Acute disseminated candidiasis is often rapidly fatal if not treated appropriately. As discussed earlier, the major clinical problem is knowing when to begin antifungal therapy before establishment of an invasive infection. Patients with a blood culture yielding Candida must receive antifungal therapy.117
Amphotericin B 0.7 mg/kg/day, usually given alone and occasionally in combination with flucytosine, is considered the standard therapy, particularly for clinically unstable patients. 104,117-119 Up to 70% of patients, including those infected with C krusei and C glabrata, will respond favorably.
Lipid formulations of AmB, dosed at 3 to 5 mg/kg/day, are used frequently in this population, who are likely to develop nephrotoxicity. However, few clinical trials have compared efficacy for treatment of candidiasis in neutropenic and HSCT patients. The majority of reports are from compassionate use of the lipid formulations in patients intolerant of or refractory to conventional AmB. 109,120-125 One prospective, randomized, double-blind comparative trial126 reported similar response rates among 231 patients with invasive candidiasis who were randomized to receive amphotericin B lipid complex 5 mg/kg/day or AmB 0.6 to 1.0 mg/kg/day.
Patients with an invasive infection caused by a susceptible C albicans isolate can be treated with fluconazole. Fluconazole therapy for candidiasis has been found to be equivalent to AmB in non-neutropenic patients. 119 Fluconazole may be considered in patients with susceptible isolates and in those not receiving prophylaxis. Patients with persistent neutropenia, signs of sepsis, or recurrent candidemia should receive a formulation of AmB. Caspofungin, an echinocandin antifungal, is approved for treating candidemia and invasive candidiasis. Caspofungin was shown to be as effective as AmB in a randomized, double-blind trial that included mostly non-neutropenic patients. There are no studies reported to date on the HSCT population.127
A majority of studies clearly indicate that removing central venous catheters is important to clear fungemia and to decrease the complications of candidiasis.128,129
Current practice in cases of candidemia is to continue therapy for at least 2 weeks after the last negative blood culture and until granulocytopenia and fever have resolved. Therapy until all signs and symptoms of the infection have been eradicated is required for patients with extensive visceral involvement. Follow-up treatment with oral fluconazole provides the opportunity to manage these cases on an outpatient basis.118,130
Although it is common for patients with a history of candidiasis to have recurrent episodes during subsequent neutropenia, it is safe to perform myeloablative therapy. 131 In this setting, one should treat prophylactically with an antifungal agent until the immunocompromising condition is resolved.
Course Number: V035D
This CME Expires on July 1, 2005; no tests will be accepted after this date.
This course is accredited by
The University of Pittsburgh School of Medicine, Center for Continuing Education
and The International Immunocompromised Host Society