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In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.

Fungal disease poses a growing threat to public health that our current antifungal therapies are not well equipped to meet. As the population of immunocompromised hosts expands, and ecological changes favor the emergence of fungal pathogens, the development of new antifungal agents, including vaccines, becomes a global priority. Here, we summarize recent advancements in the understanding of fungal pathogenesis, key features of the host antifungal immune response, and how these findings could be leveraged to design novel approaches to deadly fungal disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Posaconazole is a vital drug to treat and prevent invasive fungal infections. Several factors, such as sex, body weight, total serum proteins, dietary intake, and severe mucositis, affect posaconazole pharmacokinetics (PKs). However, the relevance of other factors that affect the PKs of posaconazole in hematopoietic stem cell transplantation (HSCT) is unknown. This study explored factors influencing the PKs of posaconazole in HSCT recipients and nontransplant patients with hematological diseases., Methods: The authors conducted a single-institution, retrospective study. Forty-two Japanese inpatients receiving oral posaconazole tablets as prophylaxis for fungal infections were enrolled in this study. A one-compartment model with first-order absorption was used as the structural pharmacokinetic model. A population PK (PopPK) analysis was performed using a nonlinear mixed-effects modeling program, using a first-order conditional estimation method with interactions. Perl-speaks-NONMEM and R were used to evaluate the goodness of fit and visualize the output., Results: In 29% of the enrolled patients, the serum concentration of posaconazole was <0.5 mcg/mL, considered the effective range. PopPK analysis revealed that the patient had undergone HSCT within 1 year, diarrhea occurred more than 5 times a day, and aspartate aminotransferase were covariates that influenced apparent clearance (CL/F). The CL/F of posaconazole was 1.43-fold higher after HSCT and 1.26-fold higher during diarrhea., Conclusions: PopPK analysis revealed that HSCT, diarrhea, and aspartate aminotransferase were factors associated with the CL/F of posaconazole. The trough concentration of posaconazole may be below the therapeutic range in a few patients with diarrhea and/or after HSCT. As invasive fungal infections in patients with hematologic diseases can be life-threatening, therapeutic drug monitoring of posaconazole is strongly recommended, and patients should be carefully monitored., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB., Patients and Methods: Patients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB., Results: Both regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05)., Discussion: These results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL)., Methods: We retrospectively reviewed clinical records of LBCL patients treated with CD19-targeted CAR T-cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T-cell infusion until disease progression, death or last follow-up., Results: Overall, 137 patients were included. Thirty six percent had received ≥3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto-HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR-T treatment. Infection-related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto-HCT, ≥3 lines of treatment and pre-lymphodepletion neutropenia., Conclusions: Infections after CAR T-cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Acute myeloid leukemia patients are at high risk for infections, which contribute to increased mortality rates of up to 70%. The use of antimicrobial prophylaxis has been shown to significantly lower rates of infection. Therefore, this retrospective study aimed to evaluate the effect of two agents that showed effective results in the literature, levofloxacin and fluconazole, as prophylaxis strategies in AML patients., Methodology: A total of 85 AML patients' medical records treated with a 7+3 induction chemotherapy protocol in the Cancer Hospital of Uberlândia from 2017 to 2021 were screened and their data was collected. Within these patients, groups for analysis were created based on whether the acting physician included an antibacterial or antifungal prophylaxis protocol during induction. Contingency tables with χ² and odds ratio tests were realized to verify associations between prophylaxis and infection. Additionally, Kaplan-Meier curves with Cox regression were developed to analyze survival., Results: The use of prophylaxis with either fluconazole or levofloxacin did not lower rates of infection, as those who with prophylaxis did not demonstrate significant differences when compared to those without (20.3-29.7%, and 12.3-23.3%, respectively). Patients who suffered a bacterial infection during induction were shown to have lower overall survival, with a similar trend seen in fungal infections., Conclusion: Bacterial and fungal infections were associated with higher rates of induction mortality and lower overall survival, and prophylaxis using fluconazole and levofloxacin did not present any significant difference in preventing these infections in this study, contrasting results found in the literature. The individuality of each treatment center should be taken into consideration and future studies should be realized to better determine the most effective methods and agents for prophylaxis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 10 9 /L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay., (© 2024. The Author(s).)

Introduction: This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis., Method: We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed., Result: We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively., Conclusion: Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Over the last decade, the therapeutic landscape for hematological malignancies (HMs) has witnessed a remarkable surge in the development of novel biological and small-molecule-targeted immunomodulatory agents. These therapies have drastically improved survival, but some come at the cost of increased risk of bacterial, viral, and/or fungal infections and on-target off-tumor immunological side effects. To mitigate such risks, physicians must be well informed about infectious complications and necessary preventive measures, such as screening, vaccinations, and antimicrobial prophylaxis. Furthermore, physicians should be vigilant about the noninfectious side effects of these agents that can mimic infections and understand their potential drug-drug interactions with antimicrobials. Strengthening and harmonizing the current surveillance and reporting system for drug-associated infections in real-world settings is essential to better ascertain the potential infections associated with these agents. In this review, we aimed to summarize the infection risks associated with novel agents used for specific HMs and outline recommended strategies for monitoring and prophylaxis., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

