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Cellulitis

by A. Damian Dhar, MD, JD

Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, rapidly spreading erythema, and edema; fever may occur, and regional lymph nodes may enlarge. Diagnosis is by appearance; cultures are sometimes helpful, but awaiting these results should not delay empiric therapy. Treatment is with antibiotics. Prognosis is excellent with timely treatment.

Etiology

  • Streptococcus pyogenes

  • Staphylococcus aureus

Cellulitis is most often caused by group A β-hemolytic streptococci (eg, Streptococcus pyogenes) or Staphylococcus aureus. 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.

Recently, methicillin-resistant S. aureus (MRSA) has become more common in the community (community-associated MRSA [CA-MRSA]). Historically, MRSA was typically confined to patients who were exposed to the organism in a hospital or nursing facility. MRSA infection should now be considered in patients with community-acquired cellulitis, particularly in those with cellulitis that is recurrent or unresponsive to monotherapy.

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.

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 spp. 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.

Symptoms and Signs

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, frequently with 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—see Erysipelas). 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 Differentiating Cellulitis and Deep Venous Thrombosis). Fever, chills, tachycardia, headache, hypotension, and delirium 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.

Differentiating Cellulitis and Deep Venous Thrombosis

Feature

Cellulitis

Deep   Venous Thrombosis

Skin temperature

Hot

Normal or cool

Skin color

Red

Normal or cyanotic

Skin surface

Peau d’orange

Smooth

Lymphangitis and regional lymphadenopathy

Frequent

Nonexistent

Diagnosis

  • Examination

  • Blood and sometimes tissue cultures for immunocompromised patients

Diagnosis is by examination. Skin and (when present) wound cultures are generally not indicated because they rarely identify the infecting organism. Blood cultures are useful in immunocompromised patients 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. Abscess should be ruled out based on clinical findings.

Prognosis

Most cellulitis resolves quickly with antibiotic therapy. Local abscesses occasionally form, requiring incision and drainage. Serious but rare complications include severe necrotizing subcutaneous infection (see 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

  • Antibiotics

Treatment is with antibiotics. When prevalence of local skin pathogens is known, empiric treatment should be directed against the most prevalent ones. For most patients, empiric treatment 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.

Initial use of empiric therapy against MRSA is not typically recommended unless risk is particularly high (eg, contact with a person who has a documented case, exposure to a documented outbreak, culture-documented local prevalence of > 10% or 15%). In high-risk cases, 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, 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 Gram-Positive Cocci: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 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.

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).

Recurrent leg cellulitis is prevented by treating concomitant tinea pedis, which often eliminates the source of bacteria residing 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.

Key Points

  • The most common pathogens causing cellulitis overall are S. pyogenes and S. aureus.

  • MRSA should be considered, 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 by the presence of 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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • AVELOX
  • BACTOCILL IN PLASTIC CONTAINER
  • PERIOSTAT, VIBRAMYCIN
  • ERY-TAB, ERYTHROCIN
  • MAXIPIME
  • FORTAZ, TAZICEF
  • ZITHROMAX
  • VANCOCIN
  • IQUIX, LEVAQUIN, QUIXIN
  • NALLPEN IN PLASTIC CONTAINER
  • AMOXIL
  • CLEOCIN
  • CUBICIN
  • KEFLEX
  • ANCEF, KEFZOL
  • No US brand name
  • TOBI, TOBREX
  • BIAXIN
  • ZYVOX

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