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Most fungal infections are common in humans. Pathogenic fungi are opportunistic but can cause fungal infection disease in patients with immunocompromised conditions, such as malignancy, chemotherapy, transplantation, acquired immunodeficiency syndrome, and usage of immunosuppressant drugs. Most invasive infections are caused by Aspergillus species, mucormycetes, Cryptococcus species, and Candida species. This article focuses on environmental fungi such as Aspergillus species and mucormycetes because the mode of transmission is different. The purpose of this article is to discuss invasive fungal infections (IFIs) caused by environmental fungi and to educate critical care nurses about infection control and risk mitigation to prevent IFIs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Children with hematologic malignancies, especially those who receive intensive chemotherapy, are at high risk for invasive mold infections (IMI) that confer substantial mortality. Randomized controlled trials support the use of antifungal prophylaxis with antimold activity as an optimal strategy for risk reduction in this population, but studies outlining the practical application of evidence-based recommendations are lacking., Procedure: We conducted a 15-year, single-institution retrospective review in a diverse cohort of children with hematologic malignancies treated with chemotherapy to determine the incidence of proven or probable IMI diagnosed between 2006 and 2020. Multivariable logistic regression was used to identify host and disease factors associated with IMI risk. We then compared the incidence and type of IMI and related factors before and after 2016 implementation of an evidence-based, risk-adapted antifungal prophylaxis algorithm that broadened coverage to include molds in patients at highest risk for IMI., Results: We identified 61 cases of proven or probable IMI in 1456 patients diagnosed with hematologic malignancies during the study period (4.2%). Implementation of an antifungal prophylaxis algorithm reduced the IMI incidence in this population from 4.8% to 2.9%. Both Hispanic ethnicity and cancer diagnosis prior to 2016 were associated with risk for IMI., Conclusion: An evidence-based, risk-adapted approach to antifungal prophylaxis for children with hematologic malignancies is an effective strategy to reduce incidence of IMI., (© 2021 Wiley Periodicals LLC.)

Invasive fungal infections are an important cause of morbidity and mortality in hospitalized patients and in the immunocompromised population. This article reviews the current epidemiology of nosocomial fungal infections in adult patients, with an emphasis on invasive candidiasis (IC) and invasive aspergillosis (IA). Included are descriptions of nosocomial infections caused by Candida auris, an emerging pathogen, and IC- and IA-associated with coronavirus disease 2019. The characteristics and availability of newer nonculture-based tests for identification of nosocomial fungal pathogens are discussed. Recently published recommendations and guidelines for the control and prevention of these nosocomial fungal infections are summarized., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Lung transplantation is an important treatment option for various end-stage lung diseases. However, survival remains limited due to graft rejection and infections. Despite that fungal infections are frequent and carry a bad prognosis, there is currently no consensus on efficacy, optimal drug, route, or duration of antifungal prophylaxis. This narrative review summarizes current strategies for antifungal prophylaxis after lung transplantation., Methods: English language articles in Embase, Pubmed, UptoDate, and bibliographies were used to assess the efficacy and safety of available antifungal agents for prophylaxis in adult lung transplant recipients., Results: Overall, there are limited high-quality data. Universal prophylaxis is more widely used and may be preferable over targeted prophylaxis. Both formulations of inhaled amphotericin B and systemic azoles are effective at reducing fungal infection rates, yet with their own specific advantages and disadvantages. The benefit of combination regimens has yet to be proven. Considering the post-transplant timing of the onset of fungal infections, postoperative prophylaxis during the first postoperative months seems indicated for most patients., Conclusions: Based on existing literature, universal antifungal prophylaxis with inhaled amphotericin B and systemic voriconazole for at least 3-6 mo after lung transplantation may be advisable, with a slight preference for amphotericin B because of its better safety profile., Competing Interests: The following authors are supported by a research fellowship: R.V. is a senior clinical research fellow of the Fund for Scientific Research Flanders (FWO). G.M.V. is supported by the Broere Charitable Foundation. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Infections occurring after CAR T-cells are a common complication. At the acute phase of treatment following CAR T-cell infusion, the exact incidence of infections is unknown given the overlapping symptoms with cytokine release syndrome. The risk factors for infection include the malignant underlying disease and its multiple treatments, and an immunosuppressive state induced by CAR-T cells themselves and the treatment of their complications. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of post-CAR infectious complications. In this review we discuss anti-infection prophylaxis and vaccination of patients undergoing CAR T-cell therapy as well as a special chapter for the specific case of COVID-19. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management and prevention of infectious complications associated with this new therapeutic approach., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Patients with invasive fungal disease (IFD) are at significant risk of morbidity and mortality. A productive partnership between patients, their carers/families, and the multidisciplinary team managing the infection and any underlying conditions, is essential. Sharing information and addressing knowledge gaps are required to ensure those at risk of IFD avoid infection, while those with suspected or confirmed infection optimise their therapy and avoid toxicities. This new addition to the Australian and New Zealand consensus guidelines for the management of IFD and antifungal use in the haematology/oncology setting outlines the key information needs of patients and their carers/families. It specifically addresses risk factor reduction, antifungal agents and adherence, and the risks and benefits of complementary and alternative therapies. Knowledge gaps are also identified to help inform the future research agenda., (© 2021 Royal Australasian College of Physicians.)

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0-18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome., (© 2021. The Author(s).)

Invasive fungal disease continues to be a cause of significant life-threatening morbidity and mortality in humans, particularly in those with a diminished immune system, such as with haematological malignancies. The mainstay of treating such life-threatening fungal infection has been antifungal drugs, including azoles, echinocandins and macrocyclic polyenes. However, like antibiotic resistance, antifungal resistance is beginning to emerge, potentially jeopardizing the effectiveness of these molecules in the treatment of fungal disease. One strategy to avoid this is the development of fungal vaccines. However, the inability to provoke a sufficient immune response in the most vulnerable immunocompromised groups has hindered translation from bench to bedside. This review will assess the latest available data and will investigate potential Aspergillus antigens and feasible vaccine techniques, particularly for vaccination of high-risk groups, including immunocompromised and immunosuppressed populations.

