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BACKGROUND: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). METHODS: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. RESULTS: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). CONCLUSIONS: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. CLINICAL TRIALS REGISTRATION: NCT03572049.

BACKGROUND: Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes. METHODS: We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap survey without personal identifiers. RESULTS: Sixty-nine cases were identified and submitted by 29 separate institutional sites. Cryptococcosis was diagnosed a median of 22 days (interquartile range, 9-42 days) after SARS-CoV-2 infection. Mortality among those with available follow-up was 72% (26/36) for the immunocompetent group and 48% (15/31) for the immunocompromised group (likelihood ratio, 4.01; P = .045). We observed a correlation between disease manifestation (central nervous system infection, proven/probable disseminated disease, and respiratory) and mortality (P = .002). CONCLUSIONS: The mortality rate of 59% for patients with cryptococcosis following SARS-CoV-2 is higher than that of modern Cryptococcus cohorts. There was an association between immunocompromised status and cryptococcal disease manifestations as well as mortality. Moreover, our series emphasizes the need for clinical and laboratory assessment of opportunistic infections beyond 30 days when concerning symptoms develop.

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.

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections.

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008–December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51–91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90–4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26–1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.

Rapid information dissemination is critical in a world changing rapidly due to global threats. Ubiquitous internet access has created new methods of information dissemination that are rapid, far-reaching, and universally accessible. However, inaccuracies may accompany rapid information dissemination, and rigorous evaluation of primary data through various forms of peer review is crucial. In an era in which high-quality information can save lives, it is critical that infectious diseases specialists are well versed in digital strategy to effectively disseminate information to colleagues and the community and diminish voices spreading misinformation. In this study, we review how social media can be used for rapid dissemination of quality information, benefits and pitfalls of social media use, and general recommendations for developing a digital strategy as an infectious diseases specialist. We will describe how the Infectious Diseases Society of America has leveraged digital strategy and social media and how individuals can amplify these resources to disseminate information, provide clinical knowledge, community guidance, and build their own person brand. We conclude in providing guidance to infectious diseases specialists in aiming to build and preserve public trust, consider their audience and specific goals, and use social media to highlight the value of the field of infectious diseases.

Abstract Introduction Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala. Methods We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ 200 copies/ml. Results Of 664 participants, 13.3% had VNS and 7.1% had PV. In univariable analysis disaggregated by gender, low income, poor education, perceived difficulty attending healthcare, and alcohol use were associated with VNS in men while low CD4 at diagnosis, multiple prior ART regimens and treatment interruptions were significant in both genders. Multiple prior ART regimens (adjusted Odds Ratio (aOR) 2.82, [95% confidence interval (CI) 1.59, 4.99], p

The Mycoses Study Group Education and Research Consortium is a collective of clinicians, researchers, and educators with the common goal to advance awareness, diagnosis, and management of invasive fungal diseases. Clinical Mycology Today, the Mycoses Study Group Education and Research Consortium's biennial meeting, is dedicated to discussing the most pressing contemporary issues facing the field of clinical mycology, promoting clinical, translational, and basic science collaborations, and mentoring the next generation of clinical mycologists. Here, we review the current opportunities and challenges facing the field of mycology that arose from discussions at the 2022 meeting, with emphasis on novel host risk factors, emerging resistant fungal pathogens, the evolving antifungal pipeline, and critical issues affecting the advancement of mycology research. [ABSTRACT FROM AUTHOR]

Background: Risk factors for mortality and MDR-TB in Guatemala are poorly understood. We aimed to identify risk factors to assist in targeting public health interventions. Methods: We performed a retrospective study of adults with pulmonary TB reported to the Guatemalan TB Program between January 1, 2016 and December 31, 2017. The primary objective was to determine risk factors for mortality in pulmonary TB. The secondary objective was to determine risk factors associated with MDR-TB. Results: Among 3,945 patients with pulmonary TB, median age was 39 years (IQR 25–54), 59% were male, 25% of indigenous ethnicity, 1.1% had MDR-TB and 3.9% died. On multivariable analysis, previous TB treatment (odds ratio [OR] 3.57, CI 2.24–5.68 [p

