700. Risk Factors and Molecular Epidemiology of Acute and Chronic Norovirus Infection at a Large Tertiary Care Cancer Center

Abstract Background Norovirus (NoV) is the leading cause of viral diarrhea in patients with cancer. In this study, we describe risk factors associated with acute and chronic NoV infection in this patient population. Methods We identified 132 patients with NoV diarrhea (using stool RT PCR) between 2016-2020 at University of Texas MD Anderson Cancer Center (MDACC). Patient data, including demographics, clinical characteristics, NoV treatments, and complications were retrospectively extracted from charts. Stool samples were analyzed for NoV genogroups and genotypes. We compared characteristics and outcomes of patients with acute diarrhea (< 14day; AD) versus chronic diarrhea ( >14day or recurrences within 12 weeks; CD) and analyzed the data using Pearson Chi square or Fisher’s exact for categorical variables and Wilcoxon rank-sum test for continuous variables. Results Of 132 patients identified, 124 had an underlying cancer (39 solid tumor, 85 hematological malignancies, Table 1). On univariate analysis, CD patients were more likely to have a hematological malignancy (p=0.002), be a hematopoietic stem cell recipient (p= 0.013), have a history of gastrointestinal graft versus host disease (p= 0.011), or have received immunosuppressants or steroids in the 90 days before diarrhea onset (p=0.001, Table 2). CD patients had significantly lower white blood cell counts (p=0.038), absolute neutrophil counts (p=0.049), IgG levels (p= 0.001), and serum albumin levels (p=0.002) at the time of NoV diagnosis (Table 3). Patients with CD more often received symptomatic or NoV targeting treatment, including anti-diarrheal (p=0.005), nitazoxanide (p< 0.001), intravenous immune globulin (p=0.017), and oral IgG (p=0.042). CD patients more often had diarrheal recurrence in the first 4 weeks (p=0.001) or the second month (p< 0.001) after initial diagnosis and needed enteral or parenteral nutrition (p=0.004). We genotyped NoV in 67 patients (Figure 1), resulting in identification of the following genogroups: GI (n=9, 13%), GII.4 (n=23, 34%), and other types of GII (n=35, 52%). Genotype diversity was higher in patients with CD than AD (Figure 1). Conclusion In patients with cancer, CD from NoV is associated with severe immunosuppression, is refractory to therapy and can be caused by a variety of NoV genotypes/genogroups. Disclosures Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support) Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support)

Conclusion. Fluoroquinolone-resistant Campylobacter infections were acquired domestically and internationally. Exposure to chicken products and handling raw seafood were reported more often among fluoroquinolone-resistant cases. Whole genome sequencing of Campylobacter isolates provides predicted resistance data. Coupling predicted resistance data with exposure data facilitates better understanding of source attribution of different strains.
Disclosures. Methods. We identified 132 patients with NoV diarrhea (using stool RT PCR) between 2016-2020 at University of Texas MD Anderson Cancer Center (MDACC). Patient data, including demographics, clinical characteristics, NoV treatments, and complications were retrospectively extracted from charts. Stool samples were analyzed for NoV genogroups and genotypes. We compared characteristics and outcomes of patients with acute diarrhea (< 14day; AD) versus chronic diarrhea ( >14day or recurrences within 12 weeks; CD) and analyzed the data using Pearson Chi square or Fisher's exact for categorical variables and Wilcoxon rank-sum test for continuous variables.

