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Background: COVID-19-associated mucormycosis (CAM) is associated with high morbidity and mortality. MUNCO is an international database used to collect clinical data on cases of CAM in real time. Preliminary data from the Mycotic Infections in COVID-19 (MUNCO) online registry yielded 728 cases from May to September 2021 in four South Asian countries and the United States. A majority of the cases (694; 97.6%) consisted of a mucormycosis infection. The dataset allowed for the analysis of the risk factors for adverse outcomes from CAM and this analysis is presented in this paper. Methods: The submission of cases was aided by a direct solicitation and social media online. The primary endpoints were full recovery or death measured on day 42 of the diagnosis. All patients had histopathologically confirmed CAM. The groups were compared to determine the contribution of each patient characteristic to the outcome. Multivariable logistic regression models were used to model the probability of death after a CAM diagnosis. Results: The registry captured 694 cases of CAM. Within this, 341 could be analyzed as the study excluded patients with an unknown CAM recovery status due to either an interruption or a lack of follow up. The 341 viable cases consisted of 258 patients who survived after the completion of treatment and 83 patients who died during the period of observation. In a multivariable logistic regression model, the factors associated with an increased risk of mortality include old age (OR = 1.04, 95% CI 1.02–1.07, p = 0.001), history of diabetes mellitus (OR 3.5, 95% CI 1.01–11.9, p = 0.02) and a lower BMI (OR 0.9, 95% CI 0.82–0.98, p = 0.03). Mucor localized to sinus disease was associated with 77% reduced odds of death (OR = 0.23, 95% CI 0.09–0.57, p = 0.001), while cerebral mucor was associated with an increased odds of death (OR = 10.96, 95% CI 4.93–24.36, p = ≤0.0001). Conclusion: In patients with CAM, older age, a history of diabetes and a lower body mass index is associated with increased mortality. Disease limited to the sinuses without a cerebral extension is associated with a lower risk of mortality. Interestingly, the use of zinc and azithromycin were not associated with increased mortality in our study. [ABSTRACT FROM AUTHOR]

Background: Mucormycosis is a rare but critical infection. Due to its rarity, there is scarce evidence about the longitudinal changes in the epidemiology of mucormycosis in the US., Objectives: We investigated the longitudinal epidemiology, detailed clinical characteristics, treatment and outcomes of patients with mucormycosis within the US Veterans Health Administration (VHA) over 20-year period., Patients/methods: All adult patients who were admitted to an acute-care hospital with a diagnosis of mucormycosis within the VHA from January 2003 to December 2022., Results: Our study included 201 patients from 68 hospitals. Incidence rates of mucormycosis increased from 1.9 per 100,000 hospitalisations in 2003 to 3.3 per 100,000 hospitalisations in 2022, with a peak incidence at 5.9 per 100,000 hospitalisations in 2021, when the Delta wave of COVID-19 hit the US. Rhino-orbital (37.3%) and pulmonary mucormycosis (36.8%) were the most common types of infection. Diabetes mellitus (59.1%) and leukaemia (28.9%) were most common comorbidities predisposing to mucormycosis. Use of posaconazole or isavuconazole increased over time. The 90-day and 1-year mortalities were 35.3% and 49.8%, respectively. The mortality was lower in more recent years (2013-2017, 2018-2022) compared to earlier years (2003-2007). Age ≥65 (adjusted odds ratio [aOR]: 3.47, 95% CI 1.59-7.40), leukaemia as a comorbidity (aOR: 2.66, 95% CI 1.22-5.89) and central nervous system infection (aOR: 10.59, 95% CI 2.81-44.57) were significantly associated with higher 90-day mortality., Conclusions: Our longitudinal cohort study suggests the increasing incidence rates but lower mortality of mucormycosis over this 20-year period., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Rhino-orbital cerebral mucormycosis (ROCM) is a rare infection caused by an invasive fungus and found predominantly in immunocompromised patients. The presentation of ROCM ranges from a mild headache, fever, and sinusitis to vision loss, altered mental status, and facial disfigurement secondary to local tissue invasion. ROCM can cause significant morbidity and mortality and requires prompt diagnosis with timely evaluation by surgical and infectious disease specialists. Cases of ROCM have been reported extensively in internal medicine, infectious disease, and otolaryngology literature. However, there are very few reports in emergency medicine literature in the United States. A 72-year-old woman presented to the Emergency Department (ED) with altered mental status, 4 days of left-sided facial numbness and weakness, and sudden facial pain, swelling, and erythema. Laboratory analysis was consistent with diabetic ketoacidosis. Noncontrast computed tomography of the head and magnetic resonance imaging of the brain demonstrated findings indicative of invasive fungal infection of the left sinus and orbit with extension to the cavernous sinus and surrounding cranial nerves. She was initiated on broad-spectrum antifungals, but based on the extent of the infection, was not a surgical candidate. She subsequently transitioned to a comfort-based plan of care and died 6 days after initial ED presentation. Early recognition and initiation of treatment can potentially mitigate the devastating outcomes of ROCM, therefore it is critical to be aware of this condition and have a high level of suspicion in susceptible patients. [ABSTRACT FROM AUTHOR]

