Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are ...considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections.
We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies.
Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%–85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%–51%, p 0.053). In Kaplan–Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days).
While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.
Context. Supernova remnants interacting with molecular and atomic clouds are interesting X-ray sources for studies of broadband nonthermal emission. X-ray line emission in these systems can be ...produced by different processes, such as low-energy cosmic rays (LECRs) interacting with the cloud and fast ejecta fragments moving in the cloud. Aims. This paper is aimed at studying the origin of the non-thermal X-ray emission of the southwestern limb of SN 1006 beyond the main shock to determine whether the emission is due to LECRs diffusing in the cloud or to ejecta knots moving into the cloud. Methods. We analyzed the X-ray emission of the southwestern limb of SN 1006, where the remnant interacts with an atomic cloud, using three different X-ray telescopes: NuSTAR , Chandra , and XMM-Newton . We also performed a combined spectro-imaging analysis of this region. Results. Our analysis of the nonthermal X-ray emission of the southwestern limb of SN 1006 interacting with an atomic cloud has led to the detection of an extended X-ray source in the atomic cloud, approximately 2 pc upstream of the shock front. The source is characterized by a hard continuum (described by a power law with photon index Γ ∼ 1.4) and by Ne, Si, and Fe emission lines. The observed flux suggests that the origin of the X-ray emission is not associated with LECRs interacting with the cloud. On the other hand, the spectral properties of the source, together with the detection of an IR counterpart visible with Spitzer -MIPS at 24 μm, are in good agreement with the general expectations for a fast ejecta fragment moving within the atomic cloud. Conclusions. We detected X-ray and IR emission from a possible ejecta fragment, with an approximate radius of 1 × 10 17 cm and approximate mass of 10 −3 M ⊙ at about 2 pc out of the shell of SN 1006, in the interaction region between the southwestern limb of the remnant and the atomic cloud.
Introduction
‘Real-world’ data for mold-active triazoles (MATs) in the treatment of invasive fungal infections (IFIs) are lacking. This study evaluated usage of MATs in a disease registry for the ...management of IFIs.
Methods
Data were collected for this multicenter, observational, prospective study from 55 US centers, between March 2017 and April 2020. Eligible patients received isavuconazole, posaconazole, or voriconazole as MAT monotherapy (one MAT) or multiple/sequenced MAT therapy (more than one MAT) for prophylaxis or treatment. Patients were enrolled within 60 days of MAT initiation. The primary objective was to characterize patients receiving a MAT and their patterns of therapy. The full analysis set (FAS) included eligible patients for the relevant enrollment protocol, and the safety analysis set (SAF) included patients who received ≥ 1 MAT dose.
Results
Overall, 2009 patients were enrolled in the SAF. The FAS comprised 1993 patients (510 isavuconazole; 540 posaconazole; 491 voriconazole; 452 multiple/sequenced MAT therapies); 816 and 1177 received treatment and prophylaxis at study index/enrollment, respectively. Around half (57.8%) of patients were male, and median age was 59 years. Among patients with IFIs during the study, the most common pathogens were
Aspergillus fumigatus
in the isavuconazole (18.2% 10/55) and voriconazole (25.5% 12/47) groups and
Candida glabrata
in the posaconazole group (20.9% 9/43); the lungs were the most common infection site (58.2% 166/285). Most patients were maintained on MAT monotherapy (77.3% 1541/1993), and 79.4% (1520/1915) completed their MAT therapies. A complete/partial clinical response was reported in 59.1% (591/1001) of patients with a clinical response assessment. Breakthrough IFIs were reported in 7.1% (73/1030) of prophylaxis patients. Adverse drug reactions (ADRs) were reported in 14.7% (296/2009) of patients (3.9% 20/514 isavuconazole; 11.3% 62/547 posaconazole; 14.2% 70/494 voriconazole).
Conclusions
In this ‘real-world’ study, most patients remained on their initial therapy and completed their MAT therapy. Over half of patients receiving MATs for IFIs had a successful response, and most receiving prophylaxis did not develop breakthrough IFIs. ADRs were uncommon.
Background. Galactomannan is an Aspergillus-specific polysaccharide released during aspergillosis and is detected by the quantitative serum galactomannan index (GMI) test. Preclinical and preliminary ...clinical reports have suggested a good correlation between GMI and aspergillosis outcome. Methods. We reviewed the literature to assess the strength of correlation between GMI and aspergillosis outcome using the κ correlation coefficient. We included 27 studies that enrolled patients with hematological cancer and proven or probable aspergillosis and that used sequential GMI testing. We examined the 3 following outcomes: survival (survival vs. death), global outcome (survival vs. death including autopsy findings), and autopsy outcome (autopsy findings only). Results. Overall, 257 patients fulfilled criteria for proven or probable aspergillosis and were eligible for outcome evaluation. Correlation between GMI (within ≤1 week before outcome) and defined outcomes was excellent, with κ correlation coefficients of 0.8737 (95% confidence interval, 0.8140–0.9333; P<.001) and 0.9123 (95% confidence interval, 0.8617–0.9629; P<.001) for survival and global outcome, respectively. Most importantly, the κ correlation coefficient for autopsy outcome was high (0.8498; 95% confidence interval, 0.5608–1.000; P<.001). Furthermore, the κ correlation coefficient for all outcomes was comparable across age groups (pediatric and adult patients) and treatment modalities, including allogeneic transplantation. This strong correlation is also supported by extensive preclinical data and recent clinical reports. Conclusions. We conclude that serum GMI is a good marker of aspergillosis outcome.
