Improved Prophylaxis and Treatment of Fungal Infections
Although drugs from different pharmacological classes (polyenes, echinocandins and azoles) are available to treat post-transplant fungal infections, the best outcomes are achieved when preventive measures are successful.
Preventing fungal infections
Strategies to reduce the risk of invasive fungal infections (IFIs) include using HEPA filters, laminar flow isolation, reverse isolation, special diets and gut sterilization. [1,2] Despite efforts to keep transplant patients from contacting common fungi, the overall incidence of post-transplant IFIs remains between 8% and 15%. [3]
Other preventive strategies include:
Tapering corticosteroids, which are risk factors for developing IFIs, as soon as possible
Using non-myeloablative regimens, which reduce tissue injury/susceptibility to IFIs
Use of post-transplant G-CSF to accelerate neutrophil recovery
Prophylactic use of fluconazole to prevent Candida albicans invasion [4]
Treating fungal infections
Aspergillus and Candida species are the two most common fungi to infect transplant patients. Periods of greatest susceptibility vary depending upon the post-transplant stage:
Pre-engraftment, 0-30 days post-transplant: Aspergillus, Candida species
Post-engraftment, 30-100 days post-transplant: Aspergillus, Candida species
Late phase, >100 days post-transplant: Aspergillus species
Numerous drugs are available to treat post-transplant infections of Aspergillus, Candida and other fungal species. Table 1 lists the most common drugs used to treat fungal infections.
Fungal species
Drug(s)
Candida
Fluconazole Amphotericin B and lipid formulations Caspofungin Voriconazole Itraconazole Anidulofungin Posaconazole
Aspergillus
Voriconazole Amphotericin B Itraconazole
Table 1. Drugs available to treat fungal infections. [4,5]
Some more resistant fungi including Fusarium and Zygomycetes may develop and are often insensitive to the more commonly used anti-fungals, although a 2006 study of posaconazole found that it can be effective against Zygomycetes infections. [6]
Outcomes are best for patients who are diagnosed quickly, treated as soon as possible and given the maximum tolerated doses. Combination anti-fungal therapies can also be administered, but to date there have been no randomized, comparative clinical trials to determine whether combination therapy is superior to single-agent therapy. [7]
Diagnostic blood and tissue assays to detect IFIs are available, but clinical studies indicate that initiating drug therapy at the first sign of infection — such as febrile neutropenia — improves outcomes. [3]
References
Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: Recommendations of Centers for Disease Control, the Infectious Disease Society of America, and the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2000; 6(6) Suppl:659-713. http://www2.us.elsevierhealth.com/inst/serve?action=searchDB&searchDBfor=iss&id=jbbmt000066b
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