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A 74-year-old man is evaluated in the emergency department for a 3-day history of fever and chills as well as confusion. He has a 5-week history of a nonhealing ulcer on the plantar surface of his left foot. He has diabetes mellitus, hypertension, and peripheral vascular disease for which he takes metformin, glyburide, lisinopril, chlorthalidone, and aspirin. He has no known medication allergies.

On physical examination, temperature is 39.0 °C (102.2 °F), blood pressure is 92/60 mm Hg, pulse rate is 108/min, and respiration rate is 18/min. He appears ill and is slow to respond. Examination of the left foot discloses a 3.5 × 2.5-cm ulcer with surrounding erythema and warmth. A foul odor and edema and tenderness involving the entire foot are noted. Pedal pulses are absent. The underlying bone is detected with a metal probe.

Laboratory studies indicate a leukocyte count of 21,500/µL (21.5 × 109/L) with 18% band forms. Serum electrolyte levels and kidney function tests are normal.

A radiograph of the left foot indicates no subcutaneous gas or foreign bodies.

Which of the following is the most appropriate empiric antimicrobial regimen?

A. Aztreonam and metronidazole
B. Cefazolin and metronidazole
C. Clindamycin and gentamicin
D. Vancomycin and meropenem

MKSAP Answer and Critique

The correct answer is D. Vancomycin and meropenem.

The most appropriate empiric treatment of this patient is vancomycin and meropenem. This patient is experiencing a septic syndrome and limb-threatening foot infection. Limb-threatening infections are characterized by extensive spreading cellulitis, extending far beyond the wound or ulcer, with systemic illness and possible sepsis with ulcers extending deep into the subcutaneous tissue, as well as tissue ischemia. Limb-threatening infections are polymicrobial, including staphylococci, streptococci, enteric gram-negative rods, Pseudomonas aeruginosa, and anaerobes. Ideally, a biopsy of the affected bone and deep soft tissues should be attempted before empiric antimicrobial therapy is initiated. However, in the setting of sepsis and a limb-threatening infection in a patient with diabetes mellitus, antimicrobial therapy using agents directed at suspected pathogens should urgently be administered. Surgical debridement will also be required. Patients with severe infections should receive parenteral therapy. Pending the results of microbiologic cultures, vancomycin and meropenem would be an appropriate combination of agents, predictably supplying broad coverage against the potential pathogens of concern.

Because they are not active against gram-positive cocci, aztreonam and metronidazole would not provide coverage against streptococci and staphylococci. Although metronidazole has excellent activity against anaerobic gram-negative bacilli, the narrow spectrum of activity of cefazolin versus many gram-negative bacilli, as well as its inactivity against methicillin-resistant strains, may be inadequate.

Because of clindamycin’s methicillin-resistant activity, this agent cannot reliably treat serious infections potentially involving staphylococci.

The use of gentamicin or other aminoglycosides to provide coverage against aerobic gram-negative bacilli in empiric antibiotic regimens for treatment of complex diabetic foot infections is not currently recommended because of the narrow toxicity-to-benefit ratio with such use. In addition, aminoglycosides may exhibit diminished antimicrobial activity in a necrotic, anaerobic environment.

Key Point

• In the setting of sepsis and a limb-threatening infection in a patient with diabetes mellitus, antimicrobial therapy with agents directed at suspected pathogens should urgently be administered.

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