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.

Six-year experience with GM test in hematological patients in a public Brazilian tertiary hospital.

Invasive fungal infection (IFI) is frequent in patients with hematologic malignancies or submitted hematopoietic stem cell transplantation (HSCT). OBJECTIVES: To evaluate the role of the GM (galactomannan) test in prescribing therapeutic antifungals; to determine invasive aspergillosis (IA) frequency, the factors associated with positive GM test, and the in-hospital mortality. METHODS: We conducted a retrospective observational study including patients aged 18 or over with hematological malignancy or submitted to HSCT. GM test was measured twice weekly. The hypothesis of IFI was considered in patients with neutropenia and persistent fever despite broad-spectrum antibiotics. RESULTS: A total of 496 patients were evaluated; the mean of GM tests performed per patient was 4.2 (+3.1), and 86 (17.3 %) had positive results. IFI was diagnosed in 166 (33.5 %) and IA in 22 (24.6 %) patients. Positive GM test was more frequent in patients with IFI (72.2 % and 25.1 %; OR 8.1; 95 % CI 4.8 - 13.8), and was associated with therapeutic antifungals prescription (52, 9 % and 20.5 %; OR 4.3, 95CI% 2.0 - 9.4), as well as lung abnormalities on HRCT (45.3% vs. 21.5 %; OR 3.0, 95 %CI 1.4 - 6.5). Mortality was 31.6 %. In the multivariate analysis, the variables associated with mortality were the hypothesis of IFI (OR 6.35; 95 % CI 3.63-11.12.0), lung abnormalities on HRCT (57.9 % and 26.9 %; OR 2 0.6; 95 % CI 1.5 - 4.4), and positive GM test (57.9 % and 26.9 %; OR 2.7 95 % CI 1.6 - 4.5). CONCLUSIONS: Positive GM test was associated with lung abnormalities on HRCT and with the introduction of therapeutic antifungals. If adequate anti-mold prophylaxis is available, the GM test should not be used as screening, but to investigate IFI in high-risk patients. The diagnosis of IFI, positive GM test and lung abnormalities on HRCT were predictors of hospital mortality in patients with hematological malignancies or undergoing HSCT.

Incidence of invasive fungal diseases in inflammatory bowel disease patients: A nationwide study in South Korea.

BACKGROUND: Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. OBJECTIVES: This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis and pneumocystosis, in IBD patients in South Korea using nationwide data. PATIENTS/METHODS: A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis and pneumocystosis, while the secondary outcome involved analysing the risk factors associated with each specific infection. RESULTS: The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis and pneumocystosis in IBD patients were 0.71 per 1000 person-years (PYs), 0.15 per 1000 PYs and 0.12 per 1000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value <.001) and Pneumocystosis (adjusted p-value = .012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumour necrotic factor agents or the Charlson comorbidity index. CONCLUSION: Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.

[Analysis of clinical characteristics and risk factors of death in critical burn patients complicated with invasive fungal infection].