The pathogenic fungus Batrachochytrium dendrobatidis has caused declines of amphibians worldwide. Yet our understanding of how water quality influences fungal pathogenicity is limited. Here, we reviewed experimental studies on the effect of water quality on this pathogen to determine which parameters impacted disease dynamics consistently. The strongest evidence for protective effects is salinity which shows strong antifungal properties in hosts at natural levels. Although many fungicides had detrimental effects on the fungal pathogen in vitro, their impact on the host is variable and they can worsen infection outcomes. However, one fungicide, epoxiconazole, reduced disease effects experimentally and likely in the field. While heavy metals are frequently studied, there is weak evidence that they influence infection outcomes. Nitrogen and phosphorous do not appear to impact pathogen growth or infection in the amphibian host. The effects of other chemicals, like pesticides and disinfectants on infection were mostly unclear with mixed results or lacking an in vivo component. Our study shows that water chemistry does impact disease dynamics, but the effects of specific parameters require more investigation. Improving our understanding of how water chemistry influences disease dynamics will help predict the impact of chytridiomycosis, especially in amphibian populations affected by land use changes., (© 2024 The Authors. Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Introduction: Diverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role in AD by increasing an individual's vulnerability to various infections, which could contribute to neurodegeneration. If true, then vaccines that have heterologous effects on immunity, extending beyond protection against the targeted disease, may hold a potential for AD prevention., Methods: We evaluated the associations of common adult infections (herpes simplex, zoster (shingles), pneumonia, and recurrent mycoses), and vaccinations against shingles and pneumonia, with the risks of AD and other dementias in a pseudorandomized sample of the Health and Retirement Study (HRS)., Results: Shingles, pneumonia and mycoses, diagnosed between ages 65 and 75, were all associated with significantly increased risk of AD later in life, by 16 %-42 %. Pneumococcal and shingles vaccines administered between ages 65-75 were both associated with a significantly lower risk of AD, by 15 %-21 %. These effects became less pronounced when AD was combined with other dementias., Discussion: Our findings suggest that both the pneumococcal polysaccharide vaccine and the live attenuated zoster vaccine can offer significant protection against AD. It remains to be determined if non-live shingles vaccine has a similar beneficial effect on AD. This study also found significant associations of various infections with the risk of AD, but not with the risks of other dementias. This indicates that vulnerability to infections may play a more significant role in AD than in other types of dementia, which warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Working with aquatic organisms often requires handling multiple individuals in a single session, potentially resulting in cross-contamination by live pathogens or DNA. Most researchers address this problem by disposing of gloves between animals. However, this generates excessive waste and may be impractical for processing very slippery animals that might be easier to handle with cotton gloves. We tested methods to decontaminate cotton or nitrile gloves after contamination with cultured Batrachochytrium dendrobatidis (Bd) or after handling heavily Bd-infected Xenopus laevis with layered cotton and nitrile gloves. Bleach eliminated detectable Bd DNA from culture-contaminated nitrile gloves, but gloves retained detectable Bd DNA following ethanol disinfection. After handling a Bd-infected frog, Bd DNA contamination was greatly reduced by removal of the outer cotton glove, after which either bleach decontamination or ethanol decontamination followed by drying hands with a paper towel lowered Bd DNA below the detection threshold of our assay. These results provide new options to prevent pathogen or DNA cross-contamination, especially when handling slippery aquatic organisms. However, tradeoffs should be considered when selecting an animal handling procedure, such as the potential for cotton gloves to abrade amphibian skin or disrupt skin mucus. Disposing of gloves between animals should remain the gold standard for maintaining biosecurity in sensitive situations.

Introduction and Objectives: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis., Materials and Methods: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP)., Results: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12-0.41; p<0.001; I 2 =0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14-0.69; p=0.004; I 2 =0%)., Conclusions: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Invasive fungal infections (IFIs) contribute to morbidity and mortality during acute myeloid leukaemia (AML) treatment. Without prophylaxis, IFI rate during AML treatment in Thailand is high and results in a high mortality rate and a prolonged hospital stay., Aim: To evaluate the cost-utility of antifungal therapy (AFT) prophylaxis during AML treatment., Methods: We assessed the cost-utility of AFT available in Thailand, including posaconazole (solution), itraconazole (solution and capsule), and voriconazole. A hybrid model consisting of a decision tree and the Markov model was established., Results: The costs to prevent overall IFI using any AFT were all lower than the treatment cost of a non-prophylaxis group, resulting in a saving of 808-1507 USD per patient. Prevention with voriconazole prophylaxis showed the highest quality-adjusted life years (QALYs = 3.51, incremental QALYs = 0.23), followed by posaconazole (QALYs = 3.46, incremental QALY = 0.18) and itraconazole solution (QALYs = 3.45, incremental QALYs = 0.17). Itraconazole capsule reduced QALY in the model. For invasive aspergillosis prevention, posaconazole and voriconazole both resulted in better QALYs and life year savings compared with no prophylaxis. However, posaconazole prophylaxis was the only cost-saving option (976 USD per patient)., Conclusion: Posaconazole, itraconazole solution and voriconazole were all cost saving compared with no prophylaxis for overall IFI prophylaxis, with voriconazole being the most cost-effective option. Posaconazole and voriconazole were both cost effective for invasive aspergillosis prevention but only posaconazole was cost saving. A change in reimbursement policy for the use of AFT prophylaxis during intensive AML treatment could provide both clinical benefits to patients and substantial economic benefits to healthcare systems., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Invasive fungal diseases (IFDs) play an important role in the supportive care of paediatric patients with acute leukaemia and those undergoing allogeneic haematopoietic cell transplantation, and they are associated with significantly decreased overall survival rates in affected individuals. Relative to adults, children and adolescents are distinct in terms of host biology, predisposing conditions, presentation and epidemiology of fungal diseases, and in the pharmacology of antifungal agents. The paediatric development of antifungal agents has moved forward in a coordinated manner, and major advances have been made regarding concepts and recommendations for the prevention and treatment of IFDs. However, antifungal therapy is increasingly complex, and a solid knowledge of the available options is needed more than ever for successful management. This narrative review provides a summary of the paediatric development of agents that have been recently approved (anidulafungin, posaconazole) or are in advanced stages of development (isavuconazole). It also reviews the emerging evidence for the efficacy of echinocandins for prophylaxis of invasive aspergillosis, presents new data on alternative dosing regimens of echinocandins and voriconazole, and provides a brief overview of new antifungal agents in clinical development that are expected to be developed for paediatric patients., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)

