John R. Perfect, MD

The emergence of resistance and changes in the spectrum ofCandida infections have led to an increased interest in susceptibilitytesting of antifungal drugs. Such testing may be particularly useful inpatients with invasive candidiasis who have been previously treated withazole antifungals, those whose infections are not responding to treatment,and those with infections caused by non-albicans species of Candida.The choice of a specific antifungal depends on the clinical statusof the patient, the relative toxicity and efficacy of the drug in the givenpatient population, the infecting species and antifungal susceptibilityof the isolate, and the patient’s prior exposure to antifungal agents.Infectious Diseases Society of America recommendations for the initialmanagement of candidemia and acute disseminated candidiasisinclude an azole, caspofungin, amphotericin B (AmB), or a combinationof fluconazole plus AmB. Caspofungin and voriconazole show goodactivity against most Candida species and may be good alternatives forpatients with Candida glabrata and Candida krusei infections and forthose with relapsing infections.

Considering the significant morbidity and mortality associated withinvasive fungal infections in immunocompromised patients, it is particularlyimportant to make the diagnosis as early as possible and tomake best use of the available antifungal drugs for prophylaxis andtreatment. The newer antifungal drugs include the lipid products ofamphotericin B, such as amphotericin B lipid complex (ABLC) andliposomal amphotericin B; voriconazole (a triazole); and caspofungin(an echinocandin). ABLC and liposomal amphotericin B are as effectiveas amphotericin B deoxycholate but are less nephrotoxic; ABLC isprobably the drug of choice for zygomycosis. Voriconazole is approvedfor use in the treatment of invasive aspergillosis and may have a role inpreventing breakthrough fungal infections in patients with persistentfever and neutropenia. Caspofungin is effective against both invasiveaspergillosis and invasive candidiasis.

Candidiasis and aspergillosis are the most common fungal infectionsin hematopoietic stem cell transplant recipients and other hematology/oncology patients. Strategies for reducing the morbidity and mortalityassociated with these infections include antifungal prophylaxis,empiric therapy in patients with persistent fever and neutropenia, andpreemptive therapy. Antifungal therapies include amphotericin B deoxycholate,lipid formulations of amphotericin B, the triazoles (fluconazole,itraconazole, and voriconazole), and the echinocandins (caspofunginand the investigational agents micafungin and anidulafungin).Fluconazole is a reasonable choice for the treatment of invasive candidiasisif the patient has not previously received a triazole and theinstitution has a low incidence of triazole resistance. If resistance is aconcern, an echinocandin, such as caspofungin, is an appropriate option.Voriconazole may be the initial choice in most patients with invasiveaspergillosis. If patients are intolerant of or refractory to conventionaltherapy, effective alternatives include a lipid formulation of amphotericinB or an echinocandin.