Abstract Purpose Patients with persistent or recurrent neutropenic fevers at risk of invasive fungal disease (IFD) are treated empirically with antifungal therapy (AFT). Early treatment using a ...diagnostic-driven (DD) strategy may reduce clinical and economic burdens. We compared costs and outcomes of both strategies from a UK perspective. Methods An empirical strategy with conventional amphotericin B deoxycholate (C-AmB), liposomal amphotericin B (L-AmB), or caspofungin was compared with a DD strategy (initiated based on positive ELISA results for galactomannan antigen) and/or positive results for Aspergillus species on polymerase chain reaction assay) using C-AmB, voriconazole, or L-AmB in a decision-analytic model. Rates of IFD incidence, overall mortality, and IFD-related mortality in adults expected to be neutropenic for ≥10 days were obtained. The empirical strategy was assumed to identify 30% of IFD and targeted AFT to improve survival by a hazard ratio of 0.589. AFT-specific adverse events were obtained from a summary of product characteristics. Resource use was obtained, and costs were estimated by using standard UK costing sources. All costs are presented in 2012 British pounds sterling. Findings Total costs were 32% lower for the DD strategy (£1561.29) versus the empirical strategy (£2301.93) due to a reduced incidence of adverse events and decreased use of AFT. Administration of AFT was reduced by 41% (DD strategy, 74 of 1000; empirical strategy, 125 of 1000), with similar survival rates. Implications This study suggests that a DD strategy is likely to be cost-saving versus empirical treatment for immunocompromised patients with persistent or recurrent neutropenic fevers.
Introduction
Scedosporium apiospermum and Lomentospora prolificans (Scedosporium/Lomentospora) species are emerging, multi‐resistant pathogens that cause life‐threatening illnesses among lung ...transplant (LTx) recipients. The current epidemiology and management in LTx are unknown.
Methods
We performed a retrospective single center audit of all sputum/bronchoscopy samples for Scedosporium/Lomentospora species in LTx patients over a 24‐year period (1995‐2019). Patients were diagnosed as colonized or with invasive fungal disease.
Results
From a cohort of 962 LTx recipients, 30 patients (3.1%) cultured Scedosporium/Lomentospora (1.2%, 1.9%, respectively). There were no isolates from 1995 to 2013, with multiple yearly isolates thereafter. Nineteen (63%) cases were classified as IFD, and 11 (37%) as colonization. The median time to first culture from transplantation was 929 days (Interquartile‐range IQR 263‐2960). Most patients (63%) had received antifungals prior to the first positive culture of Scedosporium/Lomentospora for other fungal infection. The most common antifungal used for treatment of Scedosporium/Lomentospora was posaconazole (n = 16; 53%). Median duration of therapy was 364 days (IQR 164‐616). Treatment was associated with improved lung function over 6 months (median FEV1 increased from 1.3LIQR 0.9‐1.8L to 1.8LIQR 1.1‐2.3 P = .05). Six patients cultured Scedosporium/Lomentospora prior to transplantation, and no survival disadvantage was seen as compared to our whole LTx cohort (P = .8).
Conclusion
Our single center 24‐year experience suggests that the incidence of Scedosporium/Lomentospora is increasing. Scedosporium/Lomentospora is typically isolated several years after LTx, and requires prolonged anti‐fungal treatment that is usually associated with improved in lung function. Culture of Scedosporium/Lomentospora prior to LTx did not pose a survival disadvantage. Further surveillance is required to fully characterize implications of these organisms for LTx recipients.
We present a case of endobronchial fusariosis following bilateral sequential lung transplantation for idiopathic pulmonary arterial hypertension in a 13 years old boy who was treated successfully ...with posaconazole and nebulized amphotericin B. We discuss the role of nebulized amphotericin B in treating invasive pulmonary fungal disease in children. To our knowledge, this is the first pediatric case of endobronchial fusariosis reported in the literature.
