Risk Factors For Fungal Infection Research Articles

Epidemiology of fungal infection after hepatobiliary surgeries at National Liver Institute Hospital (Menoufia University)

Objectives To estimate the incidence rate of fungal infections after hepatobiliary surgery and identification of the risk factors. Background Candidemia and disseminated candidiasis are major causes of morbidity and mortality in hospitalized patients, especially in the ICU, the incidence of invasive candidiasis is on a steady rise because of increasing use of multiple antibiotics and invasive procedures carried out in the ICUs. Participants and methods A prospective cohort hospital-based study was carried out at the National Liver Institute, Menoufia University. The studied group was 210 patients, all of them were examined thoroughly, their data were registered and sampled two times, one at the day of admission to be sure that they are free of fungal infection and the second was after hepatobiliary surgery. A predesigned questionnaire was used, which includes data about personal history, medical history, and suggested risk factors for fungal infections. Results In the present study, the incidence rate of fungal infection among patients who had hepatobiliary surgeries in National Liver Institute was found (45.2%) and by logistic regression analysis of data indicated that the most relevant factors for fungal infection were age (P < 0.001), antibiotic use (P < 0.05), liver disease (P < 0.05), central venous catheter (P < 0.05), urinary catheter (P < 0.05), and ICU hospitalization more than 48 h (P < 0.001). Conclusion High incidence of fungal infection after hepatobiliary surgeries is considered a great health problem. The main risk factors of fungal infection are low immunity, chronic disease, diabetes, hepatitis B virus and/or hepatitis C virus infection, cancer, anemias, organ transplantation, blood transfusion, had central venous catheter, intravenous catheter, had abdominal drain, urinary catheter, parenteral nutrition, history of past operations, and hospitalized in the ICU more than 48 h.

Analysis of clinical characteristics of 43 patients with pulmonary mycosis diagnosed by pathology

To observe the etiological distribution, clinical presentations and imaging features of pulmonary mycosis that is diagnosed by pathology. The etiological distribution, clinical presentations and imaging features of patients with pulmonary mycosis, who were collected in the Affiliated Hospital of Jining Medical University from January 2018 to July 2020, were retrospectively analyzed. The diagnosis of all the patients were confirmed by pathological examination, of lung or bronchi tissue that were obtained through operation, bronchoscope or percutaneous lung puncture biopsy. There were 26 patients' (60.47%, 26/43) pathological specimens were obtained by operation, 14 cases (32.56%, 14/43) were obtained by bronchoscope, and 3 cases (6.98%, 3/43) were obtained by percutaneous lung puncture biopsy. Of the 43 patients who were diagnosed pulmonary mycosis by pathology, 27 patients (62.79%, 27/43) suffered from pulmonary aspergillosis, 11 patients (25.58%, 11/43) suffered from pulmonary cryptococcosis, 3 patients (6.98%, 3/43) suffered from pulmonary mucormycosis, and 2 patients (4.65%, 2/43) suffered from pulmonary candidiasis. There were 27 patients (62.79%, 27/43) with pulmonary fungal disease complicating risk factors of fungal infection, including diabetes mellitus (23.26%,10/43), malignant tumor (16.28%, 7/43), bronchiectasis (9.30%, 4/43), hepatitis B virus (HBV) carrier (6.98%, 3/43), taking glucocorticoids (4.65%, 2/43), pulmonary tuberculosis (4.65%, 2/43), and chemotherapy following colon carcinoma operation (2.33%, 1/43). The common clinical presentations included cough (55.81%, 24/43), expectoration (48.84%, 21/43), hemoptysis (37.21%, 16/43), fever (20.93%, 9/43), gasping (18.60%, 8/43), chest pain (16.28%, 7/43), and hoarseness (3.13%, 1/43). Imaging features of chest included lung nodes in 20 cases (46.51%, 20/43), vascular welt sign in 12 cases (27.91%, 12/43), exudative process in 10 cases (23.26%, 10/43), lung mass or consolidation in 8 cases (18.60%, 8/43), cavitary lesions in 7 cases (16.28%, 7/43), thicken bronchus wall and narrow lumina in 6 cases (13.95%, 6/43), air crescent in 5 cases (11.63%, 5/43). The pulmonary aspergillosis and cryptococcosis are mainly in pulmonary mycosis diagnosed by pathology. The common complications are diabetes mellitus and malignant tumor. The common clinical presentations are cough, expectoration, and hemoptysis. The main imaging features of chest are lung nodes and vascular welt sign can be found in most of pulmonary cryptococcosis.

