Purpose of reviewThe burden of invasive fungal infection is increasing worldwide, largely due to a growing population at-risk. Most serious human fungal pathogens enter the host via the respiratory tract. Early identification and treatment of invasive fungal respiratory infections (IFRIs) in the immunocompromised host saves lives. However, their accurate diagnosis is a difficult challenge for clinicians and mortality remains high.Recent findingsThis article reviews IFRIs, focussing on host susceptibility factors, clinical presentation, and mycological diagnosis. Several new diagnostic tools are coming of age including molecular diagnostics and point-of-care antigen tests. As diagnosis of IFRI relies heavily on invasive procedures like bronchoalveolar lavage and lung biopsy, several novel noninvasive diagnostic techniques are in development, such as metagenomics, ‘volatilomics’ and advanced imaging technologies.SummaryWhere IFRI cannot be proven, clinicians must employ a ‘weights-of-evidence’ approach to evaluate host factors, clinical and mycological data. Implementation studies are needed to understand how new diagnostic tools can be best applied within clinical pathways. Differentiating invasive infection from colonization and identifying antifungal resistance remain key challenges. As our diagnostic arsenal expands, centralized clinical mycology laboratories and efforts to ensure access to new diagnostics in low-resource settings will become increasingly important.
Objectives To assess the performance of T2Candida for the diagnosis of invasive candidiasis (IC) against gold standards of candidaemia or consensus IC definitions, and to evaluate the impact of T2Candida on antifungal drug prescribing. Methods A retrospective review was undertaken of all T2Candida (T2MR technology, T2 Biosystems) performed from October 2020 to February 2022. T2Candida performance was evaluated against confirmed candidaemia or against proven/probable IC within 48 hours of T2Candida, and its impact on antifungal drug prescriptions. Results T2Candida was performed in 61 patients, with 6 (9.8%) positive results. Diagnostic performance of T2Candida against candidaemia had a specificity of 85.7% and negative predictive value (NPV) of 96.8%. When comparing T2Candida results with consensus definitions of IC, the specificity and NPV of T2Candida was respectively 90% (54/60) and 98.2% (54/55) for proven IC, and 91.4% (53/58) and 96.4% (53/55) for proven/probable IC. Antifungals were initiated in three of six patients (50%) with a positive T2Candida result. Thirty-three patients were receiving empirical antifungals at the time of T2Candida testing, and a negative result prompted cessation of antifungals in 11 (33%) patients, compared with 6 (25%) antifungal prescriptions stopped following negative beta-d-glucan (BDG) testing in a control population (n = 24). Conclusions T2Candida shows high specificity and NPV compared with evidence of Candida bloodstream infection or consensus definitions for invasive Candida infection, and may play an adjunctive role as a stewardship tool to limit unnecessary antifungal prescriptions.
Background:Patients with acute myeloid leukaemia (AML) who receive early specialist palliative care (SPC) input report improved quality of life. However, rates of SPC referral for haematology patients have been found to be lower than for other types of malignancy. New therapies for AML allow for treatment of patients with relapsed disease and those who might previously have been judged unfit for treatment. Treating this patient group creates significant resource implications for the utilization of SPC services and this burden is likely to increase further in the future Aims:We aimed to audit the care provided at our centre to patients with AML and high-risk MDS (HR-MDS) against palliative care related quality metrics to highlight unmet palliative care needs. Methods:We leveraged routinely collected data from the electronic heath record system (EHRS) at a large tertiary haematooncology centre to describe the clinical course of all adult patients with newly diagnosed AML and HR-MDS between Apr 2019 and Oct 2022. The cohort was identified using the departmental database of AML patients. We excluded patients <18 years of age, patients with APML and those managed solely in other hospitals after their initial diagnosis. A data pipeline was constructed to extract data for each patient from the EHRS. Patient mortality data were from national mortality records. All data were analysed in R studio 3.1.4. Results:278 AML or HR-MDS patients were diagnosed and treated at UCLH during the study period. 131/278 (47%) patients had died as of 13/2/2023. 115/131 (88%) patients received chemotherapy for AML before death (40 high intensity induction regimen, 54 venetoclax containing regimen, 21 low intensity regimen). 34/131 (26%) patients received chemotherapy within the last 28 days of life (range 2-28). Total days spent hospitalized from diagnosis to death was higher for those treated with intensive induction regimens (mean 104 days) than venetoclax containing regimens (mean 62 days) (two sample t test, p= 0.001). The median number of days patients spent hospitalised in the last 90 days of life was 26 days (range 2-90 days).103/278 (37%) patients were formally referred for inpatient SPC review during an inpatient admission. Of these, 64 died (62% of referrals died, 48% of all those who died were referred). 21 patients were first referred to the palliative care team within the last week of life and 6 patients were referred within 24 hours of death. 12 patients were referred to the palliative care team within 30 days of diagnosis. The majority 37/67 (55%) of patients who died whilst an inpatient at UCLH had an inpatient referral to SPC. Initial treatment regimen did not affect rates of SPC referral for those who died (Fisher's exact test, OR 1.18, p = 0.8).
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