Mold Infections Research Articles

When and how do we stop antifungal treatment for an invasive mould infection in allogeneic haematopoietic cell transplant recipients?

Limited data exist to describe end-of-treatment (EOT) parameters of antifungal therapy for invasive mould infections (IMI). In a 10-year cohort of consecutive adult allogeneic haematopoietic cell transplant recipients with proven/probable IMI, we describe treatment duration and patient profile at EOT. There were 61 patients with 66 proven/probable IMI identified: 47/66 (71%) invasive aspergillosis (IA), 11/66 (17%) mucormycosis, and 8/66 (12%) other-IMI. Excluding 5 (8%) patients lost to follow-up, treatment was prematurely discontinued due to death or palliative care in 29/56 (51.8%) patients. Antifungal treatment was completed in 27 (48.2%) patients, for a median duration of 280 days (IQR: 110, 809): 258 (IQR: 110, 1905) and 307.5 (99, 809) days in IA and non-IA IMI, respectively. Treatment was continued after 90 and 180 days in 43/56 (76.8%) and 30/56 (53.6%) patients, respectively. At EOT, most patients were not neutropenic (ANC: 2.12 G/L, IQR: 0.04, 5.3), with CD4+ counts at 99 cells/μl (IQR: 0, 759) and immunoglobulins at 5.6 g/L (IQR: 2.3, 10.6). Most patients (16/27, 59.3%) were not receiving steroids at EOT, while 14/27 (53.9%) were on another type of immunosuppression. Amongst 15 patients with imaging at EOT, 12 (80%) had complete/partial radiologic response. Any chart documentation or an infectious disease consultation on treatment discontinuation was observed in 12/56 (21%) and 11/56 (20%) patients, respectively. Long treatment courses are observed in patients with IMI, due to prolonged immunosuppression. Although immune reconstitution and radiological response were frequently observed at EOT, consistent documentation of treatment discontinuation based on well-defined parameters is lacking.

Triazole Priming as an Adaptive Response and Gateway to Resistance in Aspergillus fumigatus.

Invasive aspergillosis (IA), caused predominantly by Aspergillus fumigatus, is the most common opportunistic mold infection in immunocompromised patients. Resistance of A. fumigatus to triazoles has been increasingly reported, leading to poor outcomes of IA to the front-line azoles. Triazole resistance is in part driven by exposure to agricultural azoles through mechanisms that are poorly understood beyond mutations in ergosterol biosynthetic genes. Priming is defined as a process in which prior exposures to sublethal stressful stimuli, such as antimicrobial drugs, can enhance the ability of pathogens to withstand reexposure to the same or other stressors. Here, we describe, for the first time, triazole priming, where exposure of conidia of three A. fumigatus strains to subinhibitory concentrations of either agricultural (tebuconazole difenoconazole, epoxiconazole) or medical triazoles (voriconazole) increases germination and growth during subsequent reexposure to subinhibitory triazole challenge. We demonstrate that priming in A. fumigatus is class specific to triazoles, is not confined to a particular isolate, and is retained for extended periods in primed dormant conidia, but is not transferred to subsequent generations. Furthermore, azole priming at subinhibitory triazole concentrations increased the frequency of development of stable resistance development at inhibitory triazole exposures. Triazole priming could have far-reaching clinical implications in generating resistance due to the widespread use of agricultural triazoles or breakthrough IA in patients with subtherapeutic serum levels of azoles.

Keeping health care linens clean: Underrecognized hazards and critical control points to avoid contamination of laundered health care textiles

Outbreaks of health care-associated infections, particularly invasive mold infections, have been linked to environmental contamination of laundered health care textiles. Contamination may occur at the laundry or health care facility. This report highlights underrecognized hazards, control points, and actions that infection preventionists can take to help decrease the potential for patient exposure to contaminated health care textiles. Infection preventionists can use the checklists included in this report to assess laundry and health care facility management of laundered health care textiles.

Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma

AbstractCAR T-cell therapy has revolutionized the treatment of hematologic malignancies, although its use may be complicated by toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported after CAR T-cell therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal prophylaxis strategies are widely debated. We performed a single-center retrospective study of 280 adults receiving CD19 CAR T-cell therapy for non-Hodgkin lymphoma (NHL) from December 2017 through September 2021. Patients did not receive routine antiyeast or antimold prophylaxis. IFD was identified between day of cell infusion and last follow-up. Cumulative incidence functions were calculated at 100 days and 18 months based on time to IFD, using dates of IFD-free death, initiation of salvage treatment, and hematopoietic cell transplantation as competing risks. Eight patients (2.9%) developed IFD, including 3 Pneumocystis jirovecii pneumonia, 3 invasive mold infections (IMIs), and 2 invasive yeast infections (IYIs). The 100-day cumulative incidence of IFD accounting for competing risks was 1.8% (95% confidence interval [CI], 0.8% to 4.4%). Among the 280 patients, early toxicities including CRS (85%) and ICANS (55%) and late toxicities after day 30 including grades 3 and 4 neutropenia (41%) and low CD4 T-cell count (20%) were common. IFD was rare among patients who received CD19 CAR T-cell therapy for NHL in the absence of routine antifungal prophylaxis, despite frequent toxicities. These results suggest that, in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated.

COVID-19-associated fungal infections in Iran: A systematic review.

ObjectivesThis systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran.MethodsPubMed, Web of Science, Scopus, Cochrane Library, SID, Magiran, IranDoc, and Google Scholar were searched for Persian and English articles published from January 1, 2020, to November 5, 2021, using a systematic search strategy. Studies on Iranian patients suffering from CAFIs were included in the review.ResultsTwenty-two studies comprising 169 patients were retrieved. Reported CAFIs included candidiasis (85, 50.30%), mucormycosis (35, 20.71%), aspergillosis (29, 17.16%), fusariosis (6, 3.55%), three cases caused by rare pathogens (Rhodotorula mucilaginosa, Diaporthe foeniculina, and Sarocladium kiliense) and 11 (6.51%) uncharacterized mold infections. The most common underlying diseases were diabetes (67/168, 39.88%), cardiovascular diseases (55/168, 32.74%), and hypertension (43/168, 25.59%). The use of antibiotics (111/124, 89.52%), corticosteroids (93/132, 70.44%), and mechanical ventilation (66, 51.16%) were the most common predisposing factors. Totally, 72 (50.35%) of 143 patients with CAFIs died (data were not available for 26 patients).ConclusionFungal infections are evident to be a complication of COVID-19 in Iran; thus, clinicians should consider them as a differential diagnosis, especially in patients with comorbidities and previous antibiotic or corticosteroid use.

Extensive non-coding sequence divergence between the major human pathogen Aspergillus fumigatus and its relatives.

Invasive aspergillosis is a deadly fungal disease; more than 400,000 patients are infected worldwide each year and the mortality rate can be as high as 50-95%. Of the ~450 species in the genus Aspergillus only a few are known to be clinically relevant, with the major pathogen Aspergillus fumigatus being responsible for ~50% of all invasive mold infections. Genomic comparisons between A. fumigatus and other Aspergillus species have historically focused on protein-coding regions. However, most A. fumigatus genes, including those that modulate its virulence, are also present in other pathogenic and non-pathogenic closely related species. Our hypothesis is that differential gene regulation - mediated through the non-coding regions upstream of genes' first codon - contributes to A. fumigatus pathogenicity. To begin testing this, we compared non-coding regions upstream of the first codon of single-copy orthologous genes from the two A. fumigatus reference strains Af293 and A1163 and eight closely related Aspergillus section Fumigati species. We found that these non-coding regions showed extensive sequence variation and lack of homology across species. By examining the evolutionary rates of both protein-coding and non-coding regions in a subset of orthologous genes with highly conserved non-coding regions across the phylogeny, we identified 418 genes, including 25 genes known to modulate A. fumigatus virulence, whose non-coding regions exhibit a different rate of evolution in A. fumigatus. Examination of sequence alignments of these non-coding regions revealed numerous instances of insertions, deletions, and other types of mutations of at least a few nucleotides in A. fumigatus compared to its close relatives. These results show that closely related Aspergillus species that vary greatly in their pathogenicity exhibit extensive non-coding sequence variation and identify numerous changes in non-coding regions of A. fumigatus genes known to contribute to virulence.

