Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective.

Invasive fungal disease (IFD) remains a significant cause of morbidity and mortality in children undergoing transplantation. There is a growing armamentarium of novel antifungal agents recently approved for use or in late stages of clinical development. The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed.

Donor-derived endemic mycoses after solid organ transplantation: A review of reported cases.

BACKGROUND: Donor-derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor-derived infections (DDI) were included. RESULTS: Twenty-four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor-derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2-35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4-48) months after transplantation. The single reported possible donor-derived talaromycosis occurred in a man whose organ donor had at-risk travel to Southeast Asia. Collectively, the majority of donors had high-risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor-derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%). CONCLUSION: Donor-derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.

Treatment Failure and Adverse Events After Amoxicillin-Clavulanate vs Amoxicillin for Pediatric Acute Sinusitis.

Importance: Acute sinusitis is one of the most common indications for antibiotic prescribing in children, with an estimated 4.9 million such prescriptions in the US annually. Consensus does not exist regarding the optimal empirical antibiotic. Objective: To compare amoxicillin-clavulanate vs amoxicillin for the treatment of acute sinusitis in outpatient children. Design, Setting, and Participants: Cohort study of children and adolescents aged 17 years or younger with a new outpatient diagnosis of acute sinusitis and a same-day new prescription dispensation of amoxicillin-clavulanate or amoxicillin in a nationwide health care utilization database. Propensity score matching was used to mitigate confounding. Exposure: A new prescription dispensation of amoxicillin-clavulanate or amoxicillin. Main Outcomes and Measures: Treatment failure, defined as an aggregate of a new antibiotic dispensation, emergency department or inpatient encounter for acute sinusitis, or inpatient encounter for a sinusitis complication, was assessed 1 to 14 days after cohort enrollment. Adverse events were evaluated, including gastrointestinal symptoms, hypersensitivity and skin reactions, acute kidney injury, and secondary infections. Results: The cohort included 320 141 patients. After propensity score matching, there were 198 942 patients (99 471 patients per group), including 100 340 (50.4%) who were female, 101 726 (51.1%) adolescents aged 12 to 17 years, 52 149 (26.2%) children aged 6 to 11 years, and 45 067 (22.7%) children aged 0 to 5 years. Treatment failure occurred in 1.7% overall; 0.01% had serious failure (an emergency department or inpatient encounter). There was no difference in the risk of treatment failure between the amoxicillin-clavulanate and amoxicillin groups (relative risk [RR], 0.98 [95% CI, 0.92-1.05]). The risk of gastrointestinal symptoms (RR, 1.15 [95% CI, 1.05-1.25]) and yeast infections (RR, 1.33 [95% CI, 1.16-1.54]) was higher with amoxicillin-clavulanate. After patients were stratified by age, the risk of treatment failure after amoxicillin-clavulanate was an RR of 0.98 (95% CI, 0.86-1.12) for ages 0 to 5 years; RR was 1.06 (95% CI, 0.92-1.21) for 6 to 11 years; and RR was 0.87 (95% CI, 0.79-0.95) for 12 to 17 years. The age-stratified risk of adverse events after amoxicillin-clavulanate was an RR of 1.23 (95% CI, 1.10-1.37) for ages 0 to 5 years; RR was 1.19 (95% CI, 1.04-1.35) for 6 to 11 years; and RR was 1.04 (95% CI, 0.95-1.14) for 12 to 17 years. Conclusions and Relevance: In children with acute sinusitis who were treated as outpatients, there was no difference in the risk of treatment failure between those who received amoxicillin-clavulanate compared with amoxicillin, but amoxicillin-clavulanate was associated with a higher risk of gastrointestinal symptoms and yeast infections. These findings may help inform decisions for empirical antibiotic selection in acute sinusitis.

Infections and risk factors for infection-related mortality after pediatric allogeneic hematopoietic stem cell transplantation in Mexico: A single center retrospective study.