Establishment and Validation of a Nomographic Model for Individualized Prediction of Invasive Pulmonary Fungal Infection after Chemotherapy for Hematologic Tumor

To retrospectively analyze the risk factors of invasive pulmonary fungal infection after chemotherapy in patients with hematologic tumor and to establish and validate related nomographic models. 368 patients with hematologic tumor who were treated with chemotherapy were collected. The influencing factors of invasive pulmonary fungal infection after chemotherapy were analyzed by univariate and multivariate logistic regression. Based on the analyzed risk factors, the nomogram prediction model was established and verified internally. Of the 368 patients with hematologic tumor, 35.33 % (130/368) had fungal infection after chemotherapy and 64.67 % (238/368) had non-fungal infection. Univariate and multivariate logistic regression analysis showed that hypoproteinemia (Odds ratio=3.220, 95 % confidence interval: 1.886~5.496), broad-spectrum antibiotic use ≥2 kinds (Odds ratio=2.616, 95 % confidence interval: 1.514~4.518), broadspectrum antibiotic duration ≥7 d (Odds ratio=2.444, 95 % confidence interval: 1.455~4.103), duration of agranulocytosis ≥7 d (Odds ratio=3.112, 95 % confidence interval: 1.804~5.368), cytomegalovirus or Epstein-Barr virus infection (Odds ratio=6.170, 95 % confidence interval: 3.304~11.524) were risk factors for fungal infection after chemotherapy in patients with hematologic tumors. Based on the above five risk factors, the prediction model of nomogram was established and verified by Bootstrap method for 500 times. The calibration curve fitted well with the standard curve. The receiver operating characteristic curve area under the curve was 0.762, 95 % confidence interval: 0.7095-0.8146 and the Hosmer-Lemeshow test p>0.05, which indicated that the prediction model of nomogram had good discrimination and accuracy. Hypoproteinemia, broad-spectrum antibiotic use ≥2 kinds, broad-spectrum antibiotic duration ≥7 d, duration of agranulocytosis ≥7 d and cytomegalovirus or Epstein-Barr virus infection are the risk factors of concurrent fungal infection after chemotherapy in patients with hematologic tumor. After verification, the constructed nomogram has high discrimination and accuracy, which has dual guiding significance for clinical screening of high-risk population and making individualized prevention and treatment measures.

90. Incidence and Risk Factors for Inappropriate Use of Non-culture Based Fungal Assays: Implication for Diagnostic Stewardship

BackgroundCulture-based diagnostic tests are the gold standard for diagnosing invasive fungal diseases (IFDs). Because these tests have low sensitivity, non-culture-based fungal assays (NCBFAs) have been used increasingly to help diagnose IFDs. However, little is known about inappropriate use of NCBFAs. We aimed to investigate inappropriate use of NCBFAs in a tertiary academic hospital in Tokyo, Japan.MethodsThis retrospective cohort study included all patients who underwent testing with beta-D glucan (BDG) between January and March 2018, or galactomannan antigen (GMA) or cryptococcal antigen (CRAG) between January and June 2018. Patients who had received hematopoietic stem cell or solid organ transplantations were excluded. Appropriateness was assessed according to the previously published study. We compared patients with appropriate and inappropriate use of NCBFAs. Risk factors for inappropriate use were evaluated using multivariate logistic regression analysis.ResultsOf 1,140 patients (BDG, 1,009; GMA 273; CRAG, 310) who underwent tests, 470 patients (BDG, 394; GMA, 138; CRAG, 164) were included in this study. Four hundred thirty-eight patients (93.2%) were aged 18 or older. About 80% of NCBFAs (BDG, 334 patients [74.8%]; GMA, 117 patients [74.8%]; CRAG, 146 patients [89.0%]) were deemed inappropriate. The factors associated with inappropriate NCBFAs use included specialties of ordering physicians, risk factors for fungal infections, and recommendation from infectious disease physicians (Table). Sixty-four patients (13.6%) underwent three inappropriate NCBFAs simultaneously. Furthermore, during the study period, 408 patients (35.8%) with inappropriate NCBFAs underwent the same assays repeatedly during the study period; 643 times for BDG, 163 times for GMA, and 192 times for CRAG.The Factors Associated with Inappropriate Use of Non-Culture Based Fungal Assays ConclusionWe found a large proportion of NCBFAs were deemed inappropriate and it was mostly driven by ordering physicians who generally care for transplant patients. Because inappropriate use of NCBFAs could lead to additional inappropriate tests and treatment with substantial costs to patients and health systems, diagnostic stewardship targeting NCBFAs is urgently needed.Disclosures All Authors: No reported disclosures