Objective: To investigate the clinical characteristics and risk factors of critical burn patients complicated with invasive fungal infection. Methods: A retrospective case series study was conducted. From January 2017 to December 2022, 88 critical burn patients combined with invasive fungal infection who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 61 males and 27 females, aged 26-74 years. Data on invasive fungal infection sites and the detection of pathogens in patients were recorded. According to the survival outcome within 28 days after admission, the patients were divided into survival group (63 cases) and death group (25 cases). The following data of patients were compared between the two groups, including the basic data and injuries of patients at admission such as age, sex, body weight, total burn area, combination of inhalation injury, combination of hypertension and diabetes, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score, and admission time after burns, the levels of blood biochemical indexes within 24 h after admission such as white blood cell count, platelet count, red blood cell count, monocyte count, neutrophil count, lymphocyte count, alanine transaminase, aspartate transaminase, glucose, creatinine, urea nitrogen, D-dimer, galactomannan (GM), 1,3-ß-D glucan, and creatine kinase, the application of invasive procedures and vasoactive drugs during the treatment such as continuous renal replacement therapy, ventilator-assisted breathing, tracheotomy, deep vein catheterization, skin grafting >2 times, the levels of infection indicators on post admission day (PAD) 1, 3, 7, and 14 including C-reactive protein (CRP), procalcitonin, lactic acid, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the detection of pathogens in the process of treatment. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, chi-square test, Mann-Whitney U test, and Bonferroni correction. Multivariate logistic regression analysis was performed to screen the independent risk factors that affected death of critical burn patients complicated with invasive fungal infection. Results: The main sites of invasive fungal infection were the wounds (67 cases) and blood stream (46 cases), with Candida fungi (58 strains) as the main strain for fungi infection, and there were a total of 30 cases of infection with mixed pathogenic bacteria. Compared with those in survival group, the APACHE Ⅱ score, proportions of combination with inhalation injury and hypertension of patients in death group were significantly increased (t=2.11, with χ2 values of 6.26 and 9.48, respectively, P<0.05), while the other basic data and injury condition had no significant changes (P>0.05). Compared with those in survival group, the levels of D-dimer, GM, and 1,3-ß-D glucan of patients in death group were significantly increased within 24 h after admission (with t values of 2.42, 2.05, and 2.21, respectively, P<0.05), while the other blood biochemical indexes within 24 h after admission, as well as the proportions of applying invasive procedures and application of vasoactive drugs during the treatment process were not significantly changed (P>0.05). The levels of infection indicators of patients on PAD 1 and 3 were similar between the two groups (P>0.05). The procalcitonin level on PAD 7 and the levels of CRP, procalcitonin, lactic acid, IL-6, and TNF-α on PAD 14, as well as the proportion of infection with mixed pathogenic bacteria of patients in death group were significantly higher than those in survival group (with t values of 4.69, 3.89, 6.70, 6.14, 4.65, and 3.26, respectively, χ2=12.67, P<0.05). Multivariate logistic regression analysis showed that combination with inhalation injury, combination with hypertension, and infection with mixed pathogenic bacteria were independent risk factors for death of critical burn patients complicated with invasive fungal infection (with odds ratios of 5.98, 4.67, and 6.19, respectively, 95% confidence intervals of 1.42-15.39, 1.41-25.28, and 1.86-20.58, respectively, P<0.05). Conclusions: The main sites of infection in critical burn patients complicated with invasive fungal infection are the wounds and blood stream, with Candida fungi as the main strain for fungi infection, and a large proportion of infection with mixed pathogenic bacteria. The combined inhalation injury, combined hypertension, and infection with mixed pathogenic bacteria are the independent risk factors for the death of those patients.

Invasive fungal diseases in patients with autoimmune diseases: a case series from the French RESSIF network.

OBJECTIVES: We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality. METHODS: We analysed cases of IFD associated with AID from the surveillance network of invasive fungal diseases (Réseau de surveillance des infections fongiques invasives, RESSIF) registry of the French national reference centre for invasive mycoses. We studied association of AID-specific treatments with 30-day mortality. We analysed total lymphocyte and CD4-T cell counts in patients with Pneumocystis jirovecii pneumonia (PCP). RESULTS: From 2012 to 2018, 549 individuals with IFD and AID were included, mainly with PCP (n=227, 41.3%), fungemia (n=167, 30.4%) and invasive aspergillosis (n=84, 15.5%). Rheumatoid arthritis (RA) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) were the most frequent AID in PCP (n=55 and 25, respectively) and invasive aspergillosis (n=15 and 10, respectively), inflammatory bowel diseases (IBDs) were predominant in fungemia (n=36). At IFD diagnosis, 365 (66.5%) patients received glucocorticoids (GCs), 285 (51.9%) immunosuppressants, 42 (7.7%) tumor necrosis factor (TNF)-α blockers, 75 (13.7%) other biologics. Mortality at 30 days was 28.1% (143/508). Fungemia and high-dose GCs were independently associated with higher 30-day mortality. In PCP patients, lymphopenia <1500/mm3 was frequent (132/179, 73.7%) even if CD4+T cell count exceeded 200/mm3 in 56/78 patients (71.8%) (median 472.5/mm3, IQR 160-858). CONCLUSION: IFD associated with AID occurs primarily in RA, AAV and IBD, especially when treated with GCs and immunosuppressants. Mortality is high, especially for patients on high-dose GCs. Lymphopenia may help identify risk of PCP, but normal CD4+T cell count does not rule out the risk. Further studies are needed to assess the individual risk factors for IFD.

