Candidemia, a bloodstream infection caused by Candida species, remains a major clinical challenge in hospitals worldwide. The infection is associated with high mortality, prolonged hospitalization, and substantial healthcare costs. Although antifungal therapies and diagnostic technologies have advanced, delayed diagnosis, changing Candida species distributions, antifungal resistance, and treatment complexity continue to limit clinical outcomes.
A comprehensive review published in iFungi on July 2, 2026, provides a thorough analysis of these challenges. Led by Wenqiang Chang from Shandong University, along with a team of researchers from multiple institutions across China. The authors emphasize that progress in candidemia management will require closer integration of rapid diagnosis, susceptibility-guided treatment, antimicrobial stewardship, and development of new therapeutic approaches.
"The epidemiology of candidemia is shifting dramatically," said Wenqiang Chang, corresponding author of the review. "While Candida albicans has historically been the most common causative agent, non-albicans species now account for over half of cases worldwide. Species such as Candida glabrata , Candida parapsilosis , and the emerging multidrug-resistant Candida auris present unique therapeutic challenges due to their distinct resistance profiles." The review highlights that these differences make species identification and local epidemiological information increasingly important for treatment decisions
One of the most important challenges is the delay between infection and diagnosis. Blood culture remains the diagnostic gold standard, but it can require substantial time and has limited sensitivity, particularly in patients who have already received antifungal treatment. Newer approaches, including molecular assays, metagenomic sequencing, CRISPR-based detection, alternative biomarkers, imaging technologies, and machine-learning approaches, may provide faster or complementary information. However, the authors caution that no single technology currently provides a complete solution. They therefore highlight multimodal diagnosis, in which culture, serological testing, and molecular methods serve complementary roles, as an important direction for clinical practice.
Treatment presents another major challenge. For critically ill patients with suspected candidemia, timely empirical antifungal therapy is important, while subsequent treatment should be adjusted according to Candida species and antifungal susceptibility. The review also draws attention to antifungal tolerance, biofilm-associated persistence, and multidrug resistance, which can contribute to incomplete fungal clearance and recurrence. "Antifungal resistance is no longer a niche concern—it is a global health threat," said Wenqiang Chang. " Candida auris , for instance, exhibits fluconazole resistance rates of 70% to 90%, and resistance to echinocandins and amphotericin B is also emerging. We need robust antifungal stewardship programs and susceptibility-guided therapy to combat this trend."
Combination therapy may offer another option for selected difficult infections. Although monotherapy remains the standard approach for candidemia, the review identifies potential roles for combination regimens in refractory infections, multidrug-resistant Candida infections, and cases that do not respond adequately to single-agent therapy. The authors stress that such strategies require careful evaluation of efficacy, toxicity, and clinical context rather than routine application
The review also highlights a growing pipeline of antifungal candidates with mechanisms distinct from established therapies. These include next-generation echinocandins such as rezafungin, Gwt1 inhibitors such as fosmanogepix, next-generation azoles, and agents directed at novel fungal targets. The authors note that new targets with limited cross-resistance to existing drugs could become particularly important as multidrug-resistant Candida continues to challenge current treatment options
Looking to the future, the review explores the application of artificial intelligence in predictive diagnostics, vaccine-based prophylaxis such as the NDV-3A vaccine candidate, nutritional immunomodulation, and synergistic treatment strategies combining natural compounds with conventional antifungals. "The future of candidemia management lies in an integrated precision-medicine framework," Chang said. "By combining AI-driven risk stratification, targeted prophylaxis, and personalized therapeutic approaches, we can move toward earlier diagnosis and more effective treatment." Achieving this goal will require interdisciplinary collaboration and rigorous clinical validation to translate emerging technologies and therapeutic strategies into effective clinical practice.
This review systematically examines key bottlenecks in the early diagnosis of candidemia, detection of antifungal resistance, and treatment decision-making, synthesizes evidence across studies, and proposes an integrated management framework linking risk stratification, rapid diagnosis, and precision treatment, providing a clear roadmap for addressing this infection associated with high mortality. By connecting emerging scientific questions with urgent clinical needs, it offers valuable guidance for researchers pursuing innovation and clinical translation and for clinicians optimizing diagnostic and treatment decisions, with important implications for combating drug-resistant fungal infections and improving patient outcomes.
Other contributors include Haojie Dong, Minghui Song, Jingfang Sun, Xiaoyi Luan, Ming Zhang, Yeji Wang, Yuemei Dong, and Lintao Sai from Shandong University, Xuzhou Medical University, and affiliated hospitals.
This work was supported by the National Natural Science Foundation of China (No. 82273975).
D OI Link:
https://doi.org/10.26599/iFungi.2026.9670005
About the Authors
Dr. Wenqiang Chang is a Professor and Doctoral Supervisor at Shandong University. He is a recipient of the National High-level Young Talent program, a Distinguished Mid-young Scholar (First Level) of Shandong University, and a recipient of the Shandong Provincial Outstanding Youth Science Fund. His research primarily focuses on the discovery of antifungal agents. As principal investigator, he has led more than 10 projects, including Programs of the National Natural Science Foundation of China, as well as the Shandong Provincial Outstanding Youth Science Foundation. He has also participated in 9 additional research initiatives, such as the Major New Drug Development Program of the Ministry of Science and Technology and key projects of the National Natural Science Foundation. Dr. Chang has published over 40 academic papers as (co-)first or corresponding author in international journals including Science Advances , Nature Communications , and Cell Chemical Biology . He has filed or been granted 8 patents and has received the Second Prize of the Natural Science Award from the Ministry of Education and the Second Prize of the Shandong Provincial Natural Science Award. He serves as a committee member of the Chemotherapy Pharmacology Committee of the Chinese Pharmacological Society and the Mycology Committee of the World Chinese Physicians Association, and is an Editorial Board Member of the journal The Cell Surface . For more information, please pay attention to his research homepage https://www.pharm.sdu.edu.cn/info/1345/20490.htm
iFungi
Comprehensive Review on Candidemia: Epidemiology, Diagnosis, Treatment, and Future Directions
30-Jun-2026