OBJECTIVE: To identify the type of infections and risk factors for infection-related mortality (IRM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective cohort study of patients <16 years of age treated in 2010-2019 was conducted. Unadjusted hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CIs) were estimated using Cox regression. Cumulative incidence was calculated. RESULTS: Data for 99 pediatric patients were analyzed. The myeloablative conditioning was the most used regimen (78.8%) and the hematopoietic stem cell source was predominantly peripheral blood (80.8%). Primary graft failure occurred in 19.2% of patients. Frequency of acute graft-versus-host disease was 46.5%. Total of 136 infectious events was recorded, the most common of which were bacterial (76.4%) followed by viral infection (15.5%) and then fungal infection (8.1%). The best predictors for infection subtypes where the following: a) for bacterial infection (the age groups of 10.1-15 years: aHR = 3.33; 95% CI: 1.62-6.85 and. >15 years: aHR = 3.34; 95% CI: 1.18-9.45); b) for viral infection (graft versus host disease: aHR = 5.36; 95% CI: 1.62-17.68), however, for fungal infection statistically significant predictors were not identified. Related mortality was 30% (n = 12). Increased risk for infection-related mortality was observed in patients with unrelated donor and umbilical cord stem cells recipients (HR = 3.12; 95% CI: 1.00-9.85). CONCLUSIONS: Frequencies of infections and infection-related mortality appear to be similar to those reported. Unrelated donors and stem cells from umbilical cord recipients were associated with a high risk of mortality.

[Fungal peritoneal dialysis catheter-related exit-site infection combined with tunnel infection: A case report].

Peritoneal dialysis (PD) catheter-related infection (i.e. exit-site infection and tunnel infection) is one of the main causes of PD-related peritonitis. If it cannot be controlled effectively, it could lead to PD technique failure. Therefore, timely and effective diagnosis and treatment and active prevention so as to reduce PD catheter-related infection is an important treatment goal in PD patients. PD catheter exit-site infection (ESI) and tunnel infection can be caused by a variety of microorganisms, mainly bacteria, while fungi are very rare. Few public data can be used to guide treatment of PD catheter-related fungal infection, and there is no related report in China till now. Once fungal peritonitis occurred, the patient can only withdraw from PD treatment. Here, we report a case of fungal PD catheter ESI combined with tunnel infection which was successfully diagnosed and treated in our PD center. A 71-year-old woman came to clinic because of "PD for 5 years, secretions from exit site for 8 days and aggravation for 1 day". The patient suffered from peritonitis, ESI and tunnel infection for many times in the past 5 years, involving a variety of pathogens. Eight days before, she found white viscous discharge from exit site. The subcutaneous cuff completely came out of it and rubbed its skin. The Schaefer exit-site score was 3 points. Due to the suspected ESI 2 months before, the discharge swab for bacterial culture was positive for Pseudomonas aeruginosa, so the exit site swab for bacterial culture was done again, and gentamicin injection was applied topically once a day for empirical treatment. The exit site was evaluated one day before: The subcutaneous tunnel was significantly swollen and slightly tender at 2.5 cm away from the exit site, and with white medium amount of viscous secretions. The exit-site score increased to 4 points. Routine test of dialysis effluent was (-). The bacterial culture of the exit-site discharge was rechecked twice, and Candida parapsilosis was positive for two times, so the diagnosis of fungal PD catheter ESI combined with tunnel infection was clear. Immediately we searched for the causes of ESI and tunnel infection. We found that the patient had a suspicious history of gray toenail on the foot. The toenail smear was positive for fungi and visible hyphae. She washed feet with hands every day, and washed clothes on a low bench every day, which made the exit-site and tunnel squeezed for a long time. Based on the above causes, we gave her comprehensive treatment as follows: For ESI and tunnel fungal infections, fluco-nazole was used systemically according to the drug sensitivity results, and miconazole cream was applied to the exit-site locally. For the subcutaneous cuff that came out completely, daily iodophor disinfection was given locally. At the same time, local antifungal treatment was given to the foot. We followed up closely during treatment, evaluated the exit-site every 2-3 days, and took photos of the exit-site to dynamically observe the effect. After 14 days of treatment, the exit-site score continued to be 0-1, the bacterial culture of the exit-site was negative, the cuff culture was negative, and the tunnel B-ultrasound was normal. The patient had been followed up regularly once a month for 60 months, no ESI and tunnel infection occurred. Fungal PD catheter ESI and tunnel infection are rare complications of PD. When the standard anti-infection treatment is ineffective, the possibility of fungal infection should be considered, so as to avoid prolonged use of antibiotics, aggravating fungal infection, and even progressing to fungal peritonitis, leading to withdrawal from PD. Accurate exit-site evaluation is helpful for timely diagnosis and early treatment of ESI and tunnel infection. The exit-site discharge culture and drug sensitivity test before treatment are helpful to identify the pathogen and adjust subsequent treatment. At the same time, repeated discharge culture is required in order to exclude positive fungal culture results caused by contamination. Once fungal catheter-related infection is diagnosed, we should search for possible causes actively, subsequent targeted and comprehensive treatment plays a decisive role for the prognosis of patients.