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.

Invasive aspergillosis in liver transplant recipients.

BACKGROUND: Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. METHODS: We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. RESULTS: The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. CONCLUSION: IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.

Effect of invasive aspergillosis on risk for different causes of death in older patients with acute myeloid leukaemia or high-risk myelodysplastic syndrome.

PURPOSE: Study objectives were to estimate the cumulative incidence of death due to different causes of death (CODs) and investigate the effect of invasive aspergillosis (IA) on each separate COD in a cohort of older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) included in the Haemato-Oncology Foundation for Adults in the Netherlands (HOVON) 43 randomized controlled trial. METHODS: Pre-collected data from the trial was obtained from the HOVON data center and relevant clinical information was extracted. The cumulative incidence of death due to different CODs was estimated with a competing risk model and the association between each COD and prognostic factors, including IA, were investigated with a cause-specific hazard Cox regression model. RESULTS: In total 806 patients were included, mean age of 70 years and 55% were male. The cumulative incidences of death due to leukaemia or infection at 3, 6, 12 and 36 months were 0.06, 0.11, 0.23, 0.42 and 0.17, 0.19, 0.22, 0.25 respectively. Incidence of IA was 21% and diagnosis of IA up until the final chemotherapy cycle was associated with an increased risk of dying from leukaemia (cause-specific hazard ratio (CSHR): 1.75, 95% CI 1.34-2.28) and a trend was seen for infection (CSHR: 1.36, 95% CI 0.96-1.91). CONCLUSION: Leukaemia was the most likely cause of death over time, however in the first year after diagnosis of AML or high-risk MDS infection was the most likely cause of death. Patients with IA had a relatively increased risk of dying from leukaemia or infection.

Endoscopic Endonasal Optic Nerve Decompression in a Patient With Invasive Fungal Sinusitis Invasion Into the Orbital Apex: Intraoperative Video and Literature Review.

Invasive fungal sinusitis (IFS) is rare but potentially fatal in immunocompromised patients. Orbital extension of IFS can cause visual loss or ophthalmoplegia, and the rate of recovery of visual acuity can be low even after treatment with antifungal agents and sinus surgery. In this case, optic nerve decompression with the endoscopic endonasal approach was successful for the treatment of visual loss in a patient with IFS with orbital apex extension. The authors describe the recovery of visual acuity after optic nerve decompression in a patient with IFS who had exhibited visual loss caused by invasion into the orbital apex. The authors also provide an intraoperative video and literature review.

[Bacterial and fungal co-infection: an association of criminals to look for]. / Co-infection bactérienne et fongique : une association de malfaiteurs à chercher.

INTRODUCTION: Mucorales are fungi that cause opportunistic infections. Its incidence increases. CASE REPORT: We report case of a 68-year-old woman with myelodysplastic syndrome responsible for prolonged neutropenia, hospitalized for pneumonia and sinusitis caused by Pseudomonas aeruginosa. But, despite antibiotic therapy, the patient's health deteriorated with discovery of systemic emboli on CT-scan and died. Sinus biopsies performed before her death diagnosed invasive fungal infection (Mucorales). CONCLUSION: Mucorales co-infections are rare but have already been described. Any invasive fungal infection should be searched on the event of any clinical suspicion: ground (neutropenia), lack of response to well-conducted antibiotic therapy, rapidly unfavorable outcome. The presence of other microbiological documentation do not must stop the search of invasive fungal infection, because it could have short-term life-threatening impact.

