Cellulitis in the face of antibiotic resistance

Mr. W, a 60-year-old with type 2 diabetes mellitus, bumped his right shin on the dresser in his bedroom. Three days later, he experienced increasing pain over the shin and observed redness and mild swelling. After examining the area and taking a history, the man's primary-care clinician diagnosed cellulitis.

Cellulitis is an acute infection and inflammatory response in the dermis and subcutaneous tissue, commonly seen by providers in primary care, emergency medicine, and surgery. In the United States, the annual incidence is approximately two to three cases per 100 people.1,2 A break in the skin allows entry of bacteria. Most cases of cellulitis are uncomplicated and treated in the outpatient setting with oral antibiotics. However, the rapid rise of resistance in gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), has made the selection of empiric therapy more difficult. Prompt and effective therapy is crucial because cellulitis has the potential to progress to serious illness in other parts of the body by contiguous spread or via the lymphatic or circulatory system.

Portals of bacterial entry

Cellulitis occurs where the skin has been broken. Trauma (including contusions, abrasions, lacerations, and puncture wounds), insect bites, animal and human bites, surgical wounds, burns, sites of IV catheter insertion or IV injection of illicit drugs (skin-popping), and even small, imperceptible cracks in the skin predispose patients to cellulitis.

The infection is also associated with other skin conditions, including abscesses, furuncles, carbuncles, impetigo, varicella, and tinea pedis. When assessing patients with lower-extremity cellulitis, clinicians must be sure to examine the feet for interdigital dermatophytic infections and treat as necessary with topical antifungal agents.

Who is at risk?

Mr. W's diabetes and his age put him at increased risk for cellulitis. Persons with diabetes mellitus are 1.8 times more likely to develop cellulitis than those without diabetes.3 Sensory neuropathy, atherosclerotic disease, and immune alterations all predispose the diabetic patient to skin and soft-tissue infections. Elderly persons and patients with other forms of immunocompromise are also at increased susceptibility. Additional risk factors include chronic steroid use, impaired peripheral circulation (peripheral arterial disease and venous stasis), chronic edema, obesity, and lymphadenectomy following tumor excision, e.g., after a mastectomy.

Presenting signs and symptoms Like Mr. W, patients with cellulitis usually complain of localized pain and swelling and may have a history of trauma, bite, dermatitis, or surgery. The lower extremities are the most common site for cellulitis, but any part of the body can be involved. On examination, the affected skin is erythematous and warm, with edema and tenderness. The borders are usually irregular but defined; marking the borders with an indelible pen allows objective assessment of progression or resolution. Regional lymphadenopathy may be present. Make note of any breaks in the skin, lymphangitic streaking, peripheral edema, diminished peripheral pulses, or heart murmur. Fever and chills are signs of systemic involvement.

Causative organisms

Streptococcus pyogenes (also known as group A b-hemolytic streptococcus [GABHS]) and S. aureus are the most common causative agents of community-acquired cellulitis in immunocompetent persons. Cellulitis associated with abscesses, furuncles, or carbuncles is usually caused by S. aureus. In contrast, cellulitis that is diffuse, i.e., not associated with a defined portal of entry or purulence, is commonly caused by GABHS or a streptococcus plus S. aureus.4

Some situations require consideration of other causes: In immunocompromised persons, cellulitis may be due to gram-negative bacteria, and pneumococci may cause a particularly malignant form of cellulitis that develops through the bacteremic route. Cellulitis in the setting of a deep diabetic foot ulcer may have a wider spectrum of potential pathogens. Important historic clues to other causes of cellulitis include animal and human bites, water contact, trauma, and surgery (Table 1).

Differential diagnoses

Necrotizing fasciitis, an infection of the fascia of deep muscle, should be considered in the differential diagnosis of cellulitis. Overlying cellulitis often accompanies necrotizing fasciitis. An early clue to this diagnosis is pain disproportionate to the skin findings. Late findings include purple bullae, skin sloughing, crepitus, and systemic toxicity. Without surgical debridement, necrotizing fasciitis is fatal.

Noninfectious diseases can also mimic cellulitis and should be considered, particularly if the patient does not respond to appropriate antimicrobial therapy. Common noninfectious masqueraders include superficial and deep venous thrombosis, contact dermatitis, insect stings, tick bites, gout, fixed drug eruptions, and erythema nodosum.5

Diagnostic studies

Diagnosis is based on appearance of the skin and patient history. In these days of increasing antibiotic resistance, drainage from an abscess or weeping wound associated with cellulitis should be sent for culture and sensitivities. Material from needle aspiration of inflamed skin or skin biopsy can be cultured in cases of cellulitis without purulence, abscess, or a necrotic lesion, but this is usually not required. Instead, these procedures may be reserved for patients with unusual predisposing factors.

Because <5% of blood cultures are positive, they are not indicated in typical cases of cellulitis. Indications for blood cultures include significant fever and chills, severe immunocompromise, periorbital cellulitis, and cellulitis superimposed on lymphedema.6 A polymorphonuclear leukocytosis is often present with cellulitis; a complete blood cell count and differential may help gauge the severity of infection and the hematologic response.

In most cases of cellulitis, radiologic studies are unnecessary. Plain x-rays or CT is used when subjacent osteomyelitis is suspected, as in patients with a diabetic foot ulcer and cellulitis. When differentiating cellulitis from necrotizing fasciitis proves difficult, CT or MRI may show edema or fluid collection along the fascial plane. In cases in which you suspect necrotizing fasciitis, however, do not delay surgical exploration for a definitive diagnosis.

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