Invasive Non-Candida Fungal Infections in Acute Burns-A 13-Year Review of a Single Institution and Review of the Literature.

The past decade has demonstrated increased burn wound infections with atypical invasive fungal organisms. The range of previously regiospecific organisms has expanded, and plant pathogens are increasingly represented. Our institution sought to examine changes in severe fungal non-Candida infections in our patients, via retrospective review of patients admitted to our burn center from 2008 to 2021. We identified 37 patients with atypical invasive fungal infections. Non-Candida genera included Aspergillus (23), Fusarium (8), Mucor (6), and 13 cases of 11 different species, including the second-ever human case of Petriella setifera. Three fungi were resistant to at least one antifungal. Concomitant infections included Candida (19), Staphylococcus and Streptococcus (14), Enterococcus and Enterobacter (13), Pseudomonas (9), and 14 additional genera. Complete data was available for 18 patients, who had a median of 3.0 (IQR 8.5, range 0-15) additional bacteria required a median of 1 (IQR 7, range 0-14) systemic antibacterials and 2 (IQR 2.5, range 0-4) systemic antifungals. One case of total-drug-resistant Pseudomonas aeruginosa required bacteriophage treatment. One case of Treponema pallidum was found in infected burn wound tissue. Every patient required Infectious Disease consultation. Eight patients became bacteremic and one developed Candida fermentatifungemia. There were five patient deaths (13.8%), all due to overwhelming polymicrobial infection. Burn patients with atypical invasive fungal infections can have severe concomitant polymicrobial infections and multidrug resistance with fatal results. Early Infectious Disease consultation and aggressive treatment is critical. Further characterization of these patients may provide better understanding of risk factors and ideal treatmentpatterns.

Therapeutic contact lens-related infection by a novel pathogenic fungus Coniochaeta hoffmannii-a case report.

This study aims to report a rare instance of corneal decompensation brought on by Coniochaeta hoffmannii fungus invasion of a bandage contact lens (BCL). A 71-year-old man with pseudophakic bullous keratopathy (PBK) had BCL treatment for four months to symptomatically reduce pain and itching in his right eye. However, the patient unexpectedly lost his vision. The slit-lamp examination revealed an edematous cornea; the extensive direct inspection raised suspicion of BCL. For morphological characterization, the BCL extracted was inoculated onto 5% sheep blood agar and PDA. By Sanger sequencing method the isolate's genomic DNA was molecularly identified as C. hoffmannii.

Endemic or regionally limited parasitic and fungal infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.

There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.

Sequential low-dose CT thorax scans to determine invasive pulmonary fungal infection incidence after allogeneic hematopoietic cell transplantation.

