Fungal Infection Rates Research Articles

Risk factors for invasive fungal infection in 5-azacytidine treated patients with acute myeloid leukemia and myelodysplastic syndrome.

The rate of invasive fungal infection (IFI) in patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) receiving 5-azacytidine is incompletely defined and published recommendations for mold-active fungal prophylaxis in such patients vary according to source. We performed a retrospective cohort study in order to identify contemporary IFI rates and infection-related mortality in relation to known risk factors and the use of antifungal prophylaxis. One hundred and seventeen patients receiving 5-azacytidine for MDS and low blast count AML were identified, of whom 71 (61%) received antifungal prophylaxis. The IFI rate was 7.7% across the entire cohort: 5.6% in those receiving prophylaxis vs 10.9% in the subgroup who did not (P=.30). The presence of neutropenia at three months of treatment was associated with increased IFI risk (hazard ratio [HR] 8.29; (95% confidence interval [CI)] 1.61-42.6; P=.01), and on multivariate analysis, IFI was independently associated with increased all-cause mortality risk (HR 8.37; 95% CI 3.67 - 19.11; P<.0001). These data further highlight the risk of IFI in this population and support the use of mold-active prophylaxis in neutropenic patients receiving 5-azacytidine for MDS and AML.

Efficacy and safety of isavuconazole compared with voriconazole as primary antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.

When compared to voriconazole, isavuconazole is a safer and as effective primary antifungal prophylaxis during the first 3 months after allogeneic hematopoietic cell transplant, with lower rates of hepatotoxicity, and similar rates of fungal infections and all-cause mortality.

Ergot Alkaloids Mycotoxins in Cereals and Cereal-Derived Food Products: Characteristics, Toxicity, Prevalence, and Control Strategies

Ergot alkaloids (EAs) are a group of mycotoxins that are mainly produced from the plant pathogen Claviceps. Claviceps purpurea is one of the most important species, being a major producer of EAs that infect more than 400 species of monocotyledonous plants. Rye, barley, wheat, millet, oats, and triticale are the main crops affected by EAs, with rye having the highest rates of fungal infection. The 12 major EAs are ergometrine (Em), ergotamine (Et), ergocristine (Ecr), ergokryptine (Ekr), ergosine (Es), and ergocornine (Eco) and their epimers ergotaminine (Etn), egometrinine (Emn), egocristinine (Ecrn), ergokryptinine (Ekrn), ergocroninine (Econ), and ergosinine (Esn). Given that many food products are based on cereals (such as bread, pasta, cookies, baby food, and confectionery), the surveillance of these toxic substances is imperative. Although acute mycotoxicosis by EAs is rare, EAs remain a source of concern for human and animal health as food contamination by EAs has recently increased. Environmental conditions, such as low temperatures and humid weather before and during flowering, influence contamination agricultural products by EAs, contributing to the appearance of outbreak after the consumption of contaminated products. The present work aims to present the recent advances in the occurrence of EAs in some food products with emphasis mainly on grains and grain-based products, as well as their toxicity and control strategies.

Changes in the Endophytic Fungal Community Associated with Pilosocereus royenii (Cactaceae) Infested by the Invasive Hypogeococcus sp. (Hemiptera: Pseudococcidae)

Entire communities of columnar cacti such as Pilosocereus royenii are being devastated by the infestation of the invasive mealybug Hypogeococcus sp. in Puerto Rico. This insect was first described as Hypogeococcus pungens, but later studies suggest it might be a different, undescribed specie of Hypogeococcus. The use of common insecticides results in a limited control strategy because this insect inhabits deformed plant tissue and covers itself with a protective wax. Generally, endophytic fungi provide the host plant with defenses against biotic and abiotic factors through the production of bioactive compounds that increase plant defenses and their ability to attack pathogens. We studied the community of cultivatable endophytic fungi associated with P. royenii to establish its possible role in the survival of cacti infested with Hypogeococcus sp. We assessed fragments of surface-sterilized plant tissue from asymptomatic and cacti infested by Hypogeococcus sp. The rate of fungal infection and relative frequency of fungal morphotypes isolated from plant tissue was calculated as well as the similarity of the fungal community among individuals. Asymptomatic and infested P. royenii individuals presented similar fungal infection rates. Fungal colonies were isolated from asymptomatic P. royenii tissue and from affected individuals, representing a total of 34 fungal morphotypes. Infested individuals harbored an endophytic fungal community with greater similarity to each other compared to the asymptomatic individuals.