Background: Although the success rate of resuscitation in preterm infants is increasing, the long length of hospital stay in preterm infants and the need for more invasive operations, coupled with the widespread use of empirical antibiotics, have increased the prevalence of fungal infections in preterm infants in neonatal intensive care units (NICUs) year on year., Objective: The present study aims to explore the risk factors of invasive fungal infections (IFI) in preterm infants and to identify some prevention strategies., Methods: A total of 202 preterm infants with a gestational age of 26 weeks to 36+6 weeks and a birth weight of less than 2,000 g, admitted to our neonatal unit during the 5-year period from January 2014 to December 2018, were selected for the study. Among these preterm infants, six cases that developed fungal infections during hospitalization were enrolled as the study group, and the remaining 196 infants who did not develop fungal infections during hospitalization were the control group. The gestational age, length of hospital stay, duration of antibiotic therapy, duration of invasive mechanical ventilation, indwelling duration of the central venous catheter, and duration of intravenous nutrition of the two groups were compared and analyzed., Results: There were statistically significant differences between the two groups in the gestational age, length of hospital stay, and duration of antibiotic therapy., Conclusion: A small gestational age, a lengthy hospital stay, and long-term use of broad-spectrum antibiotics are the high-risk factors for fungal infections in preterm infants. Medical and nursing measures to address the high-risk factors might reduce the incidence of fungal infections and improve the prognosis in preterm infants.

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes., Methods: Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model., Results: By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD., Conclusions: Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Talaromycosis marneffei has been increasing in recent years. Our understanding of this disease has gradually deepened through extensive basic and clinical research, but there are still many limitations. In this article, by incorporating the latest research advancements, we discuss important issues in managing Talaromycosis marneffei trends, aiming to guide effective prevention and control of the disease, improving public health, and reducing the healthcare burden.

The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

As a mainstay of treatment for acute lymphoblastic leukemia (ALL), vincristine's side effect profile is well known. Parallel administration of the antifungal fluconazole has been shown to interfere with the metabolism of vincristine, potentially resulting in increased side effects. We conducted a retrospective chart review to determine whether concomitant administration of vincristine and fluconazole during pediatric ALL induction therapy impacted the frequency of vincristine side effects, namely, hyponatremia and peripheral neuropathy. We also evaluated whether the incidence of opportunistic fungal infections was impacted by fluconazole prophylaxis. Medical charts of all pediatric ALL patients treated with induction chemotherapy at Children's Hospital and Medical Center in Omaha, NE, from 2013 to 2021 were retrospectively reviewed. Fluconazole prophylaxis did not significantly impact the rate of fungal infections. We found no correlation between fluconazole use and increased incidence of hyponatremia or peripheral neuropathy, which supports the safety of fungal prophylaxis with fluconazole during pediatric ALL induction therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

What Is This Summary About?: People with blood-related conditions have a higher chance of getting invasive fungal infections (IFIs). IFIs are severe fungal infections that can lead to death. Only a few medications, known as antifungals, exist that can be used to prevent IFIs, and sometimes they can cause very bad side effects. Isavuconazole is an antifungal which has been approved to treat IFIs, but it has not been approved to prevent IFIs. In this study, we reviewed published studies that looked at how well isavuconazole prevented IFIs in people who have a higher chance of getting IFIs., What Were the Results?: This review showed that isavuconazole could be effective at preventing IFIs in people with blood-related conditions, as well as being a safe medication., What Do the Results of the Study Mean?: Isavuconazole can prevent IFIs in people who have a higher chance of getting IFIs. Guidelines should consider that patients need new antifungals to prevent IFIs, and more research needs to be done to see which medicines work best, and which have fewer side effects. Clinical Trial Registration: Please note that 7 studies included in this review were planned studies (1 prospective, 6 retrospective), 2 were real- world studies, 1 of which was registered as a clinical trial NCT03019939 (ClinicalTrials.gov).