Central Kentucky horse pastures contain significant populations of tall fescue ( Schedonorus arundinacea (Schreb.) Dumort) infected with an endophyte ( Epichloë coenophialum (Morgan-Jones and Gams) Bacon and Schardl) known to produce several ergot alkaloids, with ergovaline in the highest concentration. While most classes of horses are not adversely affected by average levels of ergovaline in pastures, late term pregnant mares have a low tolerance to ergovaline and the related ergot alkaloids. Endophyte-infected tall fescue has been known to cause prolonged gestation, thickened placenta, dystocia, agalactia, and foal and mare mortality. The University of Kentucky Horse Pasture Evaluation Program utilizes ergovaline and endophyte testing, as well as pasture species composition, to calculate ergovaline in the total diet in broodmare pastures. This data is used to develop detailed management recommendations for individual pastures. Application of these recommendations has led to reduced tall fescue toxicity symptoms on these farms, as well as improved pasture management and improved forage quality and quantity.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

The co-evolutionary arms race between disease-causing agents and their insect victims is ancient and complex - leading to the development of specialised attack and defence strategies. Among such strategies is the capacity of fungal and oomycete pathogens to deploy degradative enzymes, notably proteases, to facilitate infection directly across the integument. To counter these proteases, insects such as the greater wax moth Galleria mellonella release metalloprotease inhibitors and other immune factors to thwart the invading fungus. To date, molecular-based confirmation of insect metalloprotease inhibitor's incontrovertible role in antifungal defence has been lacking. We targeted the IMPI gene for suppression using RNAi and exposed those insects to the entomopathogenic fungus Metarhizium brunneum ARSEF4556. Levels of IMPI were reduced significantly in the integument (10-fold) and fat body (5-fold) of RNAi-treated insects when compared to control larvae, and displayed a significantly higher mortality rate. We also surveyed candidate immune/detoxification gene expression levels (e.g., DOPA decarboxylase, galiomycin) in three tissues (integument, midgut, fat body) in order to gauge any potential non-target effects of RNAi. The loss of IMPI via RNAi compromises antifungal defences and leaves G. mellonella vulnerable to infection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: The author has no funding or conflicts of interest to disclose.

The development of effective vaccines against fungal infections requires the induction of protective, pathogen-specific cell-mediated immune responses. Here, we asked whether combination adjuvants based on delta inulin (Advax) formulated with Toll-like receptor (TLR) agonists could improve vaccine protection mediated by a fungal recombinant protein, Bl-Eng2 (i.e., Blastomyces endoglucanase 2), which itself harbors an immunodominant antigen and dectin-2 agonist/adjuvant. We found that Bl-Eng2 formulated with Advax3 containing TLR9 agonist or Advax8 containing TLR4 agonist provided the best protection against pulmonary infection with Blastomyces dermatitidis, being more effective than complete Freund's adjuvant or Adjuplex. Advax3 was most efficient in inducing gamma interferon (IFN-γ)- and interleukin-17 (IL-17)-producing antigen-specific T cells that migrated to the lung upon Blastomyces dermatitidis infection. Mechanistic studies revealed Bl-Eng2/Advax3 protection was tempered by neutralization of IL-17 and particularly IFN-γ. Likewise, greater numbers of lung-resident T cells producing IFN-γ, IL-17, or both IFN-γ and IL-17 correlated with fewer fungi recovered from lung. Protection was maintained after depletion of CD4 + T cells, partially reduced by depletion of CD8 + T cells, and completely eliminated after depletion of both CD4 + and CD8 + T cells. We conclude that Bl-Eng2 formulated with Advax3 is promising for eliciting vaccine-induced antifungal immunity, through a previously uncharacterized mechanism involving CD8 + and also CD4 + T cells producing IFN-γ and/or IL-17. Although no licensed vaccine exists as yet against any fungal disease, these findings indicate the importance of adjuvant selection for the development of effective fungal vaccines. IMPORTANCE Fungal disease remains a challenging clinical and public health problem. Despite medical advances, invasive fungal infections have skyrocketed over the last decade and pose a mounting health threat in immunocompetent and -deficient hosts, with worldwide mortality rates ranking 7th, even ahead of tuberculosis. The development of safe, effective vaccines remains a major hurdle for fungi. Critical barriers to progress include the lack of defined fungal antigens and suitable adjuvants. Our research is significant in identifying adjuvant combinations that elicit optimal vaccine-induced protection when formulated with a recombinant protective antigen and uncovering the mechanistic bases of the underlaying vaccine protection, which will foster the strategic development of antifungal vaccines.

Objective: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM)., Methods: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analyzed among patients exposed to prophylaxis by univariable analysis., Results: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100 000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06)., Conclusions: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored., (© 2021 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including β-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts  in vitro . Therapeutic effects have been seen in animal models  in vivo , and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from  in vitro, in vivo  and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections., Competing Interests: Competing interests: PMB is Stroke Association Professor of Stroke Medicine and is a NIHR Emeritus Senior Investigator; he is chief investigator of the BEET-Winter and PROTECT-CH trials and was chief investigator of 6 trials of GTN in acute stroke; he has received honoraria as Chair of the Steering Committee for DiaMedica. AG is co-chief investigator of the PROTECT-CH trial. AJW holds shares in HeartBeet Ltd, which receives a royalty from James White Drinks Ltd, which manufactures active nitrate-containing and placebo nitrate-depleted beetroot juice used in clinical studies. All the authors are investigators in the BEET-Winter trial. The authors have no association with any of the companies mentioned in this review., (Copyright: © 2021 Bath PM et al.)

Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including β-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts  in vitro . Therapeutic effects have been seen in animal models  in vivo , and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from  in vitro, in vivo  and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections., Competing Interests: Competing interests: PMB is Stroke Association Professor of Stroke Medicine and is a NIHR Emeritus Senior Investigator; he is chief investigator of the BEET-Winter and PROTECT-CH trials and was chief investigator of 6 trials of GTN in acute stroke; he has received honoraria as Chair of the Steering Committee for DiaMedica. AG is co-chief investigator of the PROTECT-CH trial. AJW holds shares in HeartBeet Ltd, which receives a royalty from James White Drinks Ltd, which manufactures active nitrate-containing and placebo nitrate-depleted beetroot juice used in clinical studies. All the authors are investigators in the BEET-Winter trial. The authors have no association with any of the companies mentioned in this review., (Copyright: © 2021 Bath PM et al.)

Background: Children with complete DiGeorge anomaly (cDGA) have congenital athymia plus a myriad of other challenging clinical conditions. The term cDGA encompasses children with congenital athymia secondary to 22q11.2DS, CHARGE syndrome (coloboma, heart defects, choanal atresia, growth or mental retardation, genital abnormalities, and ear abnormalities and/or deafness), and other genetic abnormalities. Some children have no known genetic defects. Since 1993, more than 100 children with congenital athymia have been treated with cultured thymus tissue implantation (CTTI). Naïve T cells develop approximately 6 to 12 months after CTTI. Most of the children had significant comorbidities such as heart disease, hypoparathyroidism, and infections requiring complex clinical care post cultured thymus tissue implantation (CTTI)., Objective: The purpose of this guidance is to assist multidisciplinary teams in caring for children with cDGA both before and after CTTI., Methods: Thirty-one specialists, in addition to the authors, were asked to share their experience in caring for children with cDGA at Duke University Health System, before and after CTTI. These specialists included physicians, nurses, dentists, therapists, and dieticians., Results: The goal of a multidisciplinary approach is to have children in the best possible condition for receiving CTTI and provide optimal care post CTTI through development of naïve T cells and beyond. The CTT (cultured thymus tissue) must be protected from high doses of steroids which can damage CTT. Organs must be protected from adverse effects of immunosuppression., Conclusion: Creating a multidisciplinary team and a detailed plan of care for children with cDGA is important for optimal outcomes.

Background: Invasive fungal infections (IFIs) are a leading cause of morbidity and death in immunocompromised patients. Data on efficacy and pharmacokinetics of posaconazole in pediatric patients are rare (1 to 5). Herein, we retrospectively analyzed adolescent patients who had received posaconazole as antifungal prophylaxis., Methods: We retrospectively analyzed patients who received posaconazole as primary or secondary antifungal prophylaxis., Results: A total of 34 adolescent patients, 19 men (55.9%) and 15 women (44.1%) with a mean age of 15.8±2.1 years were included. Twenty-five of 34 (73.5%) patients were on primary and nine of 34 (26.5%) patients were on secondary antifungal prophylaxis. Diagnosis of the patients receiving posaconazole as primary antifungal prophylaxis were acute myeloid leukemia (n=12, 48%), hematopoietic stem cell transplantation (n=7, 28%), acute lymphoblastic leukemia (n=5, 20%), and Fanconi aplastic anemia (n=1, 4%). Five patients (55.6%) with hematopoietic stem cell transplantation, 1 patient with acute myeloid leukemia (11.1%), 1 patient with Fanconi aplastic anemia (11.1%), and 2 (22.2%) patients with chronic granulomatous disease received posaconazole as secondary antifungal prophylaxis. Twelve of 25 (48%) patients receiving posaconazole as primary antifungal prophylaxis were complicated by IFI; 4 of them were proven, 6 probable, and 2 with possible IFI. Three of 9 patients (33.3%) receiving posaconazole as secondary antifungal prophylaxis was complicated by IFI (P=0.29), 2 of them were probable and 1 was possible IFI. Five of 25 patients (20%) receiving posaconazole as primary prophylaxis died because of IFI., Conclusion: Improvement of antifungal prophylaxis in patients with high risk of invasive infections seems clearly necessary, and analyzing serum posaconazole levels and individualizing dosing may be 1 approach to improve outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Fungal pathogens, among other stressors, negatively impact the productivity and population size of honey bees, one of our most important pollinators (1, 2), in particular their brood (larvae and pupae) (3, 4). Understanding the factors that influence disease incidence and prevalence in brood may help us improve colony health and productivity. Here, we examined the capacity of a honey bee-associated bacterium, Bombella apis, to suppress the growth of fungal pathogens and ultimately protect bee brood from infection. Our results showed that strains of B. apis inhibit the growth of two insect fungal pathogens, Beauveria bassiana and Aspergillus flavus, in vitro . This phenotype was recapitulated in vivo ; bee broods supplemented with B. apis were significantly less likely to be infected by A. flavus. Additionally, the presence of B. apis reduced sporulation of A. flavus in the few bees that were infected. Analyses of biosynthetic gene clusters across B. apis strains suggest antifungal candidates, including a type 1 polyketide, terpene, and aryl polyene. Secreted metabolites from B. apis alone were sufficient to suppress fungal growth, supporting the hypothesis that fungal inhibition is mediated by an antifungal metabolite. Together, these data suggest that B. apis can suppress fungal infections in bee brood via secretion of an antifungal metabolite. IMPORTANCE Fungi can play critical roles in host microbiomes (5-7), yet bacterial-fungal interactions are understudied. For insects, fungi are the leading cause of disease (5, 8). In particular, populations of the European honey bee (Apis mellifera), an agriculturally and economically critical species, have declined in part due to fungal pathogens. The presence and prevalence of fungal pathogens in honey bees have far-reaching consequences, endangering other species and threatening food security (1, 2, 9). Our research highlights how a bacterial symbiont protects bee brood from fungal infection. Further mechanistic work could lead to the development of new antifungal treatments.