The impact of temperature patterns during storage of Scots pine and Norway spruce seeds on their germination and fungal infection rates

Relevance of the study. One of the ways to maintain the genetic diversity of forest-forming species is to preserve highquality seed material ex situ. However, the relationship between the diversity of pathogenic mycobiota and the duration and methods of forest tree seed storage remains underexplored. The results of research into this problem can be used in forest seed production and forest phytopathology.Materials and methods. For our study we used seeds ofРinus sylvestris L. and Picea abies (L.) Karst. of the orthodox type, harvested in the period of 1996–2011 and stored under different temperatures: +20°С, +4°С, –18°С, and in liquid nitrogen vapor (–182°С) since 2011. Prior to their storage, seed samples were dried to a moisture content of 4.2–4.4% and hermetically packed. Seed germination was tested before and after three, five and eight years of storage, following GOST 13056.6-97 standards. The level of seed infection and the composition of pathogenic fungi were assessed.Results. After eight years of storage at +20°С, pine and spruce seed germination capacity decreased by 13–60%, depending on the year of harvesting. Seed storage at –18°С and –182°С allowed us to prevent seed infection and preserve seed viability. In most cases, the germination energy and germination capacity were negatively correlated with the level of seed infection. The diversity of pathogenic (mold) fungi on the surface of seeds was represented by ten genera; the most common were saprotrophs: Aspergillus P. Micheli, Penicillium Link, Rhizopus Ehrenb., Scopulariopsis Bainier.Conclusion. At the present stage of research, the success of seed storage at low and ultralow temperatures was demonstrated. We recommend cryopreservation for the long-term storage of improved and valuable seeds.

Symbiotic NCR Peptide Fragments Affect the Viability, Morphology and Biofilm Formation of Candida Species.

The increasing rate of fungal infections causes global problems not only in human healthcare but agriculture as well. To combat fungal pathogens limited numbers of antifungal agents are available therefore alternative drugs are needed. Antimicrobial peptides are potent candidates because of their broad activity spectrum and their diverse mode of actions. The model legume Medicago truncatula produces >700 nodule specific cysteine-rich (NCR) peptides in symbiosis and many of them have in vitro antimicrobial activities without considerable toxicity on human cells. In this work we demonstrate the anticandidal activity of the NCR335 and NCR169 peptide derivatives against five Candida species by using the micro-dilution method, measuring inhibition of biofilm formation with the XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay, and assessing the morphological change of dimorphic Candida species by microscopy. We show that both the N- and C-terminal regions of NCR335 possess anticandidal activity as well as the C-terminal sequence of NCR169. The active peptides inhibit biofilm formation and the yeast-hypha transformation. Combined treatment of C. auris with peptides and fluconazole revealed synergistic interactions and reduced 2-8-fold the minimal inhibitory concentrations. Our results demonstrate that shortening NCR peptides can even enhance and broaden their anticandidal activity and therapeutic potential.

Risk Factors and Rates of Fungal Infection in Lung Transplant Recipients Who Receive Posaconazole and Inhaled Amphotericin Combination Prophylaxis Therapy