Background Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research. Methods Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions to identify commonalities and perceived gaps and to formulate recommendations. The 2 groups then reconvened to develop consensus recommendations. Results IFD patients and their caregivers shared experiences reflecting the typically lengthy prediagnosis, acute treatment, long-term treatment, and posttreatment recovery stages of IFD. They reported substantial physical, psychological, and financial burdens associated with the IFD experience, particularly related to delayed diagnoses. They reaffirmed a need for coordinated patient-centered education, peer support, and advocacy to document the burden of serious fungal infections. Mycology experts discussed strategies to address gaps in the mycology field, such as insufficient training, inadequate workforce support, and a need to partner more with patient groups. Conclusions A summit involving patients with IFD, family caregivers, and mycology experts identified a substantial nonclinical burden of disease associated with IFD. Patients and mycology experts prioritized several goals for education, advocacy, and research to raise awareness of IFD and improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Cryptococcosis is one of the most common life-threatening opportunistic mycoses worldwide. Insidious presentation and slow onset of symptoms make it difficult to recognize, complicating the diagnostic process. Delays in diagnosis may lead to increased mortality. We aim to determine the frequency of missed opportunities for diagnosis of cryptococcosis and its effects on mortality. Methods: To estimate the proportion of individuals with a potentially missed diagnosis for cryptococcosis in hospitalized patients, we conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases from 2005 to 2015 from eight states. All hospitalized adult patients diagnosed with cryptococcal infection or cryptococcal meningitis were included. Potentially missed diagnoses were defined as admissions coded for a procedure or diagnosis suggestive of cryptococcosis in the 90-days prior to the initial cryptococcosis admission. Generalized estimating equations models were used to evaluate the association between underlying comorbidities and potential missed diagnosis of cryptococcosis and 90-day all-cause in-hospital mortality. Findings: Of 5,354 patients with cryptococcosis, 2,445 (45·7%) were people living with HIV (PLWH). Among PLWH, 493/2,445 (20·2%) had a potentially missed diagnosis, of which 83/493 (16·8%) died while hospitalized compared with 265/1,952 (13·6%) of those without a potentially missed diagnosis (relative risk [RR] 1·04, 95% CI 0·99–1·09). Among HIV-negative patients, 977/2,909 (33·6%) had a potentially missed diagnosis, of which 236/977 (24·2%) died while hospitalized compared with 298/1,932 (15·4%) of those not missed (RR 1·12, 95% CI 1·07–1·16). Interpretation: Missed opportunities to diagnose cryptococcosis are common despite highly efficacious diagnostic tests and are associated with increased risk of 90-day mortality in HIV-negative patients. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality. Funding: National Center for Advancing Translational Sciences, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.

Invasive fungal infection (IFI) is a rare but serious complication of traumatic injury. The purpose of this article is to review the epidemiology, natural history, mycology, risk factors, diagnosis, treatment, and outcomes associated with post-traumatic IFI in military and civilian populations. The epidemiology of post-traumatic IFI is poorly characterized, but incidence appears to be rising. Patients often suffer from severe injuries and require extensive medical interventions. Fungi belonging to the order Mucorales are responsible for most post-traumatic IFI in both civilian and military populations. Risk factors differ between these cohorts but include specific injury patterns and comorbidities. Diagnosis of post-traumatic IFI typically follows positive laboratory results in the appropriate clinical context. The gold standard of treatment is surgical debridement in addition to systemic antifungal therapy. Patients with post-traumatic IFI may be at greater risk of amputation, delays in wound healing, hospital complications, and death as compared to trauma patients who do not develop IFI. More research is needed to understand the factors surrounding the development and management of post-traumatic IFI to reduce the significant morbidity and mortality associated with this disease.

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART (p = 0.60). Insurance status reached statistical significance with 38% of survivors having private insurance versus only 8% having private insurance in the late mortality group (p = 0.05). High mortality persists despite the advent of modern ART, implicating a contribution from social determinants of health, such as private insurance. Larger studies are needed to elucidate the role of these factors in the mortality of PWH.