A 62-year-old man is evaluated in the outpatient clinic for new-onset muscle pain and weak… — USMLE Step 3

A 62-year-old man is evaluated in the outpatient clinic for new-onset muscle pain and weakness. Two weeks ago, he was discharged from the hospital to complete a 6-week course of outpatient intravenous daptomycin for methicillin-resistant *Staphylococcus aureus* (MRSA) osteomyelitis of the right first metatarsal. He reports diffuse aching in his thighs, shoulders, and lower back that began 3 days ago and has progressively worsened. He now has difficulty climbing stairs. He has no chest pain, shortness of breath, or new focal neurologic deficits. His right foot wound is healing well with no erythema or purulent drainage.

Vital signs are within normal limits. Physical examination reveals diffuse proximal muscle tenderness and $4/5$ strength in the bilateral hip flexors and shoulder abductors.

Laboratory evaluation shows:

Laboratory Test	Result	Reference Range
Serum creatinine	$1.0$ mg/dL	$0.7-1.3$ mg/dL
Creatine phosphokinase (CPK)	$2,450$ U/L	$55-170$ U/L
Aspartate aminotransferase (AST)	$85$ U/L	$10-40$ U/L
Alanine aminotransferase (ALT)	$42$ U/L	$10-40$ U/L

Which of the following is the most appropriate next step in the management of this patient?

A
Continue daptomycin and decrease the administration frequency to every 48 hours
Discontinue daptomycin and initiate intravenous vancomycinAnswer
C
Discontinue daptomycin and initiate intravenous ceftriaxone
D
Order magnetic resonance imaging of the right foot
E
Continue daptomycin and obtain a right upper quadrant abdominal ultrasound

Answer

Discontinue daptomycin and initiate intravenous vancomycin

The correct answer is to discontinue daptomycin and initiate intravenous vancomycin. Daptomycin is associated with skeletal muscle toxicity, ranging from asymptomatic CPK elevation to severe rhabdomyolysis. Guidelines require baseline and weekly CPK monitoring during therapy. Daptomycin should be permanently discontinued if a patient develops unexplained signs or symptoms of myopathy (e.g., muscle aches, weakness) in conjunction with a CPK elevation greater than

5

times the upper limit of normal (ULN), or an asymptomatic CPK elevation greater than

10

times the ULN. This patient is highly symptomatic and has a CPK

>14

times the ULN. Because he is only two weeks into a six-week course for MRSA osteomyelitis, an alternative bactericidal agent with adequate bone penetration, such as intravenous vancomycin, must be promptly initiated.

Step-by-Step Solution

Analyze the clinical presentation and medication history.

The patient developed diffuse proximal muscle weakness and extreme CPK elevation while receiving daptomycin therapy.

Daptomycin is a lipopeptide antibiotic known to cause dose-dependent myopathy and rhabdomyolysis, requiring routine CPK monitoring.

Evaluate the laboratory findings to identify the source of abnormalities.

CPK is markedly elevated (

>14

times the upper limit of normal). AST is mildly elevated while ALT is near normal.

The AST elevation is secondary to skeletal muscle breakdown, not hepatotoxicity. The profound CPK elevation combined with clinical symptoms confirms daptomycin-induced myopathy.

Determine the appropriate treatment modification.

Daptomycin must be discontinued immediately, and an alternative agent for MRSA osteomyelitis (such as vancomycin) must be initiated.

Continuing daptomycin when symptomatic myopathy is present risks severe rhabdomyolysis and acute kidney injury. Vancomycin provides necessary, appropriate coverage for the ongoing MRSA bone infection.

Key Concept

Patients receiving daptomycin require weekly monitoring of creatine phosphokinase (CPK) levels. The medication must be discontinued immediately if the patient develops symptomatic myopathy with a CPK

>5

times the upper limit of normal, or an asymptomatic CPK elevation

>10

times the upper limit of normal.

Estimated Time:1m 15s

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