A fatal SARS-coronavirus-2 induced bone marrow aplasia complicated with invasive fungal infection and severe neutropenic enterocolitis.

BACKGROUND: Immunization against the coronavirus disease 2019 (COVID-19) began in January 2021 in Iran; nonetheless, due to a lack of vaccination among children under 12, this age group is still at risk of SARS-CoV-2 infection and its complications. CASE PRESENTATION: SARS-CoV-2 infection was diagnosed in a 6-year-old girl who had previously been healthy but had developed a fever and pancytopenia. The bone marrow aspiration/biopsy demonstrated just hypocellular marrow without signs of leukemia. She was worked up for primary and secondary causes of pancytopenia. Except for a repeated reactive HIV antibody/Ag P24 assay, all test results were inconclusive. After a thorough diagnostic investigation, the cross-reactivity of the HIV antibody/Ag P24 test with SARS-CoV-2 antibodies was confirmed. The patient did not develop any COVID-19-related signs and symptoms, but she did get a severe invasive fungal infection and neutropenic enterocolitis. She died as a result of disseminated intravascular coagulopathy. CONCLUSION: It is critical to recognize children infected with SARS-CoV-2 who exhibit atypical clinical manifestations of COVID-19, such as persistent pancytopenia. SARS-CoV-2 infection can cause severe and deadly consequences in children; thus, pediatricians should be aware of COVID-19's unusual signs and symptoms mimicking other conditions such as aplastic anemia.

Incidence of invasive fungal infections in patients with hematological malignancies receiving ibrutinib therapy in south-east Austria.

Since the broad implementation of ibrutinib therapy, an increasing number of studies have been reported on invasive fungal infections (IFI) associated with ibrutinib administration. We conducted a retrospective cohort study in three hospitals in south-east Austria in order to assess the local epidemiology of ibrutinib associated IFIs. A total of 113 patients with underlying hematological malignancy were included in the study. During the study period, a single IFI episode was observed, which corresponds to an IFI incidence of 2.3 cases per 100 person years (95% CI: 0.12-11.47). IFIs during ibrutinib therapy seem to be a rare event in case of absent additional risk factors for IFIs.

Ibrutinib is an effective drug used to treat a variety of blood cancers, but it might increase risk for life-threatening invasive fungal infections (IFIs). In our study, a low number (1 IFI per 43 patient years) of patients on ibrutinib developed an IFI.

[Value of the Diagnostic-Driven Therapy with Voriconazole in Patients with Hematological Disorders Complicated by Invasive Fungal Disease].

OBJECTIVE: To explore the value of the diagnostic-driven therapy with voriconazole in patients with hematological disorders complicated by invasive fungal disease (IFD). METHODS: A total of 111 patients with hematological disorders complicated by IFD, treated with voriconazole in the hematology department of the General Hospital of South Theatre Command from July 2019 to July 2020, were retrospectively analyzed to compare the differences between the empirical therapy and the diagnostic-driven therapy on the treatment time of voriconazole, hospitalization days and antifungal efficacy. SPSS 23.0 was used for statistical analysis of data. RESULTS: Compared with the diagnostic-driven therapy group, the empirical therapy group had more IFD high-risk patients, including a higher proportion of agranulocytosis patients (95.2% vs 69.5%, P=0.003). However, there were no significant differences on the treatment time of voriconazole, hospitalization days and antifungal efficacy of voriconazole between the two groups. CONCLUSION: Using diagnostic-driven therapy in relatively IFD low-risk patients can obtain similar therapeutic outcomes and prognosis as empirical therapy in high-risk patients. Either of two strategies can be used in clinical practice according to the individual conditions of patients.

Fatal invasive aspergillosis in a child with chronic granulomatous disease.