Background: Mucormycosis (zygomycosis) is an invasive fungal infection that carries a high risk of morbidity and mortality. Uncontrolled diabetes mellitus and other immunocompromising conditions are risk factors for mucormycosis development. We here describe the differences in characteristics and outcomes of mucormycosis among solid organ transplant, hematological malignancy, and diabetes mellitus groups at our institution.Methods: We conducted a retrospective chart review over the period of 2009-2020, with identifying patients using the International Classification of Diseases, Ninth and Tenth Revisions. Clinical, laboratory, and outcome data were collected.Results: There were 28 patients identified: 7 solid organ transplant, 3 hematological malignancy, and 18 diabetes mellitus patients were included in the study. Three solid organ transplant patients experienced an episode of rejection, and another 3 had cytomegalovirus infection prior to presenting with mucormycosis. Four of seven solid organ transplant patients had a history of diabetes mellitus, but the median hemoglobin A1C was lower than in the diabetes mellitus group (6.3 vs 11.5; P = .006). The mortality rate difference between solid organ transplant and diabetes mellitus was not statistically significant: 2/7 (28.57%) vs 5/18 (27.78%); P = .66. Patients with bilateral disease (pulmonary or sinus) had significantly higher mortality (80% vs 13%, P = .008). There was no difference in mortality outcomes among the different types of antifungal therapies administered.Conclusion: A multispecialty approach is imperative in mucormycosis therapy. While the underlying risk factors were different, the outcomes were comparable for the solid organ transplant and diabetes mellitus groups. Future larger and longitudinal studies are recommended. [ABSTRACT FROM AUTHOR]

Background: The body of evidence on cutaneous mucormycosis is largely derived from case reports or single‐centre databases. Objectives: Our study aimed to describe incidence, predisposing factors and inpatient outcomes of cutaneous mucormycosis in the United States. Methods: We conducted a population‐based retrospective study using the National Inpatient Sample 2016‐17 data. Fifty‐six discharges had a diagnosis of cutaneous mucormycosis on the International Classification of Diseases, tenth revision. Descriptive analysis was performed for the demographics, predisposing factors, length of stay (LOS), cost and inpatient mortality. The NIS represents 20% of all discharges in the United States, which allowed us to estimate the national incidence of cutaneous mucormycosis. Results: An estimated total of 280 admissions occurred between 2016 and 2017, indicating 3.9 cases per million admissions across the United States. The estimated incidence rate was 0.43 cases per million people per year. Median age was 49.5 (19–59) years, 44.6% were female, and 54.9% were Caucasian. We identified haematologic malignancies (48.2%) and solid organ transplantations (10.7%), often accompanied by skin/soft tissue or post‐procedural infections, were the most common predisposing conditions. Median LOS was 15 (6–31) days, median total charges were 187,030 (65,962–446,265) USD, and in‐hospital mortality rate was 16.1%. Conclusions: In current clinical practice, physicians may encounter cutaneous mucormycosis most commonly in severely immunocompromised hosts with haematologic malignancies or transplantations, accompanied by skin/soft tissue or post‐procedural infections. A high index of suspicion and prompt tissue sampling in at‐risk groups is important to improve the outcomes. [ABSTRACT FROM AUTHOR]

