MKSAP: 52-year-old man with fatigue and fever

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

A 52-year-old man is admitted to the hospital with fatigue and fever of 3 days’ duration. He is a health care worker and has a bicuspid aortic valve. He takes no medications.

Blood cultures are obtained at the time of admission, and he is started on empiric vancomycin for possible endocarditis.

On hospital day 2, his initial blood cultures become positive for gram-positive cocci in clusters, and on hospital day 3, his blood cultures grow methicillin-resistant Staphylococcus aureus. Susceptibility to vancomycin is intermediate (MIC = 4 µg/mL).

On hospital day 4, the patient continues to appear ill. Temperature is 38.6 °C (101.5 °F), blood pressure is 105/65 mm Hg, and pulse rate is 110/min. On cardiopulmonary examination, the lungs are clear, and a grade 2/6 systolic ejection murmur is heard at the right upper sternal border, but there is no evidence of heart failure or septic emboli.

Which of the following is the most appropriate management?

A: Discontinue vancomycin and begin daptomycin
B: Discontinue vancomycin and begin linezolid
C: Discontinue vancomycin and begin trimethoprim-sulfamethoxazole
D: Increase vancomycin dose

MKSAP Answer and Critique

The correct answer is A: Discontinue vancomycin and begin daptomycin. This item is available to MKSAP 16 subscribers as item 10 in the Infectious Disease section.

In this patient, vancomycin should be discontinued and daptomycin should be initiated. The causative pathogen is a vancomycin-intermediate Staphylococcus aureus (VISA), which has a minimal inhibitory concentration (MIC) of 4 micrograms/mL to vancomycin. Although vancomycin is a reasonable initial choice for empiric therapy for treating a possible methicillin-resistant S. aureus (MRSA) bloodstream infection, daptomycin is recommended as an alternative to vancomycin for treatment of bloodstream infection caused by vancomycin-intermediate S. aureus, particularly in patients treated with vancomycin who do not appear to be responding to treatment. Daptomycin is a bactericidal agent, which has been studied extensively for treatment of bloodstream infections due to S. aureus, including MRSA. Daptomycin retains activity against many strains of S. aureus with elevated MICs to vancomycin (≥2 micrograms/mL).

Linezolid has activity against S. aureus but is not indicated for the treatment of bloodstream infection.

Recently, trimethoprim-sulfamethoxazole has been used more frequently for treatment of MRSA skin infection, but it is not recommended as a primary agent for the treatment of bloodstream infection.

Because of the intermediate sensitivity of the identified organism to vancomycin, optimal pharmacodynamic targets may not be possible by increasing the vancomycin dose. To avoid treatment-related toxicity, the use of an alternative agent is preferred versus increasing the vancomycin dose.

Key Point

  • Daptomycin is recommended for treatment of bloodstream infections caused by methicillin-resistant Staphylococcus aureus when the minimal inhibitory concentration to vancomycin is more than 2 micrograms/mL.

This content is excerpted from MKSAP 16 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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