Invasive fungal disease (IFD) during neutropenia goes along with a high mortality for patients after allogeneic hematopoietic cell transplantation (alloHCT). Low-dose computed tomography (CT) thorax shows good sensitivity for the diagnosis of IFD with low radiation exposure. The aim of our study was to evaluate sequential CT thorax scans at two time points as a new reliable method to detect IFD during neutropenia after alloHCT. We performed a retrospective single-center observational study in 265/354 screened patients admitted for alloHCT from June 2015 to August 2019. All were examined by a low-dose CT thorax scan at admission (CT t0) and after stable neutrophil recovery (CT t1) to determine the incidences of IFD. Furthermore, antifungal prophylaxis medications were recorded and cohorts were analyzed for statistical differences in IFD incidence using the sequential CT scans. In addition, IFD cases were classified according to EORTC 2008. At CT t0 in 9.6% of the patients, an IFD was detected and antifungal therapy initiated. The cumulative incidence of IFD in CT t1 in our department was 14%. The use of Aspergillus-effective prophylaxis through voriconazole or posaconazole decreased CT thorax t1 suggesting IFD is statistically significant compared to prophylaxis with fluconazole (5.6% asp-azol group vs 16.3% fluconazole group, p = 0.048). In 86%, CT t1 was negative for IFD. Low-dose sequential CT thorax scans are a valuable tool to detect pulmonary IFDs and guide antifungal prophylaxis and therapies. Furthermore, a negative CT t1 scan shows a benefit by allowing discontinuation of antifungal medication sparing patients from drug interactions and side effects.

Invasive fungal diseases impact on outcome of childhood ALL - an analysis of the international trial AIEOP-BFM ALL 2009.

In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enrolled in the international, multi-center clinical trial AIEOP-BFM ALL2009 were screened for proven/probable IFD, defined according to the updated EORTC/MSG consensus definitions. In a total of 6136 children (median age 5.2 years), 224 proven/probable IFDs (65 yeast and 159 mold) were reported. By logistic regression, the risk for proven/probable IFDs was significantly increased in children ≥12 years and those with a blast count ≥10% in the bone marrow on day 15 (P < 0.0001 each). Proven/probable IFDs had a 6-week and 12-week mortality of 10.7% and 11.2%, respectively. In the multivariate analysis, the hazard ratio for event-free and overall survival was significantly increased for proven/probable IFD, age ≥12 years, and insufficient response to therapy (P < 0.001, each). Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis.

Acremonium (Sarocladium) periprosthetic joint infection: case report, literature review, and proposed antifungal regimen.

BACKGROUND: Fungal periprosthetic joint infections are rare. Acremonium osteoarticular infections are scarcely reported. Variable susceptibility to antifungal agents have been reported and optimal pharmacotherapy has yet to be established. Here we illustrate an Acremonium osteoarticular infection involving a prosthetic joint and present an antifungal regimen that had led to treatment success. CASE PRESENTATION: A 60-year-old female with a body mass index (BMI) of 40 had left total knee arthroplasty done in 2012 with a cementless implant for knee osteoarthritis. In 2019, the patient had asymptomatic, progressive osteolysis with fracture and migration of the femoral component warranting replacement. Eleven months later, the patient developed significant pain, redness, and swelling in the left leg and knee concerning for periprosthetic joint infection that failed outpatient antibiotic treatment. Further investigation revealed infection by Acremonium species. A revision of the joint was successfully completed, and the patient was placed on voriconazole for one year. Subsequent cultures did not yield any fungal growth. CONCLUSION: While an optimal antifungal regimen for periprosthetic joint infections has not been well established, voriconazole is a relatively safe and effective agent that can be used as a long-term therapy. With variable susceptibility testing in reported isolates, individualized antifungal susceptibility should be used to guide therapy for Acremonium infections.

Fungal infection and colonization in lung transplant recipients with chronic lung allograft dysfunction.

