Invasive Candidiasis in 2026: Harmonizing Global and US Guidance in an Era of Diagnostic and Stewardship Complexity

Contemporary management of invasive candidiasis (IC) continues to evolve as new diagnostics, antifungal agents, and stewardship priorities reshape the landscape across intensive care, surgical, and infectious diseases practice. Synthesizing guidance from the 2025 multidisciplinary review, the 2024 American Thoracic Society guideline, the 2016 Infectious Diseases Society of America recommendations, and the 2025 ECMM/ISHAM/ASM global guideline, this article highlights the most substantive developments in diagnostic strategy, empiric therapy, treatment selection, and ophthalmologic evaluation. These shifts reflect a broader move toward diagnostic precision, restrained empiric therapy, and globally harmonized stewardship practices, reinforced by influential analyses such as the 2021 Clinical Infectious Diseases β-D-glucan review and the 2023 New England Journal of Medicine ophthalmology overview.¹

Diagnostic Strategy: A More Nuanced and Context-Driven Framework

Blood cultures remain the cornerstone of invasive candidiasis diagnosis, yet all contemporary reviews reaffirm their limitations—most notably their modest sensitivity of approximately 40–50% and their inherently delayed positivity. As a result, non-culture diagnostics have taken on a larger, though still carefully circumscribed, role in the diagnostic algorithm. Current U.S. guidance recommends integrating assays such as β-D-glucan (BDG), T2Candida, and PCR selectively in high-risk ICU patients, emphasizing that these modalities must complement, rather than replace, traditional culture-based approaches.^2-6

BDG testing, in particular, has undergone substantial re-evaluation. The 2021 Clinical Infectious Diseases review underscored that BDG serves best as an adjunctive tool whose utility depends heavily on clinical context and pretest probability. Newer guidelines build on this perspective: higher diagnostic thresholds (generally above 80 pg/mL) and serial sampling are now favored to improve specificity, while clinicians are advised to interpret both false positives (e.g., hemodialysis exposure, β-lactam antibiotics, cellulose-containing infusions) and false negatives within the broader clinical framework. Molecular tools such as T2Candida support earlier detection and more rapid initiation of therapy, but their limited positive predictive value and high cost have prevented widespread adoption. Their use is now largely restricted to persistently high-suspicion cases in which cultures remain negative despite clinical deterioration.

In contrast, the 2025 ECMM/ISHAM/ASM global guideline maintains a more conservative posture, reiterating that conventional culture and microscopy remain the primary diagnostic modalities worldwide. In many settings—especially where assay reliability and pretest probability vary significantly—biomarker and molecular testing are recommended only in specific, validated clinical circumstances.

Empiric and Prophylactic Therapy: A Marked Contraction Across Guidelines

One of the most notable shifts across recent publications is the narrowing of indications for empiric antifungal therapy. Whereas the 2016 IDSA guideline permitted a relatively broad application of empiric antifungals in ICU patients with unexplained fever and classic risk factors, the 2024 ATS guideline and the 2025 multidisciplinary review now limit empiric or prophylactic antifungal use almost exclusively to select high-risk groups. These include patients with severe necrotizing pancreatitis, recurrent gastrointestinal perforation, hemodynamic instability with additional risk factors, or high-risk intra-abdominal catastrophes.

Routine empiric antifungal therapy in nonneutropenic, nontransplant critically ill patients is no longer supported by current evidence. The European consensus parallels this reduction, recommending empiric treatment primarily for patients with septic shock, clinical deterioration without another explanation, or a high burden of risk factors such as prolonged ICU stay, multiple indwelling catheters, or heavy Candida colonization.

Therapeutic Selection and Stewardship: Echinocandins at the Center of Care

Across all modern guidelines, echinocandins continue to represent the cornerstone of invasive candidiasis treatment thanks to their potent fungicidal activity, safety profile, and efficacy against most clinically relevant species. This includes the newer once-weekly echinocandin rezafungin, whose pharmacokinetic properties add flexibility in certain clinical scenarios. Liposomal amphotericin B remains the agent of choice when echinocandin resistance or intolerance is a concern, as well as for select species with intrinsic resistance patterns. Step-down therapy with fluconazole or voriconazole is increasingly reserved for situations in which clinical stability has been achieved, organism susceptibility has been confirmed, and source control has been adequately addressed.