The influence of air pollution on respiratory allergies, asthma and wheeze in childhood in Hungary.

Higher exposure to air pollution may contribute to the increased prevalence of allergic diseases in children. The study investigated the associations between the prevalence of childhood respiratory diseases and long-term exposure to NO2, SO<inf>2</inf>, PM<inf>10</inf>, especially some surrogates in schoolchildren in Hungary. We also analyzed the possible modification effects of some confounders by interaction analysis. A total of 6771 children aged 8-9-year-old residing at their current addresses since their births with air pollution monitoring stations were selected into this analysis. Health outcomes and their possible determinants, as well as surrogates of air pollution were surveyed by using a standardized questionnaire. Long-term exposure to PM<inf>10</inf>, NO2, and SO<inf>2</inf> was calculated at settlement level derived from daily average concentrations of pollutants. Descriptive and analytical statistical methods were applied. NO2 levels were positively associated with respiratory allergies and asthma. Decreased risk for ragweed, any other pollen, house dust mite and animal fur allergy was detected with PM<inf>10</inf> level. There were significant associations between respiratory allergies to ragweed, any other pollen, house dust mite, animal fur, wheeze symptoms and living or attending school nearby a factory, power station or bus station as well as living in a home with intensive noise or vibration. Gender, parental atopy, home mold and early respiratory infection were significant effect modifiers in some cases. The results of this study indicate that respiratory health in children is adversely affected by air pollutants.

Postharvest biological control of Botrytis cinerea and the mechanisms underlying the induction of disease resistance in grapes by Lactobacillus plantarum CM-3

Biological control by microbial antagonists has been proposed as a viable strategy for the control of postharvest diseases in fruit. In the present study, biocontrol efficacy of the bacterial antagonist Lactobacillus plantarum CM-3 against gray mold infection on harvested grapes was documented along with the underlying physiological and molecular mechanisms responsible for biocontrol activity. In this regard, a transcriptomic analysis of the response of grapes to L. plantarum CM3 was conducted. Results indicated that L. plantarum CM-3 significantly decreased the level of natural postharvest decay in grapes without causing any adverse effects on quality traits. Treatment of grapes with L. plantarum CM-3 (1 × 109 CFU mL−1) resulted in a 55 % reduction in disease incidence caused by Botrytis cinerea. Meanwhile, L. plantarum CM-3 enhanced the activity of several enzymes in grapes that are closely associated with defense, including POD, PPO, CAT, APX, PAL, and GLU. RNA-seq analysis indicated extensive changes in the gene expression profile of grape berries in response to being treated with L. plantarum CM-3. In total, 1,327 differentially expressed genes (DEGs) were identified, among which 78.1 % (1,037) were upregulated and 21.9 % (290) were downregulated. Numerous pathways were strongly influenced by the L. plantarum CM-3 treatment, including signal perception and transduction, maintenance of reactive oxygen species (ROS) homeostasis, transcriptional and post-transcriptional regulation, primary metabolic pathways, and secondary metabolism. Additionally, the expression of 22 DEGs linked to enhancing disease resistance was analyzed by RT-qPCR and their expression levels were found to well correspond with the results obtained in the analysis of the RNA-seq data. Our data indicate that L. plantarum CM-3 can enhance host resistance by altering the expression of defense genes and their corresponding proteins, including PR1, WRKY33, WRKY22, PTI6 and peroxidase isoenzyme. Collectively, results of our study indicate that L. plantarum CM-3 treatment enhances the disease resistance of harvested grapes through a comprehensive and complex regulatory network. These findings provide new information on the molecular mechanism responsible for the enhancement of host disease resistance in grapes by L. plantarum CM-3. It also demonstrates a biocontrol strategy that can be used to elicit defense responses in fruit against fungal pathogens.