Despite the wide variety of strategies developed to combat pathogenic microorganisms, the infectious diseases they cause remain a worldwide health issue. Hence, the search for new disinfectants, which prevent infection spread, constitutes an extremely urgent task. One of the most promising methods is the use of photoactive compounds - photosensitizers, capable of generating reactive oxygen species, in particular, singlet oxygen (O2(1Δg)), which causes rapid and effective death of microorganisms of all types. In this work, we propose the utilization of the powdered cluster complex (Bu4N)2[{Mo6I8}(OTs)6] as a photoactive additive to commercially available fluoroplastic lacquer F-32L to create heterogeneous self-sterilizing coatings. We show that soaking of the prepared films in water for 60 days did not lead to a decrease in their photosensitization properties indicating their excellent stability. Moreover, the use of the cluster complex in the solid state allowed significant expansion of the operating wavelength range, which covers the UV region and a large part of the visible region (250-650 nm). The films displayed high photoantimicrobial activity against five common pathogens (bacteria and fungi) under white-light irradiation. Overall, the properties demonstrated make these materials promising for practical use in everyday outdoor and indoor disinfection since they are active under both sunlight and artificial lighting.

Harmful fungi in nature not only cause diseases in plants, but also fungal infection and poisoning when people and animals eat food derived from crops contaminated with them. Unfortunately, such fungi are becoming increasingly more resistant to traditional synthetic antifungal drugs, which can make prevention and control work increasingly more difficult to achieve. This means they are potentially very harmful to human health and lifestyle. Antifungal peptides are natural substances produced by organisms to defend themselves against harmful fungi. As a result, they have become an important research object to help deal with harmful fungi and overcome their drug resistance. Moreover, they are expected to be developed into new therapeutic drugs against drug-resistant fungi in clinical application. This review focuses on antifungal peptides that have been isolated from bacteria, fungi, and other microorganisms to date. Their antifungal activity and factors affecting it are outlined in terms of their antibacterial spectra and effects. The toxic effects of the antifungal peptides and their common solutions are mentioned. The mechanisms of action of the antifungal peptides are described according to their action pathways. The work provides a useful reference for further clinical research and the development of safe antifungal drugs that have high efficiencies and broad application spectra.

Tacrolimus, an immunosuppressant prescribed to reduce the risk of organ rejection, is metabolized by cytochrome P450 and is a substrate for P-glycoprotein. Many medications affect tacrolimus concentrations, making it difficult to maintain exposure within its narrow therapeutic index. Clotrimazole troches, prescribed to posttransplant recipients immediately for the first 30 days for oral candidiasis prevention, are considered nonsystemic. However, data suggest a potential drug interaction, affecting tacrolimus exposure. To assess the magnitude of the effect of clotrimazole on tacrolimus trough levels, 97 kidney transplant recipients, on a stable dose of tacrolimus, were retrospectively evaluated. Tacrolimus trough concentrations were analyzed 7 and 14 days before and after discontinuation of clotrimazole. The median change in tacrolimus trough level was -1.3 ng/mL (confidence interval, -2.5, -1.0; P < .001) at day 7 and -2.8 ng/mL (confidence interval, -3.3, -1.6; P < .001) at day 14 after clotrimazole discontinuation, from a median baseline of 8.9 ng/mL. Overall, a reduction in tacrolimus level was observed in 60% of patients after discontinuation of clotrimazole. When assessing the effect of race and sex, no influence was found on the degree of change in tacrolimus level after clotrimazole discontinuation. In conclusion, clotrimazole exerts a significant interaction on tacrolimus where close monitoring of tacrolimus trough levels after discontinuation of clotrimazole is warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Invasive fungal infections threaten lung transplant outcomes with high associated morbidity and mortality. Pharmacologic prophylaxis may be key to prevent posttransplant invasive fungal infections, but cost, adverse effects, and absorption issues are barriers to effective prophylaxis. Trends in fungal infection diagnostic strategies utilize molecular diagnostic methodologies to complement traditional histopathology and culture techniques. While lung transplant recipients are susceptible to a variety of fungal pathogens, Candida spp. and Aspergillus spp. infections remain the most common. With emerging resistant organisms and multiple novel antifungal agents in the research pipeline, it is likely that treatment strategies will continue to evolve., Competing Interests: None declared., (Thieme. All rights reserved.)

Fungi are an integral part of the mammalian microbiota colonizing most if not all mucosal surfaces and the skin. Maintaining stable colonization on these surfaces is critical for preventing fungal dysbiosis and infection, which in some cases can lead to life threatening consequences. The epithelial barriers are protected by T cells and additional controlling immune mechanisms. Noncirculating memory T cells that reside stably in barrier tissues play an important role for host protection from commensals and recurrent pathogens due to their fast response and local activity, which provides them a strategic advantage. So far, only a few specific examples of tissue resident memory T cells (TRMs) that act against fungi have been reported. This review provides an overview of the characteristics and functional attributes of TRMs that have been established based on human and mouse studies with various microbes. It highlights what is currently known about fungi specific TRMs mediating immunosurveillance, how they have been targeted in preclinical vaccination approaches and how they can promote immunopathology, if not controlled. A better appreciation of the host protective and damaging roles of TRMs might accelerate the development of novel tissue specific preventive strategies against fungal infections and fungi-driven immunopathologies., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 LeibundGut-Landmann.)

