935. A Hospital Cluster of the Emerging Drug-resistant Yeast Saprochaete clavata

Background Saprochaete clavata, an ascomycetous yeast intrinsically resistant to echinocandins, is a rare yet emerging pathogen associated with invasive infections in immunosuppressed patients, particularly those with haematological malignancies. It is commonly misidentified as the closely-related S. capitata. Outbreaks have been associated with a high mortality rate of >50%, due in part to delayed diagnosis and resistance to commonly-used antifungals. Environmental source identification is challenging, although dishwashers and milk flasks have been implicated in previous hospital clusters. Methods We describe a cluster of five haematology-oncology patients with disseminated S. clavata infections between April 2020 and April 2021 following current or recent admissions to the same ward. Results All had prolonged (median=24 days, range=9-210) and profound immunosuppression from chemotherapy and/or stem cell transplantation for acute myeloid leukaemia (n=3) or lymphoma (n=2) at the time of culture positivity. Four were severely neutropaenic (median=0.08/mm3, range=0.01-0.26). Median patient age was 62 years (range=58-73). S. clavata was isolated from blood (n=3), urine (n=2), and liver tissue (n=1) samples. Whole genome sequencing of these isolates was performed to confirm the presence of an outbreak. All patients received empirical treatment with intravenous caspofungin before culture-guided therapy with intravenous liposomal amphotericin B +/- oral flucytosine. Two of the five patients died although both had advanced refractory malignancy. Detailed environmental sampling of fridges/freezers, drains, and vents in patient rooms and clean areas for handling or storage of food and medication failed to identify a clear point source despite isolation of multiple environmental organisms. No further cases have emerged after intensification of the cleaning regimen in these areas. Conclusion Our experience highlights the emerging threat of drug-resistant yeasts particularly in the immunocompromised. Management of such outbreaks requires a multidisciplinary approach incorporating antifungal stewardship, infection control, and environmental microbiology, alongside close clinical liaison between haemato-oncologists and infection specialists. Disclosures All Authors: No reported disclosures

The Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias

In response to emerging discoveries, questions are mounting as to what factors are responsible for the progression of plasma cell dyscrasias and what determines responsiveness to treatment in individual patients. Recent findings have shown close interaction between the gut microbiota and multiple myeloma cells. For instance, that malignant cells shape the composition of the gut microbiota. We discuss the role of the gut microbiota in (i) the development and progression of plasma cell dyscrasias, and (ii) the response to treatment of multiple myeloma and highlight faecal microbiota transplantation as a procedure that could modify the risk of progression or sensitize refractory malignancy to immunotherapy.

Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. Methods We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients’ tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. Results The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. Conclusions Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

Comprehensive Analysis of the Transcriptional Expressions and Prognostic Value of S100A Family in Pancreatic Ductal Adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. Methods We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics, and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients’ tissue samples. The drug relations of S100As were also analyzed by using Drugbank. Results The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. Conclusions Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. Methods We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics, and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients’ tissue samples. The drug relations of S100As were also analyzed by using Drugbank. Results The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. Conclusions Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

Gastric Electrical Stimulation Is an Effective Treatment Modality for Refractory Gastroparesis in a Postsurgical Patient with Pancreatic Cancer

Gastroparesis-related hospital visits contribute significantly to healthcare costs. Gastroparesis can lead to chronic symptoms, such as nausea, vomiting, bloating, early satiety, and abdominal pain. It can result in a significant impairment of quality of life. Diabetes and postsurgery are common causes for gastroparesis, but most cases of gastroparesis are idiopathic in presumed etiology. Malignancy-related gastroparesis has also recently been described in the literature, and pancreatic cancer is a malignancy commonly associated with gastroparesis. Whipple surgery for pancreatic cancer is often complicated by gastroparesis during its postoperative course. We report a case where gastric electrical stimulation was an effective treatment option in the treatment of refractory malignancy-related gastroparesis.

The Current Role of Osteoclast Inhibitors in Patients with Prostate Cancer

Purpose. Prostate cancer (PCa) is one of the most frequently diagnosed malignancies worldwide. Hormonal deprivation therapy is a well-established treatment for locally advanced or metastatic diseases but exposes patients to the risk of osteoporosis and fragility fractures. Furthermore, the tropism of the PCa cells to osseous metastases increases the incidence of skeletal-related events (SREs). Methods. A nonsystematic review of the international literature was performed in respect to the use of osteoclast inhibitors zoledronic acid (ZA) and denosumab (DEN) in PCa patients. Results. DEN and ZA have proved their efficacy in preventing osteoporosis and bone mass loss in patients treated with hormonal therapy with no proven superiority of one agent over the other. However, the effectiveness in reducing fragility fractures has been proved only for DEN so far. In metastatic-free castrate-sensitive high-risk PCa patients, ZA has not shown any efficacy in preventing osseous metastasis, and evidence is lacking in favor or against the use of DEN. The use of osteoclasts inhibitors had no evident positive effect in overall and disease-specific survival in this group of patients. In advanced castrate-refractory malignancy, DEN has shown clinical superiority over ZA in preventing new SRE but not in overall survival. Conclusion. Superiority of DEN over ZA has been proved only in advanced castrate refractory disease in terms of preventing new SRE. In the rest of the cases, the selection of either agent should be based on the clinical condition of each patient and the cost of the treatment.