Occurrence of Candidemia in Patients with COVID-19 Admitted to Five ICUs in France.

Whether severe COVID-19 is by itself a significant risk factor for the development of candidemia currently remains an open question as conflicting results have been published. We aim to assess the occurrence of candidemia in patients with severe COVID-19 admitted to the intensive care unit (ICU). We conducted a retrospective study on patients with severe SARS-CoV-2-related pneumonia admitted to 5 ICUs in France who were specifically screened for fungal complications between March 2020 and January 2021. The study population included a total of 264 patients; the median age was 56 years old and most of them were male (n = 186; 70.5%) and immunocompetent (n = 225; 87.5%), and 62.7% (n = 153/244) were on extracorporeal membrane oxygenation support. Microbiological analysis included 4864 blood culture samples and beta-glucan test performed on 975 sera. Candidemia was diagnosed in 13 (4.9%) patients. The species involved were mainly C. albicans (n = 6) and C. parapsilosis (n = 5). Almost all patients (12/13; 92.3%) had a colonization by yeasts. ICU mortality was not significantly impacted by the occurrence of candidemia. Unrelated positive beta-glucan tests were observed in 49 patients (23.4%), including 6 with mold infections and 43 with false positive results. In our series, patients with severe SARS-CoV-2-related pneumonia seemed at low risk of developing invasive candidiasis.

Isavuconazole for COVID-19-Associated Invasive Mold Infections.

Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated aspergillosis (CAPA), and COVID-19-associated mucormycosis (CAM). Among all studies which reported treatment of CAPA, approximately 10% of patients were reportedly treated with isavuconazole. Considering 14 identified studies that reported the use of isavuconazole for CAPA, isavuconazole was used in 40% of patients (95 of 235 treated patients), being first-line monotherapy in over half of them. We identified six studies that reported isavuconazole use in CAM, either alone or in combination therapy. Overall, isavuconazole was used as therapy in 13% of treated CAM patients, frequently as combination or sequential therapy. The use of isavuconazole in CAPA and CAM is complicated by the challenge of achieving adequate exposure in COVID-19 patients who are frequently obese and hospitalized in the ICU with concomitant renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO). The presence of data on high efficacy in the treatment of aspergillosis, lower potential for drug–drug interactions (DDIs) and for subtherapeutic levels, and no risk of QT prolongation compared to other mold-active azoles, better safety profile than voriconazole, and the possibility of using an intravenous formulation in the case of renal failure are the advantages of using isavuconazole in this setting.

P1382: RUXOLITINIB USE IN A REAL WORLD ACUTE AND CHRONIC GRAFT VERSUS HOST DISEASE COHORT IN THE NETHERLANDS: A RETROSPECTIVE STUDY