PurposeFungal prophylaxis is recommended after lung transplantation (LT) to prevent anastomotic complications and invasive fungal infections. The optimal regimen is unknown and the incidence of and risk factors for fungal colonization and infection are incompletely understood.MethodsWe performed a single-center, retrospective cohort study of subjects who underwent LT between 12/1/2015 and 12/31/2019. Per protocol, subjects received 2 months of posaconazole (posa) and inhaled amphotericin (IA) after LT. Surveillance bronchoscopy was performed at 2 weeks, 1-month (mo), 2-mo, 3-mo, 6-mo, and 12-mo after LT. Bronchoalveolar lavage microbiology data and CT imaging were reviewed to identify incidence of fungal colonization and infection (defined as tracheobronchitis or invasive fungal infection) within 1 year after LT. We calculated incidence rates (IR) for fungal colonization and infection. We used univariate logistic regression to test selected potential predictors for fungal colonization and infection.ResultsTwo hundred thirty-six subjects underwent LT during the study period and 54 had a positive fungal culture within the first year. The IR of positive fungal culture was 0.29/person-year, fungal colonization 0.19/person-year, and fungal infection 0.1/person-year. Aspergillus spp (n = 49, 90.7%) was most common. Mean age was 58.2 ± 10.3 years versus 57.4 ± 12.7 years among all LT recipients (p = 0.67). Latinx subjects were 2.9 times more likely to have a positive fungal culture than non-Latinx subjects (95% CI 1.41-5.9) (Table 1). There was no association between gender or LT indication and likelihood of positive culture (Table 1).ConclusionRates of fungal colonization and infection within 1 year after LT were low using a combined regimen of 2 months of posa and IA. Latinx LT recipients had a higher likelihood of positive fungal culture. Further research is needed to understand possible environmental contributors to this finding. Fungal prophylaxis is recommended after lung transplantation (LT) to prevent anastomotic complications and invasive fungal infections. The optimal regimen is unknown and the incidence of and risk factors for fungal colonization and infection are incompletely understood. We performed a single-center, retrospective cohort study of subjects who underwent LT between 12/1/2015 and 12/31/2019. Per protocol, subjects received 2 months of posaconazole (posa) and inhaled amphotericin (IA) after LT. Surveillance bronchoscopy was performed at 2 weeks, 1-month (mo), 2-mo, 3-mo, 6-mo, and 12-mo after LT. Bronchoalveolar lavage microbiology data and CT imaging were reviewed to identify incidence of fungal colonization and infection (defined as tracheobronchitis or invasive fungal infection) within 1 year after LT. We calculated incidence rates (IR) for fungal colonization and infection. We used univariate logistic regression to test selected potential predictors for fungal colonization and infection. Two hundred thirty-six subjects underwent LT during the study period and 54 had a positive fungal culture within the first year. The IR of positive fungal culture was 0.29/person-year, fungal colonization 0.19/person-year, and fungal infection 0.1/person-year. Aspergillus spp (n = 49, 90.7%) was most common. Mean age was 58.2 ± 10.3 years versus 57.4 ± 12.7 years among all LT recipients (p = 0.67). Latinx subjects were 2.9 times more likely to have a positive fungal culture than non-Latinx subjects (95% CI 1.41-5.9) (Table 1). There was no association between gender or LT indication and likelihood of positive culture (Table 1). Rates of fungal colonization and infection within 1 year after LT were low using a combined regimen of 2 months of posa and IA. Latinx LT recipients had a higher likelihood of positive fungal culture. Further research is needed to understand possible environmental contributors to this finding.

Experience with Posaconazole Use for Fungal Prophylaxis Immediately Post Heart Transplant

Purpose Fungal infections, specifically mucormycosis, are associated with high morbidity and mortality in the immunocompromised host. Noting a recent elevation in our rates of fungal infections, we sought to avoid mucormycosis and other post-Orthotopic Heart Transplant (OHT) fungal infections through the implementation of a systematic antifungal prophylaxis protocol. Methods Posaconazole was selected as the antifungal of choice, given provided mucormycosis coverage not provided by other azoles. We developed a Posaconazole Prophylaxis Protocol (PPP) consisting of post-operative day 1 initiation of posaconazole for a 3-month duration with a goal posaconazole trough level 1000-2000 ng/mL. At time of posaconazole discontinuation, a 2-fold dose escalation of tacrolimus dosing was implemented and bi-weekly tacrolimus levels drawn for 2 weeks to ensure goal calcineurin inhibitor levels. If strong cyp3A4 interactions or prolonged QTc prohibited posaconazole, isavuconazole was used. If early cessation of posaconazole-therapy was necessary, surveillance chest imaging was obtained with chest CT scans. Results In the 13-month period following initiation of our PPP 50 patients underwent OHT. All but one (49/50) patients received therapeutic posaconazole or in the case of drug-drug interactions, isavuconazole. 2/50 were transitioned to isavuconazole due to QT prolongation. 5/50 had posaconazole interruption with the most common reason being liver enzyme elevation (4/50). 45/50 tolerated the 3-month period on systemic azole prophylaxis. During this period there were no systemic fungal infections. Conclusion Our initial 13-month experience with a systematic 3-month antifungal prophylaxis protocol appears to be feasible, safe, and associated with uniform prevention of mucormycosis and other fungal infections that have previously proven to be highly morbid in our OHT recipients.