Background: Mold-active primary antifungal prophylaxis (PAP) is routinely recommended in neutropenic patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing remission-induction chemotherapy (RIC). Isavuconazole (ISAV) is an extended spectrum mold-active triazole and has superior tolerability and fewer significant drug-drug interactions compared with other triazoles., Methods: In our investigator-initiated, phase 2 trial, treatment-naive adult patients with AML or MDS starting RIC received ISAV per the dosing recommendations in the US label until neutrophil recovery (absolute neutrophil count [ANC] ≥ 0.5 × 109/L) and attainment of complete remission, occurrence of invasive fungal infection (IFI), or for a maximum of 12 weeks. The primary endpoint was the incidence of proven/probable IFI during ISAV PAP and up to 30 days after the last dose., Results: Sixty-five of 75 enrolled patients received ISAV PAP (median age, 67 years, median ANC at enrollment, 0.72 × 109/L). Thirty-two patients (49%) received oral targeted leukemia treatments (venetoclax, FTL3 inhibitors). Including the 30-day follow-up period, probable/proven and possible IFIs were encountered in 4 (6%) and 8 patients (12%), respectively. ISAV trough serum concentrations were consistently > 1 µg/mL, showed low intraindividual variation, and were not significantly influenced by chemotherapy regimen. Tolerability of ISAV was excellent, with only 3 cases (5%) of mild to moderate elevations of liver function tests and no QTc prolongations., Conclusions: ISAV is a safe and effective alternative for PAP in patients with newly diagnosed AML/MDS undergoing RIC in the era of recently approved or emerging small-molecule antileukemia therapies., Clinical Trials Registration: NCT03019939., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Breakdown of the developmentally immature epidermal barrier may permit entry for micro-organisms leading to invasive infection in preterm infants. Topical emollients may improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in preterm infants., Objectives: To assess the effect of topical application of emollients (ointments, creams, or oils) on the risk of invasive infection and mortality in preterm infants., Search Methods: We searched CENTRAL via Cochrane Register of Studies (CRS) Web and MEDLINE via Ovid (updated 08 January 2021) and the reference lists of retrieved articles., Selection Criteria: Randomised or quasi-randomised controlled trials that assessed the effect of prophylactic application of topical emollient on the risk of invasive infection, mortality, other morbidity, and growth and development in preterm infants., Data Collection and Analysis: We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on mortality and invasive infection., Main Results: We included 22 trials with a total of 5578 infant participants. The main potential sources of bias were lack of clarity on the methods used to generate random sequences and conceal allocation in half of the trials, and lack of masking of parents, caregivers, clinicians, and investigators in all of the trials. Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in healthcare facilities in high-income countries. Meta-analyses suggested that topical ointments or creams may have little or no effect on invasive infection (RR 1.13, 95% confidence interval (CI) 0.97 to 1.31; low certainty evidence) or mortality (RR 0.94, 95% CI 0.82 to 1.08; low certainty evidence). Fifteen trials (3492 infants) assessed the effect of topical plant or vegetable oils. Most of these trials were undertaken in low- or middle-income countries and were based in healthcare facilities. One large (2249 infants) community-based trial occurred in a rural field practice in India. Meta-analyses suggested that topical oils may reduce invasive infection (RR 0.71, 95% CI 0.52 to 0.96; I² = 52%; low certainty evidence) but have little or no effect on mortality (RR 0.94, 95% CI 0.82 to 1.08, I² = 3%; low certainty evidence). One trial (316 infants) that compared petroleum-based ointment versus sunflower seed oil in very preterm infants in Bangladesh showed little or no effect on invasive infection (RR 0.91, 95% CI 0.57 to 1.46; low certainty evidence), but suggested that ointment may lower mortality slightly (RR 0.82, 95% CI 0.68 to 0.98; RD -0.12, 95% CI -0.23 to -0.01; number needed to treat for an additional beneficial outcome 8, 95% CI 4 to 100; low certainty evidence). One trial (64 infants) that assessed the effect of coconut oil versus mineral oil in preterm infants with birth weight 1500 g to 2000 g in India reported no episodes of invasive infection or death in either group (very low certainty evidence)., Authors' Conclusions: The level of certainty about the effects of emollient therapy on invasive infection or death in preterm infants is low. Since these interventions are mostly inexpensive, readily accessible, and generally acceptable, further good-quality randomised controlled trials in healthcare facilities, and in community settings in low- or middle-income countries, may be justified., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) are at high risk for invasive fungal disease (IFD)., Methods: This multicenter, randomized, open-label trial planned to enroll 560 children and adolescents (3 months to <21 years) undergoing allogeneic HCT between April 2013 and September 2016. Eligible patients were randomly assigned to antifungal prophylaxis with caspofungin or a center-specific comparator triazole (fluconazole or voriconazole). Prophylaxis was administered from day 0 of HCT to day 42 or discharge. The primary outcome was proven or probable IFD at day 42 as adjudicated by blinded central review. Exploratory analysis stratified this evaluation by comparator triazole., Results: A planned futility analysis demonstrated a low rate of IFD in the comparator triazole arm, so the trial was closed early. A total of 290 eligible patients, with a median age of 9.5 years (range 0.3-20.7), were randomized to caspofungin (n = 144) or a triazole (n = 146; fluconazole, n = 100; voriconazole, n = 46). The day 42 cumulative incidence of proven or probable IFD was 1.4% (95% confidence interval [CI], 0.3%-5.4%) in the caspofungin group vs 1.4% (95% CI, 0.4%-5.5%) in the triazole group (P = .99, log-rank test). When stratified by specific triazole, there was no significant difference in proven or probable IFD at day 42 between caspofungin vs fluconazole (1.0%, 95% CI, 0.1%-6.9%, P = .78) or caspofungin vs voriconazole (2.3%, 95% CI, 0.3%-15.1%, P = .69)., Conclusions: In pediatric HCT patients, prophylaxis with caspofungin did not significantly reduce the cumulative incidence of early proven or probable IFD compared with triazoles. Future efforts to decrease IFD-related morbidity and mortality should focus on later periods of risk., Trial Registration: NCT01503515., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Despite improvements in neonatal intensive care, the outcomes of extremely-low-birth-weight infants (ELBWIs) with surgical diseases remain to be improved. We started administering enteral miconazole (MCZ) to ELBWIs from 2002 to prevent fungal infection. Since then, the incidence of intestinal perforation has significantly decreased. We investigated this prophylactic effect of MCZ against necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) and explored a new prophylactic concept against intestinal perforation., Methods: We designed a historical cohort study to evaluate the effect of MCZ for intestinal perforation in ELBWIs who underwent treatment in our neonatal intensive-care unit between January 1998 and December 2005. We divided these cases into two groups: the Pre-MCZ group and the Post-MCZ group. We compared the morbidity, clinical outcomes and pathological features of NEC and FIP., Results: The rate of intestinal perforation with NEC was significantly reduced after the introduction of MCZ (p = 0.007, odds ratio; 3.782, 95% confidence interval; 1.368-12.08). The pathological findings of NEC specimens showed that the accumulation of inflammatory cells was significantly reduced in the Post-MCZ group when compared with the Pre-MCZ group (p < 0.05)., Conclusions: The efficacy of the enteral administration of MCZ on intestinal perforation with NEC highlights a new prophylactic concept in the clinical management of ELBWIs.