Conclusion.
In patients with cancer, CD from NoV is associated with severe immunosuppression, is refractory to therapy and can be caused by a variety of NoV genotypes/genogroups. Background. Ibezapolstat, a DNA polymerase IIIC inhibitor, currently in Phase 2 clinical development for treatment of C. difficile infection (CDI). Its unique mechanism of action targets low G+C content Gram-positive bacteria primarily Firmicutes including C. difficile. Phase I healthy volunteer results demonstrated a favorable microbiome profile suggestive of an anti-recurrence effect. The purpose of this study was to report clinical outcomes, pharmacokinetics, and microbiome changes from this Phase 2a clinical study and to continue to test for anti-recurrence microbiome properties.
Methods. Ibezapolstat 450 mg was given twice daily for 10 days to patients with mild-moderate CDI defined as diarrhea plus a positive C. difficile toxin test. Test of cure was evaluated at day 12 and sustained clinical cure at day 38. Stool samples were evaluated for C. difficile cultures and microbiome changes.
Results. Ten subjects (female: 50%) aged 50 ±15 years were enrolled. All ten subjects experienced a clinical cure by the test of cure visit at day 12 and all 10 subjects experienced a sustained clinical cure at the day 38 visit. Ibezapolstat was well tolerated with 1 adverse event (nausea) probably related to drug. Ibezapolstat systemic exposure was minimal with no plasma level reaching 1 ug/mL any time during therapy. Ibezapolstat colonic concentrations averaged 400 ug/g stool at day 3 and greater than 1,000 ug/g by day 10 of dosing. Six of the seven available baseline stool samples grew toxigenic C. difficile of various ribotypes including RT078-226 and RT014-020 (Ibezapolstat MIC range: 0.25-1 ug/mL). Follow-up cultures were no growth starting from day 3 stool cultures. Microbiome changes included overgrowth of Actinobacteria and/or Firmicute phylum species while on therapy.
Conclusion. Favorable clinical efficacy and safety results were observed in ibezapolstat patients with CDI including 100% clinical cure and sustained clinical cure. These results begin to validate our approach to ibezapolstat development in that the favorable microbiome effects seen in healthy Phase 1 volunteers may be predictive of beneficial patient outcomes, including low rates of recurrence. These results support the continued clinical development of ibezapolstat.

Session: P-33. Enteric Infection
Background. In the United States, an estimated 179 million acute gastroenteritis (AGE) episodes occur each year. Identifying factors contributing to AGE susceptibility and severity is important to address the high disease burden of AGE among adults. The primary objective of this analysis was to identify risk factors for all-cause AGE, norovirus-associated AGE and severe AGE among hospitalized adults.
Methods. We analyzed data from 1029 inpatient AGE cases and 624 non-AGE controls enrolled prospectively from December 1, 2016 -November 30, 2019 from 5 Veterans Affairs Medical Centers (Atlanta, Bronx, Houston, Los Angeles, Palo Alto). Standardized patient interviews and medical chart abstractions were conducted to collect demographics, exposure history, and underlying medical conditions. Stool samples from participants were tested for 22 pathogens using the BioFire Gastrointestinal Panel. Severity of AGE was determined using a 20-point modified Vesikari score (MVS) and severe AGE was defined as a MVS score of ≥ 11. Multivariate logistic regression was performed to assess associations between potential risk factors and outcomes.
Conclusion. Our findings suggest that inpatients with HIV or severe renal disease, on immunosuppressive therapy, or in contact with a person with AGE within household are at higher risk for all-cause AGE. Patients with these medical conditions should be monitored for AGE related hospitalizations and may benefit from targeted AGE prevention messaging.
Disclosures Background. Chronic peritonitis is an unusual manifestation of coccidiomycosis (CM) that is challenging to diagnose and manage due to its propensity for relapse. It is even more unusual to diagnose peritoneal CM in the pediatric population, with only two other cases reported in the literature.
Methods. We present the case of a previously healthy 5-year-old Filipino female in Florida who was diagnosed with peritoneal CM. After months of unintentional weight loss and worsening abdominal distention, she presented to medical care. Imaging revealed significant abdominal ascites and nodularities throughout the peritoneum. The peritoneal fluid demonstrated a lymphocytic pleocytosis and infectious workup was benign. CA125 levels were elevated, but peritoneal adenosine deaminase was within normal limits. A biopsy of the affected tissue revealed diffuse granulomas surrounding spherules that were positive on GMS and PAS staining, concerning for CM. Exposure history revealed that she was raised in California and moved to Florida one year prior to presentation. Complement fixation titers were significantly elevated at ≥ 1:512 and immunodiffusion titers were positive. A Coccidioides PCR was sent from the tissue to the Mayo clinic and was positive, and fungal cultures from the tissue grew C. immitis/posadasii. Immunologic workup was reassuring. She was started on oral Fluconazole with rapid resolution of her symptoms.