Strain Distribution and Drug Susceptibility of Invasive Fungal Infection in Clinical Patients With Systemic Internal Diseases.

BackgroundPatients with systemic internal diseases present high risks for invasive fungal infections, which results in increased morbidity and mortality. Identification of high-risk departments and susceptibility systems could help to reduce the infective rate clinically. Correct selection of sensitive anti-fungal drugs not only could improve the cure rate but also could reduce the adverse reactions and complications caused by long-term antifungal drug treatment, which can be especially important in patients with serious systemic diseases. Therefore, the distribution changes of invasive fungal strains in patients with systemic internal diseases and the choice of antifungal drugs in clinical practice should be updated.ObjectiveThis work aimed to investigate the incidence, strain distributions, and drug susceptibility of invasive fungal strains isolated from patients with systemic internal diseases.MethodsSamples were collected from 9,430 patients who were diagnosed with internal diseases in our hospital from January to December 2018. We then cultured and identified the fungal strains using API 20C AUX. We performed drug sensitivity analysis via the ATB Fungus-3 fungal susceptibility strip. Resistance was defined using the revised Clinical Laboratory Standardization Committee of United States breakpoints/epidemiological cutoff values to assign susceptibility or wild-type status to systemic antifungal agents.ResultsA total of 179 patients (49 female, 130 male) with fungal infection were included. The high-incidence departments were determined to be the respiratory department (34.64%), intensive care unit (ICU; 21.79%), and hepatology department (9.50%). The susceptible systems for infection were the respiratory tract (sputum, 68.72%, 123/179; secretion retained in the tracheal catheter, 3.35%, 6/179), urinary tract (urine, 9.50%, 17/179), and gastrointestinal tract (feces, 9.50%, 17/179). The major pathogens were Candida (90.50%), Aspergillus (8.93%), and Cryptococcus neoformans (0.56%). The infective candida subgroups were Candida albicans (70.95%), Candida krusei (6.15%), Candida glabrata (5.59%), Candida parapsilosis (3.91%), and Candida tropicalis (3.91%). The susceptibility of non-Aspergillus fungi for amphotericin B was 100.0%. The susceptibility rates of 5-fluorocytocine (5-FC) and voriconazole were 72.73 and 81.82%, respectively, for C. krusei, 98.43 and 100% for C. albicans, and 100% for both drugs for C. glabrata, C. parapsilosis, and C. tropicalis. The susceptibility rates of fluconazole and itraconazole were 0 and 54.55%, respectively, for C. krusei, 20 and 20% for C. glabrata, and 57.14 and 57.14% for C. tropicalis. The resistance rate of C. tropicalis for both fluconazole and itraconazole was 41.43%.ConclusionPatients in the respiratory department, ICU, and hepatology department presented high rates of invasive fungal infections and should include special attention during clinical treatment. The respiratory tract, urinary tract, and gastrointestinal tract were the susceptible systems. Candida, especially C. albicans, was the main pathogen. From the perspective of drug sensitivity, amphotericin B should be given priority in treating the non-Aspergillus fungi infection in patients with systemic internal diseases, while the susceptibility of invasive fungal strains to azoles was variant. These data might provide clinical evidence for the prevention and treatment of invasive fungal infection in patients with systemic internal diseases.

Post-Translational Modifications Drive Success and Failure of Fungal-Host Interactions.

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.

Why do zombies clean themselves? An initial test of the antimicrobial hypothesis in a parasite‐host relationship

The emerald jewel wasp Ampulex compressa attacks the cockroach Periplaneta americana which serves as the host of the parasite and injects venom directly into the cockroach’s central nervous system. The cockroach responds by excessive grooming and cleaning its entire body with its legs and mandibles. The antimicrobial hypothesis suggests that self-grooming is adaptive for the parasite because it decreases ectoparasite and fungal infection rates from the cockroach’s cuticle in order to prevent infection of the wasp’s larvae. We demonstrated under laboratory conditions that microbial prevalence was not higher in stung cockroaches experimentally prevented from self-grooming than in self-groomed ones.