A diet rich in nutrients should be implemented in order to boost the immune system and prevent infections. To investigate which nutrients are commonly consumed, an anonymous survey was given to 120 individuals and their responses were collected. The respondents answered questions relating to their health status, and their consumption of nutrients and supplements that produce immunomodulating effects. The participants were also asked about any prior viral, bacterial or fungal infections experienced, and in particular, infection frequency, course, and duration. The data collected were subjected to a statistical analyses to assess the relationship between the reported frequency of infections and nutrients consumed including vitamins D3, A, C, E, selenium, zinc, iron, β-carotene, omega-3 fatty acids as well as live active probiotic bacteria. The findings show that vitamin and mineral supplementation did not positively affect the duration, frequency, or course of infections in the surveyed sample. An exception was vitamin D3 supplementation that was correlated to sporadic incidence of viral infections. Conversely, immunity was positively affected by consumption of natural nutrients contained in whole food (vitamin C, iron, selenium, omega-3 fatty acids), evidenced by lower incidences and milder courses of infection.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CAR-T constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CAR-T therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CAR-T cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CAR-T therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CAR-T cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CAR-T cell therapy.

Batrachochytrium dendrobatidis ( Bd ) is an important fungal pathogen present in wild hellbender ( Cryptobranchus alleganiensis ) populations that appears to cause disease during novel exposure and acute stress. Hellbender repatriation efforts are ongoing to combat declining populations, but mortality by chytridiomycosis (disease from Bd ) after release has been reported. The goal was to determine whether a safe antifungal agent could be administered and provide prolonged plasma concentrations without repeated handling. A subcutaneous implant impregnated with 24.5 mg of terbinafine was tested in three juvenile eastern hellbenders ( C. a. alleganiensis ) raised in human care, and plasma terbinafine concentrations were recorded from weekly to biweekly for 141 days. Plasma concentrations were variable, with peak plasma concentrations of 1,610, 112, and 66 ng/ml between 28 and 56 days postimplant. Although all hellbenders achieved plasma concentrations above the published minimum inhibitory concentration for terbinafine against Bd zoospores (63 ng/ml) at several time points, only one individual remained above this threshold for more than two consecutive time intervals. Results show the potential for these implants as a prophylaxis for chytridiomycosis in captive-to-wild hellbender releases. However, further investigation will be needed to determine the plasma concentrations required to achieve prophylaxis in vivo and implant reliability.