Background: Preclinical data showed that Janus Kinase (JAK) signaling plays an important role in the pathogenesis of Graft versus Host Disease (GVHD) and several clinical studies showed remarkable clinical efficacy in both acute and/or chronic steroid-refractory (SR)-GVHD patients. However, these clinical results have not yet been repeated in real world cohorts with long term follow-up. Furthermore, infectious complications have not been highlighted in published clinical trials whilst these remain a significant problem in daily practice. Aims: To assess the response of acute and/or chronic SR-GVHD patients to ruxolitinib treatment and to assess side-effects of ruxolitinib treatment occurring in adult acute and/or chronic SR-GVHD patients. Methods: We performed a retrospective analysis of 121 consecutive patients treated with ruxolitinib for either acute or chronic GVHD. Patients were included from 3 academic centers in the Netherlands from 2014 to 2019. Patients provided written informed consent, with the exception of deceased patients in accordance with the local ethics committee. Patient data were extracted by personnel from an independent CRO to minimize reviewer bias. Patient data were anonymized. Results: 121 patients were included in the study of whom 54 were diagnosed with acute and 67 patients with chronic GVHD. Selected baseline characteristics are depicted in Table 1. The overall response rate at day 28 of acute GVHD was 70% (38/54) with a complete response in 50% of patients (27/54). At timepoint 6 months after initiation of ruxolitinib for chronic GVHD, the majority of patients showed stable disease. The overall response rate at 6 months in chronic GVHD was 28% (19/67) with a complete response in 13% of patients (9/67). Ruxolitinib use was mainly complicated by infections and hematological toxicity. Of the reported (S)AE’s possibly related to ruxolitinib, 38% were infectious and 13% were hematological. Severity of infections ranged from grade 1 to grade 5, median grade 2. Most infections were viral (43%), followed by bacterial (19%) and fungal or mould infections (14%). During follow up mortality was 14,9% (18 patients) of which 6 cases were due to uncontrolled GVHD, 5 cases due to infections and 3 patients died of relapse of their primary malignancy, 4 patients died of other causes. Image:Summary/Conclusion: In a real world cohort of GVHD patients treated with ruxolitinib we observed in patients with acute GVHD a complete response rate at day 28 of 50%. Overall response rate at 6 months in cGVHD patients was 28%. Infectious adverse events were common in both acute and chronic GVHD patients and were mainly caused by viral pathogens.

Impact of Cell Free DNA Mold Polymerase Chain Reaction Panel on Healthcare-Associated Infection Investigation

Background Molds are ubiquitous in the environment but can cause severe opportunistic infections in immunocompromised patients. In 2021, the Hospital Laboratory introduced a highly sensitive cell free DNA mold polymerase chain reaction (cfDNA PCR) test. Infection Prevention and Control (IPC) saw an increase in positive mold results raising concern for potential hospital exposure. A modified mold healthcare-associated infection (HAI) investigation algorithm was created, integrating clinical correlation into test interpretation. In this retrospective study we assess the effect of the new cfDNA mold PCR panel on the rate of positive tests and describe the effect of the modified algorithm on HAI investigation. Methods We used the institutional IPC database to review all positive mold tests among oncology and stem cell transplant (SCT) patients between 2017–2021. We compared the monthly rate of positive tests meeting HAI definition and investigations conducted per year before and after the introduction of the cfDNA mold PCR panel. We evaluated the effect of the modified mold HAI algorithm on the number of HAI investigations. Results Between 2017–2021 there were 15 positive mold tests meeting HAI definition in the oncology and SCT units. 50% Aspergillus species, 14.3% Rhizopus species, 14.3% Fusarium species and 21.4% (all in 2021) mucor species. The average positivity rate was 0.29 between 2017–2020 compared to 0.58 per month in 2021 after the introduction of the cfDNA mold PCR panel (P < 0.05). There were 5 HAI investigations in the past 5 years of them 4 in 2021. Mold HAI investigation was done twice after implementation of the revised algorithm. Conclusions The new cfDNA mold PCR panel caused a significant increase in the rate of positive mold infections reported in the immunocompromised units. The modified mold HAI algorithm that integrated clinical correlation led to improved identification of HAI and better utilization of IPC resources. Molds are ubiquitous in the environment but can cause severe opportunistic infections in immunocompromised patients. In 2021, the Hospital Laboratory introduced a highly sensitive cell free DNA mold polymerase chain reaction (cfDNA PCR) test. Infection Prevention and Control (IPC) saw an increase in positive mold results raising concern for potential hospital exposure. A modified mold healthcare-associated infection (HAI) investigation algorithm was created, integrating clinical correlation into test interpretation. In this retrospective study we assess the effect of the new cfDNA mold PCR panel on the rate of positive tests and describe the effect of the modified algorithm on HAI investigation. We used the institutional IPC database to review all positive mold tests among oncology and stem cell transplant (SCT) patients between 2017–2021. We compared the monthly rate of positive tests meeting HAI definition and investigations conducted per year before and after the introduction of the cfDNA mold PCR panel. We evaluated the effect of the modified mold HAI algorithm on the number of HAI investigations. Between 2017–2021 there were 15 positive mold tests meeting HAI definition in the oncology and SCT units. 50% Aspergillus species, 14.3% Rhizopus species, 14.3% Fusarium species and 21.4% (all in 2021) mucor species. The average positivity rate was 0.29 between 2017–2020 compared to 0.58 per month in 2021 after the introduction of the cfDNA mold PCR panel (P < 0.05). There were 5 HAI investigations in the past 5 years of them 4 in 2021. Mold HAI investigation was done twice after implementation of the revised algorithm. The new cfDNA mold PCR panel caused a significant increase in the rate of positive mold infections reported in the immunocompromised units. The modified mold HAI algorithm that integrated clinical correlation led to improved identification of HAI and better utilization of IPC resources.