366. Characteristics and Outcomes of COVID-19 Patients with Fungal Infections

BackgroundThere is concern that patients with coronavirus disease 2019 (COVID-19) are at risk of developing secondary bacterial and fungal infections; however, data on the clinical characteristics and outcomes of COVID-19 patients with fungal infections are limited. We evaluated the risk factors and mortality of hospitalized COVID-19 patients with fungal infections.MethodsThis was a retrospective chart review of 51 patients with fungal infections at an 877-bed teaching hospital in Detroit, Michigan from March through May 2020. Demographic data, comorbidities, complications, treatment, and outcomes, including relapse, readmission and mortality were collected. We performed a descriptive analysis.ResultsA total of 51 patients with fungal infections were included, in which 31 (60.8%) had confirmed or suspected COVID-19 infection. Of the COVID-19 patients, the average age was 66 years and the majority (54.9%) were female. The average length of stay (LOS) was 29.3 days. Aspergillus sp. (2 A. fumigatus, 1 A. niger) were isolated in 3 (10%) patients while 23 (74.2%) had candidemia diagnosed via blood culture or T2Candida® Panel. One had a positive serum galactomannan. The average time from admission to diagnosis was 13 days. Significant comorbidities included hypertension (74%), diabetes (51.6%), coronary artery disease (25.8%), congestive heart failure (32.2%), chronic kidney disease (22.6%), and malignancy (16.1%). Most patients received steroids (83.9%) and broad-spectrum antibiotics (80.6%), had a central line (80.6%), and required intensive care unit management (90%). Only 71% were treated with antifungals. One patient with candidemia relapsed due to poor source control; two were readmitted within 30 days. In-hospital mortality rate was 51.6% among COVID-19 patients.ConclusionCOVID-19 patients with fungal infections had multiple comorbidities, prolonged hospitalization and predisposing risk factors for fungal infections with a high in-hospital mortality rate. Prevention of fungal infections in COVID-19 patients is paramount.Disclosures All Authors: No reported disclosures

Incidence of filamentous fungii in normal oral mucosa of rural workers in the region of Frutal, MG

Working conditions give rise to health problems in a complex way, where specialist services are not always capable of finding a solution.Epidemiological studies evaluate these infections, both superficial and deep, and some of these studies perform an evaluation with regard to working and living conditions and the health of workers in a variety of areas. However, there are no bibliographical references in respect of filamentous fungal contamination of the oral cavity, related to rural labour activity.AIMS: To evaluate the incidence of fungal contamination in the normal oropharyngeal region of sugarcane, orange and pineapple plantation workers, in the municipality of Frutal, in the Brazilian state of Minas Gerais. METHODS: This constitutes a prospective, longitudinal study of the cohort type, of 60 temporary workers for each crop, making a comparison with the environment. The collection and analysis of material from the workers and from the environment followed the timing of each culture, designated as (t0), (t1) and (t2). RESULTS: Worker contamination occurred at the second interval of the study. Of the orange grove workers, 1.6% (N=1) were contaminated by F. subglutinans. In the sugarcane plantation, 8.3% (N=5) of workers were contaminated, 5% (N=3) by A. niger and 3.3%(N=2) by F. moniliforme. The two volunteers infected by A. niger were simultaneously infected by C. albicans. Of the sixty pineapple plantation workers analysed, 13.3% (N=8) were contaminated with F. subglutinans. CONCLUSIONS: This study showed that working with the pineapple crops was found to be a risk factor for fungal infection in the oral mucosa, when compared to the orange crop. Fungal contamination also occurred with the sugarcane crop, when compared to the reference group. Other factors, such as age, alcohol consumption, smoking, family income and ethnicity were not deemed to be statistically significant in the incidence of infection.

The effect of fruit on the extracellular enzyme profiles of fungi.

