1410. Neonatal Herpes Simplex Virus (HSV) Infection: Is It the Only Pathogen?

Abstract Background Neonatal HSV infection is associated with substantial morbidity and mortality. Therefore, prompt identification and treatment of infected neonates is paramount. At Nationwide Children’s Hospital (NCH), Columbus, OH all neonates admitted in the first 2 weeks (up to 2010) and 4 weeks (since 2010) of age are evaluated for HSV infection in addition to routine bacterial and other viral infections. The frequency of co-infection with HSV and other potential pathogens is not fully known. Methods Retrospective review of the medical records of infants admitted to NCH with a diagnosis of neonatal HSV infection from 2001 to 2019. Patients less than 6 weeks of age were identified by review of the NCH Virology and Molecular Laboratory results for all positive HSV PCRs obtained from any body site as well as by discharge ICD-9 and ICD-10 codes for HSV infection. Medical records were reviewed for demographic, clinical, laboratory, outcome data, and maternal history of genital HSV lesions at or before delivery. Occurrence of positive bacterial and/or viral co-detection were identified. The data were managed using REDCap electronic data capture tools hosted at NCH. Results There were 93 infants with neonatal HSV infection (mean age, 9.5 days [IQR, 7-15]; 42%, HSV1; 53%, HSV-2). 32 infants had central nervous system infection (CNS) while 31 had Skin-Eye-Mouth (SEM) infection and 30 had Disseminated Disease. Mortality was 15% (n=14). Only 3 mothers had active genital HSV lesions at delivery. Of the 93 infants, 5 (5%) had bacterial (n=2) or viral (n=3) co-infections. All of the infants only had mucosal sites positive for HSV 1 (n=4) or 2 (n=1). Of the 2 infants with bacterial infection, 1 had bacteremia due to viridans streptococci while the other one had necrotizing enterocolitis and a positive blood culture for Clostridium butyricum. The 3 infants with viral co-detection also were full term and all had positive enterovovirus PCR tests (1, blood, throat; 1, blood and ceerebrospinal fluid (CSF); 1, CSF) Conclusion 5% of infants with neonatal HSV infection had bacterial or enteroviral co-infection. These findings have important implications in the management of neonates evaluated for possible sepsis. Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

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81. SARS-CoV-2 RNAemia and Disease Severity in Pediatric Coronavirus Disease 2019 (COVID-19)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.081 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S52-S53

Author(s):

Cameron Mertz ◽

Rebecca M Glowinski ◽

Sara Mertz ◽

Colin L Peachey ◽

Lauren Miller ◽

...

Keyword(s):

Clinical Laboratory ◽

Severe Disease ◽

Panel Member ◽

Supplemental Oxygen ◽

Outcome Data ◽

Hospitalized Children ◽

Research Support ◽

Review Panel ◽

Convenience Sample ◽

Blood Samples

Abstract Background Children with COVID-19 may develop severe disease. In hospitalized adults, detection of plasma SARS-CoV-2 RNAemia ranges from 19% to 42% and has been associated with worse clinical outcomes. A similar association in children remains unexplored. We determined the frequency of SARS-CoV-2 RNAemia in children hospitalized with COVID-19 and evaluated its potential association with severe disease. Methods Single center prospective study that enrolled hospitalized children and adolescents ≤21 years old with COVID-19 from March 2020-April 2021 at Nationwide Children’s Hospital, Columbus, OH. Nasopharyngeal (NP) and blood samples were obtained and SARS-CoV-2 RNA was quantified using a real time PCR assay targeting the N1 gene. Pertinent demographic, clinical, laboratory, and outcome data were evaluated. Results We enrolled a convenience sample of 103 hospitalized children (median age, 9 years; range, 3 days-21 years) who had confirmed SARS-CoV-2 infection and both NP and blood samples obtained (Table 1). Overall, 27 (26%) patients with COVID-19 had SARS-CoV-2 RNAemia. Compared with patients who had undetectable RNAemia, those with SARS-CoV-2 RNAemia had significantly higher nasopharyngeal RNA loads (8.1 vs. 4.9 log10 copies/mL; p=0.0006), fever (78 vs 54%; p=0.02), receipt of supplemental oxygen (37% vs 14%; p=0.02), and treatment with anti-COVID-19 medications (30% vs 12%; p=0.04). In addition, patients with SARS-CoV-2 RNAemia were more likely to require intensive care (40%% vs. 20%, p= 0.04) and had longer hospitalization (2.56 vs 2.15 days; p=0.03). There were no COVID-19 related deaths. Table 1. Demographic, clinical, laboratory and virology characteristics of study patients Conclusion The frequency of SARS-CoV-2 RNAemia in pediatric patients was 26% and its finding was associated with worse clinical in-hospital outcomes, similar to that reported in adults. Testing for SARS-CoV-2 RNAemia in children may help identify those who could benefit from more intensive supportive care as well as antiviral and anti-inflammatory medications. Disclosures Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

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Abstract 17113: Secondary Infections Are Common in Patients Hospitalized for COVID-19 and Are Associated With Severe Outcomes

Circulation ◽

10.1161/circ.142.suppl_3.17113 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Elizabeth R Anderson ◽

Tariq Azam ◽

Husam Shadid ◽

Michael Pan ◽

Hanna Berlin ◽

...