All guideline bodies highlight the central importance of antifungal stewardship. The emphasis is on minimizing unnecessary exposure to broad-spectrum antifungals, using diagnostics judiciously, and coordinating care across ID, critical care, pharmacy, and surgical teams. This reflects a growing awareness of rising antifungal resistance—particularly involving FKS mutations—as well as the significant financial and ecological costs associated with overuse.

Ophthalmology and Ocular Candidiasis: Clarifying When and How to Screen

Ocular involvement—including chorioretinitis and endophthalmitis—occurs in a minority of candidemia cases, generally between 1% and 9%, and many patients remain asymptomatic. Nevertheless, infectious diseases guidelines continue to recommend ophthalmologic evaluation for all candidemic patients. The nuance lies in the timing and target population for screening. While the IDSA and global guidelines endorse comprehensive screening particularly for symptomatic individuals or those at elevated risk, the American Academy of Ophthalmology advocates a more symptom-based approach, endorsing routine fundoscopy primarily for symptomatic or outpatient-acquired candidemia while allowing for deferred evaluation of asymptomatic inpatients.¹

Treatment considerations for ocular involvement also continue to evolve. Because echinocandins have poor intraocular penetration, they are not recommended for ocular candidiasis. Instead, fluconazole or voriconazole are preferred when isolates are susceptible, while liposomal amphotericin B plays a central role in cases of resistance or intolerance. Severe manifestations such as endophthalmitis may require intravitreal antifungal therapy or even vitrectomy. Systemic therapy is typically continued for four to six weeks in the presence of symptomatic chorioretinitis or endophthalmitis, while shorter durations may be sufficient when disease is isolated, asymptomatic, and spares the macula. ¹

Evidence Base and Influential Publications Shaping Contemporary Practice

Several key publications have shaped the current consensus. The 2021 BDG review brought long-needed clarity to the strengths and limitations of non-culture diagnostics and emphasized their adjunctive use. The 2025 ECMM/ISHAM/ASM guideline provided a global standard for diagnostic priorities, first-line antifungal selections, and stewardship considerations, while the 2024 ATS guideline and 2025 multidisciplinary review sharpened the focus on restricted empiric therapy, integrated diagnostic pathways, and ICU-specific considerations. The 2023 NEJM review on ocular fungal infections helped standardize expectations regarding ophthalmologic involvement and antifungal penetration into ocular structures.

Translating Guideline Changes Into Clinical Practice

Clinicians caring for patients with suspected or confirmed invasive candidiasis should adopt a more deliberate, context-driven approach to diagnostics, incorporating non-culture modalities selectively and always in conjunction with clinical assessment. Empiric antifungal therapy should be reserved for clearly defined high-risk populations rather than applied broadly across the ICU. Echinocandins should remain the first-line agents for initial therapy, with transitions to oral azoles occurring only when isolates are proven susceptible and patients demonstrate clinical stability. Ophthalmologic evaluation should be performed for all candidemia patients, though the urgency and setting may vary based on symptoms and whether infection was acquired in or out of the hospital. Finally, antifungal stewardship principles should be integrated into all phases of care to mitigate resistance and improve clinical precision.

Conclusion

The management of invasive candidiasis in 2025 reflects a broader global convergence toward diagnostic precision, minimized empiric antifungal exposure, echinocandin-centered therapy, and a more risk-based approach to ophthalmologic evaluation. These updates underscore the importance of multidisciplinary collaboration and stewardship, positioning clinicians to better navigate the complexities of fungal diagnostics and treatment in critical care and beyond. As evidence continues to evolve, local adaptation of these best practices—guided by the full recommendations of the referenced guidelines—will remain essential.

References

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