In recent years, the number of diseases caused by fungal pathogens has increased significantly. Many species of fungi are pathogenic for plants, causing a threat to food production and to humans, and are among the causes of chronic diseases. The aim of the study is to determine the enzyme profiles of fungi, depending on the different types of fruit with which they have contact, and to determine the differences in these profiles in relation to the substrate on which they are grown. Six strains of fungi identified as Cladosporium sphaerospermum, Fusarium poae, Alternaria alternata, Penicillium expansum, Penicillium verucosum and Acremonium strictum, isolated from fruits, were selected and analyzed for enzymatic profiles. The enzymatic activity was assessed using the API ZYM test (bioMerieux, France). In the majority of the 6 fungal strains isolated from fruits, enzymes belonging to glycol-hydrolases were the most active. The exception was Acremonium strictum, where phosphatases dominated. Among most fungal isolates, the enzymes β- glucosidase and N-acetyl-β-glucosaminidase showed the highest activity. The highest β-glucosidase activities were found in Cladosporium sphaerospermum and Penicillium expansum. On the other hand, lipase, α-fucosidase and α-chymotrypsin showed the least activity. The least activity of these enzymes or their complete absence was observed in Fusarium poae, Alternaria alternata, Penicillium expansum and Acremonium strictum. The activity of hydrolytic enzymes in the isolated fungi depended on the addition of fruit and the type of medium. Individual fruits can increase or decrease the activity of the enzymes. Fungi present in fruit have pathogenic properties and can be possible risk factors for fungal infections.

Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria

BackgroundAntibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing.ResultsWhile the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate.ConclusionsWe demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition.ACGvW8Xb2T7sNiinSps9YKVideo abstract.

LYMPHOCYTOPENIA AND NEUTROPHILIA DETERMINED FUNGAL INFECTION OCCURRENCE AND MORTALITY AFTER LIVER TRANSPLANTATION

Introduction: Fungal infection in liver recipients remains a critical challenge with high mortality and morbidity. Immunosuppression regimen renders patients more vulnerable to fungal infection after liver transplantation. However, the mechanisms of immune status and its role in predicting post-transplant mortality are still undetermined. Materials and Methods: Adult patients received liver transplantation were recruited in a retrospective cohort from February 2018 to October 2019 in Beijing Tsinghua Changgung Hospital. The post-transplant immune cell subpopulations and peri-operation demographics were analyzed in patients with or without post-transplant fungal infections. Univariate and multivariate logistic regression were performed to identify risk factors for post-transplant fungal infections. The correlation between recipient immune status and post-transplant 90-day mortality was further investigated by ROC and Kaplan-Meier analysis. Results and Discussion: Thirty-six out of 164 (22%) patients were presented post-transplant fungal infections with median occurrence time of POD4 (1-287). In terms of fungi species, 27 (75%) were from Candida species, 6 (16.7%) were from Aspergillus species, and 3 (8.3%) were other fungal infections. And the infection site distributed in upper respiratory tract (17, 47.2%), lower respiratory tract (2, 5.6%), intra-abdominal cavity (11, 30.6%), bloodstream (3, 8.3%), urine (2, 5.6%) and wound (1, 2.8%). In comparison with non-infection patients, the lymphocyte population in blood was found significantly lower in fungal infection patients (5.0% vs 8.6%, p=0.007), while neutrophil increase was simultaneously observed (90.7% vs 83.3%, p=0.004). In addition, subpopulation analysis indicated the decrease of CD19+ B cell (26.2% vs 16.8%, p=0.069), but increase of CD3-CD16+CD56+ NK cell (7.0% vs 10.9%, p=0.001) and CD3+CD8+ CTL (20.9% vs 28.8%, p=0.120). By univariate and multivariate analysis, neutrophilia (percentage≥90.05%) was identified as an independent risk factor for post-transplant fungal infection (HR=3.529, 95%CI: 1.017-12.245, p=0.047, Table 1). By ROC analyses, lymphocytopenia and neutrophilia as well as the neutrophil-to-lymphocyte (N/L) ratio increase was found to have predictive value for 90-day mortality (Fig. 1A-C). And 90-day mortality divided by cut-off values of lymphocyte, neutrophil and N/L ratio was significantly different between groups (Fig. 1D-F). Conclusion: Altered immune status was the independent risk factor for fungal infections after liver transplantation. Lymphocytopenia and neutrophilia, as well as increased N/L ratio, were valuable predictors of fungal infection-related post-transplant mortality.

Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial

BackgroundSystemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants.MethodsA prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age ≤ 32 weeks and/or birth weight of ≤ 1500 g with risk factors for fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1 ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall mortality rates and nystatin-related adverse drug reactions during the study period were also documented.ResultsA total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.8 and 56.3%, respectively; relative risk 0.559; 95% confidence interval 0.357–0.899; p-value = 0.009). There were five cases of SFI, all of which were found in the control group (p-value = 0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period.ConclusionsNystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups.Trial registrationNCT03390374. Registered 4 January 2018 - Retrospectively registered.

Risk factors for fungal infection in extremely low birthweight infants registered in the Korean neonatal network from 2013 to 2015: Male sex and hypotension.

In Korea, improvement in the survival rates of extremely low birthweight (<1,000g) infants has led to neonatal infection, especially fungal infection (FI), in the neonatal intensive care unit. The purpose of this study was to determine the risk factors for FI by analyzing the incidence of FI in extremely low birthweight infants in Korea. Data from 5,320 very low birthweight (<1,500g) infants registered from 2013 to 2015 in the Korean Neonatal Network were analyzed. The infants were divided into two groups based on the presence or absence of FI. Among infants, 1,524 with gestational ages of <27weeks and birthweights of <1,000g were included. The incidence of FI was 7.3% (111/1,524) and mortality of the infants with FI was 40% (44/111). The mean gestational age of infants with FI was 24.8±1.0weeks, which was significantly lower than those without FI. After logistic regression, being male, and having hypotension within 7days of birth were independent risk factors for FI. Moreover, hypotension was strongly associated with mortality in FI. Adverse outcomes such as severe bronchopulmonary dysplasia, bacteremia, and abnormal hearing test occurred more frequently in infants with FI than non-FI. As male sex and hypotension within 7days of birth increased the risk of developing FI in infants with gestational ages of <27weeks and birthweights of <1,000g, preventive strategies to reduce the incidence of FI are required for infants with risk factors for the development of FI.

Risk Factors for Fungal Infection in a Ventricular Assist Device Cohort

Ventricular assist device (VAD) infections are an important cause of morbidity and mortality. Fungal infections are associated with poor outcomes and risk factors to predict infection warrant characterization. A retrospective cohort study of continuous-flow 2nd or 3rd generation VAD devices placed at Northwestern Memorial Hospital from July 2008 to September 2018 was performed. VAD-specific and VAD-related infections were characterized according to 2013 ISHLT definitions. Early infections were defined as occurring less than or equal to 60 days from the date of VAD implantation, late infections were defined as greater than 60 days. Binary logistic regression analysis comparing fungal to non-fungal bacterial infections identified significant risk factors. Summary and comparative statistics were performed using IBM® SPSS Statistics version 25.0. 86 infections occurred in 433 VAD implantations. 93.0% (n = 80) were non-fungal and 7.0% (n = 6) were fungal. Independent risk factors for fungal infection when compared to bacterial infections were early VAD infection (66.6% vs 11.3%, p = 0.000), ischemic cardiomyopathy as an underlying diagnosis (83.3% vs 38.7%, p = 0.033), 3rd generation VAD device (100% vs 53.7%, p = 0.027), polymicrobial infection (83.3% vs 28.8%, p = 0.006), concurrent infection with a multi-drug resistant organism in the same device (66.6% vs 21.2%, p = 0.013) as shown in Table 1. Patients with fungal infections had a higher mortality rate (66.6% vs 27.5%, p = 0.044). Risk factors for fungal infection compared to bacterial infections in VADs are ICM, 3rd generation devices, polymicrobial infection, and concurrent MDRO infections. Mortality is higher in VAD patients with fungal infections.