1756. Prediction of Bloodstream Infection Prior to Onset of Symptoms by Plasma Metagenomic Sequencing in Pediatric Patients With Relapsed or Refractory Malignancy (PREDSEQ)

Background Patients undergoing treatment for relapsed or refractory malignancies are at high risk of life-threatening bloodstream infection (BSI). A predictive screening test for BSI might allow pre-emptive therapy, but no validated test is currently available. We tested the hypothesis that plasma metagenomic next generation pathogen sequencing (NGS) would predict BSI before the onset of attributable symptoms. Methods We enrolled 31 pediatric patients receiving for treatment relapsed or refractory malignancy in an IRB-approved prospective cohort study (PREDSEQ) of predictive sequencing. Episodes of febrile neutropenia or documented infection were collected prospectively from the medical record. BSI was defined according to NHSN criteria. Control Samples were defined as samples collected ≥7 clear days before or after any fever or documented infection. Residual clinical samples were stored for NGS; after filtering human sequences, reads were aligned to a curated pathogen database, and organisms above a predefined threshold were reported (Karius Inc., Redwood City, CA). Only bacteria and fungi were included in this analysis. Results A total of 11 BSI episodes occurred in 9 participants (Table 1) during the study period. Predictive sensitivity of NGS in the 2 days before onset of infection (n = 9) was 78% (95% CI 45–94%), and diagnostic sensitivity on the day of infection (n = 11) was 82% (95% CI 52–95%). Specificity of NGS for development of fever or infection within 7 days (n = 16) was 81% (95% CI 57–93%). NGS was positive up to 6 days prior to onset of BSI. In samples collected before or during documented infections, NGS also identified additional bacteria and fungi that were not detected by standard clinical testing. Conclusion Plasma NGS shows promise for the detection of BSI prior to onset of symptoms in high-risk patients. Disclosures K. Goggin, Karius Inc.: Investigator, Research support. K. L. Chan, Karius Inc.: Employee, Salary. D. Hollemon, Karius Inc.: Employee, Salary. A. Ahmed, Karius, Inc.: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. R. Hayden, Roche Molecular: Scientific Advisor, Consulting fee. Abbott Molecular: Scientific Advisor, Consulting fee. Quidel: Scientific Advisor, Consulting fee. C. Gawad, Karius Inc.: Investigator, Research support. J. Wolf, Karius Inc.: Investigator, Research support.

1071. Impact of Standard vs. Prolonged Courses of Antibiotics for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia (SAB) in Patients With Hematologic Malignancies

Background The optimal treatment duration for uncomplicated SAB (U-SAB) is unknown in patients with hematologic malignancies. The goal of this study was to evaluate the impact of antibiotic duration on outcomes in patients with hematologic malignancies and U-SAB. Methods This was a multicenter, retrospective cohort study of adult patients with hematologic malignancies and U-SAB treated with standard (2 weeks) or prolonged (&gt;2 weeks) antibiotic therapy. U-SAB was defined as defervescence and culture clearance within 96 hours of index culture and the absence of: endocarditis, implanted prostheses, metastatic sites of infection, and bone/joint involvement. Patients with SAB therapy &lt;10 days and those with inadequate source control were excluded. The primary outcome was a composite global clinical cure: absence of relapse SAB, absence of SAB progression, and survival at 60 days following index SAB. Results Of 89 included patients, 51% received a standard antibiotic duration for U-SAB. The median age of the entire cohort was 56 and majority was male (60%). Neutropenia was present at index culture in 53% of patients, and acute leukemia (48%) and lymphoma (26%) were the most common underlying malignancies. Other baseline characteristics were similar between the two groups except more patients in the standard duration group had relapsed/refractory malignancy (51% vs. 25%, P = 0.016), central-line source (71% vs. 48%, P = 0.032), and antibiotic prophylaxis prior to index SAB (42% vs. 18%, P = 0.021). Median duration of treatment in the standard group was 15 days vs. 28 days in the prolonged duration group. No differences in global clinical cure and other clinical outcomes were seen between groups (Figure 1). On multivariable logistic regression analysis, only relapsed/refractory malignancy was identified as an independent predictor of global clinical failure (odds ratio, OR, 9.43; 95% confidence interval, CI, 1.17–76.9; P = 0.035). Duration of treatment was not associated with global clinical cure (OR, 2.92; 95% CI, 0.51–16.7; P = 0.23). Conclusion No differences in clinical outcomes were seen in patients with active hematologic malignancies who received 2 weeks vs. &gt;2 weeks of antibiotic therapy for the treatment of U-SAB, although confirmation of our findings in a larger study is warranted. Disclosures All authors: No reported disclosures.