Background. A simple test to identify recovery of CMV-specific T-cell immunity following hematopoietic stem cell transplantation (HSCT) could assist clinicians in managing CMV-related complications. ...Methods. In an observational, multicenter, prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV, an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine staining. Results. At 3 months after HSCT, participants who developed CMV disease (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n = 25) had significantly lower CD8+ T-cell production of interferon-γ (IFN-γ) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a negative predictive value of 98% for identifying participants at risk of further CMV reactivation. Participants experiencing CMV reactivation compared with patients without CMV reactivation had a reduced proportion of polyfunctional (IFN-γ+/tumor necrosis factor α–positive) CD4+ and CD8+ T cells and a higher proportion of interleukin 2–secreting cells (P = .01 and P = .002, respectively). Conclusions. Quantifying CMV-specific T-cell immunity after HSCT can identify participants at increased risk of clinically relevant CMV-related outcomes.
Objectives
Influenza causes significant morbidity and mortality, especially in high‐risk populations. Although current vaccination regimens are the best method to combat annual influenza disease, ...vaccine efficacy can be low in high‐risk groups, such as haematopoietic stem cell transplant (HSCT) recipients.
Methods
We comprehensively assessed humoral immunity, antibody landscapes, systems serology and influenza‐specific B‐cell responses, together with their phenotypes and isotypes, to the inactivated influenza vaccine (IIV) in HSCT recipients in comparison to healthy controls.
Results
Inactivated influenza vaccine significantly increased haemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. Systems serology revealed increased IgG1 and IgG3 antibody levels towards the haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased frequencies of total, IgG class‐switched and CD21loCD27+ influenza‐specific B cells, determined by HA probes and flow cytometry. Strikingly, 40% of HSCT recipients had markedly higher antibody responses towards A/H3N2 vaccine strain than healthy controls and showed cross‐reactivity to antigenically drifted A/H3N2 strains by antibody landscape analysis. These superior humoral responses were associated with a greater time interval after HSCT, while multivariant analyses revealed the importance of pre‐existing immune memory. Conversely, in HSCT recipients who did not respond to the first dose, the second IIV dose did not greatly improve their humoral response, although 50% of second‐dose patients reached a seroprotective HAI titre for at least one of vaccine strains.
Conclusions
Our study demonstrates efficient, although time‐dependent, immune responses to IIV in HSCT recipients, and provides insights into influenza vaccination strategies targeted to immunocompromised high‐risk groups.
In this study, we found inactivated influenza vaccine (IIV) significantly increased hemagglutination inhibition (HAI) titres, hemagglutinin (HA)‐specific B cells and HA head‐specific IgG1 and IgG3 antibodies in haematopoietic stem cell transplant (HSCT) recipients, similar to healthy controls. Higher HAI titres with broader cross‐reactivity were observed in HSCT recipients with greater time‐interval after HSCT. Two doses of IIV only boosted the humoral responses marginally in low responders.
Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing ...candidaemia in Australia.
These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™.
A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance.
We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.
Summary
Bloodstream infections (BSIs) caused by Candida species are increasing in incidence, and are associated with high mortality rates, which are due in part to a delay in the administration of ...appropriate antifungal therapy. Earlier identification of yeast isolates from blood cultures may improve clinical outcomes. Identification of a Candida as albicans or non‐albicans species depends on the presence or absence of germ tubes. Conventionally, germ tube test (GTT) is performed on colonies grown on agar plate after 24–48 h of incubation. In the present study, the GTT was performed earlier on an aliquot taken from blood culture bottle, after yeast cells were seen in Gram stain and the results were compared with the GTT using the conventional method. Thirty‐one consecutive bloodstream isolates of yeast were included in this prospective study over 10 months. There was 100% concordance between the two GTT methods. Final identification was confirmed by standard laboratory procedures. The performance of GTT directly from blood culture bottles has important implications for early, appropriate therapy in patients with candidaemia.
Cytomegalovirus (CMV) infection can be a challenging clinical problem in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis. Clinical presentation is difficult to ...distinguish from an underlying disease flare. Several diagnostic modalities are now available and when combined can aid clinicians in the identification of patients who are most likely to benefit from antiviral therapy. The aim of this article is to review the available literature and outline a practical approach to the diagnosis and management of CMV in patients with IBD.
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