We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron ...stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.
Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we ...studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.
This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is ...defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.
Ce protocole national de diagnostic et de soins (PNDS) français inclut les patients pédiatriques et adultes atteints d’uvéite chronique non-infectieuse (UCNI) ou d’uvéite récurrente non-infectieuse (URNI). L’uvéite chronique non infectieuse est définie comme une uvéite qui persiste pendant au moins 3 mois ou avec des rechutes fréquentes survenant moins de 3 mois après l’arrêt du traitement. L’uvéite récurrente non-infectieuse est définie par des épisodes répétés d’uvéite séparés par des périodes d’inactivité d’au moins 3 mois en l’absence de traitement. Certaines de ces UCNI et URNI sont isolées. D’autres sont associées à des maladies qui peuvent toucher différents organes, comme les uvéites associées à certains types d’arthrite juvénile idiopathique, les spondylarthropathies de l’adulte ou les maladies systémiques de l’enfant et de l’adulte comme la maladie de Behçet, les granulomatoses ou la sclérose en plaques. Les diagnostics différentiels des pseudo-uvéites, parfois liées à une néoplasie, et des uvéites d’origine infectieuse sont discutés, ainsi que les différentes formes d’uvéites en fonction de leur localisation anatomique principale (antérieure, intermédiaire, postérieure ou panuvéite). Sont également décrits les symptômes, les mécanismes physiopathologiques connus, les examens complémentaires ophtalmologiques et extra-ophtalmologiques utiles, la prise en charge thérapeutique, le suivi et les informations utiles sur les risques associés à la maladie ou au traitement. Enfin, ce protocole présente des informations plus générales sur le parcours de soins, les professionnels impliqués, les associations de patients, les adaptations de l’environnement scolaire ou professionnel et d’autres mesures qui peuvent être mises en œuvre pour gérer les répercussions de ces maladies chroniques. Les corticostéroïdes locaux ou systémiques étant généralement nécessaires, ces traitements et les risques liés à leur utilisation prolongée font l’objet d’une attention particulière et de recommandations spécifiques. Les mêmes informations sont fournies pour les traitements immunomodulateurs systémiques, les immunosuppresseurs, incluant parfois les anticorps anti-TNFα ou d’autres biothérapies. Les recommandations importantes pour la prise en charge des patients sont mises en évidence dans des tableaux récapitulatifs.
Donors not meeting standard criteria, such as those with bacteremia, are now being used in response to the increasing need for organs for transplantation. Recommended strategies to prevent the ...occurrence of donor‐derived bacteremia include the use of directed antibiotic prophylaxis. However, this approach does not eliminate the risk of infection transmission. Similarly, the management of organ recipients from donors with infective endocarditis (IE) remains uncharacterized. We report 2 cases of donor‐derived bacterial infections in liver transplant recipients despite pathogen‐specific antibiotic prophylaxis. In both instances, the donors had documented IE treated with appropriate antimicrobial therapy and clearance of bacteremia. Recipients had very distinctive clinical outcomes likely related to pathogen virulence and the extent of donor infection. Persistent infection in the transplanted liver should be suspected in organ recipients of a liver from donors with IE, despite the absence of bacteremia at the time of death and organ procurement. For eradication, recipients may require prolonged pathogen‐directed antimicrobial therapy, such as is used for endovascular infections. Prompt recognition of donors with IE, appropriate notification, and prolonged antibiotic prophylaxis are key to reducing the risk of such donor‐derived infections.
Emerging opportunistic yeast infections Miceli, Marisa H, MD; Díaz, José A, MD; Lee, Samuel A, Dr
The Lancet infectious diseases,
02/2011, Letnik:
11, Številka:
2
Journal Article
Recenzirano
Summary A growing population of immunosuppressed patients has resulted in increasingly frequent diagnoses of invasive fungal infections, including those caused by unusual yeasts. The incidence of ...non-albicans species of Candida is increasing compared with that of Candida albicans , and several species, such as Candida glabrata and Candida krusei , may be resistant to azole antifungal therapy. Trichosporon species are the second most common cause of fungaemia in patients with haematological malignant disease and are characterised by resistance to amphotericin and echinocandins and poor prognosis. Rhodotorula species belong to the family Cryptococcaceae, and are a cause of catheter-related fungaemia, sepsis, and invasive disease in severely immunosuppressed patients. An increasing number of sporadic cases of invasive fungal infections by non-neoformans cryptococci have been reported in immunocompromised hosts, especially for patients with advanced HIV infection or cancer who are undergoing transplant. Other uncommon yeasts that can cause invasive disease in severely immunosuppressed patients include Geotrichum, Hansenula, Malassezia , and Saccharomyces . Host immune status is a crucial determinant of the type of invasive fungal infection a patient is at risk for. Diagnosis can be challenging and relies heavily on traditional cultures of blood and other sterile sites, although serum (1,3)-β-D-glucan testing might have an adjunctive role. Although rare yeasts are emerging as opportunistic human pathogens, diagnosis remains challenging and treatment suboptimal.
Food protein–induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; ...high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.
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