Role of newer azoles in surgical patients

Fungal infection has become an important cause of morbidity and mortality in critically ill surgical patients. Surgical patients at highest risk for invasive mycoses include those undergoing extensive abdominal surgery, those with underlying malignancy or other immunosuppressive conditions, and patients undergoing transplantation. Nosocomial candidemia remains a major complication for patients in surgical intensive units; however, the epidemiology of invasive fungal infection continues to change with molds and yeasts other than Candida albicans emerging as important causes of infection especially in immunosuppressed patients. This changing epidemiology has resulted in the need for an expanded armamentarium of antifungal therapies. One effective approach has been the utilization of higher doses of well-tolerated azoles, such as fluconazole, particularly against yeasts with dose-dependent susceptibility. Alternatively, the presumptive use of therapeutic doses of fluconazole may be indicated in intensive care unit patients with persistent leukocytosis and fever in whom a source of fever cannot be identified, particularly if the patient is extensively colonized at mucosal sites with yeast. New azoles with an expanded spectrum of activity are in development. These include agents include voriconazole, which has activity against resistant yeasts and molds and is in phase III clinical trials, posaconazole (Sch 56592) and ravuconazole (BMS-207147)-both of which are less advanced in clinical development, but which also offer an expanded spectrum of activity. Other new azoles with expanded activity are still in the early phases of development. In this review, strategies for optimizing use of the clinically available new azoles and the potential for new agents are discussed.