Keyword(s):

Prospective Observational Study ◽

Viral Infections ◽

Clinical Laboratory ◽

Secondary Infection ◽

Kidney Injury ◽

Outcome Data ◽

Hospitalized Patients ◽

Secondary Infections ◽

Life Threatening ◽

The Mean

Background: Secondary infections occur in 10-15% of critically ill sepsis patients. Anecdotal reports suggest secondary infections are common in coronavirus disease 2019 (COVID-19), however data are lacking. We examine the rate of secondary infections in hospitalized patients with COVID-19 and its impact on the cytokine surge and in-hospital outcomes. Methods: The Michigan Medicine Covid-19 Cohort (M2C2) is an ongoing prospective observational study in which detailed clinical, laboratory and outcome data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without respiratory symptoms were not included in this cohort. We define secondary infections as physician-diagnosed and treated bacterial or viral infections secondary to SARS-CoV-2. Results: Of 553 COVID-19 patients hospitalized at Michigan Medicine, 191 (34.5%) developed a secondary infection during hospitalization. The mean age of patients with a secondary infection was 60 years, 61.3% were male compared to 58.8 years, 53.5% male in patients with no secondary infection. Bacterial pneumonia, including ventilator-associated pneumonia, was the most prevalent secondary infection among hospitalized patients (78.5%). Other secondary infections included urosepsis (14.1%), bacteremia (16.8%), and 17.3% of patients developed other types of infections such as shingles and clostridium difficile. 25.8% of patients without secondary infections received antibiotics during their admission compared to 47.1% of patients with secondary infections. Multiple secondary infections (>1) occurred in 43 (8.2%) of patients. Patients with secondary infections were more likely to develop acute kidney injury (78.0% vs. 38.3%, p<0.0001), acute respiratory distress syndrome (78.0% vs. 22.3%, p<0.0001), and death (26.2% vs. 10.2%, p<0.0001) during their hospitalization compared to patients without secondary infections. Conclusions: Secondary infections are common in hospitalized patients with COVID-19 and are associated with life-threatening complications and high mortality. This study suggests that secondary infection prevention may be especially important in COVID-19 patients.

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484. Identification of Early Features to Differentiate Hospitalized Children Admitted for Suspected MIS-C from Alternative Diagnoses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.683 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S343-S344

Author(s):

Matthew T Clark ◽

Danielle A Rankin ◽

Anna E Patrick ◽

Alisa Gotte ◽

Alison Herndon ◽

...

Keyword(s):

Clinical Laboratory ◽

Panel Member ◽

Laboratory Evaluation ◽

Categorical Variables ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Unequal Variances ◽

Chi Squared ◽

Early Features

Abstract Background Multi-system inflammatory syndrome in children (MIS-C) is a rare consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C shares features with common infectious and inflammatory syndromes and differentiation early in the course is difficult. Identification of early features specific to MIS-C may lead to faster diagnosis and treatment. We aimed to determine clinical, laboratory, and cardiac features distinguishing MIS-C patients within the first 24 hours of admission to the hospital from those who present with similar features but ultimately diagnosed with an alternative etiology. Methods We performed retrospective chart reviews of children (0-20 years) who were admitted to Vanderbilt Children’s Hospital and evaluated under our institutional MIS-C algorithm between June 10, 2020-April 8, 2021. Subjects were identified by review of infectious disease (ID) consults during the study period as all children with possible MIS-C require an ID consult per our institutional algorithm. Clinical, lab, and cardiac characteristics were compared between children with and without MIS-C. The diagnosis of MIS-C was determined by the treating team and available consultants. P-values were calculated using two-sample t-tests allowing unequal variances for continuous and Pearson’s chi-squared test for categorical variables, alpha set at < 0.05. Results There were 128 children admitted with concern for MIS-C. Of these, 45 (35.2%) were diagnosed with MIS-C and 83 (64.8%) were not. Patients with MIS-C had significantly higher rates of SARS-CoV-2 exposure, hypotension, conjunctival injection, abdominal pain, and abnormal cardiac exam (Table 1). Laboratory evaluation showed that patients with MIS-C had lower platelet count, lymphocyte count and sodium level, with higher c-reactive protein, fibrinogen, B-type natriuretic peptide, and neutrophil percentage (Table 2). Patients with MIS-C also had lower ejection fraction and were more likely to have abnormal electrocardiogram. Conclusion We identified early features that differed between patients with MIS-C from those without. Development of a diagnostic prediction model based on these early distinguishing features is currently in progress. Disclosures Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support James A. Connelly, MD, Horizon Therapeutics (Advisor or Review Panel member)X4 Pharmaceuticals (Advisor or Review Panel member)

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301. Detection of Pneumococcal Pneumonia During SARS-CoV-2 Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.503 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S257-S257

Author(s):

Anne Watkins ◽

Devyn Yolda-Carr ◽

Isabel M Ott ◽

Maura Nakahata ◽

Adam Moore ◽

...