The assessment of beauty salon client awareness of risk factors relating to skin and nail fungal infections of the feety

Abstract Introduction: Fungal infections of the skin and nails are one of the most common skin diseases in the world. The ever-growing number of fungal infections is caused by genetic factors, lack of prevention and insufficient knowledge about risk factors relating to fungal infections. The aim of the project was to assess the awareness of beauty salon clients to fungal infections of the skin and nails of the feet, with a particular emphasis on the factors contributing to infection. Materials and methods: The study was conducted among 125 clients of beauty salons. The data was collected via an anonymous questionnaire comprising 30 questions. Results: The majority of respondents (84% of women and 70% of men) considered the swimming pool as the main risk factor for fungal infection of the feet. The respondents listed specialists to whom they would turn after noticing suspicious skin changes on their feet. These were dermatologists (18% of responding women and 38% of responding men) as well as podologist (35% of responding women and 23% of responding men). However, the majority of respondents (45% of responding men and 33% of responding women) would use an over-the-counter antifungal medicine, easily obtained in a pharmacy, in case of suspected fungal nail infection (onychomycosis), without consulting a physician. Conclusions: Most respondents know the risk factors contributing to fungal infections. However, a high percentage of them have low awareness of the actions to be taken when onychomycosis is suspected.

Infection risk after paediatric liver transplantation.

Infections after liver transplantation (LT), despite prophylactic therapy, are still important causes of morbidity and mortality in children. Although underlying disease and immunosuppression along with the complexity of LT procedure are the major predispositions to infections, there still might be under recognised factors predisposing infections in paediatric LT. In this study, we retrospectively analysed the risk factors of bacterial, viral, and fungal infections after LT in a series of 167 children (median =5 yr.). Of all children, 112 (67%) experienced infections: 93 (55.7%) bacterial, 56 (33.5%) viral and 15 (9%) fungal. Multilogistic regression analysis showed that the need of immunosuppressive switch increased total, bacterial, and viral infection risk 5.3, 2.5, and 2.5 times, respectively, (p=0.001, p=0.021, and p=0,019, respectively). Re-LT increased bacterial infection risk 4.2 times (p=0.040). Viral infection risk was 10 times higher in children who had more than two re-laparotomies (p=0,002). Children who had post-LT, cytomegalovirus (CMV) infection had 5.6 times increased risk for fungal infection (p=0.035). In conclusion, infection is still an important morbidity in paediatric LT and is in close relationship with other morbidities such as surgical complications. CMV infection, itself, is an independent risk factor for fungal infection.

PS1552 THE INCIDENCE RATES AND RISK FACTORS OF ATYPICAL INFECTIONS IN PATIENTS WITH LYMPHOMA WHO RECEIVED AUTOLOGOUS STEM CELL TRANSPLANTATION

Background:Autologous stem cell transplantation (ASCT) is an intermediate risk group for infections according to National Comprehensive Cancer Network (NCCN) guideline. Based on the risk of infection, experts recommend prophylaxis for fungal infections with fluconazole or micafungin if mucositis is accompanied, and prophylaxis for Pneumocystitis jirovecii (P. jirovecii) infection with trimethoprim‐sulfamethoxazole (TMP‐SMX) for 3 to 6 months after transplantation. For varicella zoster virus (VZV) reactivation, acyclovir or famcyclovir or valacyclovir is recommended as prophylaxis for 6 to 12 months after ASCT. However, there is a lack of evidence to support this guideline.Aims:In this study we performed a nationwide population‐based study to provide information regarding the incidence and risk factors of atypical infections such as fungal, viral or PJP in patients were performed ASCT in the South Korea.Methods:Using the Korean Health Insurance Review and Assessment Service database, the patients with lymphoma who received ASCT from 2003 to 2016 were retrospectively analyzed. Atypical infection is identified by international classification of disease (ICD) codes of each infection or ATC(Anatomical Therapeutic Chemical) codes of medicines for treatment. Oral Candidiasis, Herpes simplex virus (HSV), and Epstein‐Barr virus (EBV) infection were excluded because these are considered to non‐pathogenic in clinical field. The patients undergoing allogenic stem cell transplantation (AlloSCT) were excluded.Results:The total number of patients with lymphoma undergoing ASCT was 2147, median age was 48 years (range 2–70). The cumulative incidence of fungal infection is 10.4%, viral is 20.0% and PJP is 5.5% in lymphoma. In multivariate analysis, TBI (HR 1.702, p = 0.0390), and previous fungal infection (HR 1.701, p = 0.0398) were independent significant risk factors for fungal infection. The multivariate analysis showed that TBI (HR 2.524, p &lt; 0.0001), previous infection history (HR 1.351, p = 0.0046) and prophylaxis (HR 1.633, p = 0.0001) were independent risk factors for viral infection. The multivariate analysis showed that prophylaxis (HR 2.647, p = 0.0002) were independent risk factors for PJP infection.Summary/Conclusion:In this study, patients with lymphoma who underwent ASCT showed relative high risk of viral infection (CIR 20.0%) and previous viral infection, TBI conditioning and non‐prophylaxis were independent risk factors for viral infection. So patients with lymphoma who planed ASCT should be considered prophylaxis for 2years after ASCT. Especially, patient who treated with TBI conditioning and have previous viral infection should receive prophylactic anti‐viral agents.