The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as Aspergillus spp., Candida spp. and Pneumocystis jirovecii. In response to this, prophylactic and pre-emptive antifungal treatment strategies have been developed and implemented for high-risk patient populations. The benefit by risk reduction needs to be carefully weighed against potential harm caused by prolonged exposure against antifungal agents. This includes adverse effects and development of resistance as well as costs for the healthcare system. In this review, we summarise evidence and discuss advantages and downsides of antifungal prophylaxis and pre-emptive treatment in the setting of malignancies such as acute leukaemia, haematopoietic stem cell transplantation, CAR-T cell therapy, and solid organ transplant. We also address preventive strategies in patients after abdominal surgery and with viral pneumonia as well as individuals with inherited immunodeficiencies. Notable progress has been made in haematology research, where strong recommendations regarding antifungal prophylaxis and pre-emptive treatment are backed by data from randomized controlled trials, whereas other critical areas still lack high-quality evidence. In these areas, paucity of definitive data translates into centre-specific strategies that are based on interpretation of available data, local expertise, and epidemiology. The development of novel immunomodulating anticancer drugs, high-end intensive care treatment and the development of new antifungals with new modes of action, adverse effects and routes of administration will have implications on future prophylactic and pre-emptive approaches., Competing Interests: Declaration of competing interest RS has received speaker honoraria by Pfizer. DN has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. MO works as Scientific Support Representative for Taconic Biosciences GmbH. JP has received honoraria from Associates of Cape Cod, Gilead Sciences, Swedish Orphan Biovitrum, and Pfizer, research funding from Merck & Co., and Pfizer and is a stakeholder of AbbVie Inc., and Novo Nordisk. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pardes, Pfizer, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Abbvie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, Shionogi; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, The Prime Meridian Group; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Stocks from CoRe Consulting, and EasyRadiology. JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals Inc.; has received speaker honoraria by Pfizer Inc., Gilead and AbbVie; has been a consultant to Gilead, Produkt&Markt GmbH, Alvea Vax. And Micron Research, and has received travel grants by German Society for Infectious Diseases (DGI e.V.) and Meta-Alexander Foundation. JAN and IR have nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This meta-analysis aimed to assess the efficacy and safety of fluconazole for the prevention of invasive fungal infections (IFI) in very low birth weight infants (VLBWI) and to provide a basis for the clinical use. A detailed search of Pubmed, Embase, Cochrane Library and other databases was performed to carefully screen eligible randomized controlled clinical studies to assess the safety and efficacy of fluconazole in very low birth weight infants in terms of the incidence of invasive fungal infections, fungal colonization rate, and mortality. Our research indicated that the application of fluconazole did not result in intolerable adverse reactions in patients. Fluconazole is effective in preventing invasive fungal infections in very low birth weight infants without serious adverse effects. The dose and frequency of fluconazole in very low birth weight infants still needs to be evaluated in consequent studies., (© 2023. The Author(s).)

Background: Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication. The comparative prophylactic efficacy of antifungals in this patient population has not been reported, and an analysis is warranted., Methods: This retrospective, matched cohort, single-center study, included AML, MDS, or HCT patients who began treatment or underwent transplant between January 1, 2015 and July 31, 2021. Isavuconazole patients were matched 1:2 with patients receiving posaconazole or voriconazole prophylaxis., Results: A total of 126 patients were included, 42 received isavuconazole, 81 received posaconazole, and three received voriconazole. The majority of patients were male receiving secondary IFI prophylaxis while receiving steroids for treatment of GVHD. The incidence of possible, probable or proven IFI was 16.7% in the isavuconazole group compared to 10.7% in the posaconazole and voriconazole group (OR 1.28, 95% CI -0.9-1.4; p = .67). Hepatotoxicity occurred in 16 total patients, 14 receiving posaconazole and two receiving isavuconazole., Conclusion: Patients who received isavuconazole prophylaxis during AML induction therapy or post-HCT experienced a similar incidence of breakthrough fungal infections compared to those who received posaconazole or voriconazole. These results suggest no difference in antifungal prophylactic efficacy; however larger prospective comparative studies are needed., (© 2023 Wiley Periodicals LLC.)

Deceased donor and organ perfusion fluid cultures are obtained in order to inform recipient antimicrobial management and therefore reduce the risk of donor-derived bacterial and fungal infections. However, important heterogeneity exists in laboratory practice across organ procurement organizations and clinical management of culture results across transplant centers. While not standardized, the clinical approach to donors with positive bacterial and/or fungal cultures should be informed by the risk of donor-derived infection (DDI) and the consequence of organ non-utilization and account for potential unintended effects of antimicrobial use in the recipient. In this review, we summarize the literature on bacterial and fungal DDIs, describe the significance of positive cultures by anatomic site, and summarize current guidance on the management of positive cultures from donors or preservation fluids., (© 2023 Wiley Periodicals LLC.)

