Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 30-year-old woman is evaluated for a 2-day history of increasing pain in the right antecubital fossa and biceps. She reports daily injection drug use. Medical history is otherwise unremarkable, and she takes no prescription medications.

On physical examination, temperature is 39.7 °C (103.5 °F), blood pressure is 90/56 mm Hg, pulse rate is 120/min, and respiration rate is 28/min. BMI is 28. She appears ill. No lymphangitis or right axillary or epitrochlear lymphadenopathy is evident. The right biceps area is extremely tender and warm, with multiple track marks, woody induration, edema, and overlying ecchymotic bullous lesions.

Laboratory studies:

Leukocyte count	23,000/µL (23 × 109/L) (80% neutrophils, 12% band forms, 8% lymphocytes)
Aspartate aminotransferase	55 U/L
Bilirubin, total	2.0 mg/dL (34.2 µmol/L)
Creatinine	1.7 mg/dL (150 µmol/L)
Electrolytes:
Sodium	135 mEq/L (135 mmol/L)
Potassium	4.2 mEq/L (4.2 mmol/L)
Chloride	95 mEq/L (95 mmol/L)
Bicarbonate	16 mEq/L (16 mmol/L)

No gas or foreign body is seen on plain radiographs of the right arm and shoulder.

In addition to emergent surgical evaluation, which of the following is the most appropriate empiric treatment?

A: Ceftriaxone plus metronidazole
B: Doxycycline plus ciprofloxacin
C: Penicillin plus clindamycin
D: Vancomycin plus piperacillin-tazobactam

MKSAP Answer and Critique

The correct answer is D: Vancomycin plus piperacillin-tazobactam.

This patient has necrotizing fasciitis and should receive empiric treatment with vancomycin plus piperacillin-tazobactam. Clues to a potential necrotizing skin infection include systemic toxicity (abnormal liver and kidney function, metabolic acidosis) with fever, chills, and hypotension. The patient’s pain may be disproportionate to the physical examination findings. Skin changes can evolve rapidly and become ecchymotic, vesiculobullous, and gangrenous in appearance. “Woody” induration is also characteristic. Prompt surgical intervention is indicated as the primary treatment, with concurrent antibiotic therapy. The microbiologic cause can be monomicrobial or polymicrobial. Until the microbiology is determined, empiric therapy should be broad and consist of coverage against mixed aerobic and anaerobic gram-positive and gram-negative organisms, including methicillin-resistant Staphylococcus aureus (MRSA). Recommended regimens include vancomycin, linezolid, or daptomycin plus one of the following: piperacillin-tazobactam, a carbapenem (such as imipenem or meropenem), or metronidazole with either ceftriaxone or a fluoroquinolone. Polymicrobial infections are generally seen in patients with gastrointestinal and genitourinary infections, pressure ulcers, or at injection sites in patients using illicit drugs.

Ceftriaxone plus metronidazole alone provides broad-spectrum coverage against many organisms, but lacks MRSA activity. The addition of vancomycin or linezolid to this regimen would be needed until the microbiologic causes of necrotizing fasciitis are determined.

Doxycycline plus ciprofloxacin or ceftriaxone is the recommended regimen for patients with monomicrobial Aeromonas hydrophila–associated necrotizing skin infection. Patients who are immunocompromised, including those with liver disease and cancer, are at increased risk for serious skin infections and bacteremia/sepsis with this gram-negative bacillus. Wound infection usually occurs by inoculation through the skin. A. hydrophila is found in freshwater environments, but may also be present in brackish water. This regimen would not provide reliable empiric coverage against anaerobic bacteria or MRSA.

If Streptococcus pyogenes is confirmed by Gram stain and culture as the cause of necrotizing fasciitis, then penicillin plus clindamycin is recommended, particularly with associated toxic shock syndrome. Clindamycin is included because it inhibits toxin production and remains effective even in the presence of a high inoculum of bacteria. This regimen also would not provide adequate empiric coverage against gram-negative aerobic bacteria.

Key Point

• Patients with necrotizing fasciitis should receive empiric treatment with broad-spectrum antimicrobials that include coverage of aerobic and anaerobic gram-positive and gram-negative organisms, including methicillin-resistant Staphylococcus aureus, until microbiology is determined.

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