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0–2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2–8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0–24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM difference = 187.6 ng·h/mL, 95% CI: 64.9, 310.4 ng·h/mL). Analysis of data from other assessment modalities failed to discern biologically relevant differences between treatment groups. We conclude that meaningful differences were evident for visual lameness assessment and cortisol from MEL and FLU treatment versus the positive control. Further clinical research is needed toward development of a model that will create reproducible events that are more pronounced in severity and duration of lameness which can be validated as a substitute for naturally occurring lameness cases. [ABSTRACT FROM AUTHOR]

Introduction: Prophylaxis and treatment of invasive aspergillosis (IA) and mucormycosis (IM) within a real-world US inpatient setting is undocumented since the introduction of isavuconazole. This retrospective medical record review aimed to describe characteristics, triazole use, and outcomes among inpatients across the USA who initiated antifungal monotherapy (AFMT) as prophylaxis or treatment of IA/IM. Methods: A convenience sample of US physicians abstracted data from randomly selected records of hospitalized patients aged ≥ 18 years initiating AFMT (amphotericin B, isavuconazole, voriconazole, or posaconazole) as prophylaxis or treatment of IA/IM between 2013 and 2017. Retrieved data included background characteristics, dosage and duration of AFMT, healthcare resource use, and survival. Characteristics and outcomes were compared (prophylaxis vs treatment) using Fisher's exact and one-way analysis of variance tests where applicable. Exploratory Kaplan–Meier analyses described overall and inpatient survival. Results: Physicians (n = 23) retrieved 124 patient records (43 prophylaxis; 81 treatment). Median duration of first-line AFMT was 14 days (range 1–603 days) and 19 days (range 3–351 days) in the prophylaxis and treatment groups, respectively. One patient received second-line therapy. Median duration of hospitalization was 29 days (range 4–259 days) and 31 days (range 6–980 days) in the prophylaxis and treatment groups, respectively. Admission to intensive care occurred in 14% and 52% of patients in the prophylaxis and treatment groups, respectively. At the time of data retrieval, overall and inpatient survival rates in the prophylaxis group were 88% and 87%, respectively, and in the treatment group were 66% and 76%, respectively. Conclusions: This study documented real-world prophylactic and therapeutic AFMT use for IA/IM and associated outcomes among hospitalized patients in the USA since approval of isavuconazole. IA/IM were associated with lengthy hospital stays commonly requiring intensive care. Prophylactic and therapeutic AFMT dosages and duration generally followed recommendations and switching between agents was rare. Funding: Astellas Pharma Global Development, Inc., Northbrook, IL, USA. [ABSTRACT FROM AUTHOR]

Case reports have identified invasive fungal diseases in persons who use cannabis, and fungal contamination of cannabis has been described. In a large health insurance claims database, persons who used cannabis were 3.5 (95% CI 2.6-4.8) times more likely than persons who did not use cannabis to have a fungal infection in 2016. [ABSTRACT FROM AUTHOR]

Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development., Competing Interests: Potential conflicts of interest. P. C. was employed at the Food and Drug Administration until 31 December 2020. S. N.'s contributions occurred entirely while she worked at the Food and Drug Administration. She is currently employed by Johnson & Johnson, and as an employee her travel to conferences/meetings is covered; she also owns Johnson & Johnson stock or stock options. D. A. is an employee and own shares of Scynexis. A. D. of DaneStat Consulting is a statistical consultant for the Pharmaceutical and Biotechnology Industry; he has acted as a consultant for Adaigo, AN2, Achaogen, Allecra, Amicrobe, Amplyx, Artizan, Bioscript, Bugworks, CARBX, Cidara, Closed Loop Medicine, Correvio, ContraFect, DaVolterra, Destiny, F2G, Entasis, Gates, Geom, GSK, Gyroscope, Humanigen, Kymab, Liverpool University, Melinta, Mironid, Modis, Nabriva, Orca, Pfizer, Phico, Pled, Quince, Roche, SFunga, Scynexis, Spero, Sinovent, SNIPR Biome, TenNor, Transcrip, VenatoRx, and Zavante (payments to DaneStat Consulting). He also reports as the independent statistician on data safety monitoring boards for a number of companies, including Aridis, ContraFect Midatech, Pfizer, Pled, Rare Thyroid, Sanofi, and Transcrip. M. R. H. reports support as a full-time employee of Amplyx Pharmaceuticals, a biotech company that was developing fosmanogepix, and received stock potions and a salary. T. S. is a full-time employee of and owns stock or stock options in Cidara Therapeutics. W. H. reports grants or contracts from F2G and Pfizer; personal consulting fees from F2G, Amplyx, Pfizer, Mundipharma, and Gilead (payments to DaneStat Consulting); participation on F2G's advisory board; a role as National Institutes of Health Research Specialty Co-lead for Infection; and a data sharing agreement with Astellas without any financial commitment. T. J. W. has received grants for experimental and clinical antimicrobial pharmacology and therapeutics to his institution from Allergan, Amplyx, Astellas, Lediant, Medicines Company, Merck, Scynexis, and Tetraphase; has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Leadiant, Medicines Company, Merck, Methylgene, Pfizer, and Scynexis; reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas, Leadiant, Scynexis, Shinogi, Statera, and T2 Biosystems; and reports a leadership or fiduciary role in the Medical Mycological Society of the Americas. P. P. reports grants from Merck, Astellas, Scynexis, Cidara, and F2G and consulting fees from F2G and Cidara. L. K. reports support as a full-time employee of Astellas Pharma Global Development. J. H. R. is chief medical officer and director of F2G, operating partner and consultant for Advent Life Sciences, and expert in residence for Wellcome Trust. He sits on the scientific advisory boards of Bugworks Research, Basilea Pharmaceutica, Forge Therapeutics, Novo Holdings, and Roche Pharma Research & Early Development and is a shareholder in AstraZeneca Pharmaceuticals, F2G, Advent Life Sciences, Macrolide Pharmaceuticals, and Bugworks Research. He has also received consulting fees from Phico Therapeutics, ABAC Therapeutics, Polyphor, Heptares Therapeutics, Gangagen, Meiji Seika Pharma, Basilea Pharmaceutica International, Allecra Therapeutics, Forge Therapeutics, SinSa Labs, AtoxBio, Peptilogics, F. Hoffmann-LaRoche, Novo Holdings, Innocoll, Vedanta, Progenity, Nosopharm, Roivant Sciences, and Shionogi. K. A. M. is founder and chief executive officer of MycoMed Technologies and a consultant and advisory board member for Cidara Therapeutics and Sfunga Therapeutics. She has consulted for Amplyx Pharmaceuticals, Astellas Pharma, Advaxis, Chimerix, F2G, Genentech, Incyte, Merck & Co, OncoSec, RTI Surgical, Scynexis. and Vical. She receives authorship and editorial royalties from UpToDate and a grant from Merck, owns shares in Pearl Diagnostics and Sfunga Therapeutics, and is an employee of Sfunga Therapeutics. L. O. Z. has received research funding and/or personal honoraria for consulting or speaking from Pulmocide, Pfizer, Merck, Astellas, Cidara, Scynexis, F2G, Amplyx, Gilead, Therapeutics, Viracor, Octapharma, Biotoscana, Stendhal, Mayne, Takeda, RealTime Labs, and Viracor. L. O. Z. also reports honoraria from F2G, Pfizer, and Gilead; participation on a data safety monitoring board or advisory board for Octapharma, Cidara, F2G, and Pfizer; and leadership roles as president for the Mycoses Study Group and Education Consortium, president-elect for the Immunocompromised Host Society, senior editor for Journal of Antimicrobial Chemotherapy, and an associate editor for Clinical Infectious Diseases. J. F. reports being a US government employee. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for BelleTorus Corporation, Hoth Therapeutics, Moberg Pharmaceuticals, and Ortho-dermatologics. Dr Gold, Author Smith, Author Benedict, and Dr Lockhart have no conflicts of interest to declare.

Drowned organ donors can be exposed to environmental molds through the aspiration of water; transplantation of exposed organs can cause invasive mold infections in recipients. We describe 4 rapidly fatal cases of potentially donor-derived invasive mold infections in the United States, highlighting the importance of maintaining clinical suspicion for these infections in transplant recipients.

Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019-2021. During 2020-2021, patients hospitalized with COVID-19-associated fungal infections had higher (48.5%) in-hospital mortality rates than those with non-COVID-19-associated fungal infections (12.3%). Improved fungal disease surveillance is needed, particularly during respiratory virus pandemics.

Background: Mucormycosis is a rare but devastating fungal infection primarily affecting immunocompromised patients such as those with hematological malignancy, bone marrow and solid organ transplantation, and patients with diabetes, and, even more rarely, immunocompetent patients. The objective of this study was to assess the prevalence and burden, both clinical and economic, of mucormycosis among hospitalized patients in the U.S. Methods: This is a retrospective study using the Premier PerspectiveTM Comparative Database, with more than 560 participating hospitals covering 104 million patients (January 2005-June 2014). All hospitalizations in the database were evaluated for the presence of mucormycosis using either an ICD-9 code of 117.7 or a positive laboratory result for Mucorales. Hospitalizations were further required to have prescriptions of amphotericin B or posaconazole to be considered as mucormycosis-related hospitalizations. The prevalence of mucormycosis-related hospitalizations among all hospital discharges was estimated. Mortality rate at discharge, length of hospital stay, and readmission rates at 1 and 3 months were evaluated among mucormycosis-related hospitalizations. Cost per hospital stay and average per diem cost (inflated to 2014 USD) were reported. Results: The prevalence of mucormycosis-related hospitalizations was estimated as 0.12 per 10,000 discharges during January 2005-June 2014. It increased to 0.16 per 10,000 discharges if the definition of mucormycosis was relaxed to not require the use of amphotericin B or posaconazole. The median length of stay was 17 days, with 23% dead at discharge; readmission rates were high, with 30 and 37% of patients readmitted within one and three months of discharge, respectively. The average cost per hospital stay was $112,419, and the average per diem cost was $4,096. Conclusions: The study provides a recent estimate of the prevalence and burden of mucormycosis among hospitalized patients. The high clinical and economic burden associated with mucormycosis highlights the importance of establishing active surveillance and optimizing prophylactic and active treatment in susceptible patients. [ABSTRACT FROM AUTHOR]

Background Mucormycosis is a rare and potentially fatal fungal infection occurring primarily in severely immunosuppressed patients. Because it is so rare, reports in the literature are mainly limited to case reports or small case series. The aim of this study was to evaluate inpatient mortality, length of stay (LOS), and costs among a matched sample of high-risk patients with and without mucormycosis in a large nationally representative database. Methods We conducted a retrospective analysis using the 2003-2010 Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS). The NIS is a nationally representative 20% sample of hospitalizations from acute care US hospitals, with survey weights available to compute national estimates. We classified hospitalizations into four mutually exclusive risk categories for mucormycosis: A- severely immunocompromised, B- critically ill, C- mildly-moderately immunocompromised, D- major surgery or pneumonia. Mucormycosis hospitalizations ("cases") were identified by ICD-9-CM code 117.7. Non-mucormycosis hospitalizations ("non-cases") were propensity-score matched to cases 3:1. We examined demographics, clinical characteristics, and hospital outcomes (mortality, LOS, costs). Weighted results were reported. Results From 319,366,817 total hospitalizations, 5,346 cases were matched to 15,999 non-cases. Cases and non-cases did not differ significantly in age (49.6 vs. 49.7 years), female sex (40.5% vs. 41.0%), White race (53.3% vs. 55.9%) or high-risk group (A-49.1% vs. 49.0%, B-20.0% vs. 21.8%, C-25.5% vs. 23.8%, D-5.5% vs. 5.4%). Cases experienced significantly higher mortality (22.1% vs. 4.4%, P < 0.001), with mean LOS and total costs more than 3-fold higher (24.5 vs. 8.0 days and $90,272 vs. $25,746; both P < 0.001). Conclusions In a national hospital database, hospitalizations with mucormycosis had significantly higher inpatient mortality, LOS, and hospital costs than matched hospitalizations without mucormycosis. Findings suggest that interventions to prevent or more effectively treat mucormycosis are needed. [ABSTRACT FROM AUTHOR]