Aflatoxins and Ochratoxin A in Red Chili (Capsicum) Powder from Tunisia: Co-Occurrence and Fungal Associated Microbiota

.&#x0D; Background: Mycotoxins are produced in foods as a result of mold infection of crops before and after harvest. The aim of this report was to assess, for the first time in Tunisia, the contamination of red chili powder with Aflatoxins (AFs) and Ochratoxin A (OTA) and to identify the associated microbiota.&#x0D; Methods: Fifty-five samples of red Capsicum powder (Capsicum annuum) were screened for AFs and OTA and toxigenic fungal species. Mycotoxins were extracted using immunoaffinity columns and quantified by High Performance Liquid Chromatography (HPLC). Dilution method was realized for fungal isolation and confirmed Polymerase Chain Reaction (PCR) analysis. Data were statistically analysed using statistical software (version 5.0).&#x0D; Results: Mycotoxins levels in 5 out of 55 samples were above the European Union (EU) limit. The highest co-occurrence of mycotoxins was found between AFB1 and OTA (39/55 samples). Aspergillus flavus and Aspergillus niger were the most toxigenic species identified. The highest level of molds contamination found in Capsicum powder reached 7.91×106 Colony Forming Unit (CFU)/g.&#x0D; Conclusion: The co-occurrence of two important mycotoxins (OTA and AFB1) observed in this study, alarm us about the hygienic risk raised by Tunisian consumers and raise the need to improve the production process for red Capsicum powder in Tunisia.

The Combination Treatment of Fosmanogepix and Liposomal Amphotericin B Is Superior to Monotherapy in Treating Experimental Invasive Mold Infections.

ABSTRACTInvasive pulmonary aspergillosis (IPA), invasive mucormycosis (IM), and invasive fusariosis (IF) are associated with high mortality and morbidity. Fosmanogepix (FMGX) is a first-in-class antifungal in clinical development with demonstrated broad-spectrum activity in animal models of infections. We sought to evaluate the benefit of combination therapy of FMGX plus liposomal amphotericin B (L-AMB) in severe delayed-treatment models of murine IPA, IM, and IF. While FMGX was equally as effective as L-AMB in prolonging the survival of mice infected with IPA, IM, or IF, combination therapy was superior to monotherapy in all three models. These findings were validated by greater reductions in the tissue fungal burdens (determined by quantitative PCR) of target organs in all three models versus the burdens in infected vehicle-treated (placebo) or monotherapy-treated mice. In general, histopathological examination of target organs corroborated the findings for fungal tissue burdens among all treatment arms. Our results show that treatment with the combination of FMGX plus L-AMB demonstrated high survival rates and fungal burden reductions in severe animal models of invasive mold infections, at drug exposures in mice similar to those achieved clinically. These encouraging results warrant further investigation of the FMGX–plus–L-AMB combination treatment for severely ill patients with IPA, IM, and IF.