Application Value of Metagenomics Next Generation Sequencing of Alveolar Lavage Fluid Metagenome in Unexplained Pulmonary Infection

To explore the application value of metagenomics next generation sequencing of alveolar lavage fluid metagenome in unexplained pulmonary infection. A total of 40 patients with pulmonary infection diagnosed in our hospital from January 2020 to December 2020 were collected. All patients underwent routine blood cell analysis, C-reactive protein, procalcitonin, 1,3-Beta-D glucan test, galactomannan test, sputum smear, sputum culture, blood culture+drug sensitivity, chest computed tomography and other examinations. In addition, sputum, broncho alveolar lavage fluid, blood, pleural effusion and other samples were collected to detect etiology and metagenomics next generation sequencing. Traditional laboratory methods detected pathogens in 60.00 % (24/40) samples, while metagenomics next generation sequencing detected pathogens in 87.50 % (35/40) samples. 12 cases were completely consistent with the traditional method; the results of 5 cases of metagenomics next generation sequencing were partially consistent with those of traditional methods. In these 5 cases, metagenomics next generation sequencing detected potential pathogens which were not detected by traditional methods; In 7 cases, the results of traditional methods were inconsistent with metagenomics next generation sequencing. Chlamydia psittaci was detected in 2 cases by metagenomics next generation sequencing. The results of etiological diagnosis showed that there was no difference in the positive rates of bacterial infection and fungal infection between metagenomics next generation sequencing and traditional methods (p>0.05). The positive rate of metagenomics next generation sequencing virus infection was 84.62 % (11/13), which was significantly higher than that of traditional methods 38.46 % (5/13) (p<0.05). In addition, 7 patients were diagnosed as atypical pathogen infection and the positive rate of metagenomics next generation sequencing was 100 % (7/7), which was significantly higher than that of traditional methods (14.29 %, 1/7) (p<0.05). For difficult and critical patients with infection, using metagenomics next generation sequencing to detect pathogens can improve the early detection rate of pathogens, achieve accurate and individualized treatment, shorten the length of hospital stay and reduce the mortality.

Study on infection of blueberry explants with different antibiotics

The effects of streptomycin sulfate, carbendazim, penicillin and nystatin on the inhibition of fungi and bacteria in blueberry explants were studied. The results showed that the addition of streptomycin sulfate or penicillin with different concentrations in the medium had a certain inhibitory and killing effect on bacteria in blueberry explant contamination, while the addition of carbendazim or nystatin had a certain inhibitory and killing effect on fungi in blueberry explant contamination. When the concentration of streptomycin sulfate in the medium reached 60units / mL, the highest survival rate was 44.0%, and the bacterial infection rate was the lowest. When the concentration of carbendazim in the medium was 0.4 mg/mL, the survival rate reached 40.5%, and the fungal infection rate decreased greatly. When the penicillin concentration in the medium reached 40mg/mL, the lowest infection rate of bacteria was 4.0%, and the highest survival rate was 31.5%. When the concentration of nystatin in the medium reached 40mg/L, the highest survival rate was 34.5%. Therefore, streptomycin sulfate had better inhibitory effect on bacteria, while carbendazim had better inhibitory effect on fungi, which provided reference for future research.

742. Breakthrough Invasive Fungal Infections with Isavuconazonium Sulfate versus Voriconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia (AML) who Received Induction Chemotherapy

BackgroundFungal infections in patients with hematologic malignancies are associated with high mortality. Primary antifungal prophylaxis has been shown to be a more effective strategy than treating a documented infection. This retrospective analysis aims to compare the rates of breakthrough invasive fungal infections in patients with acute myeloid leukemia (AML) who received induction chemotherapy and were prescribed voriconazole (Vori) or isavuconazonium (Isv) for primary antifungal prophylaxis.The European Organization for Research and Treatment of Cancer/ Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to categorize incidence of breakthrough invasive fungal infections bIFI into ‘possible’, ‘probable’ or ‘definite’ groups who required treatment with liposomal amphotericin B, echinocandin, and/or different triazole.MethodsThis is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML. These patients received either Vori or Isv sulfate as the primary antifungal prophylaxis at Moffitt Cancer Center between July 2017 and June 2019. Patients who were over 18 years old and received at least 10 days of uninterrupted primary antifungal prophylaxis with either Vori or Isv sulfate were included in the study. Patients with a history of stem cell or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or who received systematic antifungal, other than fluconazole, therapy within 30 days to induction chemotherapy were excluded.Results250 patients were screened for the study and out of which 118 patients met the above criteria. There was a 20.2% (18/89) break through rate of fungal infections in the Vori arm and 17.2% (5/29) in the Isv arm. In the Vori arm there were 15 possible bIFIs, 3 probable bIFIs and 0 definite bIFIs. In the Isv arm there are 2 possible bIFIs, 2 probable bIFIs and 1 definite bIFIs.ConclusionThere is no significant statistical difference (Using the Fisher Exact test statistic p=1) between the Isv and Vori in patients who received these agents for primary fungal prophylaxis for induction chemotherapy for AML at Moffitt Cancer Center between July 2017 - June 2019.Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