Background: Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events., Methods: We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low., Results: Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups., Discussion: In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Wheat rusts are the key biological constraint to wheat production in Ethiopia-one of Africa's largest wheat producing countries. The fungal diseases cause economic losses and threaten livelihoods of smallholder farmers. While it is known that wheat rust epidemics have occurred in Ethiopia, to date no systematic long-term analysis of past outbreaks has been available. We present results from one of the most comprehensive surveillance campaigns of wheat rusts in Africa. More than 13,000 fields have been surveyed during the last 13 years. Using a combination of spatial data-analysis and visualization, statistical tools, and empirical modelling, we identify trends in the distribution of wheat stem rust (Sr), stripe rust (Yr) and leaf rust (Lr). Results show very high infection levels (mean incidence for Yr: 44%; Sr: 34%; Lr: 18%). These recurrent rust outbreaks lead to substantial economic losses, which we estimate to be of the order of 10s of millions of US-D annually. On the widely adopted wheat variety, Digalu, there is a marked increase in disease prevalence following the incursion of new rust races into Ethiopia, which indicates a pronounced boom-and-bust cycle of major gene resistance. Using spatial analyses, we identify hotspots of disease risk for all three rusts, show a linear correlation between altitude and disease prevalence, and find a pronounced north-south trend in stem rust prevalence. Temporal analyses show a sigmoidal increase in disease levels during the wheat season and strong inter-annual variations. While a simple logistic curve performs satisfactorily in predicting stem rust in some years, it cannot account for the complex outbreak patterns in other years and fails to predict the occurrence of stripe and leaf rust. The empirical insights into wheat rust epidemiology in Ethiopia presented here provide a basis for improving future surveillance and to inform the development of mechanistic models to predict disease spread., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants., Study Design: Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results., Results: Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36-0.86; I 2  = 58%; 10 studies; 3,470 subjects; level of evidence [LOE]: low) significantly. Similarly, lactoferrin supplementation without probiotics decreased all LOS (RR: 0.43; 95% CI: 0.29-0.62; I 2  = 0%; 8 studies; 1,209 subjects; LOE: moderate) significantly. Lactoferrin supplementation did not significantly reduce necrotizing enterocolitis (RR: 0.62; 95% CI: 0.29-1.33; I 2  = 43%; 6 studies; 3,079 subjects; LOE: low), all-cause mortality (RR: 0.74; 95% CI: 0.36-1.53; I 2  = 53%; 8 studies; 3,395 subjects; LOE: very low), bronchopulmonary dysplasia (RR: 1; 95% CI: 0.90-1.13; I 2  = 0%; 4 studies; 2,570 subjects; LOE: moderate), and threshold retinopathy of prematurity eligible for surgical treatment (RR: 0.61; 95% CI: 0.25-1.51; I 2  = 74%; 2 studies; 2,481 subjects; LOE: very low)., Conclusion: Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Cirrhotic patients are at a high risk of fungal infections. Voriconazole is widely used as prophylaxis and in the treatment of invasive fungal disease. However, the safety, pharmacokinetics, and optimal regimens of voriconazole are currently not well defined in cirrhotic patients., Design: Retrospective pharmacokinetics study., Setting: Two large, academic, tertiary-care medical center., Patients: Two hundred nineteen plasma trough concentrations (C min ) from 120 cirrhotic patients and 83 plasma concentrations from 11 non-cirrhotic patients were included., Methods: Data pertaining to voriconazole were collected retrospectively. A population pharmacokinetics analysis was performed and model-based simulation was used to optimize voriconazole dosage regimens., Results: Voriconazole-related adverse events (AEs) developed in 29 cirrhotic patients, and the threshold C min for AE was 5.12 mg/L. A two-compartment model with first-order elimination adequately described the data. The Child-Pugh class and body weight were the significant covariates in the final model. Voriconazole clearance in non-cirrhotic, Child-Pugh class A and B cirrhotic (CP-A/B) and Child-Pugh class C cirrhotic (CP-C) patients was 7.59, 1.86, and 0.93 L/hour, respectively. The central distribution volume and peripheral distribution volume was 100.8 and 55.2 L, respectively. The oral bioavailability was 91.6%. Model-based simulations showed that a loading dose regimen of 200 mg/12 hours intravenously or orally led to 65.0-75.7% of voriconazole C min in therapeutic range on day 1, and the appropriate maintenance dosage regimens were 75 mg/12 hours and 150 mg/24 hours intravenously or orally for CP-A/B patients, and 50 mg/12 hours and 100 mg/24 hours intravenously or orally for CP-C patients. The predicted probability of achieving the therapeutic target concentration for optimized regimens at steady-state was 66.8-72.3% for CP-A/B patients and 70.3-74.0% for CP-C patients., Conclusions: These results recommended that the halved loading dose regimens should be used, and voriconazole maintenance doses in cirrhotic patients should be reduced to one-fourth for CP-C patients and to one-third for CP-A/B patients compared to that for patients with normal liver function., (© 2020 Pharmacotherapy Publications, Inc.)

Pulmonary mycoses are associated with high morbidity and mortality. The current standard treatment by systemic administration is limited by inadequate local bioavailability and systemic toxic effects. Aerosolisation of antifungals is an attractive approach to overcome these problems, but no inhaled antifungal formulation is currently available for the treatment of pulmonary mycoses. Hence, the development of respirable antifungals formulations is of interest and in high demand. In this review, the recent advances in the development of antifungal formulations for pulmonary delivery are discussed, including both nebulised and dry powder formulations. Although the clinical practices of nebulised parenteral amphotericin B and voriconazole formulations (off-label use) are reported to show promising therapeutic effects with few adverse effects, there is no consensus about the dosage regimen (e.g. the dose, frequency, and whether they are used as single or combination therapy). To maximise the benefits of nebulised antifungal therapy, it is important to establish standardised protocol that clearly defines the dose and specifies the device and the administration conditions. Dry powder formulations of antifungal agents such as itraconazole and voriconazole with favourable physicochemical and aerosol properties are developed using various powder engineering technologies, but it is important to consider their suitability for use in patients with compromised lung functions. In addition, more biological studies on the therapeutic efficacy and pharmacokinetic profile are needed to demonstrate their clinical potential., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Commensal fungi are an important part of human microbial community, among which Candida albicans and Candida glabrata are two common opportunistic pathogens. Unlike the high pathogenicity of C. albicans, C. glabrata is reported to show low pathogenicity to the host. Here, by using a Galleria mellonella infection model, we were able to confirm the much lower virulence of C. glabrata than C. albicans . Interestingly, pre-exposure to live C. glabrata (LCG) protects the larvae against subsequent various lethal fungal infections, including C. albicans, Candida tropicalis, and Cryptococcus neoformans . Inconsistently, heat-inactivated C. glabrata (HICG) pre-exposure can only protect against C. albicans or C. tropicalis re-infection, but not C. neoformans . Mechanistically, LCG or HICG pre-exposure enhanced the fungicidal activity of hemocytes against C. albicans or C. tropicalis . Meanwhile, LCG pre-exposure enhanced the humoral immunity by modulating the expression of fungal defending proteins in the cell-free hemolymph, which may contribute to the protection against C. neoformans . Together, this study suggests the important role of C. glabrata in enhancing host immunity, and demonstrates the great potential of G. mellonella model in studying the innate immune responses against infections.

Purpose of Review: Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes., Recent Findings: Infections occur in 23-42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0-30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon., Summary: Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.

