Mold Infections In Patients Research Articles

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant. All patients engrafted, and all but one GT recipient had neutrophil recovery and evidence of functional correction. Eighteen patients (69%) are currently alive and 19 patients (73% of total, 90% of patients with repeat imaging performed) had evidence of radiographic improvement. With 3 exceptions, deaths were not principally related to the fungal infection and duration of antecedent infection did not correlate with death. Aspergillus species accounted for the majority of disease (50%), followed by Phellinus species (18%). Osteomyelitis and disseminated disease were common, as only 11 patients (42%) had disease restricted to pneumonia. Triazole therapy was used in all 26 patients, with combination therapy used in 25 (96%). HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD.

Concordance of Chest Radiography and Chest Computed Tomography Findings in Patients with Hematologic Malignancy and Invasive Mucormycosis: What Are the Prognostic Implications?

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging. Therefore, we reviewed 44 consecutive HM patients with probable/proven IPM at MD Anderson Cancer Center in 2000-2020 who had concurrent CCT and CXR studies performed. All 44 patients had abnormal CCTs and 39 (89%) had anormal CXR findings at IPM diagnosis. However, only 26 patients (59%) showed CCT-matching IPM-suspicious lesions on CXR. Acute Physiology and Chronic Health Evaluation II score > 18 at IPM diagnosis and breakthrough infection to Mucorales-active antifungals were the only independent risk factors for 42-day and/or 84-day mortality. Absence of neutropenia at IPM diagnosis, neutrophil recovery in neutropenic patients, and surgical revision of mucormycosis lesions were protective factors. Although not reaching significance on multivariable analysis, visualization of CCT-matching lesions on CXR was associated with significantly increased 84-day mortality (log-rank test, p = 0.033), possibly as a surrogate of extensive lesions and tissue necrosis. This observation supports the exploration of radiologic lesion kinetics as a prognostic staging tool in IPM patients.

Evaluation of Empirical and Preemptive Therapy Approaches of Invasive Mold Infections in Patients with Hematologic Malignancy

Evaluation of Empirical and Preemptive Therapy Approaches of Invasive Mold Infections in Patients with Hematologic Malignancy

The first suspected disseminated Hormographiella aspergillata infection in China, diagnosed using metagenomic next-generation sequencing: a case report and literature review

ABSTRACT Hormographiella aspergillata is a rare and emerging cause of invasive mould infections in patients with haematological malignancies, with a mortality rate of approximately 70%. Here, we present the first reported case of suspected disseminated H. aspergillata infection in China. The patient experienced a second relapse of acute myeloid leukaemia and developed neutropenia, fever, discrepant blood pressure between limbs, and cutaneous lesions limited to the left upper extremity. Since lung tissue biopsy was not feasible, metagenomic next-generation sequencing (mNGS) and panfungal polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid and blood samples were performed, which indicated probable H. aspergillata pulmonary infection. Histopathology of cutaneous lesions revealed numerous fungal hyphae within dermal blood vessels. mNGS of a skin biopsy sample identified H. aspergillata sequences, and the fungi was subsequently recovered from fungal culture, proving cutaneous H. aspergillata infection. Despite combined antifungal therapy, the patient died owing to disease progression. Additionally, 22 previously reported cases of invasive H. aspergillata infection were reviewed in patients with haematological malignancies. Thus, mNGS is a powerful diagnostic tool for the early and effective detection of invasive H. aspergillata infections, with the advantage of sequencing all potential pathogens, and providing results within 24 h.

595. Olorofim (OLO) for treatment of invasive mould infections in patients with limited or no treatment options: PK data from a Phase 2b open-label study (NCT03583164, Study 32)