Patients with chronic granulomatous disease, a primary immunodeficiency, experience granulomatous complications and recurrent life-threatening opportunistic bacterial and fungal infections. In this article, we report on a case of invasive aspergillosis in an eight-year-old boy with chronic granulomatous disease, who presented with pleural effusion and pneumonia, cerebral venous sinus thrombosis, and unusual skin lesions caused by Aspergillus fumigatus. Antifungal treatment with itraconazole and other antifungal agents, along with interferon-γ, was ineffective and the patient eventually died from cerebral venous sinus thrombosis, and intracerebral haemorrhage following increased intracranial pressure after one month. The diagnosis of invasive aspergillosis should be considered early in children presenting with invasive fungal infections, particularly those involving the central nervous system.

Oesophageal and pulmonary invasive aspergillosis in a patient with multiple myeloma.

Invasive aspergillosis (IA) is a serious fungal infection that primarily affects patients with prolonged and profound neutropenia, and compromised cell-mediated immunity. Aspergillosis of the oesophagus and gastrointestinal tract is uncommon but seen in advanced cases of disseminated IA. However, it is difficult to diagnose antemortem due to the poor specificity of the symptoms and the absence of characteristic imaging findings. Therefore, the reported cases of gastrointestinal aspergillosis have been associated with high morbidity and mortality, and frequently diagnosed postmortem. Here we present a successful outcome in a patient with relapsed and refractory multiple myeloma who had presented with febrile neutropenia, cough and dysphagia, and was diagnosed with disseminated IA comprising of pulmonary and oesophageal involvement. This case highlights the need for a high index of suspicion and the importance of invasive procedures for histopathology and molecular diagnostics to ensure an early diagnosis and therapeutic intervention.

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis.

BACKGROUND: In allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients, the inter-relationship between post-transplant cytomegalovirus (CMV) and subsequent invasive fungal infections (IFIs) is conflicting and the association of CMV serostatus with IFIs has not been evaluated. OBJECTIVES: To determine the relationship between CMV infection/serostatus and IFIs in allo-HSCT populations. DATA SOURCES: A systematic literature search was conducted from existence until 11 July 2021 using Medline, Embase and ISI Web of Science databases. STUDY ELIGIBILITY CRITERIA: Cross-sectional, prospective cohort, retrospective cohort and case-control studies that reported allo-HSCT recipients with CMV and without CMV who developed or did not develop IFIs after CMV infection. PARTICIPANTS: Allo-HSCT recipients. INTERVENTIONS: Not applicable. METHODS: A systematic search, screening, data extracting and assessing study quality were independently conducted by two reviewers. The Newcastle-Ottawa scale was used to assess risk of bias. data were analysed using the pooled effect estimates of a random-effects model. RESULTS: A total of 18 and 12 studies were included for systematic review and meta-analysis, respectively. Post-transplant CMV infection significantly increased the risk of IFIs with a pooled hazard ratio (pHR) of 2.58 (1.78, 3.74), I2 = 75%. Further subgroup analyses by timing of IFIs, CMV definitions, study continents, study design and adjustment of effect estimates showed that post-transplant CMV infection consistently increased the risk of subsequent IFIs. High-risk CMV serostatus (D-/R+) increased the risk of IFIs with a pooled odds ratio (OR) of 1.33 (1.04, 1.71), I2 = 0%, but low-risk CMV serostatus (D-/R-) decreased the risk of IFIs with a pOR of 0.69 (0.55, 0.87), I2 = 0%. CONCLUSIONS: Post-transplant CMV infection and high-risk CMV serostatus increased the risk of IFIs, but low-risk CMV serostatus decreased risk of IFIs among allo-HSCT recipients. Further studies are needed to identify at-risk allo-HSCT recipients as well as to focus on fungal diagnostics and prophylaxis to prevent this fungal-after-viral phenomenon.

[Clinical analysis of amphotericin B cholesteryl sulfate complex for injection in the treatment of invasive fungal disease for patients with hematological malignancies in 30 cases].

Objective: To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness. Methods: This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives. Results: 30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day. Conclusions: Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.