BACKGROUND: The incidence and impact of de novo fungal airway colonization and infection in lung transplant recipients (LTRs) with known chronic lung allograft dysfunction (CLAD) has not been established. We aimed to determine the 1-year cumulative incidence and risk factors of de novo fungal colonization or infection in LTRs with CLAD and assess the impact of colonization or infection on post-CLAD survival. METHODS: Prospectively collected Toronto Lung Transplant Program database and chart review were used for double-LTRs who were diagnosed with CLAD from January 1, 2016 to January 1, 2020 and who were free of airway fungi within 1 year prior to CLAD onset. International Society for Heart and Lung Transplantation definitions were used to define clinical syndromes. Cox-Proportional Hazards Models were used for risk-factor analysis. Survival analysis could not be completed secondary to low number of fungal events; therefore, descriptive statistics were employed for survival outcomes. RESULTS: We found 186 LTRs diagnosed with CLAD meeting our inclusion criteria. The 1-year cumulative incidence for any fungal event was 11.8% (7.0% for infection and 4.8% for colonization). Aspergillus fumigatus was a causative pathogen in eight of 13 (61.5%) patients with infection and six of nine (66.7%) patients with colonization. No patients with fungal colonization post-CLAD developed fungal infection. Peri-CLAD diagnosis (3 months prior or 1 month after) methylprednisolone bolus (hazards ratio: 8.84, p = .001) increased the risk of fungal events. Most patients diagnosed with fungal infections (53.8%) died within 1-year of CLAD onset. CONCLUSION: De novo IFIs and fungal colonization following CLAD onset were not common. Fungal colonization did not lead to fungal infection. Methylprednisolone bolus was a significant risk factors for post-CLAD fungal events.

Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know.

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.

[Invasive fungal infection management in patients with hematological malignancies].

Invasive fungal infections are frequently observed in patients with hematological malignancies. Thus, monitoring the immunosuppressive factors in each patient, such as neutropenia, mucosal injury, steroid consumption, cellular and humoral immunodeficiencies, etc., is important to establish an appropriate antifungal strategy. Additionally, prophylactic approaches should be planned considering the risk of fungal infection, and early clinical tests should be required in patients with persistent fever or other clinical manifestations for the timely diagnosis of invasive fungal infection. Antifungal profile, adverse effects, and clinical purposes, such as prophylaxis, empiric, preemptive, and target therapies, should be considered in antifungal agent selection.

Pathogen distribution and risk factors of bacterial and fungal infections after liver transplantation. / è‚ç§»æ¤æœ¯åŽæ—©æœŸç»†èŒä¸ŽçœŸèŒæ„ŸæŸ“ç— åŽŸä½“åˆ†å¸ƒåŠå±é™©å› ç´ .

OBJECTIVES: Liver transplant recipients have a high rate of postoperative infection, and identification of patients at high risk for bacterial and fungal infections will help prevent disease and improve long-term outcomes for them. This study aims to understand the composition, distribution, prognosis of bacterial and fungal infections within 2 months after liver transplantation and to analyze their risk factors. METHODS: The data of pathogen composition, distribution, and prognosis of bacterial and fungal infections among liver transplant recipients in the Third Xiangya Hospital of Central South University from May 2020 to October 2021 were collected, and the risk factors for these infections were analyzed. RESULTS: A total of 106 episodes of bacterial or fungal infections occurred in 71.4% of liver transplant recipients (75/105). Gram-negative bacteria were the dominant pathogenic bacteria (49/106, 46.2%), followed by Gram-positive bacteria (31/106, 29.2%). The most common Gram-negative bacterium was Acinetobacter baumannii (13/106, 12.3%). The most common Gram-positive bacterium was Enterococcus faecium (20/106, 18.9%). The most common infections were pulmonary (38/105, 36.2%) and multiple site infections (30/105, 28.6%). Six (6/105, 5.7%) patients with infections died within 2 months after liver transplantation. Univariate analysis showed that the model for end-stage liver disease (MELD) score ≥25, antibiotic use within half a month before transplantation, infections within 2 months prior to transplantation, intraoperative red blood cell infusion≥8 U, indwelling urinary tract catheter ≥4 days after transplantation, and the dosage of basiliximab use ≥40 mg were associated with infections. Multivariate logistic regression analysis revealed that only infections within 2 months prior to transplantation (OR=5.172, 95% CI 1.905-14.039, P<0.01) was an independent risk factor for bacterial and fungal infections after liver transplantation. Postoperative bacterial and fungal infections were reduced in liver transplant recipients receiving basiliximab ≥40 mg (OR=0.197, 95% CI: 0.051-0.762, P<0.05). CONCLUSIONS: The incidence of bacterial and fungal infections is high in the early stage after liver transplantation, and the mortality after infection is significantly higher than that of non-infected patients. The most common infection is respiratory infection, and the dominant pathogens is Gram-negative bacteria. Patients infected within 2 months prior to liver transplantation are prone to bacterial and fungal infections. Standard use of basiliximab can reduce the incidence of infections after liver transplantation.