Abstract Background OLO is a novel antifungal active vs. Aspergillus (including azole-resistant strains), resistant moulds (e.g., Lomentospora prolificans), and dimorphic moulds. In preclinical PKPD studies, a plasma level ≥ 0.2 µg/mL was required for efficacy similar to mould-active azoles. Methods Patients in Study 32 (N=100) received OLO (30 mg tablets) guided either by therapeutic drug monitoring (TDM) based on baseline bodyweight and OLO pre-dose plasma levels (180 to 300 mg/day x 1 d to load then 120 to 240 mg/day, given BID or TID as appropriate) or a fixed dose (150 mg BID for 1d then 90 mg BID). For each subject, OLO PK profiles were determined over 1 or 2 dosing intervals, an additional 8 to 9 scheduled pre-dose samples were taken during the initial 84 days and every 1-3 months thereafter. Food intake was not constrained. Results Geometric mean steady-state OLO PK parameters in the 90 evaluable subjects were similar between the TDM and fixed dosing groups (Table). Mean OLO pre-dose concentrations were similar over time for all 100 patients regardless of group and regimen; drug concentration variability was slightly greater when TDM was not utilized (Figure). Pre-dose levels were greater than the Cmin observed over a dosing interval in most subjects (range of pre-dose: Cmin ratio of 1 to 15.8). which may be due to food-triggered release from a deep compartment such as the liver. Exposures exceeding the PD target (≥ 0.2 µg/mL) were consistently achieved. PK parameters predicted by population PK modelling of Phase II data were in reasonable agreement with observed data (Table). Table: OLO Systemic Exposure at Steady-State [median (5th – 95th percentiles)] 1 based on 90 mg BID Conclusion OLO is a novel mechanism oral antifungal with broad-spectrum mould activity. When administered as a fixed dose (90 mg BID), adequate exposure for efficacy against invasive mycoses is achieved, without the need to confirm by TDM Disclosures Karen Cornelissen, PhD, F2G: Employee James G. Wright, PhD, F2G: Advisor/Consultant Andrew Cristinacce, MSc by Research, F2G: Advisor/Consultant Roger Bruggemann, Pharm, PhD, Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant|Mindipharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant Johan A. Maertens, MD PhD, F2G Ltd: Advisor/Consultant|Gilead Sciences Ltd: Advisor/Consultant|Mundipharma: Advisor/Consultant|Pfizer Inc: Advisor/Consultant George R. Thompson, III, MD, Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Merck: Grant/Research Support|Pfizer: DSMB|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support Sharon C. Chen, PhD MBBS, F2G PTy Ltd: Grant/Research Support|MSD Australia: Grant/Research Support John H. Rex, MD, Advent Life Sciences: Operating Partner|Advent Life Sciences: Ownership Interest|AMR Action Fund: Advisor/Consultant|AstraZeneca: Stocks/Bonds|Basilea Pharmaceutica: Advisor/Consultant|Bugworks Research, Inc.: Advisor/Consultant|F2G, Limited: Employee|F2G, Limited: Stocks/Bonds|Forge Therapeutics: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Pfizer Pharmaceuticals: Honoraria|Sumitovant: Advisor/Consultant.

870. Olorofim for the treatment of invasive mould infections in patients with limited or no treatment options: Comparison of interim results from a Phase 2B open-label study with outcomes in historical control populations (NCT03583164, FORMULA-OLS, Study 32)

Abstract Background Olorofim is a novel antifungal agent active against Aspergillus spp (including azole-resistant strains), rare, resistant moulds (e.g., Lomentospora prolificans) and dimorphic moulds. Serial images of Lomentospora prolificans infection following breast enhancement surgery: progression of healing pre- and post-olorofim therapy. Post-surgical bone/ soft tissue Lomentospora prolificans infection of the chest wall in a healthy woman was uncontrolled with available agents (D -9 visible mould in wound base). At D42/84 overall response on olorofim monotherapy was stable; wound closure with complete resolution of IFI was achieved at D322 (case previously reported, ECCMID 2020 abstract #2585). Methods Patients with limited/no treatment options for proven invasive fungal infection (IFI) or probable pulmonary invasive aspergillosis (IA) using EORTC-MSGERC criteria1 received oral olorofim (150mg BID x1d loading dose then 90mg BID). Outcomes in the first 100 patients are compared with historical controls (HCs) as well as with expected outcomes in patients with baseline highly active, uncontrolled IFI (HAU-IFI). Results All-cause mortality in IA at month 3 (includes data to Day 100, the best-fit time point for IA HC data) was 17/53 (32%, 95 CI 20–46%) for olorofim vs. 40/46 (87%, 74–95%) in HCs given either no therapy or azole monotherapy for azole-resistant IA. Successful EORTC-MSGERC overall response2 (OR, complete or partial based on clinical + radiologic + mycologic improvement) was 47%/42% in IA (Day 42/D84, n = 53), 53%/53% (L. prolificans, n=17), 55%/36% (Scedosporium, n=11), and 50%/50% (other moulds, n=8). Stable response at D42/D84 predicted extended therapy responses, especially in HAU-IFI of brain and bone (Figure). For Coccidioides (n=11) OR was limited to stable due to very slow clearance of fungal serology but clinical response was rapid. Symptoms resolved completely in 18% (2/11) by D84 vs 3% (1/29) by D1523 in comparable HCs with poorly controlled extrapulmonary Coccidioides infection; similar trends were seen for other response measures. Conclusion Olorofim is a novel oral antifungal with activity against a wide range of mould infections which are difficult to treat. Compared with relevant HCs or expected outcomes for HAU-IFI, olorofim has a positive benefit-risk profile in a well-defined population of patients with limited/no treatment options. As noted previously3, considering stable in overall success if often appropriate when assessing responses in non-IA mould IFI.