Disease control tools are needed to mitigate the effect of the fungal pathogen Batrachochytrium dendrobatidis (Bd) on amphibian biodiversity loss. In previous experiments, Bd metabolites (i.e., noninfectious chemicals released by Bd) have been shown to induce partial resistance to Bd when administered before live pathogen exposure and therefore have potential as an intervention strategy to curb Bd outbreaks. In the wild, however, amphibians inhabiting Bd-endemic ecosystems may have already been exposed to or infected with Bd before metabolite administration. It is therefore critical to evaluate the efficacy and safety of Bd metabolites applied postexposure to live Bd. We tested whether Bd metabolites administered postexposure would induce resistance, exacerbate infections, or have no effect. The results confirmed that Bd metabolites applied before pathogen exposure significantly reduced infection intensity, but Bd metabolites applied after pathogen exposure neither protected against nor exacerbated infections. These results reveal the importance of timing the application of Bd metabolites early in the transmission season for Bd-endemic ecosystems and emphasize that Bd metabolites prophylaxis may be a useful tool in captive reintroduction campaigns where Bd threatens the success of re-establishing endangered amphibian populations., (© Wildlife Disease Association 2023.)

Introduction: Acute leukemia accounts for more than 30% of all pediatric cancer cases, and of these, 15-20% are acute myeloid leukemia (AML). Children who super from AML are more likely to develop infections due to the humoral and cellular immune deficits generated by the disease and its treatment. The incidence of fungal infections is underestimated; reports show that up to 75% of fungal infections go undiagnosed until autopsy. In only 30 years, the incidence of invasive candidiasis has increased by 40-fold. Thus, the high morbidity and mortality associated with fungal infections in hematological patients make it necessary to adopt preventive measures., Methods: This work aimed to retrospectively identify pediatric patients with acute myeloid leukemia and invasive fungal diseases (IFDs) in a Latin American tertiary care hospital. A retrospective analysis of 36 clinical records of pediatric patients diagnosed with AML from 2007 to 2017 was carried out., Results: One hundred and twenty-nine hospitalizations were associated with infectious events. Thirteen patients in our study presented 15 infectious events associated with IFDs (11.6%). Two patients died because of complications related to IFDs (15.3%). The most frequent IFD type was aspergillosis, which was observed in 7 cases, followed by Candidemia, which was observed in 4 cases. The most frequent clinical manifestations were fever and respiratory distress., Discussion: Mortality due to IFD can be prevented with effective pharmacotherapy. An appropriate antifungal prophylaxis strategy still needs to be developed through larger prospective studies in Latin America., Competing Interests: The authors declare 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 © 2023 Ávila Montiel, Saucedo Campos, Avilés Robles, Murillo Maldonado, Jiménez Juárez, Silva Dirzo and Dorantes Acosta.)

Fungal diseases have posed a great challenge to global health, but have fewer solutions compared to bacterial and viral infections. Development and application of new treatment modalities for fungi are limited by their inherent essential properties as eukaryotes. The microorganism identification and drug sensitivity analyze are limited by their proliferation rates. Moreover, there are currently no vaccines for prevention. Polymer science and related interdisciplinary technologies have revolutionized the field of fungal disease management. To date, numerous advanced polymer-based systems have been developed for management of fungal diseases, including prevention, diagnosis, treatment and monitoring. In this review, we provide an overview of current needs and advances in polymer-based strategies against fungal diseases. We high light various treatment modalities. Delivery systems of antifungal drugs, systems based on polymers' innate antifungal activities, and photodynamic therapies each follow their own mechanisms and unique design clues. We also discuss various prevention strategies including immunization and antifungal medical devices, and further describe point-of-care testing platforms as futuristic diagnostic and monitoring tools. The broad application of polymer-based strategies for both public and personal health management is prospected and integrated systems have become a promising direction. However, there is a gap between experimental studies and clinical translation. In future, well-designed in vivo trials should be conducted to reveal the underlying mechanisms and explore the efficacy as well as biosafety of polymer-based products., Competing Interests: The authors declare 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 © 2023 Wu, Guo, Li, Zhou, Meng, Sun, Li, Guo, Zhang, Li and Qu.)

Background: The lipopeptide herbicolin A (HA) secreted by the biocontrol agent Pantoea agglomerans ZJU23 is a promising antifungal drug to combat fungal pathogens by targeting lipid rafts, both in agricultural and clinical settings. Improvement of HA production would be of great significance in promoting its commercialization. This study aims to enhance the HA production in ZJU23 by combining fermentation optimization and strain engineering., Results: Based on the results in the single-factor experiments, corn steep liquor, temperature and initial pH were identified as the significant affecting factors by the Plackett-Burman design. The fermentation medium and conditions were further optimized using the Box-Behnken response surface method, and the HA production of the wild type strain ZJU23 was improved from ~ 87 mg/mL in King's B medium to ~ 211 mg/mL in HA induction (HAI) medium. A transposon library was constructed in ZJU23 to screen for mutants with higher HA production, and two transcriptional repressors for HA biosynthesis, LrhA and PurR, were identified. Disruption of the LrhA gene led to increased mRNA expression of HA biosynthetic genes, and subsequently improved about twofold HA production. Finally, the HA production reached ~ 471 mg/mL in the ΔLrhA mutant under optimized fermentation conditions, which is about 5.4 times higher than before (~ 87 mg/mL). The bacterial suspension of the ΔLrhA mutant fermented in HAI medium significantly enhanced its biocontrol efficacy against gray mold disease and Fusarium crown rot of wheat, showing equivalent control efficacies as the chemical fungicides used in this study. Furthermore, HA was effective against fungicide resistant Botrytis cinerea. Increased HA production substantially improved the control efficacy against gray mold disease caused by a pyrimethanil resistant strain., Conclusions: This study reveals that the transcriptional repressor LrhA negatively regulates HA biosynthesis and the defined HAI medium is suitable for HA production. These findings provide an extended basis for large-scale production of HA and promote biofungicide development based on ZJU23 and HA in the future., (© 2023. The Author(s).)