Thermal Inactivation Kinetics and Radio Frequency Control of Aspergillus in Almond Kernels.

Mold infections in almonds are a safety issue during post-harvest, storage and consumption, leading to health problems for consumers and causing economic losses. The aim of this study was to isolate mold from infected almond kernels and identify it by whole genome sequence (WGS). Then, the more heat resistant mold was selected and the thermal inactivation kinetics of this mold influenced by temperature and water activity (aw) was developed. Hot air-assisted radio frequency (RF) heating was used to validate pasteurization efficacy based on the thermal inactivation kinetics of this target mold. The results showed that the two types of molds were Penicillium and Aspergillus identified by WGS. The selected Aspergillus had higher heat resistance than the Penicillium in the almond kernels. Inactivation data for the target Aspergillus fitted the Weibull model better than the first-order kinetic model. The population changes of the target Aspergillus under the given conditions could be predicted from Mafart’s modified Bigelow model. The RF treatment was effectively used for inactivating Aspergillus in almond kernels based on Mafart’s modified Bigelow model and the cumulative lethal time model.

Antifungals advance

Pharmaceutical firms are making progress in addressing the need for new antifungal therapies. F2G, which specializes in the treatment of rare fungal diseases, says it will receive $100 million from the Japanese firm Shionogi in a deal to develop olorofim, an antifungal agent for invasive aspergillosis and other rare mold infections. This news follows Mycovia Pharmaceuticals’ statement April 28 that the US Food and Drug Administration approved its azole antifungal Vivjoa (oteseconazole) for chronic yeast infections. The announcements reflect efforts to fill gaps in treating fungal infections, which have limited treatment options and increasing resistance . Olorofim is part of the first new class of antifungals to be developed in 20 years, according to F2G. Chief Operating Officer Mike Birch says the firm is preparing a new drug application to submit to the FDA later this year. The deal with Shionogi is focused on Europe and Asia. Olorofim works by

Multi-Mycotoxin Contamination, Mold Incidence and Risk Assessment of Aflatoxin in Maize Kernels Originating from Nepal

Occurrence of mycotoxins in staple foods is a major threat to attaining food safety in developing countries. The study investigated multi-mycotoxin contamination for the first time in Nepalese maize along with the incidence of molds in 45 samples of maize used as human food from 45 districts of Nepal. The samples were analyzed quantitatively for the presence of five different mycotoxins (total aflatoxins (AF), total fumonisins (FUM), ochratoxin (OT), zearalenone (ZEA) and (DON) deoxynivalenol) using the competitive direct ELISA technique. The most frequent occurrences were for DON (100%) and AF (78%) followed by FUM and ZEA (both 76%) and OT (62%). Interestingly, all the samples contained at least two mycotoxins while at least three or more mycotoxins were found in 87% of the samples. The most commonly reported binary, ternary and quaternary combinations were DON+AF, AF+FUM+DON and AF+FUM+ZEA+DON, respectively. The mean percentage kernel mold infection was 35.33% with Fusarium, Aspergillus, Rhizopus and Penicillium genera being the predominant molds. Six different species of Aspergillus and a single species of Fusarium were identified. The estimated daily intake, margin of exposure and risk of liver cancer from consuming maize were 30.46 ng/kg bw/day and 5.58 and 0.38 cancer cases/year/100,000 population, respectively. Since maize is the second-most consumed cereal in Nepal, the contamination levels of various mycotoxins and the incidence of molds identified in the study suggests that stricter control is needed to safeguard the health of the substantial population consuming maize as a staple diet.

Nonthermal plasma‐generated ozone inhibits human coronavirus 229E infectivity on glass surface

AbstractOzone has been used for surface disinfection to contain bacterial, fungal, mold, and certain viral infections; however, the use of ozone generated from nonthermal plasma devices have not been thoroughly investigated for surface disinfection. Here, we aimed to determine the impact of nonthermal plasma‐generated ozone (PGO) on the coronavirus. Human coronavirus 229E was exposed to PGO and its infectivity was evaluated. PGO exposure of approximately 7 ppm reduced the viral titer after 4 h. Our results indicate that PGO exposure not only reduces the expression of the viral nucleocapsid gene and spike glycoprotein levels but may also stimulate the expression of the antiviral response gene in host cells. These findings can thus be useful to support existing surface disinfection methods.