348. Cell-free plasma next-generation sequencing assists in the evaluation of invasive mold infection in patients with COVID-19: a case series

Abstract Background Distinguishing COVID-19 Associated Pulmonary Aspergillosis (CAPA) and invasive mold infections (IMIs) from other causes of secondary pneumonia in COVID-19 can be challenging. 1,3-β-D-Glucan and galactomannan are commonly utilized biomarkers for the workup of IMIs but are limited by a lack of specificity and sensitivity respectively. Cell-free plasma next-generation sequencing (cfNGS) is a promising non-invasive approach that can provide direct detection of pathogens in patient's serum. This study explored its potential role in the evaluation of secondary pneumonia in patients with COVID-19. Methods We performed a retrospective single-center observational study from March 2020 to December 2021 at Virginia Commonwealth University Medical Center, a 811-bed tertiary care center, to evaluate patients with laboratory confirmed SARS-CoV-2 virus infection who underwent cfNGS for the evaluation of CAPA. CfNGS (Karius, Inc., Redwood City, CA) was performed at the discretion of the clinical provider and we evaluated the test indication, patient history, clinical impact, correlation with serum biomarkers, and 30 day all-cause mortality. Results Thirteen patients were evaluated and none had Aspergillus species detected. One patient had Pneumocystis jirovecii on cfNGS. There was a 76.9% (10/13) concordance rate with patients’ serum fungal biomarkers. CfNGS also detected concomitant organisms in 53.8% (7/13) of our cohort. These data assisted in changes of clinical management for 84.6% (11/13) of patients and lead to the change in antifungal usage in 69.2% (9/13). Conclusion In this study, both negative and positive cfNGS test results assisted in important clinical decision making. cfNGS may have a role in the evaluation of CAPA or other IMIs in patients with COVID-19. Disclosures Megan M. Morales, MD, Karius: Paid speaker.

Indoor environment assessment of special wards of educational hospitals for the detection of fungal contamination sources: A multi-center study (2019-2021).

The hospital environment was reported as a real habitat for different microorganisms, especially mold fungi. On the other hand, these opportunistic fungi were considered hospital-acquired mold infections in patients with weak immune status. Therefore, this multi-center study aimed to evaluate 23 hospitals in 18 provinces of Iran for fungal contamination sources. In total, 43 opened Petri plates and 213 surface samples were collected throughout different wards of 23 hospitals. All collected samples were inoculated into Sabouraud Dextrose Agar containing Chloramphenicol (SC), and the plates were then incubated at 27-30ºC for 7-14 days. A total of 210 fungal colonies from equipment (162, 77.1%) and air (48, 22.9%) were identified. The most predominant isolated genus was Aspergillus (47.5%), followed by Rhizopus (14.2%), Mucor (11.7%), and Cladosporium (9.2%). Aspergillus (39.5%), Cladosporium (16.6%), as well as Penicillium and Sterile hyphae (10.4% each), were the most isolates from the air samples. Moreover, intensive care units (38.5%) and operating rooms (21.9%) had the highest number of isolated fungal colonies. Out of 256 collected samples from equipment and air, 163 (63.7%) were positive for fungal growth. The rate of fungal contamination in instrument and air samples was 128/213 (60.1%) and 35/43 (81.2%), respectively. Among the isolated species of Aspergillus, A. flavus complex (38/96, 39.6%), A. niger complex (31/96, 32.3%), and A. fumigatus complex (15/96, 15.6%) were the commonest species. According to our findings, in addition to air, equipment and instrument should be considered among the significant sources of fungal contamination in the indoor environment of hospitals.