Introduction: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections., Areas Covered: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database., Expert Opinion: Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.

Background: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery., Aim: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery., Methods: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery., Findings: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001)., Conclusion: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

At present, there is still a lack of effective invasive fungal prophylaxis therapy in liver transplant recipients (LTRs). This study aimed to analysis the latest evidence on efficacy of current prophylactic anti-fungal therapy, and systematically compare between anti-fungal agents and placebo by a fixed-effects meta-analysis in all randomised controlled trials. A network meta-analysis was performed for invasive fungal infection (IFI) among different agents in 14 randomised controlled trials, in which 10 anti-fungal approaches were identified. Overall, anti-fungal prophylaxis reduced the rate of IFI (RR 0.30, 95% CI 0.18-0.52) and proven IFI (RR 0.27, 95% CI 0.14-0.53) when compared to placebo. In the network meta-analysis, an equivalent reduction in the rate of IFI was observed in fluconazole (OR 4.70, 95% CI 1.22-18.10), itraconazole (OR 5.82, 95% CI 1.10-30.71) and Liposomal amphotericin B (LAmB, OR 5.74, 95% CI 1.29-25.58) groups when compared with placebo. Anidulafungin might be the most effective agents in IFI prevention; however, this superiority did not meet statistically significance. Our study indicated that fluconazole, echinocandins and LAmB are equivalent in efficacy. Of which, fluconazole is recommended for the prevention of IFI in LTRs due to its efficacy, economics and compliance., (© 2022 Wiley-VCH GmbH.)

Antifungal prophylaxis (AFP) is recommended for acute myeloid leukemia (AML) patients receiving the combination of venetoclax (VEN) and a hypomethylating agent (HMA), but the benefit of this practice is unclear. We identified 131 patients with newly diagnosed AML who received frontline VEN/HMA and evaluated the use of AFP and its association with invasive fungal infections (IFIs) and AML outcomes. Seventeen percent of our patients received AFP at any time. Overall incidence of any IFI ('possible,' 'probable,' or 'proven' infection, as defined by the European Mycoses Study Group) was 13%, and the incidence did not differ based on AFP use ( p =.74). Median overall survival did not differ based on AFP use or lack thereof (8.1 vs. 12.5 months, respectively; p =.14). Our findings suggest that, at an institution where the incidence of fungal infections is low, there does not appear to be a role for AFP in newly diagnosed AML patients receiving VEN/HMA.

Animal models of invasive fungal infections have been developed and are applied in a huge number of different animal species for a number of research purposes, for example, the study of pathogenesis, defense mechanisms, and therapeutic strategies. From the different models, which in most cases are based on the same fungal species and often the same strain, as in spontaneous human infections, fundamental results and knowledge of the diagnosis, progression, prophylaxis, and therapy have been achieved. However, in all models, one should be critical with respect to mimicking the disease entity of humans, which is often the focus of the research. In many of the models for instance, the time course is different to the one of humans, and in others, the propensity for localization and containment in specific organs does not parallel the situation in humans. Nevertheless, many animal models of invasive mycoses have proven valuable in a number of research areas. With regard to new generations of anti-mycotic drugs, the models play an essential role in demonstrating antifungal activity, as well as in demonstrating the absence of toxic side effects, a critical step which cannot be accomplished by in vitro studies., (© 2020 Scandinavian Societies for Medical Microbiology and Pathology.)

Background: Posaconazole is confirmed to be more effective for preventing invasive fungal infections (IFIs) than first-generation triazoles (fluconazole and itraconazole), but its economic value has not been comprehensively evaluated in China. This study compared the cost-effectiveness of these two antifungal prophylaxis regimens in hematological-malignancy patients at high risk for IFIs from the Chinese healthcare perspective., Methods: A hybrid decision tree and Markov model were built using published data to estimate the total costs and quality-adjusted life-years (QALYs) of antifungal prophylaxis with posaconazole oral suspension and first-generation triazoles. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the threshold of willingness to pay (WTP) were considered cost-effective. One-way and probabilistic sensitivity analyses were performed to assess model robustness. The regional imbalance of economic development and the tablet formulation of posaconazole were considered in the scenario analyses., Results: In the base-case analysis, posaconazole oral suspension provided an additional 0.109 QALYs at an incremental cost of $954.7, yielding an ICER of $8,784.4/QALY, below the national WTP threshold of $31,315/QALY. One-way and probabilistic sensitivity analyses showed that the results were robust. Scenario analyses showed that the base-case ICER was consistently below the WTP thresholds of all 31 Chinese provinces, with the likelihood of posaconazole being cost-effectiveness ranging from 78.1 to 99.0%. When the posaconazole oral suspension was replaced by the tablet formulation, the ICER increased to $29,214.1/QALY, still below the national WTP threshold and WTP thresholds of 12 provinces., Conclusions: Posaconazole oral suspension is a highly cost-effective regimen for preventing IFI in high-risk hematological-malignancy patients from the Chinese healthcare perspective. Posaconazole tablets may also be considered in some high-income regions of China., Competing Interests: The authors declare 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 © 2022 Shi, Ye, Xie, Dong, Jin, Wang, Fang, Shan and Lin.)

