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Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.

BackgroundCandida empyema thoracis (pleural empyema) is an uncommon manifestation of invasive candidiasis, for which optimal treatment is unknown.MethodsThis is a retrospective study of patients with Candida empyema at 2 academic medical centers from September 2006 through December 2015.ResultsWe identified 81 patients with Candida empyema (median age, 62 years; 68% men). Sixty-five percent of patients underwent surgery or an invasive intervention of the thorax or abdomen within the preceding 90 days. Candida empyema originated from intrathoracic (51%) or intra-abdominal sources (20%), spontaneous esophageal rupture (12%), pleural space manipulation (9%), and pneumonia (6%). Eighty-four percent and 41% of patients were intensive care unit residents and in septic shock, respectively, within 3 days of diagnosis. Causative species were Candida albicans (65%), Candida glabrata (26%), Candida parapsilosis (11%), Candida tropicalis (4%), Candida krusei (2%), and Candida dubliniensis (1%). Bacteria were recovered from empyemas in 51% of patients. Concurrent candidemia was diagnosed in only 2% of patients. Management included pleural drainage and antifungal treatment in 98% and 85% of patients, respectively. Mortality at 100 days was 27%, and it was highest for cases stemming from esophageal rupture (67%). Spontaneous esophageal rupture and echinocandin rather than fluconazole treatment were independent risk factors for death at 100 days (P = .003 and .04, respectively); receipt of antifungal therapy was an independent predictor of survival (P = .046).ConclusionsCandida empyema mortality rates were lower than reported previously. Optimal management included pleural drainage and fluconazole treatment. Superiority of fluconazole over echinocandins against Candida empyema needs to be confirmed in future studies.

BackgroundInvasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.MethodsTo achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.ResultsThere is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.ConclusionsThese updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Pulmonary aspergillosis has been increasingly reported following severe respiratory viral infections. Millions have been infected by SARS-CoV-2, placing large numbers of patients at-risk for COVID-19 associated pulmonary aspergillosis (CAPA). Prompt recognition of this syndrome and is paramount to improve outcomes.

Mucormycosis outbreaks have been linked to contaminated linen. We performed fungal cultures on freshly-laundered linens at 15 transplant and cancer hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%, Mucorales were recovered from >10% of linens. Studies are needed to understand the clinical significance of our findings.

Background: Pharmacists are under‐utilized as caregivers who can improve patients' access to medical treatments. In this study, effectiveness of a multidisciplinary pharmacist‐managed clinic in delivering tixagevimab–cilgavimab pre‐exposure coronavirus disease 2019 (Covid‐19) prophylaxis was determined. Methods: An observational study at the Veterans Affairs (VA) Pittsburgh Healthcare System tixagevimab–cilgavimab clinic from January 1, 2022 to January 1, 2023 was conducted. Pharmacists identified immunocompromised Veterans system‐wide, performed active (telephone) or passive (mail) outreach to those in three highest‐risk categories and a more moderate‐risk category, respectively, and prescribed and dispensed tixagevimab–cilgavimab. Results: Eligible Veterans were stratified into Categories 1 (highest‐risk; 18% [193/1089]), 2 (2% [18/1089]), 3 (17% [188/1089]), or 4 (most moderate‐risk; 63% [690/1089]). Most common underlying conditions were rheumatologic (33%, 356/1089), oncologic (20%, 214/1089), and organ transplantation (18%, 197/1089). Twenty five percent (268/1089) of patients received ≥1 tixagevimab–cilgavimab dose. Acceptance in Categories 1–3 was 63% (121/193), 78% (14/18), and 37% (70/188), respectively (51% overall). Acceptance in Category 4 was 9% (63/690; p < 0.0001 vs. Categories 1–3). To put data into context, <2% of immunosuppressed persons in the United States were reported to receive tixagevimab–cilgavimab. Acceptance was greater among Veterans with rheumatologic or oncologic diseases than those with transplant‐related or neurologic diagnoses (p < 0.0001), and among Covid‐19‐vaccinated versus non‐vaccinated Veterans (27% [261/952] and 5% [7/137], p < 0.0001). Six percent (15/268) and 5% (42/821) of treated and untreated patients, respectively, were subsequently diagnosed in‐system with Covid‐19. Conclusions: A pharmacist‐managed clinic effectively delivered tixagevimab–cilgavimab to immunocompromised Veterans, in particular those at highest Covid‐19 risk. This program is a model for pharmacist‐led clinics for other therapeutics or diseases. [ABSTRACT FROM AUTHOR]

Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.Author SummaryCandida albicans has both a benign and pathogenic association with the human host. Previous to this study, little was known in regard to how the host humoral system responds to the commensal colonization of C. albicans, as well as the development of hematogenously disseminated candidiasis. We show using a C. albicans cell surface protein microarray that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans, and undergoes stage-specific antibody responses as the yeast transitions from a benign microbe to an opportunistic fungal pathogen. Also identified were serological signatures specific for acute and convalescent stages of candidemia. Our findings provide new insight in the characterization of potential serodiagnostic antigens and vaccine candidates to the opportunistic pathogen C. albicans.

Background Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. Methods This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Results Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P <.0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P   =.007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Conclusions Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock. [ABSTRACT FROM AUTHOR]