Severe pulmonary mucorales superinfection in three influenzapatients with and without influenza-associated aspergillosis

Mucormycosisis an opportunistic fungal disease which affects immunocompromised hosts including patients with haematologic malignancies and poorly controlled diabetes mellitus. Mucorales grow invasively and are associated with high mortality even if promptly diagnosed. Viral infection like influenza can cause severe pneumonia and is associated with pulmonary aspergillosis. Here we report three separate cases of Mucorales super infection in critically-ill patients with influenza infection, one of them histologically confirmed. Two patients also had influenza-associated pulmonary aspergillosis. Two patients had fatal clinical outcome despite intensive care. The simultaneous detection of these two rare mold infections in patients with severe influenza is highly remarkable and calls for increased awareness.

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

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

Invasive mould infections in patients from floodwater-damaged areas after hurricane Harvey – a closer look at an immunocompromised cancer patient population

ObjectivesExtensive floodwater damage following hurricane Harvey raised concerns of increase in invasive mould infections (IMIs), especially in immunocompromised patients. To more comprehensively characterize the IMI landscape pre- and post-Harvey, we used a modified, less restrictive clinical IMI (mcIMI) definition by incorporating therapeutic-intent antifungal drug prescriptions combined with an expanded list of host and clinical features. MethodsWe reviewed 103 patients at MD Anderson Cancer Center (Houston, Texas), who lived in Harvey-affected counties and had mould-positive cultures within 12 months pre-/post-Harvey (36 and 67 patients, respectively). Cases were classified as proven or probable IMI (EORTC/MSG criteria), mcIMI, or colonization/contamination. We also compared in-hospital mortality and 42- day survival outcomes of patients with mcIMI pre-/post-Harvey. ResultsThe number of patients with mould- positive cultures from Harvey-affected counties almost doubled from 36 pre- Harvey to 67 post- Harvey (p < 0.01). In contrast, no significant changes in (mc)IMI incidence post-Harvey nor changes in the aetiological mould genera were noted. However, patients with mcIMIs from flood affected areas had significantly higher in-hospital mortality (p = 0.01). ConclusionsWe observed increased colonization but no excess cases of (mc)IMIs in immunosuppressed cancer patients from affected areas following a large flooding event such as hurricane Harvey.

Practice Guidelines for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis in an Intensive Care Setting.

Coronavirus disease-2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a new disease characterized by secondary Aspergillus mold infection in patients with COVID-19. It primarily affects patients with COVID-19 in critical state with acute respiratory distress syndrome, requiring intensive care and mechanical ventilation. CAPA has a higher mortality rate than COVID-19, posing a serious threat to affected individuals. COVID-19 is a potential risk factor for CAPA and has already claimed a massive death toll worldwide since its outbreak in December 2019. Its second wave is currently progressing towards a peak, while the third wave of this devastating pandemic is expected to follow. Therefore, an early and accurate diagnosis of CAPA is of utmost importance for effective clinical management of this highly fatal disease. However, there are no uniform criteria for diagnosing CAPA in an intensive care setting. Therefore, based on a review of existing information and our own experience, we have proposed new criteria in the form of practice guidelines for diagnosing CAPA, focusing on the points relevant for intensivists and pulmonary and critical care physicians. The main highlights of these guidelines include the role of CAPA-appropriate test specimens, clinical risk factors, computed tomography of the thorax, and non-culture-based indirect and direct mycological evidence for diagnosing CAPA in the intensive care unit. These guidelines classify the diagnosis of CAPA into suspected, possible, and probable categories to facilitate clinical decision-making. We hope that these practice guidelines will adequately address the diagnostic challenges of CAPA, providing an easy-to-use and practical algorithm to clinicians for rapid diagnosis and clinical management of the disease.

Genomic Diversity of Azole-Resistant Aspergillus fumigatus in the United States.

