Invasive fungal disease (IFD) remains a life-threatening complication in patients with hematological diseases. Isavuconazole was approved by the FDA for primary treatment of invasive aspergillosis and mucormycosis. While clinical trials have demonstrated its efficacy, data on its use in hematology patients remain limited. This study aims to evaluate the real-world effectiveness and safety of isavuconazole in this population. We conducted a single-center, retrospective study of hematology patients who received isavuconazole for IFD between 1 June 2022, and 31 July 2024, at West China Hospital, Sichuan University. A total of 66 patients with proven (n = 9), probable (n = 17), or possible (n = 40) IFD were included in the study. Acute leukemia (AL) was the most common underlying disease, affecting 27 patients (40.9%), followed by non-Hodgkin’s lymphoma (NHL) and myelodysplastic syndrome (MDS). Over 80.0% of patients received oral isavuconazole. At 6 weeks of follow-up, a favorable response was observed in 57.6% of patients, increasing to 71.2% at 12 weeks. Factors associated with achieving complete response in isavuconazole treatment included receiving isavuconazole as primary treatment (OR = 0.10, p = 0.01) and reaching complete/partial remission (CR/PR) of the primary hematological disease (OR = 0.07, p = 0.003). The all-cause mortality rates were under 30.0%. The use of isavuconazole as primary antifungal therapy (p < 0.05) and achieving CR/PR in the underlying hematological disease (p < 0.05) were two independent predictors of improved clinical outcomes. Adverse events were reported in 33.3% of patients, and no adverse events led to discontinuation of treatment. Our study demonstrated that isavuconazole is an effective and well-tolerated treatment for IFD in hematology patients. The oral formulation provided comparable efficacy and enhanced compliance, potentially leading to improved outcomes and optimizing the management strategy. The generalizability of our findings may be limited by the single-center, retrospective nature; further validation through prospective, multi-center studies is needed.

Differentiating invasive pulmonary aspergillosis (IPA) from colonization in patients with Aspergillus -positive blood metagenomic next-generation sequencing (mNGS) remains a clinical challenge. This study aims to evaluate the diagnostic and prognostic value of blood mNGS-derived fungal load (reads per million [RPM]) and two key serological biomarkers (galactomannan [GM] and 1,3-β-D-glucan [BDG]) in distinguishing these two entities. This retrospective study enrolled 95 patients with Aspergillus detected by blood mNGS, stratified into infection ( n = 60) and colonization ( n = 35) groups using modified EORTC/MSGERC criteria. We analyzed clinical characteristics, co-infection spectra, and serological biomarkers (GM and BDG). Diagnostic performance was evaluated via receiver operating characteristic (ROC) analysis, and prognostic factors for 28-day mortality were identified using least absolute shrinkage and selection operator-Cox regression. Distinct co-infection patterns were observed between groups: the infection group was dominated by polymicrobial co-infections, including clinically significant pathogens such as Acinetobacter baumannii , Klebsiella pneumoniae , Mucor spp., and Human cytomegalovirus ; in contrast, the colonization group primarily featured single viral co-infections. While mNGS effectively detected Aspergillus , RPM alone showed limited ability to discriminate infection from colonization, with area under the curves (AUCs) ranging from 0.406 to 0.657 across patient groups. The optimal RPM cutoff varied substantially by immune status, being highest in immunocompetent patients (RPM cutoff: 1.77). Diagnostic performance significantly improved when RPM was integrated with GM (AUC up to 0.900 at a cutoff of 0.36 optical density index) or BDG (AUC up to 0.881 pg/mL), particularly in immunocompetent individuals. RPM also correlated with albumin, hemoglobin, platelet counts, and lymphocyte counts (all P < 0.05). Multivariate analysis identified reversed halo sign (hazard ratio [HR] = 2.143), decreased ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO ₂ /FiO ₂ ; HR = 1.361), and elevated lactate dehydrogenase (HR = 1.055) as independent predictors of 28-day mortality. Blood mNGS demonstrates high sensitivity for detecting Aspergillus but requires integration with serological biomarkers to differentiate IPA from colonization. The RPM can offer prognostic utility. A multimodal strategy is crucial for early diagnosis and improving outcomes in high-risk patients. IMPORTANCE: First large-scale validation of blood mNGS for invasive pulmonary aspergillosis diagnosis—this study represents the first sizable cohort systematically evaluating blood metagenomic next-generation sequencing (mNGS) for distinguishing invasive pulmonary aspergillosis from colonization, addressing a critical gap in non-invasive diagnostic approaches for critically ill patients. Comprehensive Aspergillus co-infection profiling—we identified distinct co-infection patterns, with the infection group showing significantly higher rates of polymicrobial infections, providing crucial insights into co-infection dynamics in Aspergillosis . Optimized diagnostic integration strategy—our findings demonstrate that while mNGS-derived reads per million alone show limited diagnostic value, their integration with serological biomarkers significantly improves performance, establishing a clinically relevant multimodal diagnostic framework. Robust prognostic stratification model—through least absolute shrinkage and selection operator-Cox regression, we established a validated prognostic model identifying reversed halo sign, decreased PaO ₂ /FiO ₂ , and elevated lactate dehydrogenase as independent predictors of 28-day mortality, providing clinically actionable tools for risk stratification.

Purpose: Candidemia remains a life-threatening infection, compounded by diagnostic delays and limited prognostic tools. While metagenomic next-generation sequencing (mNGS) offers rapid pathogen detection, its prognostic utility and therapeutic impact in candidemia remain unestablished. Patients and Methods: This retrospective cohort study analyzed 97 candidemia patients with positive blood mNGS at West China Hospital (2020– 2024). Multivariable logistic regression and survival analyses identified mortality predictors, while therapeutic impacts were assessed through antifungal regimen modifications. Results: The 28-day mortality was 44.3% (43/97). Blood mNGS outperformed cultures in species identification (5 vs 4 species) and co-infection detection. Bacterial co-detections (HR=2.00, 95% CI:1.15– 3.48; p< 0.05) doubled mortality risk. SOFA score was the strongest mortality predictor (adjusted OR=1.29 per point; p< 0.001). mNGS-guided antifungal initiation reduced mortality by 52.4% in treatment-naïve patients (22.6% vs 75.0%; p< 0.05), though regimen adjustments in pretreated cases showed no benefit (p> 0.05). Notably, Candida species exhibited equivalent virulence (log-rank p> 0.05), and mNGS read counts lacked prognostic value (p> 0.05). Conclusion: mNGS transforms candidemia management by enabling early risk stratification (via SOFA scores and co-infection profiles) and precision therapy initiation. Its capacity to unmask high-risk bacterial synergists and guide time-sensitive interventions supports integration into diagnostic algorithms, particularly for culture-negative cases. Further validation of standardized mNGS protocols is warranted to maximize clinical impact.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection. Colonization is prevalent but cannot be reliably distinguished from a