702. Risk Factors for Acute Gastroenteritis Among Patients Hospitalized in 5 Veterans Affairs Medical Centers, 2016–19

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. Results Of the total AGE cases, 551 (54%) had severe AGE; 44 (4%) were norovirus positive. Risk factors for all-cause AGE vs. non-AGE controls included household contact with a person with AGE in the past 7 days (aOR=2.9, 95% CI:1.3-6.7), severe renal disease (aOR=3.1, 95% CI:1.8-5.2), human immunodeficiency virus (HIV) (aOR=3.9, 95% CI:1.8-8.5), and immunosuppressive therapy (aOR=5.6, 95% CI:2.7-11.7). Factors associated with norovirus positivity by univariate analysis were contact with a person with AGE outside (OR=4.4, 95% CI:1.6-12.0) and within (OR=5.0, 95% CI:2.2-11.5) the household in the past 7 days. Detection of any viral pathogen (aOR=4.0, 95% CI:1.7-9.5) was a risk factor for severe AGE. 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 Vincent Marconi, MD, Bayer (Consultant, Scientific Research Study Investigator)Eli Lilly (Consultant, Scientific Research Study Investigator)Gilead Sciences (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator)

Epidemiology of hospitalizations due to pesticide intoxication-associated acute kidney injury in China

Background There is a paucity of epidemiological data regarding pesticide intoxication-associated acute kidney injury (AKI). Therefore, the aim of this study was to identify the epidemiological features, risk factors, and adverse outcomes of AKI in this population. Methods The data used in this multi-center, hospitalized population-based, retrospective study were retrieved from electronic medical records. AKI was defined as an acute increase in serum creatinine according to the criteria of Kidney Disease: Improving Global Outcomes. The Charlson Comorbidity Index was used to evaluate the burden of in-hospital mortality. Results Of 3,371 adult patients in 11 hospitals, 398 (11.8%) were diagnosed with AKI (grade 1, 218 [6.5%]; grade 2, 89 [2.6%]; grade 3, 91 [2.7%]). Herbicide intoxication was associated with the highest incidence of AKI (53.5%) and higher grades of AKI. After multivariable adjustment, pesticide categories and moderate or severe renal disease were independently associated with AKI. As compared with the referred category, insecticide and herbicide intoxications were associated with a 1.3-fold (95% CI 1.688–3.245) and 3.8-fold (95% CI 3.537–6.586) greater risk of AKI. Regardless of the pesticide category, AKI was independently associated with in-hospital mortality, with odds ratios of 3.433 (95% CI 1.436–8.203) for insecticides, 2.153 (95% CI 1.377–3.367) for herbicides, and 4.524 (95% CI 1.230–16.632) for unclassified or other pesticides. Conclusion AKI is common in pesticide intoxication and associated with an increased in-hospital mortality. Herbicides pose the greatest risks of AKI and death.

Plasma exchange for the management of ANCA-associated vasculitis: the con position

Advances in the diagnosis and treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have led to continued improvement in survival and prognosis over the course of the last 4 decades. Nevertheless, the most acute and severe disease manifestations, including severe kidney disease and alveolar hemorrhage, continue to be associated with increased early mortality from disease activity or treatment complications as well as risk for the development of end-stage kidney disease (ESKD), which in turn directly affects the overall prognosis of ANCA-associated vasculitis. Plasma exchange (PLEX) has long been proposed and used for these most severe disease manifestations under the assumption that its effects are swift and supported by our understanding of the pathogenic role of ANCA. Yet convincing evidence of a beneficial effect of PLEX in ANCA-associated vasculitis has been lacking, as early studies and small trials have generated conflicting results. The controversy regarding PLEX has been accentuated recently as the largest randomized controlled trial ever conducted in ANCA-associated vasculitis, the Plasma Exchange and Glucocorticoids in Severe ANCA-associated Vasculitis trial, which was specifically designed to evaluate the efficacy of PLEX in patients with severe renal disease or alveolar hemorrhage, failed to show a difference in the combined primary outcome measure of death or ESKD in patients who received PLEX versus those who did not. In light of these disappointing results, we herein review the currently available data on PLEX for ANCA-associated vasculitis and explain why we believe that these data no longer support the use of PLEX in ANCA-associated vasculitis.

