It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Aspergillosis complicating severe influenza infection has been increasingly detected worldwide. Recently, coronavirus disease-associated pulmonary aspergillosis (CAPA) has been detected through rapid ...reports, primarily from centers in Europe. We provide a case series of CAPA, adding 20 cases to the literature, with review of pathophysiology, diagnosis, and outcomes. The syndromes of pulmonary aspergillosis complicating severe viral infections are distinct from classic invasive aspergillosis, which is recognized most frequently in persons with neutropenia and in other immunocompromised persons. Combined with severe viral infection, aspergillosis comprises a constellation of airway-invasive and angio-invasive disease and results in risks associated with poor airway fungus clearance and killing, including virus- or inflammation-associated epithelial damage, systemic immunosuppression, and underlying lung disease. Radiologic abnormalities can vary, reflecting different pathologies. Prospective studies reporting poor outcomes in CAPA patients underscore the urgent need for strategies to improve diagnosis, prevention, and therapy.
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Background. Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. Methods. Clinical data from patients with ...candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. Results. The incidence of candidemia caused by non–Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P=.002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. Conclusions. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.
Background. Invasive mold infections (IMIs) are common in individuals who have undergone hematopoietic stem cell transplantation (HSCT). We sought to determine clinical and biological risk factors ...for different IMIs during each period (early and late) after allogeneic HSCT. Methods. Cases of proven and probable IMI diagnosed in HSCT recipients at the Fred Hutchinson Cancer Research Center (Seattle, WA) from 1 January 1998 through 31 December 2002 were included. Survival was estimated with Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. Results. During the study period, 1248 patients underwent allogeneic HSCT; 163 (13.1%) received a diagnosis of probable or proven IMI. The majority of cases were caused by Aspergillus species (88%). The incidence of IMI caused by other molds remained low (<2%) over the 4-year study period. Risk factors for IMI early after HSCT and late after HSCT differed, with host variables (age) and transplant variables (human leukocyte antigen match) predominating as early risk factors and other clinical complications (graft-versus-host disease and cytomegalovirus disease) predominating later. Biological risk factors that were important during all periods included multiple cytopenias (neutropenia, lymphopenia, and monocytopenia) and iron overload. Conclusions. Risk factors for invasive aspergillosis after allogeneic HSCT are multifactorial and differ according to timing after HSCT. Increased attention should be placed on understanding the immunopathogenesis of fungal disease after HSCT.
Abstract
Background
Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood.
Methods
...A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores.
Results
In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 calculated as weight in kilograms divided by height in meters squared; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median interquartile range, 41.1 20.5–72.4) vs 18.5 10.7–31.8 days; P < .001).
Conclusion
CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.
Aspergillosis occurs at a variable incidence in people with severe coronavirus disease 2019, depending on diagnostic approach and definitions. Associated poor outcomes may be improved with early detection and antifungal therapy, warranting development of better noninvasive diagnostic and prevention strategies.
Background. Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and ...secular trends are lacking. Methods. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. Results. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. Conclusions. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.
In a speech delivered at the 2019 AAP/ASCI/APSA Joint Meeting on Apr 5, 2019 in Chicago IL, Marr thanks the member and the executive leadership team who have been instrumental to the American Society ...for Clinical Investigation over the last year. Furthermore, she recommends that anyone who wants to understand the society, or the history of physician-scientists, should invest time in reading the ASCI Presidential Addresses published in JCI.
Summary Background Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with ...invasive mould disease. Methods This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice–web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat ITT population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov , number NCT00412893. Findings 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of −1·0% (95% CI −7·8 to 5·7). Because the upper bound of the 95% CI (5·7%) did not exceed 10%, non-inferiority was shown. Most patients (247 96% receiving isavuconazole and 255 98% receiving voriconazole) had treatment-emergent adverse events (p=0·122); the most common were gastrointestinal disorders (174 68% vs 180 69%) and infections and infestations (152 59% vs 158 61%). Proportions of patients with treatment-emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 9% vs 42 16%; p=0·016), eye disorders (39 15% vs 69 27%; p=0·002), and skin or subcutaneous tissue disorders (86 33% vs 110 42%; p=0·037). Drug-related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0·001). Interpretation Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.
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