Fever in a 40-Year-Old Intravenous Drug User

John L. Brusch, MD

Disclosures

January 12, 2015

The accepted therapy for candidal IE is a lipid formulation of amphotericin B (3-5 mg/kg daily intravenously). Flucytosine (100 mg/kg/day in 4 divided doses) is synergistic with amphotericin. Serum flucytosine levels should be followed because of potential bone marrow toxicity associated with high levels of the drug. Frequent monitoring of renal function tests to detect amphotericin-associated renal failure that could lead to toxic levels of flucytosine is recommended.

The use of amphotericin alone should be discouraged because the fibrin meshwork of the vegetation protects Candida species from the fungicidal action of this drug. These recommendations pertain specifically to IE caused by C albicans, C tropicalis, or C parapsilosis. C krusei and Candida glabrata are uncommon causes of candidal valvular infection but may be resistant to amphotericin. Some may be resistant to fluconazole.

A major therapeutic challenge is the unreliability or unavailability of sensitivity testing for antifungal therapy. Some evidence suggests that the use of caspofungin, an echinocandin that is fungicidal, can be curative. The difficulty is the shortcomings antifungal sensitivity testing.

Currently, for most circumstances, removal of the infected native valve or prosthetic valve as well as drainage of any associated abscesses is preferred. No rationale supports extensive antifungal pretreatment before surgery. Postoperatively, the antifungal should be continued for at least 6 weeks, especially if intracardiac complications, such as paravalvular abscess, are noted. If the patient's clinical response is good and the bloodstream is cleared of organisms, then changing the regimen to fluconazole alone can be considered.

In addition, all intravascular lines should be removed at the beginning of therapy as potential sources of the underlying candidemia. A search for metastatic candidal infection, such as brain abscess or vertebral osteomyelitis, should be performed. The mortality rate of candidal prosthetic valve endocarditis and native valve IE has currently decreased to approximately 30%.

Likewise, in patients who cannot undergo valvular resection, lifetime suppression with fluconazole should follow the initial treatment with amphotericin. Flucytosine could be used in this role if the isolate to be suppressed is resistant to fluconazole. Such long-term suppression is also used when intracardiac spread of infection is such that risk of relapse is high despite valve resection.

A major unanswered question is how to deal with transient candidemia in the setting of a prosthetic valve, which has a 25% chance of being infected. Parenteral antifungal agents may be considered until the bloodstream is cleared.[4]

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