1490. Serious Infections Caused by Carbapenem Susceptible and Carbapenem Resistant Acinetobacter baumannii-calcoaceticus Complex - A Retrospective Review

Background Increasing resistance to available antibiotics, including carbapenems, is limiting effective treatment options for serious Acinetobacter baumannii-calcoaceticus (ABC) complex infections that are associated with high mortality. This multi-center retrospective analysis is to describe the natural history and outcomes of serious ABC infections. Methods This was a retrospective review of 125 cases of ABC infections from United States (US), Israel, Turkey and Russia. Baseline, microbiologic, treatment and outcomes data were collected from patients with hospital-acquired (HABP, n=23) or ventilator-associated bacterial pneumonia (VABP, n=26), bacteremia (n=36), urinary tract infections/acute pyelonephritis (n=16), and wound ABC infections (n=24) between 2017-2019. Results Fifty percent of cases reviewed were from the US. The median age of patients was 63 years (range 18-93), 46% were > 65 years old, 69% were male, 31% had renal failure, and 22% had septic shock. The most common co-morbidities observed were cardiac disease (41%), diabetes (32%) and moderate or severe renal disease (26%). Rates of resistance were observed as follows: ciprofloxacin 74%, ceftazidime 67%, amikacin 52% and colistin 0%. Carbapenem resistance (CR) was observed in 49% of patients. Most patients (73%) received combination therapy with 37% receiving at least 4 antibiotics. Carbapenems (40%) and penicillin/b-lactamase inhibitors (42%) were mostly used for treatment. Polymyxins were used in 18% of cases. Overall, the 28-day mortality was 34% and was highest in bacteremia (56%) and VABP (50%). CR appears to be a factor in mortality and other outcomes, as well as hospital days (table). In patients who received monotherapy, all 5 patients with CR infection died compared to 29% mortality in patients with carbapenem sensitive (CS) infection. Mortality was 70% in 20 cases when colistin was used for treatment. Conclusion Serious ABC infections are associated with substantial comorbidities and a high mortality rate despite treatment with combination therapy. CR appears to be a major factor in mortality. New antibiotics are urgently needed to treat serious ABC infections. Disclosures Khurram Rana, PharmD, Entasis Therapeutics (Employee) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Kathleen Maloney, CCRP, Entasis Therapeutics (Employee) Subasree Srinivasan, MD MPH, Entasis therapeutics (Employee)

Temocillin dosage adjustment in a preterm infant with severe renal disease: a case report

Background Temocillin is a carboxypenicillin antibiotic indicated in complicated urinary tract infections due to susceptible ESBL-producing Enterobacteriaceae. While temocillin therapeutic schemes for adult patients with normal or impaired renal function are evidence based, little is known in paediatric populations. Objectives We report herein the management of temocillin treatment in a preterm infant with end-stage renal disease. Patients and methods The patient was a 7-month-old preterm infant born at 35 weeks gestation and treated by temocillin for 10 days for a bacteraemic urinary tract infection due to a susceptible ESBL-producing Enterobacter cloacae complex strain. Temocillin was administered by continuous infusion using a loading dose of 25 mg followed by a maintenance dose of 70 mg daily. Determination of MIC and temocillin plasma and urinary concentration was performed. Results Clinical improvement was observed 24 h after the initiation of temocillin treatment. Temocillin concentrations ranged between 21.6 and 35.5 mg/L in urine between the first and the sixth day of treatment and between 47.0 and 61.8 mg/L in plasma after 6 and 10 days of treatment, respectively. Temocillin concentrations were found to be above the determined MIC of 6 mg/L. From the measured concentrations, we can postulate that 100%fT>MIC was achieved in urine and at least equal to 40% in plasma. Conclusions Temocillin dosing adjustment performed in the present reported case allowed safe and effective treatment. The strategy described herein could be used as a basis for further clinical studies relative to temocillin use in a paediatric population with renal impairment.

LB003A RANDOMIZED, DOUBLE-BLIND, ACTIVE CONTROLLED STUDY OF AVACOPAN IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS

Background and Aims Complement fragment C5a is strongly linked to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The C5a receptor (C5aR), is a G protein-coupled receptor present on neutrophils. Avacopan (previously CCX168) is an orally-administered selective antagonist of C5aR which blocks C5a-induced cell activation. Two previous Phase 2 clinical trials provided evidence of effectiveness of avacopan in AAV. This Phase 3 study evaluated the efficacy and safety of avacopan for the treatment of AAV as well as the potential of avacopan to eliminate extensive use of glucocorticoids (GC) and GC-related toxicities. Method Eligible subjects were randomized 1:1 to receive either prednisone or avacopan in combination with either a) cyclophosphamide (oral or IV) followed by azathioprine or b) rituximab (four IV infusions). Randomization was stratified by the treatment regimen (rituximab, IV cyclophosphamide, or oral cyclophosphamide), ANCA serotype, and newly-diagnosed or relapsing disease. Treatment period was 52 weeks; primary efficacy endpoints were the proportion of subjects achieving disease remission at Week 26, and sustained disease remission at Week 52. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of zero and not taking glucocorticoids for AAV within 4 weeks prior to Week 26. Sustained remission was defined as being in remission at Week 26 and sustained through Week 52 without relapse. Change in estimated glomerular filtration rate (eGFR) from baseline to week 52 was a pre-specified secondary endpoint. Results 330 subjects were randomized and dosed: 166 in the avacopan and 164 in the prednisone groups. At Week 26, 72.3% subjects achieved remission in the avacopan compared to 70.1% in the prednisone group (p<0.0001 for non-inferiority). At Week 52, 65.7% subjects achieved sustained remission in the avacopan compared to 54.9% in the prednisone group achieving both non-inferiority and superiority to prednisone group (p=0.0066 for superiority of avacopan). The avacopan arm had a significant reduction in glucocorticoid-related toxicity compared to the prednisone arm as measured by the Glucocorticoid Toxicity Index of Cumulative Worsening Score (p=0.0002) and Aggregate Improvement Score (p=0.0082). In subjects with renal disease at baseline, the avacopan group (n=134) showed a mean increase in eGFR of 7.3 mL/min/1.73 m2 from baseline to week 52 as compared to 4.1 mL/min/1.73 m2 increase in the prednisone group (n=132) (p=0.029). A pre-specified sub-group analysis showed a greater difference in the avacopan sub-group with a baseline eGFR <30 (13.7 mL/min/1.73 m2 vs. 8.2 mL/min/1.73 m2; p<.005). Conclusion Treatment with avacopan resulted in remission in patients with AAV receiving rituximab or cyclophosphamide/azathioprine at a rate that was non-inferior to the active comparator prednisone at Week 26 and superior to prednisone in sustained remission at Week 52. A significant reduction in glucocorticoid-related toxicity was observed in the avacopan vs. prednisone arms. The increase in eGFR seen with avacopan was marked among subjects with more severe renal disease. The safety profile of avacopan was acceptable for use in patients with AAV. The ADVOCATE trial demonstrated avacopan is an effective treatment for patients with AAV.

Thirty-Day Hospital Readmission and Surgical Complication Rates for Shunting in Normal Pressure Hydrocephalus: A Large National Database Analysis

BACKGROUND Research on age-related complications secondary to shunts in normal pressure hydrocephalus (NPH) is primarily limited to single-center studies and small cohorts. OBJECTIVE To determine the rates of hospital readmission and surgical complications, and factors that predict them, following shunt surgery for NPH in a large healthcare network. METHODS Surgical procedures, complications, and readmissions for adults undergoing ventricular shunting for NPH were determined using de-identified claims from a privately insured United States healthcare network in years 2007-2014. Univariate and multivariate statistics were used to determine factors that predict poor surgical outcomes. The primary outcome variable was surgical complications or readmissions (composite variable for any major perioperative complication or 30-d readmission). RESULTS The 30-d readmission rate for 974 patients with NPH who underwent ventricular shunting was 7.29%; the most common reasons for readmission were shunt-related complications, infection, hemorrhage, altered mental status, and cardiopulmonary and musculoskeletal problems. The perioperative complication rate was 21.15%, including intraparenchymal hemorrhage (5.85%) and extra-axial (subdural or epidural) hematoma (5.54%). The overall rate of having a surgical complication or 30-d readmission was 25.15%. Age did not predict surgical complication or 30-d readmission. Preoperative comorbidities independently associated with poor outcome were myocardial infarction within 1 yr (OR = 3.984, 95% CI = 1.105-14.368); existing cerebrovascular disease (odds ratio [OR] = 2.206, 95% CI = 1.544-3.152); and moderate/severe renal disease (OR = 2.000, 95% CI = 1.155-3.464). CONCLUSION The rate of complications or readmission within 30 d of ventricular shunting for NPH is 25.15%. Preoperative comorbidities of myocardial infarction within 1 yr, cerebrovascular disease, and moderate/severe renal disease are independent risk factors for poor outcome.

Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging

Chronic Kidney Disease (CKD) is a cardinal feature of methylmalonic acidemia (MMA), a prototypic organic acidemia. Impaired growth, low activity, and protein restriction affect muscle mass and lower serum creatinine, which can delay diagnosis and management of renal disease. We have designed an alternative strategy for monitoring renal function based on administration of a pH sensitive MRI agent and assessed this in a mouse model. This protocol produced three metrics: kidney contrast, ~4% for severe renal disease mice compared to ~13% and ~25% for moderate renal disease and healthy controls, filtration fraction (FF), ~15% for severe renal disease mice compared to ~79% and 100% for moderate renal disease and healthy controls, and variation in pH, ~0.45 units for severe disease mice compared to 0.06 and 0.01 for moderate disease and healthy controls. Our results demonstrate that MRI can be used for early detection and monitoring of CKD.