Role of newer azoles in surgical patients

Fungal infection has become an important cause of morbidity and mortality i n critically ill surgical patients. Surgical patients at highest risk for i nvasive mycoses include those undergoing extensive abdominal surgery, those with underlying malignancy or other immunosuppressive conditions, and pati ents undergoing transplantation. Nosocomial candidemia remains a major comp lication for patients in surgical intensive units; however, the epidemiolog y of invasive fungal infection continues to change with molds and yeasts ot her than Candida albicans emerging as important causes of infection especia lly in immunosuppressed patients. This changing epidemiology has resulted i n the need for an expanded armamentarium of antifungal therapies. One effec tive approach has been the utilization of higher doses of well-tolerated az oles, 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 persisten t leukocytosis and fever in whom a source of fever cannot be identified, pa rticularly if the patient is extensively colonized at mucosal sites with ye ast. New azoles with an expanded spectrum of activity are in development. T hese include agents include voriconazole, which has activity against resist ant yeasts and molds and is in phase III clinical trials, posaconazole (Sch 56592) and ravuconazole (BMS-207147)-both of which are less advanced in cl inical development, but which also offer an expanded spectrum of activity. Other new azoles with expanded activity are still in the early phases of de velopment. In this review, strategies for optimizing use of the clinically available new azoles and the potential for new agents are discussed.