The effects of climate change on fungal diseases with cutaneous manifestations: A report from the International Society of Dermatology Climate Change Committee

Climate change affects all aspects of ecosystems, including humans and numerous microorganisms. Fungi are especially sensitive to climate extremes. Persistently warmer temperatures at increasingly higher latitudes are contributing to ongoing expansion of the geographic ranges of known fungal pathogens. Alongside fungal species’ advancement into new territories, many have the capacity to develop thermotolerance. Consequently, a greater number of previously unharmful or underappreciated fungal species may emerge due to climate change. More frequent extreme weather events - including heat waves, drought, and flooding - also foster circumstances that favor the survival and infectivity of pathogens. We reviewed the English language literature in order to describe what is known about the effects of climate change on fungal infections with cutaneous manifestations. We included candidal infections, dermatophytoses, other mold infections, and deep fungal infections, and focused on organisms with evidence of climate sensitivity, particularly those that are emerging, spreading to new geographic regions, or both. This may provide an important tool for understanding the epidemiological patterns underlying fungal transmission, predicting future outbreaks, and adopting effective control strategies.

Invasive Mold Infections in Patients with Hematologic Malignities: The Effects of Environmental Factors

Invasive fungal infections (IFI) continue to be an important cause of morbidity and mortality in patients with hematological malignancies. Candida and Aspergillus species constitute most of the IFI in these patients.. It has been reported that most of the invasive aspergillosis epidemics are related to the construction works in the hospital. In this study, we aimed to investigate the frequency of IFI in the old and the new hospital building after relocation in patients with hematological malignancies. Of 8042 patients who were hospitalized in the Department of Hematology, Ondokuz Mayıs University Faculty of Medicine between January 2015 and September 2019, 412 patients who were initiated antifungal therapy were included in the study. The patients in the hematology clinic, which were moved to the new oncology hospital building in January 2018, were grouped as prior and after relocation, and their demographical data, hematological diagnosis, chemotherapy regimens, mortality, IFI, focus of infection, presence of central venous catheter, antifungal prophylaxis and treatment, galactomannan level, fungal culture and computed tomography (CT) findings were evaluated retrospectively. It was determined that 55% of the patients were male and the median age was 58 (range:18-93). The rate of IFI development was 5.12% (n= 412) and the rate of invasive mold infection was 1.2% (n= 145). The most common hematological disease for which antifungal treatment initiated was acute myeloid leukemia (AML) with a rate of 50% (n= 206/412). Of patients, 73% received induction chemotherapy (42%, first induction, 31% reinduction), 13.4% received consolidation therapy. Invasive mold infection was diagnosed as 40% possible, 59% probable, 1% proven. While patients had similar characteristics such as age, gender, hematological disease, chemotherapy regimens and antifungal prophylaxis prior and after transportation, the rate of development of invasive mold infection was 2.1%, 2.06 / 1000 patient days, before transportation, 1.37% (p= 0.009), 1.15/1000 patient days (p<0.001) after transportation, and it was statistically significantly lower after transportation. The median value of galactomannan antigen was detected as 0.17 (0.02-5.9). Blood cultures revealed 10.3% fungal growth and the most common growth was Candida albicans with 54.8% and Mucor spp. as mold with 3.2%. Large-scale construction works such as renovation, extension and demolition works in old hospital buildings are a permanent condition in different units. Clinicians should be aware of that infections due to opportunistic fungi can be seen in immunosuppressive patients close to such construction sites, and even cause epidemics. It should be kept in mind that these infections, which can progress with serious morbidity and mortality are difficult to treat but can be prevented by infection control measures.