethoxazole) po bid, clindamycin 300 to 450 mg po tid, and doxycycline 100 mg po bid are reasonable outpatient empiric treatments.
For more serious infections, or in those who have failed oral therapy, patients are hospitalized and given oxacillin or nafcillin 1 g IV q 6 h, or a cephalosporin (eg, cefazolin 1 g IV q 8 h). For penicillin-allergic patients or those with suspected or confirmed MRSA infection, vancomycin 15 mg/kg IV q 12 h is the drug of choice (see also Antibiotic resistance). Linezolid is another option, usually for the treatment of highly resistant MRSA, at a dose of 600 mg IV q 12 h for 10 to 14 days. Daptomycin 4 to 6 mg/kg IV once/day can be used. Teicoplanin has a mechanism of action similar to that of vancomycin. It is commonly used outside the US to treat MRSA; the usual dose is 6 mg/kg IV q 12 h for 2 doses, followed by 6 mg/kg (or 3 mg/kg) IV or IM once/day. Immobilization and elevation of the affected area help reduce edema; cool, wet dressings relieve local discomfort.
Three drugs have recently become available for acute bacterial skin and skin structure infection (ABSSSI) with S. aureus (including MRSA): ortavancin 1200 mg IV once, administered over 3 h; dalbavancin 1500 mg IV once, or 1000 mg IV once, then 500 mg IV 1 wk after the first dose infused over 30 min; tedizolid 200 mg po or IV once/day for 6 days. These drugs should be used only for cellulitis that is complex or unresponsive to other antibiotic regimens.
Cellulitis in a patient with neutropenia requires empiric antipseudomonal antibiotics (eg, tobramycin 1.5 mg/kg IV q 8 h and piperacillin 3 g IV q 4 h) until blood culture results are available.
A patient with mild cellulitis caused by mammalian bites can be treated as an outpatient with amoxicillin/clavulanate (if penicillin allergic, with a fluoroquinolone plus clindamycin or trimethoprim/sulfamethoxazole).
Cellulitis that develops after exposure to brackish or salt water should be treated with doxycycline 100 mg po bid and ceftazidime or a fluoroquinolone. Cellulitis caused by exposure to fresh water should be treated with ceftazidime, cefepime, or a fluoroquinolone. Likely infecting organisms tend to be similar in brackish and fresh water (eg, Vibrio sp, Aeromonas sp, Shewanella sp, Erysipelothrix rhusiopathiae, Mycobacterium marinum, Streptococcus iniae).
Untreated tinea pedis can predispose patients to recurrent lower extremity bacterial cellulitis; treating the fungal infection eliminates the nidus of bacteria that can reside in the inflamed, macerated tissue. If such therapy is unsuccessful or not indicated, recurrent cellulitis can sometimes be prevented by benzathine penicillin 1.2 million units IM monthly or penicillin V or erythromycin 250 mg po qid for 1 wk/mo. If these regimens prove unsuccessful, tissue culture may be required.
The most common pathogens causing cellulitis overall are S. pyogenes and 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.
Do not culture skin or wounds; however, with severe or complicated infection, culture blood and possibly tissue.
Direct antibiotic therapy against the most likely pathogens.