Background: Peritoneal dialysis-associated peritonitis can uncommonly be caused by fungal infections. When they do present, they are associated with significant mortality and morbidity. We describe a case where a sample of peritoneal dialysate fluid grew Rhodotorula muciliginosa, a yeast organism present in the normal environment which has previously been reported as rarely causing peritonitis. We believe this is the first case where the Rhodotorula spp. and its origin has been identified., Case Presentation: A 20 year old male grew Rhodotorula muciliginosa from his peritoneal dialysis fluid on three separate occasions when a fluid sample was sent following a disconnection and subsequent set change. He was not systemically unwell and his peritoneal dialysate was clear. As Rhodotorula spp. is exceedingly difficult to treat our patient had his Tenchkoff catheter removed. Subsequent samples of soil and sand from his bearded dragon and Chilean tarantula cases, kept in his bedroom where dialysis occurred, were tested. The tarantula sand was identified as the source of the Rhodotorula spp. Of note, Candida was isolated from sand from the bearded dragon case. Once his Tenchkoff was removed he was treated with an intravenous course of antifungal therapy. He has since had a new Tenchkoff catheter inserted and recommenced PD following education around pets and hygiene., Conclusions: In this era where people are keeping increasingly rare and unusual wildlife in their homes, this case highlights the need for clinician and nursing staff awareness of a patient's home environment and hobbies when they are undergoing peritoneal dialysis. Sand from our patient's tarantula case grew the colonising organism but interestingly soil from his bearded dragon case also isolated candida. This can also cause difficult to treat peritonitis.

Background: Patients with cystic fibrosis have increased morbidity/mortality due to chronic respiratory infections, which primarily originate from the environment. Infection prevention and control emphasize the importance of cleaning and disinfection of respiratory devices, however, there is a paucity of guidance on toothbrush hygiene, which have been shown to be a source of cystic fibrosis (CF) pathogens., Methods: This study examined steam disinfection of toothbrushes contaminated with clinically significant CF isolates (n = 80; Gram positive = 33; Gram negative = 32, and non-tuberculous mycobacteria = 6) and yeasts (n = 9), as well as oral streptococci (n = 26) and environmental Pseudomonas aeruginosa (n = 12)., Results: Steam disinfection eradicated all organisms tested, as well as all organisms in CF sputum applied to toothbrushes., Conclusions: Steam disinfection offers a relatively simple, cheap and available method of eliminating non-spore-forming CF pathogens on toothbrushes. Toothbrushes should be thoroughly rinsed after each use before steam disinfection, to remove plaque, epithelial cells, and residual toothpaste. Toothbrushes should be steam disinfected after each use employing a baby bottle steam disinfector, adhering to manufacturers' operating instructions and stored in the disinfector until next used within 12 to 24 hours. Toothbrushes should be replaced every 3 to 4 months, or sooner if the bristles look worn out, as well as every time a pulmonary exacerbation occurs or every time the patient is treated for a pulmonary/throat infection. Steam disinfection of toothbrushes is crucial when the patient is undergoing eradication regimes for P. aeruginosa and methicillin-resistant Staphylococcus aureus, so that the patient does not become reinfected from this source, thereby aiding eradication and enhancing patient safety., (© 2020 Wiley Periodicals LLC.)

Energy efficiency technologies are now a feature in hospital design, with active chilled beams an example of one in use worldwide. Such innovations have clear benefits but there is a paucity of information with respect to any infection control risks. We describe our experience of chilled beam technology from one of our hospitals where we faced challenges with cleaning and episodes of water ingress including condensation. We highlight the importance of infection control risk assessment in relation to new technologies and the implementation of appropriate risk mitigation., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Introduction: Infections remain a significant problem, in patients undergoing an allogeneic hematopoietic stem-cell transplant (HSCT) and efforts have been made over the years, to reduce the incidence, morbidity and mortality of infectious complications., Areas Covered: This manuscript is focused on the epidemiology, risk factors and prevention of infections after allogeneic HSCT. A systematic literature review was performed using the PubMed database, between November 2019 and January 2020, with the following MeSH terms: stem-cell transplantation, infection, fungal, bacterial, viral, prophylaxis, vaccines, prevention. The authors reviewed all the publications, and following a common revision, a summary report was made and results were divided in three sections: bacterial, fungal and viral infections., Expert Opinion: Different infections occur in the early, intermediate and late post-transplant period, due to distinct risk factors. Improved diagnostic techniques, pre-emtive therapy and better prophylaxis of immunologic complications, have reduced the morbidity and mortality of infections. The role of the gut microbiota is under careful scrutiny and may further help us to identify high-risk patients.

To prevent transmission of the pathogenic chytrid fungi Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal), hygiene protocols prescribe the single use of disposable gloves for handling amphibians. We discovered that rinse water from nitrile gloves instantly kills 99% of Bd and Bsal zoospores. Transmission experiments using midwife toads (Alytes obstetricans) and Bd, and Alpine newts (Ichthyosaura alpestris) and Bsal, show that the use of the same pair of gloves for 2 subsequent individuals does not result in significant transmission of any chytrid fungus. In contrast, handling infected amphibians bare-handed caused transmission of Bsal in 4 out of 10 replicates, but did not result in transmission of Bd. Based on the manufacturer's information, high resolution mass spectrometry (HRMS) and colorimetric tests, calcium lactate and calcium nitrate were identified as compounds with antifungal activity against both Bd and Bsal. These findings corroborate the importance of wearing gloves as an important sanitary measure in amphibian disease prevention. If the highly recommended single use of gloves is not possible, handling multiple post-metamorphic amphibians with the same pair of nitrile gloves should still be preferred above bare-handed manipulation., Competing Interests: The authors have declared that no competing interests exist.