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Role of newer azoles in surgical patients
1Department of Medicine, The University of Texas Health Science Center at San Antonio, 78229-3900, USA. patterson@uthscsa.edu
Abstract:
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.
Insights
Fungal infections are a growing threat in critically ill surgical patients, necessitating new antifungal treatments. This review discusses optimizing current azole antifungals and emerging agents to combat evolving fungal pathogens.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Pharmacology
Background:
- Invasive fungal infections pose significant morbidity and mortality risks in critically ill surgical patients.
- The epidemiology of fungal infections is shifting, with non-albicans Candida species and molds becoming more prevalent, especially in immunosuppressed individuals.
- This changing landscape necessitates an expanded range of antifungal therapies.
Purpose of the Study:
- To review current strategies for optimizing the use of available azole antifungal agents.
- To discuss the potential of new azole antifungals with expanded activity spectra.
- To address the evolving challenges in managing invasive fungal infections in surgical intensive care units.
Main Methods:
- Review of existing literature on fungal infections in surgical patients.
- Analysis of current and emerging azole antifungal drug classes and their spectra of activity.
- Discussion of treatment strategies, including dose optimization and presumptive therapy.
Main Results:
- Higher doses of fluconazole can be effective against yeasts with dose-dependent susceptibility.
- Presumptive fluconazole therapy may be warranted in specific intensive care unit (ICU) patient populations.
- Newer azoles like voriconazole, posaconazole, and ravuconazole show promise against resistant fungi and molds.
Conclusions:
- Optimizing the use of existing azoles and developing new agents are crucial for managing invasive fungal infections.
- The evolving epidemiology of fungal infections requires a proactive and adaptable therapeutic approach.
- Further research and clinical development of novel antifungal agents are essential to combat resistant fungal pathogens.