TY - JOUR
T1 - CAF to the Rescue! Potential and Challenges of Combination Antifungal Therapy for Reducing Morbidity and Mortality in Hospitalized Patients With Serious Fungal Infections
AU - Jacobs, Samantha E.
AU - Chaturvedi, Vishnu
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2024/11/1
Y1 - 2024/11/1
N2 - The global burden of invasive fungal disease is substantial and escalating. Combination antifungal therapy (CAF) may improve patient outcomes by reducing development of resistance, improving drug penetration and rate of fungal clearance, and allowing for lower and less toxic antifungal drug doses; yet, increased cost, antagonism, drug-drug interactions, and toxicity are concerns. Clinical practice guidelines recommend antifungal monotherapy, rather than CAF, for most invasive fungal diseases due to a lack of comparative randomized clinical trials. An examination of the existing body of CAF research should frame new hypotheses and determine priorities for future CAF clinical trials. We performed a systematic review of CAF clinical studies for invasive candidiasis, cryptococcosis, invasive aspergillosis, and mucormycosis. Additionally, we summarized findings from animal models of CAF and assessed laboratory methods available to evaluate CAF efficacy. Future CAF trials should be prioritized according to animal models showing improved survival and observational clinical data supporting efficacy and safety.
AB - The global burden of invasive fungal disease is substantial and escalating. Combination antifungal therapy (CAF) may improve patient outcomes by reducing development of resistance, improving drug penetration and rate of fungal clearance, and allowing for lower and less toxic antifungal drug doses; yet, increased cost, antagonism, drug-drug interactions, and toxicity are concerns. Clinical practice guidelines recommend antifungal monotherapy, rather than CAF, for most invasive fungal diseases due to a lack of comparative randomized clinical trials. An examination of the existing body of CAF research should frame new hypotheses and determine priorities for future CAF clinical trials. We performed a systematic review of CAF clinical studies for invasive candidiasis, cryptococcosis, invasive aspergillosis, and mucormycosis. Additionally, we summarized findings from animal models of CAF and assessed laboratory methods available to evaluate CAF efficacy. Future CAF trials should be prioritized according to animal models showing improved survival and observational clinical data supporting efficacy and safety.
KW - aspergillosis
KW - combination antifungal therapy
KW - cryptococcosis
KW - invasive candidiasis
KW - mucormycosis
UR - http://www.scopus.com/inward/record.url?scp=85210031058&partnerID=8YFLogxK
U2 - 10.1093/ofid/ofae646
DO - 10.1093/ofid/ofae646
M3 - Review article
AN - SCOPUS:85210031058
SN - 2328-8957
VL - 11
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 11
M1 - ofae646
ER -