Table 2. AFS metrics included in the Delphi method-based questionnaire survey.

Number	AFS metrics	Agreement rate (%)
1. Right patient (n=4)
1.1	For patients with suspected IFD, imaging, etiology, serology (such as G test, GM test, candida antigen, cryptococcus capsular polysaccharide antigen, etc.) and histopathological examinations should be completed to confirm the etiological diagnosis. If conditions permit, it is recommended to use PCR, mNGS/tNGS, nanopore sequencing and other tools to detect fungal nucleic acids to improve the diagnostic rate	91.46
1.2	When IFD patients receive empirical treatment, imaging, etiology, serology (such as G test, GM test, candida antigen, cryptococcus capsular polysaccharide antigen, etc.) examinations should be performed, combined with clinical response monitoring to comprehensively evaluate treatment efficacy, and the antifungal treatment plan should be adjusted accordingly	92.68
1.3	Low-riska and medium-riskb IFD patients with failed treatment with broad-spectrum antibiotics for 3–5 days showing persistent fever and other clinical symptoms, imaging, etiology, serology (such as G test, GM test, candida antigen, cryptococcus capsule polysaccharide antigen, etc.) and histopathological examinations should be performed as soon as possible. Meanwhile, low-risk and medium-risk IFD patients should undergo diagnosis and treatmentd	92.68
1.4	Compared with empirical therapy, diagnostic-driven therapy based on imaging and laboratory findings can improve the accuracy of IFD diagnosis, reduce the irrational use of antifungal drugs, and save medical resources	91.46
2. Right time (n=3)
2.1	Prophylactic antifungal therapy can significantly benefit high-risk patients with IFDc and is recommended for high-risk patients	75.61
2.2	There is no significant benefit from prophylactic antifungal therapy in low-risk patients with IFD, and prophylactic antifungal therapy is not recommended until definitive etiological evidence is obtained	90.24
2.3	Invasive mucormycosis is a rare fungal infection, and routine prophylactic antifungal therapy is not recommended	85.37
3. Right use (n=17)
3.1 Drug choice (n=8)
3.1.1	Antifungal therapy requires appropriate indications	97.56
3.1.2	The selection of antifungal drugs can refer to the antimicrobial spectra of the antifungal drugs	97.56
3.1.3	The selection of antifungal agents should follow evidence-based medicine guidelines	97.56
3.1.4	Breakthrough IFDe has poor prognosis, and well-tolerated, broad-spectrum, potent drugs are recommended for antifungal treatment	97.56
3.1.5	At the time of IFD treatment, the primary disease should be actively treated. To ensure the efficacy of antifungal therapy, antifungal drugs with less interactions with the drugs used to treat the primary disease should be selected	97.56
3.1.6	When multiple drugs are used concurrently, attention should be paid to the interactions of antifungal drugs with other drugs, and TDM should be performed if necessary	85.37
3.1.7	In case of intolerance to antifungal drugs or drug-related adverse reactions in IFD treatment, it is recommended to switch to antifungal drugs with enhanced safety and tolerance	100.00
3.1.8	According to the guidelines/consensus, restricted grade antifungals should be used only after discussion with the appropriate management team	87.80
3.2 Drug dosage (n=4)
3.2.1	Prophylactic antifungal therapy with triazoles in high-risk IFD patientsc should be performed with effective blood concentrations to ensure treatment effect, and TDM should be performed if necessary to avoid breakthrough IFDe	92.68
3.2.2	In IFD patients with liver and/or renal impairment, liver/renal function should be evaluated according to Child-Pugh grading criteria and/or endogenous creatinine clearance levels, and antifungal drugs and dosages should be reasonably selected on the basis of both efficacy and safety to avoid aggravating liver/renal function injury	97.56
3.2.3	According to the PK/PD characteristics of antifungal drugs, appropriate loading and maintenance doses are selected	100.00
3.2.4	If conditions permit, it is recommended to optimize the dosage of triazole antifungal drugs guided by TDM	100.00
3.3 Drug de-escalation (n=1)
3.3.1	De-escalation from broad-spectrum to narrow-spectrum antifungal drugs based on drug susceptibility data and/or clinical treatment response and efficacy	92.68
3.4 Drug duration (n=2)
3.4.1	According to IFD host immune status, infection pathogen site, type, drug susceptibility test, clinical type, disease severity and treatment response, individual treatment is given to ensure adequate treatment	97.56
3.4.2	In the course of IFD treatment, imaging, serology (such as G test, GM test, candida antigen, cryptococcus capsular polysaccharide antigen, etc.) and fungal drug resistance examinations should be performed regularly to comprehensively evaluate antifungal efficacy, determine disease outcome, and adjust the treatment duration appropriately	97.56
3.5 Drug consumption (n=2)
3.5.1	DDDf	73.17
3.5.2	LOTg	87.80

^a, low-risk group for IFD: other lymphoproliferative tumors (e.g., standard chemotherapy for lymphoma, induction therapy for myeloma, primary treatment for chronic lymphocytic leukemia), other myeloproliferative tumors, or solid tumors undergoing treatment (22). ^b, intermediate-risk group for IFD: autologous hematopoietic stem cell transplantation cases (e.g., patients at high risk for mucositis); allogeneic hematopoietic stem cell transplantation with expected neutropenia <14 days; lymphoma (e.g., receiving intensive or dose-escalation therapy) (22). ^c, high-risk for IFD: neutrophils <0.1×10⁹/L lasting >3 weeks or <0.5×10⁹/L lasting >5 weeks (e.g., allogeneic hematopoietic stem cell transplantation); glucocorticoids >1 mg/kg equivalent of prednisolone and neutrophils <1×10⁹/L for >1 week; glucocorticoid >2 mg/kg prednisolone equivalent for >2 weeks; unrelated, mismatched, or cord blood allogeneic hematopoietic stem cell transplantation; widespread or severe graft-versus-host disease; acute myeloid leukemia undergoing induction or reinduction therapy; acute lymphoblastic leukemia undergoing induction or reinduction therapy; myelodysplastic syndrome (22); ^d, diagnostic-driven therapy refers to patients with no clinical symptoms of infection or persistent neutrophil-deficiency related fever in response to broad-spectrum antimicrobial therapy. Combination of clinical imaging (e.g., imaging changes associated with aspergillus infection on chest CT) and microbiological markers (e.g., positive G test, positive GM test, positive fungal culture or microscopic examination of specimens obtained from non-sterile sites or non-sterile procedures) of IFD does not meet the antifungal therapy required for the diagnosis or clinical diagnosis of IFD; ^e, definition of breakthrough IFD: any IFD occurring during antifungal exposure, including fungi not covered by the antifungal spectrum, in patients administered prophylactic therapy, empire-based therapy, diagnostic-driven therapy, and target therapy (23). ^f, DDD, i.e., average daily dose of a particular drug used to treat the main indication in adults, as determined by the WHO Collaborating Centre for Pharmaceutical Statistical Methods based on the recommended dose of drugs commonly used in different countries, and constantly revised by an international panel of experts (24,25); ^g, LOT, which refers to the duration of antifungal therapy, can be expressed as the median number of treatment days or the average treatment duration for a specific indication (26). AFS, antifungal stewardship; IFD, invasive fungal disease; G, (1,3) β-d glucan; GM, galactomannan; PCR, polymerase chain reaction; mNGS, metagenomic next-generation sequencing; tNGS, targeted next-generation sequencing; TDM, therapeutic drug monitoring; PK/PD, pharmacokinetics/pharmacodynamics; DDD, defined daily dose; LOT, length of therapy; CT, computed tomography; WHO, World Health Organization.