Antifungal activity of immunosuppressants used alone or in combination with fluconazole.

Fungal infections remain a challenge to clinicians due to the limited available antifungals. With the increasing use of antifungals in clinical practice, drug resistance has been emerging continuously, especially to fluconazole (FLC). Thus, a search for new antifungals and approaches to overcome antifungal resistance is needed. However, the development of new antifungals is usually costly and time consuming; discovering the antifungal activity of non-antifungal agents is one way to address these problems. Interestingly, some researchers have demonstrated that several classes of immunosuppressants (calcineurin inhibitors, glucocorticoids, etc) also displayed potent antifungal activity when used alone or in combination with antifungals, especially with FLC. Some of them could increase FLC's susceptibility against resistant Candida albicans significantly reversing fungal resistance to FLC. This article reviews the antifungal activities of immunosuppressants used alone or in combination with antifungals and their potential antifungal mechanisms that have been discovered so far. Although immunosuppressive agents have been identified as risk factors for fungal infection, we believe these findings are very important for overcoming drug resistance and developing new antifungals.

Risk Factors for Fungal Infections After Liver Transplantation

Introduction Fungal infections after transplantation are associated with high morbidity and mortality. Awareness of the treating physicians and thereby early detection is key to successful treatment. Aim of the present study was to identify risk factors for fungal infections in a cohort of liver transplant recipients in the MELD era. Patients and Methods Out of 579 adult patients transplanted from 01/2012-12/2016, 33 (5.6%) patients developed fungal infections after liver transplantation. These 33 patients (mean age 48 years; LabMELD 22) were matched with 99 patients (mean age 50 years; LabMELD 22) without fungal infections after transplantation by MELD score and age. Standard donor and recipient and procedural factors were analyzed and correlated with occurrence of fungal infections and outcomes by univariable/multivariable statistics. Fungal prophylaxis is not administered at our center. Results After adjustment by multivariable analysis the Donor Risk Index (p=0.02) and dialysis after transplantation (p=0.01) were independently associated with occurrence of fungal infections. 30-day and 12-month survival in patients with fungal infections were 63.6% and 48.5%, respectively, while patients without fungal infections demonstrated 30-day and 12 month survival rates of 85.9% and 76.7%, respectively (p<0.01). Conclusions Rates of fungal infections are low after liver transplantation in the modern MELD era. Indeed, outcome is significantly diminished if fungal infections occur. Patients requiring hemodialysis after liver transplantation are under high risk of this dangerous complication and should therefore be monitored carefully.

Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Cancer.

Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenström macroglobulinemia, and mantle cell lymphoma. Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. We reviewed the electronic medical records of patients with lymphoid cancer at Memorial Sloan Kettering Cancer Center who received ibrutinib during a 5-year period from 1 January 2012 to 31 December 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by means of univariate and multivariate analyses. We analyzed findings in 378 patients with lymphoid cancer who received ibrutinib. The most common underlying cancers were chronic lymphocytic leukemia and mantle cell lymphoma. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Invasive bacterial infections developed in 23 (53.5%) of these patients, and invasive fungal infections (IFIs) in 16 (37.2%) .The majority of patients with IFIs during ibrutinib therapy (62.5%) lacked classic clinical risk factors for fungal infection (ie, neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in 6 of the 43 patients (14%). Patients with lymphoid cancer receiving ibrutinib treatment are at risk for serious infections, including IFIs.

Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib

AbstractIbrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present.

Near-fatal mucormycosis post-double lung transplant presenting as uncontrolled upper gastrointestinal haemorrhage

Invasive fungal infections in immunosuppressed transplant patients are associated with significant morbidity and mortality. We present a case of splenic mucormycosis post-double lung transplant, presenting as uncontrolled near-fatal upper gastrointestinal haemorrhage, to remind clinicians of the need to consider pre-transplant invasive fungal infection risk factors if an unexpected fungal infection arises in the post-transplant period. This case also highlights the valuable contribution of molecular technology for fungal identification but also the need for clinical correlation.