ABSTRACTAzole resistance in pathogenic Aspergillus fumigatus has become a global public health issue threatening the use of medical azoles. The environmentally occurring resistance mutations, TR34/L98H (TR34) and TR46/Y121F/T289A (TR46), are widespread across multiple continents and emerging in the United States. We used whole-genome single nucleotide polymorphism (SNP) analysis on 179 nationally represented clinical and environmental A. fumigatus genomes from the United States along with 18 non-U.S. genomes to evaluate the genetic diversity and foundation of the emergence of azole resistance in the United States. We demonstrated the presence of clades of A. fumigatus isolates: clade A (17%) comprised a global collection of clinical and environmental azole-resistant strains, including all strains with the TR34/L98H allele from India, The Netherlands, the United Kingdom, and the United States, and clade B (83%) consisted of isolates without this marker mainly from the United States. The TR34/L98H polymorphism was shared among azole-resistant A. fumigatus strains from India, The Netherlands, the United Kingdom, and the United States, suggesting the common origin of this resistance mechanism. Six percent of azole-resistant A. fumigatus isolates from the United States with the TR34 resistance marker had a mixture of clade A and clade B alleles, suggestive of recombination. Additionally, the presence of equal proportions of both mating types further suggests the ongoing presence of recombination. This study demonstrates the genetic background for the emergence of azole resistance in the United States, supporting a single introduction and subsequent propagation, possibly through recombination of environmentally driven resistance mutations.

Invasive fungal infections in ICU patients - What's New?

Invasive fungal infections are gaining increasing importance in intensive care medicine. The aim of this article is to present an update on recent developments in the field of invasive fungal infection in critically ill patients. Particular emphasis is placed on the recently described invasive mold infections in patients with acute respiratory distress syndrome due to influenza or COVID-19. Detecting high-risk patients and the optimal diagnostic and therapeutic strategies play a decisive role to improve outcome.

Characteristics and risk factors for mortality of invasive non-Aspergillus mould infections in patients with haematologic diseases: A single-centre 7-year cohort study.

SummarySince mould‐active azole prophylaxis has become a standard approach for patients with high‐risk haematologic diseases, the epidemiology of invasive fungal infections (IFIs) has shifted towards non‐Aspergillus moulds. It was aimed to identify the epidemiology and characteristics of non‐Aspergillus invasive mould infections (NAIMIs). Proven/probable NAIMIs developed in patients with haematologic diseases were reviewed from January 2011 to August 2018 at Catholic Hematology hospital, Seoul, Korea. There were 689 patients with proven/probable invasive mould infections; of them, 46 (47 isolates) were diagnosed with NAIMIs. Fungi of the Mucorales order (n = 27, 57.4%) were the most common causative fungi, followed by Fusarium (n = 9, 19.1%). Thirty‐four patients (73.9%) had neutropenia upon diagnosis of NAIMIs, and 13 (28.3%) were allogeneic stem cell transplantation recipients. The most common site of NAIMIs was the lung (n = 27, 58.7%), followed by disseminated infections (n = 8, 17.4%). There were 23.9% (n = 11) breakthrough IFIs, and 73.9% (n = 34) had co‐existing bacterial or viral infections. The overall mortality at 6 and 12 weeks was 30.4% and 39.1%, respectively. Breakthrough IFIs (adjusted hazards ratio [aHR] = 1.99, 95% CI: 1.3‐4.41, P = .031) and surgical treatment (aHR = 0.09, 95% CI: 0.02‐0.45, P = .003) were independently associated with 6‐week overall mortality. NAIMIs were not rare and occur as a complex form of infection often accompanied by breakthrough/mixed/concurrent IFIs and bacterial or viral infections. More active diagnostic efforts for NAIMIs are needed.

Invasive Mold Infections in Patients with Chronic Lymphoproliferative Disorders

This review summarizes data about epidemiology, treatment, and risk factors for invasive fungal infections (IFI) in patients affected by chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and indolent non Hodgkin lymphoma (iNHL). Despite advances in the prognosis and treatment of hematological malignancies in recent years, susceptibility to infection remains a significant challenge to patient care. A large amount of data regarding patients with acute leukemias have been published while little information is available on incidence of IFI in chronic lymphoproliferative disorders (CLD). The overall incidence of IFI in CLL patients is reported from 1.3 to 7.8% and the main risk factors are related to disease status (high-risk in relapsed/refractory disease), number of previous chemotherapy regimens, and Ig levels. In MM, most of the IFI occurred during refractory or progressive disease. The rate of IFI ranges from 0.5 to 12.3%. Neutropenia is the main risk factor in MM and risk seems to be related to its duration and severity. The overall incidence of IFI in iNHL ranges from 0.5 to 4% and the most important risk factors are disease status (high-risk in relapsed/refractory and advance stage disease) and type of treatment (high-risk for steroid administration, intensive chemotherapy with prolonged neutropenia, use of monoclonal antibodies and purine analogs).

