Antifungal Prophylaxis in Immunocompromised Hosts

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Abstract
To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.