Renal mucormycosis is a rare and potentially lethal complication of kidney transplantation. We describe two cases of renal mucormycosis following deceased donor kidney transplantation. This is the second report of renalmucormycosis following kidney transplantation in the United States, and the first case of renal mucormycosis infection presumed to be of recipient origin. Case A had an early presentation of mucormycosis isolated to the kidney allograft. He had an unexpected rise in serum creatinine and leukocytosis necessitating allograft biopsy which showedmucormycosis. He underwent transplant nephrectomy on posttransplant day 11, was treated with amphotericin B, and discharged home on posttransplant day 22. Case B had a late presentation of renal mucormycosis, preceded by a cutaneous manifestation. One year after kidney transplantation he had a nonhealing knee ulcer which on biopsy showed cutaneous mucormycosis. Treatment included aggressive debridement and amphotericin B. Allograft biopsy showed mucormycosis, necessitating transplant nephrectomy. He was discharged to a rehabilitation facility and died from noninfectious causes. Review of the published literature of renal mucormycosis cases following kidney transplantation reveals a mortality rate of more than 50%. The key to successful outcome is early recognition, prompt institution of surgical debridement of all infected tissue, and appropriate antifungal therapy. [ABSTRACT FROM AUTHOR]

Biological sex, which comprises differences in host sex hormone homeostasis and immune responses, can have a substantial impact on the epidemiology of infectious diseases. Comprehensive data on sex distributions in invasive fungal diseases (IFDs) are lacking. In this review, we performed a literature search of in vitro/animal studies, clinical studies, systematic reviews and meta-analyses of invasive fungal infections. Females represented 51.2% of invasive candidiasis cases, mostly matching the proportions of females among the general population in the United States and Europe (>51%). In contrast, other IFDs were overrepresented in males, including invasive aspergillosis (51% males), mucormycosis (60%), cryptococcosis (74%), coccidioidomycosis (70%), histoplasmosis (61%) and blastomycosis (66%). Behavioural variations, as well as differences related to biological sex, may only in part explain these findings. Further investigations concerning the association between biological sex/gender and the pathogenesis of IFDs are warranted., (© 2022 The Authors. Mycoses published by Wiley-VCH GmbH.)

Presents an abstract of the presentation `Pulmonary Zygomycosis After Allogeneic Bone Marrow Transplantation,' by Peter J. Piliero and Robert L. Deresiewicz which appeared at the 88th Annual Scientific Assembly of the Southern Medical Association from November 2-6, 1994.

Focuses on the cases of phycomycosis diagnosed at the Memorial Hospital in New York. Diseases associated with phycomycosis; Prevalence of phycomycosis at autopsy; Treatment for the disease.

The global incidence of mucormycosis has increased in recent years owing to higher numbers of individuals at risk for these infections. The diagnosis and treatment of this aggressive fungal infection are of clinical concern due to differences in species distribution in different geographic areas and susceptibility profiles between different species that are capable of causing highly aggressive infections. The purpose of this study was to evaluate the epidemiology and susceptibility profiles of Mucorales isolates in the United States over a 52-month period. Species identification was performed by combined phenotypic characteristics and DNA sequence analysis, and antifungal susceptibility testing was performed by CLSI M38 broth microdilution for amphotericin B, isavuconazole, itraconazole, and posaconazole. During this time frame, 854 isolates were included, representing 11 different genera and over 26 species, of which Rhizopus (58.6%) was the predominant genus, followed by Mucor (19.6%). The majority of isolates were cultured from the upper and lower respiratory tracts (55%). Amphotericin B demonstrated the most potent in vitro activity, with geometric mean (GM) MICs of ≤0.25 μg/ml against all genera with the exception of Cunninghamella species (GM MIC of 1.30 μg/ml). In head-to-head comparisons, the most active azole was posaconazole, followed by isavuconazole. Differences in azole and amphotericin B susceptibility patterns were observed between the genera with the greatest variability observed with isavuconazole. Awareness of the epidemiology of Mucorales isolates and differences in antifungal susceptibility patterns in the United States may aide clinicians in choosing antifungal treatment regimens. Further studies are warranted to correlate these findings with clinical outcomes.