Background: Although recommended in patients with acute myeloblastic leukaemia (AML) after induction chemotherapy, real-life use of antifungal prophylaxis (AFP) is different among centres., Materials and Methods: This is an ancillary study to a randomized trial on intensive induction chemotherapy in AML patients (ALFA-0702/NCT00932412), where AFP with posaconazole was recommended. IFIs were graded by investigators and by central reviewers according to the revised EORTC definitions. Experts conclusions were compared to the investigators' ones., Results: A total of 677 patients were included. Four AFP strategies were reported: Group-1: no AFP (n = 203, 30%), Group-2: posaconazole (n = 241, 36%), Group-3: posaconazole with other AFP (n = 142, 21%), Group-4: other AFP (n = 91, 13%). Experts graded more IFI than investigators: proven/probable IFI, 9.0% (n = 61) versus 6.2% (n = 42). The cumulative incidence at day60 of probable/proven IFI was 13.9% (Group-1); 7.9% (Group-2); 5.6% (Group-3); and 6.6% (Group-4). IFI onset was 26 (19-31) days after induction in Groups 2-3, versus 16 (9-25) days in Group 1 and 20 (12-24) days in Group 4 (P< .001). After a median follow-up of 27.5 months (0.4-73.4), the mortality rate was 38.3%, with 5.4% attributed to IFI. In multivariate analysis, IFI occurrence was an independent risk of death (HR5.63, 95%-CI 2.62-12.08, P< .001). EORTC recommendations were applied in only 57% of patients. In patients without IFI, the rate of AML complete remission was higher., Conclusions: In AML patients, AFP delayed the onset of IFI in addition of decreasing their rate. The frequent misidentification of IFI impacts their appropriate management according to recommendations. hematological remission was more frequent in patients without IFI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Preventing and reducing nosocomial infections is a public health goal. Concern about healthcare-associated fungal infections has increased in recent years due to the emergence and spread of new pathogens, increasing antifungal resistance and outbreaks in hospital settings., Aim: To investigate the presence of medically relevant fungal species on environmental surfaces in 12 intensive care units of eight hospitals in Milan, Italy., Methods: Environmental samplings, using contact plates on surfaces near bed stations and medical workstations, were conducted between November 2019 and January 2020. Fungi isolated were identified, and some were tested in vitro for antifungal susceptibility., Findings: In total, 401 environmental samples were collected from 61 bed stations and 17 medical workstations. Positive samples were found in all hospitals except one, with positivity rates ranging from 4% to 24.2%. Filamentous fungi were found mainly on infusion pumps (23.2%) and patient tables (21.2%), whereas yeasts were found mainly on computers (25%) and floors (10.9%). Fungi were isolated from 12% of total samples. Filamentous fungi, mainly Aspergillus fumigatus, grew in 70.8% of positive samples, and yeasts grew in 27.1%, mainly Candida parapsilosis (42.8%) and Candida glabrata (28.6%). Fungi were detected near patients' beds and on surfaces at workstations, indicating potential for environment-to-patient, patient-to-patient and healthcare worker-to-patient transmission., Conclusions: Surveillance in hospital settings through environmental sampling may be an important component of fungal infection prevention., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

White-nose syndrome (WNS) is a fungal disease that has caused precipitous declines in several North American bat species, creating an urgent need for conservation. We examined how microclimates and other characteristics of hibernacula have affected bat populations following WNS-associated declines and evaluated whether cooling of warm, little-used hibernacula could benefit bats. During the period following mass mortality (2013-2020), we conducted 191 winter surveys of 25 unmanipulated hibernacula and 6 manipulated hibernacula across Pennsylvania (USA). We joined these data with additional datasets on historical (pre-WNS) bat counts and on the spatial distribution of underground sites. We used generalized linear mixed models and model selection to identify factors affecting bat populations. Winter counts of Myotis lucifugus were higher and increased over time in colder hibernacula (those with midwinter temperatures of 3-6 °C) compared with warmer (7-11 °C) hibernacula. Counts of Eptesicus fuscus, Myotis leibii, and Myotis septentrionalis were likewise higher in colder hibernacula (temperature effects = -0.73 [SE 0.15], -0.51 [0.18], and -0.97 [0.28], respectively). Populations of M. lucifugus and M. septentrionalis increased most over time in hibernacula surrounded by more nearby sites, whereas Eptesicus fuscus counts remained high where they had been high before WNS onset (pre-WNS high count effect = 0.59 [0.22]). Winter counts of M. leibii were higher in hibernacula with high vapor pressure deficits (VPDs) (particularly over 0.1 kPa) compared with sites with lower VPDs (VPD effect = 15.3 [4.6]). Counts of M. lucifugus and E. fuscus also appeared higher where VPD was higher. In contrast, Perimyotis subflavus counts increased over time in relatively warm hibernacula and were unaffected by VPD. Where we manipulated hibernacula, we achieved cooling of on average 2.1 °C. At manipulated hibernacula, counts of M. lucifugus and P. subflavus increased over time (years since manipulation effect = 0.70 [0.28] and 0.51 [0.15], respectively). Further, there were more E. fuscus where cooling was greatest (temperature difference effect = -0.46 [SE 0.11]), and there was some evidence there were more P. subflavus in hibernacula sections that remained warm after manipulation. These data show bats are responding effectively to WNS through habitat selection. In M. lucifugus, M. septentrionalis, and possibly P. subflavus, this response is ongoing, with bats increasingly aggregating at suitable hibernacula, whereas E. fuscus remain in previously favored sites. Our results suggest that cooling warm sites receiving little use by bats is a viable strategy for combating WNS., (© 2021 Society for Conservation Biology.)