405. Trend in blood culture results in Washington DC during and prior to Pandemic COVID-19

BackgroundThe rate of bacterial and/or fungal infections among COVID-19 cases is reportedly low. Antimicrobial Stewardship Programs (ASPs) provide continuous surveillance of blood cultures to secure appropriate choice and duration of therapy. Comparing to historic data, we characterize our ASP experience in bacteremic surveillance during the COVID-19 pandemic.MethodsConsecutive blood cultures at the Washington DC VA Medical Center were captured in an ASP-driven decision support software system (TheraDoc, Premier/DSS Inc) between Jan 1st 2018-May 31st 2020. In the setting of an established ASP, the organism positive cultures were reviewed over the first five months (Jan-May) of each of the three years collected. Results of cultures were characterized as either pathogenic gram positive (MSSA/MRSA/Enterococci/PSSP/PRSP/Strep sp.), pathogenic aerobic and anaerobic gram negative organisms and a skin contaminant-category (GPRs/skin flora/CNS).ResultsOver 3 yrs, 528 patients had 1464 positive cultures from among 8727 admissions, 83638 inpatient-days. The proportion of pathogenic GP bacteria and pathogenic GN bacteria were not statistically significantly different 38% (2018) vs 37% (2019) vs 39% (2020) and 33%, 31%, 27% respectively. There was slight trend in the increase of pathogenic GP 9.6 vs 9.5 vs 11.7 per 1,000 inpatient days and skin contaminant-category with 12.0 vs 11.0 vs. 14.1 per 1,000 patient days from 2019 to 2020. We noted a dramatic shift in culture surveillance report during the peak COVID-infection rates (March-April), notable for several weeks of few to no culture positive results. When broken down by month, variability was noted (data not shown). COVID-19 infected patients represented 9.0% (7/78) of positive blood culture results in 2020 Jan-May, only 5.1% (4/78) were treated as non-contaminants and were related to indwelling catheters or urosepsis.ConclusionOverall and adjusted rates of the blood cultures sent during the pandemic months in 2020 were comparable to the comparative years. Surveillance revealed short term changes in patterns which may have reflected the pandemic induced changes to admissions. COVID-19 infected patients rarely experienced line and hospital acquired bactermia/fungemia, most during the recovery period.Disclosures All Authors: No reported disclosures

1291. Safety of Isavuconazole Compared with Voriconazole as Primary Antifungal Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients

BackgroundVoriconazole (VCZ) is used as mold active primary antifungal prophylaxis (AFP) after allogenic hematopoietic cell transplant (HCT) but is frequently discontinued due to adverse events (AE), variable pharmacokinetics and drug-drug interactions. Limited data exists on the safety of Isavuconazole (ICZ) as AFP in HCT patients (pts). The study objectives were to compare 1) rates of AFP premature discontinuation (d/c), 2) changes in transaminases values from start to end of treatment (EOT) and 3) rates of invasive fungal infections (IFI) and all-cause mortality by Day (D) +180 post HCT between VCZ and ICZ AFP.MethodsThis is a matched cohort analysis of 95 pts enrolled in a clinical trial of ICZ AFP from 7/1/2017-10/31/2018 (ICZ-cohort) and 210 pts who received VCZ AFP standard of care between 9/1/2014-12/31/2015 at MSKCC (VCZ-cohort). The cohorts were matched using propensity scores (Table 1). AFP was administered for 75-100 days per institutional guidelines. Premature d/c of AFP was defined as d/c for IFI or AE by D +100 post HCT or interruption of >14 days for any reason. The cumulative incidence function and log rank test were used to compare groups. Mean transaminase values were compared using paired T-tests.Table 1. Baseline characteristics ResultsThe median (Interquartile range) duration of AFP was 94 (87-100) days and 76 (23-94) days in ICZ and VCZ cohorts respectively (p< 0.0001). Premature d/c occurred in 14/95 (14.7%) of ICZ and 92/210 (43.8%) of VCZ cohorts (p< 0.0001) (Figure 1). The most common cause for AFP d/c was hepatotoxicity: ICZ-cohort: 5/95 (5.26%) vs VCZ-cohort: 48/210 (22.8%). Transaminases at EOT and up to 14 days were increased in VCZ but not ICZ cohort (Figure 2). IFI occurred in 3.15% (3/95) in ICZ-cohort and 2.85% (6/210) in VCZ-cohort (p=0.88) (Figure 3). In ICZ-cohort IFI included 3 Candida bloodstream infections (BSI) occurring on ICZ AFP. In VCZ-cohort IFI included one Candida BSI after VCZ d/c, and 5 probable mold infections; 3/5 with serum galactomannan > 0.5 and 2 with beta-D-glucan > 80. IFI occurred on VCZ in 1 pt and after VCZ premature d/c in 5 pts. All-cause mortality was 6.31% (6/95) in ICZ-cohort and 2.85% (6/210) in VCZ-cohort (p=0.089).Figure 1. Cumulative incidence of premature discontinuation of AFP by D+100 Figure 2. Transaminases at baseline,end of treatment (EOT), EOT +7 days and EOT +14 days in ICZ- and VCZ cohorts Figure 3. Cumulative incidence of IFI by day +180 ConclusionThere was less premature discontinuation and hepatotoxicity with ICZ AFP, but no increase in IFI or death compared to VCZ AFP in allogeneic HCT pts.Disclosures Yeon Joo Lee, MD, MPH, Ansun BioPharma (Scientific Research Study Investigator)Astellas Pharma (Scientific Research Study Investigator) Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Dionysios Neofytos, MD, Basilea (Advisor or Review Panel member)Gilead (Advisor or Review Panel member)MSD (Advisor or Review Panel member, Research Grant or Support)Pfizer (Advisor or Review Panel member, Research Grant or Support) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

Invasive Bacterial and Fungal Infections After Pediatric Cardiac Surgery: A Single-center Experience.

Discrimination of infectious and noninfectious complications in children with inflammatory signs after cardiac surgery is challenging. Given the low prevalence of infectious complications after heart surgery, there might be a risk of excessive antibiotic usage. We performed this study to determine the rate of invasive bacterial or fungal infections in children after cardiac surgery at our institution and to evaluate our postoperative management. This single-center retrospective observational cohort study included children 16 years of age or younger who underwent cardiac surgery at our institution between January 2012 and December 2015. We analyzed 395 surgical procedures. Thirty-five postoperative invasive bacterial or fungal infections were detected in 29 episodes (7%, 0.42 per 100 admission days). Among bacterial infections, the most common infection sites were bacteremia and pneumonia, accounting for 37% (13/35) and 23% (8/35) of infections respectively. The rate of postoperative infections was associated with surgical complexity score and length of postoperative pediatric intensive care unit (PICU) stay. In 154 (43%) of 357 episodes without microbiologically documented infection, uninterrupted postoperative antibiotic administration was continued for more than 3 days and in 80 (22%) for more than 5 days. The rate of postoperative bacterial or fungal infection at our institution is comparable to current literature. High surgical complexity score and prolonged length of PICU stay were risk factors for bacterial or fungal infections in this patient population.

Infectious Complications of BCMA-Targeted and CD19-Targeted Chimeric Antigen Receptor T-Cell Immunotherapy

Infectious Complications of BCMA-Targeted and CD19-Targeted Chimeric Antigen Receptor T-Cell Immunotherapy

CYP3A inhibitors and impact of these agents on outcomes in patients with acute myeloid leukemia treated with venetoclax plus azacitidine on the VIALE-A study

CYP3A inhibitors and impact of these agents on outcomes in patients with acute myeloid leukemia treated with venetoclax plus azacitidine on the VIALE-A study

A dose‐dense short‐term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high‐risk Burkitt lymphoma or high‐grade B‐cell lymphoma: safety and efficacy results of the “CARMEN” phase II trial

A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n=16), HGBL (n=3) or double-hit lymphoma (n=1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate=90%; 95% confidence interval (CI)=77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI=60-80%) and 75% (95% CI=66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.