Zygomycosis is an angioinvasive fungal infection with a high mortality rate. Cutaneous zygomycosis is the second most common form of the disease, typically characterized by necrotic eschars in an immunocompromised host. We report an unusual case of superficial intertrigo resistant to conventional therapies caused by Mucor circinelloides in a patient with HIV and diabetes. [ABSTRACT FROM AUTHOR]

Background Mold-active antifungal prophylaxis (ppx) is recommended in neutropenic patients with newly diagnosed AML or MDS. ISAV is an extended spectrum triazole with superior tolerability, reliability of absorption, fewer drug–drug interactions, lack of QTc prolongation or need for therapeutic drug monitoring, approved for the treatment of invasive aspergillosis (IA) and mucormycosis. NCT03019939 is an investigator-initiated, phase 2 trial of PAP with ISAV in patients with AML/MDS. Methods Treatment-naïve adult patients with AML or MDS initiating remission-induction chemotherapy (RIC) received ISAV per the dosing recommendations in the United States label until recovery from neutropenia (neutrophils (ANC) ≥ 0.5 × 109/L) and attainment of complete remission (CR), occurrence of proven or probable invasive fungal infection (IFI, EORTC/MSG criteria), or for a maximum of 12 weeks. The primary endpoint was incidence of proven/probable IFI during the study period (up to 30 days from the last dose of ISAV). Results 67 patients were enrolled (April 28, 2017 to February 14, 2019) and 60 patients were eligible for assessment (median age 67 years, 57 patients with AML, median ANC on enrollment was 660). Reasons for study completion were achievement of CR with ANC recovery (n = 35), completion of 12 weeks of PAP (n = 9), possible IFI (n = 7), investigator decision (n = 3), death (n = 2, 1 disease progression, 1 cardiac arrest), proven/probable IFI (n = 3), and mild transaminitis, possibly ISAV-related (n = 2). The median durations of neutropenia and ISAV ppx were 33 (7–86) and 31 (7–86) days, respectively. One microbiologically-proven (gluteal abscess due to Candida glabrata) and 2 cases of probable breakthrough IFIs (probable IA with positive galactomannan) occurred (IFI incidence 5%). ISAV trough serum concentrations were available in 31 patients on both day 8 (median 3.74 µg/mL, 2.03–7.65) and day 15 (median 4.10 µg/mL, 2.17–9.25), and were not significantly different. Conclusion ISAV is a safe and effective alternative for PAP in patients with newly diagnosed AML/MDS undergoing RIC, with a breakthrough (proven/probable) IFI rate of 5%. ISAV serum levels were adequate in patients with AML/MDS undergoing RIC. Pharmacological features make ISAV attractive for PAP in the era of recently approved or emerging small-molecule AML therapies. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 wounds) injured in Afghanistan (2009-2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales.

Background: Isavuconazole use in the real-world setting has not been extensively described. Subgroups of patients with particular prognostic significance, such as previous triazole prophylaxis or treatment and the important subgroup treated empirically for invasive fungal infection, have beforehand been excluded from trials., Objectives: We aimed to determine treatment response and safety in these patients at a large US transplant and cancer centre., Patients/methods: We conducted a retrospective cohort study of all adult inpatients administered ≥3 doses of isavuconazole between June 2015 and October 2017., Results: Ninety-one adults were identified. Six (7%) received primary prophylaxis, 10 (11%) treatment then secondary prophylaxis and 75 (82%) treatment only. Overall treatment response was 62%. Six-week mortality was 24%. Sixty-three per cent of 32 patients treated with isavuconaozle following prophylaxis with another antifungal agent exhibited a treatment response. Among 49 patients switched from treatment with another agent, 53% had a treatment response. Thirty-four patients received isavuconazole empirically, and 65% demonstrated a treatment response. Individuals given isavuconazole prophylaxis developed no breakthrough invasive fungal infections. One patient discontinued isavuconazole due to hepatotoxicity., Conclusions: Real-world isavuconazole use appears safe and is associated with treatment responses in varied patients including critically important subgroups previously unreported., (© 2019 Blackwell Verlag GmbH.)

As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival., (© 2014 Blackwell Verlag GmbH.)