Introduction: Invasive fungal diseases (IFDs) are a significant cause of morbidity and mortality among immunocompromised patients. Safe and effective antifungal medications used for prophylaxis and treatment are pivotal in their management. Posaconazole is a promising triazole antifungal agent., Areas Covered: The authors discuss the pharmacological properties of posaconazole, including pharmacokinetics/pharmacodynamics, safety and tolerability profile, together with efficacy data for prophylaxis and treatment as well as its use in special populations based on current literature., Expert Opinion: Posaconazole has a favorable safety and tolerability profile; however, caution is advised when co-administered with agents that are CYP3A4 inhibitors, because their concentration may significantly increase, and their levels should be closely monitored. It has an extended spectrum of activity against yeasts and filamentous fungi. It is successfully used as prophylaxis for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and post-hematopoietic cell transplantation (HCT) with graft-versus-host disease (GVHD). It is the first line treatment for oropharyngeal candidiasis and is also used as a salvage treatment for refractory IFDs. Currently available formulations include the oral suspension, delayed-release tablets and solution for intravenous infusion, all with different PK/PD properties and indications. Its use in children and adolescents is currently being examined in Phase-II clinical trials.

The increasing study of emerging wildlife pathogens and a lack of policy or legislation regulating their translocation and use has heightened concerns about laboratory escape, species spillover, and subsequent epizootics among animal populations. Responsible self-regulation by research laboratories, in conjunction with institutional-level safeguards, has an important role in mitigating pathogen transmission and spillover, as well as potential interspecies pathogenesis. A model system in disease ecology that highlights these concerns and related amelioration efforts is research focused on amphibian emerging infectious diseases. Whereas laboratory escape of amphibian pathogens has not been reported and may be rare compared with introduction events from trade or human globalization, the threat that novel disease outbreaks with mass mortality effects pose to wild populations warrants thorough biosecurity measures to ensure containment and prevent spillover. Here, we present a case study of the laboratory biosecurity concerns for the emerging amphibian fungal pathogen Batrachochytrium salamandrivorans. We conclude that proactive biosecurity strategies are needed to integrate researcher and institutional oversight of aquatic wildlife pathogens generally, and we call for increased national and international policy and legislative enforcement. Furthermore, taking professional responsibility beyond current regulations is needed as development of legal guidance can be slow at national and international levels. We outline the need for annual laboratory risk assessments, comprehensive training for all laboratory personnel, and appropriate safeguards specific to pathogens under study. These strategies are critical for upholding the integrity and credibility of the scientific community and maintaining public support for research on wildlife diseases.

Infections are a major cause of morbidity and can result in mortality in long-term survivors after allogeneic hematopoietic cell transplantation. Chronic graft-versus-host disease and delayed immune reconstitution are recognized risk factors. Different strategies must be utilized depending on the individual patient's situation but include prolonged antimicrobial prophylaxis and vaccination. Some important infections due to pathogens preventable by vaccination are pneumococci, influenza, varicella-zoster virus, and SARS-CoV-2. Despite the fact that such recommendations have been in place for decades, implementation of these recommendations has been reported to be poor., (Copyright © 2021 by The American Society of Hematology.)

Children, adolescents, and young adults receiving intensive chemotherapy for acute myeloid leukemia or high-risk or relapsed acute lymphoblastic leukemia sustain prolonged periods of neutropenia that predispose them to invasive fungal disease (IFD). For many decades the standard of care for these patients was to initiate empirical antifungal therapy after a period of prolonged fever and neutropenia. Recent publications have yielded important evidence on the utility of different diagnostic and therapeutic approaches aimed at reducing the impact of IFD among these patients during these vulnerable periods. This case-based review highlights and interprets the published data to provide context for the IFD diagnostic and therapeutic recommendations proposed in multiple published guidelines. Personalized approaches are offered at points where evidence is lacking. Time points where specific knowledge gaps exist are identified along the clinical trajectory of the prolonged neutropenic period to illustrate areas for future investigation., (Copyright © 2021 by The American Society of Hematology.)

Objectives: The objective of the study was to assess the tolerability and effectiveness of micafungin prophylaxis during the neutropenic phase in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Methods We conducted a retrospective study of 73 consecutive adults receiving antifungal prophylaxis with micafungin bridged to voriconazole/itraconazole in our center from July 2013 to March 2018. Clinical and transplant-related demographics and data on fungal infection post-transplant were collected. Results Micafungin was effective in 71 (97.3%) leukopenic patients. The fungal-free survival was 91.8%, 80.6%, and 77.6% respectively at 30, 60, and 100 days after HSCT. All patients had no micafungin-related adverse events. Conclusions The utility of micafungin bridged to voriconazole/ itraconazole for antifungal prophylaxis after HSCT is beneficial.