Clinical Manifestations of Pulmonary Mucormycosis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A 21-Case Series Report and Literature Review.

Introduction: Mucormycosis is a rare, invasive disease caused by opportunistic pathogens related to the Mucorales order with high fatality rates in immunocompromised hosts, especially in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis and treatment of pulmonary mucormycosis in recipients of allo-HSCT remains challenging. Purpose: The aim of this study is to summarize and analyze the clinical features of pulmonary mucormycosis in recipients of allo-HSCT to explore further clinical research directions for this rare fungal infection in the particular populations. Methods: We retrospectively reviewed pulmonary mucormycosis in patients who received allo-HSCT in our hospital from January 2010 to December 2020. A total of 21 patients fulfilled the diagnostic criteria for pulmonary mucormycosis according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. Demographic and clinical data, mycological and histopathological records, and treatment and prognosis data were collected. Clinical variables were compared between survivors and nonsurvivors. The survival days of patients with and without graft-versus-host disease (GVHD) and hemoptysis were compared separately. Results: Most of the recipients of allo-HSCT were male patients with a mean age of 43 years. Acute myeloid leukemia (AML) was the most common primary hematologic malignancy. Extrapulmonary involvement accounted for 28.6%, of the cases, including central nervous system (n = 5) and skin and soft tissue (n = 1). The median time to infection was 96 days after allo-HSCT. Clinical presentations were nonspecific, including fever (76.2%) and cough (85.7%), as well as dyspnea (19.0%), chest pain (38.1%), and hemoptysis (61.9%). Ground-glass infiltrates (95.0%) and nodules/masses (80%) were the most common radiographic patterns on chest CT. The most common pathogen was Rhizopus (63.2%), and breakthrough infection accounted for 90.5%. Fifteen of the patients died within one year, and the median time from diagnosis to death was 47 days. Conclusion: Mucormycosis is a fatal infection disease. Opportunistic infections in recipients of allo-HSCT are mainly breakthrough infections and may have a seasonal distribution (summer and autumn) and more cases of death in autumn. The marked reversed halo sign can be seen both in the initial stage of infection and after antifungal treatment. In our case series, patients with pulmonary mucormycosis with extrapulmonary involvement 100% died within one year. There are more patients with GVHD before infection and hemoptysis in nonsurvivors than survivors within 100 days. Patients with GVHD before infection and hemoptysis have a shorter survival time than those without.

Outcomes of antifungal prophylaxis for newly diagnosed AML patients treated with a hypomethylating agent and venetoclax.

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.

Successful treatment of disseminated Verruconis gallopava infection in a heart transplant recipient: A case report.

PURPOSE: To describe a case of disseminated Verruconis gallopava infection in a cardiac transplant recipient that was successfully treated with oral posaconazole and intravenous anidulafungin. SUMMARY: A 51-year-old male initially presented with pulmonary manifestations, but subsequently developed cutaneous lesions, fungemia, osteomyelitis of the hip requiring excision, and eventually brain abscesses over the course of 3 months. The patient was successfully treated with various antifungal agents throughout his treatment course and was eventually discharged on oral posaconazole and intravenous anidulafungin. He remained on oral posaconazole suppressive therapy and had had no recurrence of fungal infection after 31 months of follow-up. CONCLUSION: On the basis of this case report, intravenous anidulafungin and chronic suppressive therapy with oral posaconazole can successfully treat disseminated V. gallopava infections.