Sequential systematic anti-mold prophylaxis with micafungin and voriconazole results in very low incidence of invasive mold infections in patients undergoing allogeneic hematopoietic stem cell transplantation.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk for invasive mold infections (IMI). The goal of the study is to describe the incidence and outcome of IMI in patients after allo-HSCT in a large cohort of patients receiving anti-mold prophylaxis. We conducted a retrospective review of 988 consecutive adults who underwent allo-HSCT in our center from 2008 through 2014. Standard prophylaxis consisted of micafungin 150mg IV daily from admission to day +7±3 followed by voriconazole until day +75 to +100. Cases meeting criteria for proven or probable IMI according to EORTC-MSG criteria were included. Median age at HSCT was 54years. The most common diagnoses were acute myeloid leukemia (n=351, 36%) and lymphoid malignancies (n=248, 25%). Matched related or unrelated donors (URD) were used in 686 (69%) patients, mismatched URD in 142 (14%) and cord blood units in 154 (16%). Twenty-one patients were diagnosed with IMI after allo-HSCT, 19 probable and 2 proven, and one patient was diagnosed postmortem. Microbiological diagnosis was established in 9 cases, 5 of them being Aspergillus. One-year cumulative incidence (CI) of IMI was 1.6% (95% CI 0.9-2.5) while 12-week overall survival after IMI was 39% (95% CI 24-65) Analyzed by disease, there was a trend for a higher 1-year CI of IMI in patients with ALL (5% [95% CI 1.6-11.4]) when compared with AML (1.4%), MDS (1.5%) and lymphoma (1.2%), P=.06. The 1-year CI of IMI after transplantation is low in patients receiving anti-mold prophylaxis with micafungin bridged to voriconazole, although these infections are associated with a higher risk of mortality.

Changing Epidemiology of Invasive Mold Infections in Patients Receiving Azole Prophylaxis

Breakthrough invasive mold infections (IMIs) that occur during posaconazole or voriconazole prophylaxis are rare complications for which epidemiological data are lacking. This retrospective analysis comparing 24 microbiologically documented breakthrough with 66 nonbreakthrough IMIs shows a shift towards non-Aspergillus molds with a significantly increased proportion of rare multidrug-resistant molds.

Hyperglycemia as a possible risk factor for mold infections-the potential preventative role of intensified glucose control in allogeneic hematopoietic stem cell transplantation.

Diabetes mellitus (DM) is well-known as a disorder that increases the risk of infectious diseases. Various reports have shown that innate immunity is impaired in patients with DM, which is considered to be a major cause of increased risk of infectious diseases. However, there is a paucity of data about the actual risk of mold infections in patients with DM. Several treatment procedures, such as solid organ transplantation and hematopoietic stem cell transplantation (HSCT), are intrinsically associated with a high risk of mold infections and also correlated with an increased risk of post-transplant DM. Therefore, we could assume that organ transplant recipients or HSCT recipients with DM are at quite high risk of mold infections. Here, we aim to summarize the information about the increased risk of mold infections in patients with DM, and propose possible interventions such as intensive glucose control to reduce this risk in patients with DM.

Disseminated Cunninghamella bertholletiae Infection During Induction Chemotherapy in a Girl with High-Risk Acute Lymphoblastic Leukemia

Invasive fungal infections in children with acute lymphoblastic leukemia have been a major cause of mortality. Recent reports have described increasing incidence of invasive non-Aspergillus mold infections in patients with hematological malignancies. It is always challenging to treat invasive fungal infection and underlying hematological malignancies successfully. Here we report a girl with high-risk acute lymphoblastic leukemia who developed disseminated Cunninghamella bertholletiae infection during induction chemotherapy. This case illustrates the difficulties of diagnosis and treatment of invasive C. bertholletiae infection. It also highlights the necessity for physicians to keep high suspicion and awareness for this infrequent fungal infection.