Keyword(s):

Pneumococcal Pneumonia ◽

Viral Infections ◽

Panel Member ◽

Upper Respiratory Tract ◽

Diagnostic Systems ◽

Research Support ◽

Review Panel ◽

Syncytial Virus ◽

The Relationship ◽

Research Grant

Abstract Background Streptococcus pneumoniae (pneumococcus) is a common colonizer of the upper respiratory tract and can progress to cause invasive and mucosal disease. Additionally, infection with pneumococcus can complicate respiratory viral infections (influenza, respiratory syncytial virus, etc.) by exacerbating the initial disease. Limited data exist describing the potential relationship of SARS-CoV-2 infection with pneumococcus and the role of co-infection in influencing COVID-19 severity. Methods Inpatients and healthcare workers testing positive for SARS-CoV-2 during March-August 2020 were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and for inpatients only, serotype-specific urine antigen detection (UAD) assays (to identify pneumococcal pneumonia). A multinomial multivariate regression model was used to examine the relationship between pneumococcal detection and COVID-19 severity. Results Among the 126 subjects who tested positive for SARS-CoV-2, the median age was 62 years; 54.9% of subjects were male; 88.89% were inpatients; 23.5% had an ICU stay; and 13.5% died. Pneumococcus was detected in 17 subjects (13.5%) by any method, including 5 subjects (4.0%) by RT-qPCR and 12 subjects (13.6%) by UAD. Little to no bacterial growth was observed on 21/235 culture plates. Detection by UAD was associated with both moderate and severe COVID-19 disease while RT-qPCR detection in saliva was not associated with severity. None of the 12 individuals who were UAD-positive died. Conclusion Pneumococcal pneumonia (as determined by UAD) continues to occur during the ongoing pandemic and may be associated with more serious COVID-19 outcomes. Detection of pneumococcal carriage may be masked by high levels of antibiotic use. Future studies should better characterize the relationship between pneumococcus and SARS-CoV-2 across all disease severity levels. Disclosures Akiko Iwasaki, PhD, 4Bio (Consultant, Advisor or Review Panel member)Adaptive Biotechnologies (Consultant, Advisor or Review Panel member)Blavatnik (Grant/Research Support)HHMI (Grant/Research Support)Mathers (Grant/Research Support)NIH (Grant/Research Support)Spring Discovery (Grant/Research Support)Spring Discovery (Consultant, Advisor or Review Panel member)Vedanta InProTher (Consultant, Advisor or Review Panel member)Yale School of Medicine (Grant/Research Support) Nathan D. Grubaugh, PhD, Tempus Labs (Consultant) Ronika Alexander-Parrish, RN, MAEd, Pfizer (Employee, Shareholder) Adriano Arguedas, MD, Pfizer (Employee) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) Daniel Weinberger, PhD, Affinivax (Consultant)Merck (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support) Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support)

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1089. Health Resource Utilization and Costs Associated with Multi-Virus Infection after Allogeneic Hematopoietic Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1275 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S573-S574

Author(s):

Joshua A Hill ◽

Richard T Maziarz ◽

Seung Hyun Moon ◽

Aastha Chandak ◽

Zhiji Zhang ◽

...

Keyword(s):

Research Study ◽

Viral Infections ◽

Scientific Research ◽

Panel Member ◽

First Year ◽

Health Resource ◽

Research Support ◽

Health Resource Utilization ◽

Review Panel ◽

Study Investigator

Abstract Background Reactivation or infection with multiple double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplant (allo-HCT) has been associated with increased morbidity in single center studies. We used a large US claims database to compare health care reimbursements and health resource utilization (HRU) between allo-HCT patients with no versus multiple infections due to CMV, BKV, EBV, JCV, AdV, and HHV-6. Methods We used the Decision Resources Group Real World Evidence Data Repository to identify allo-HCT recipients from 1/1/12-12/31/17. We grouped BKV, EBV and JCV due to lack of specific diagnosis codes and calculated reimbursements from submitted charges using a reimbursement to charge ratio of 0.425. We describe reimbursements and HRU in the 1-year post allo-HCT for patients with 1 vs. 2 vs. ≥ 3 vs. no dsDNA viral infections. We also used a generalized linear model to determine reimbursements stratified by the presence or absence of any acute or chronic graft-versus-host diseases (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, baseline costs, and follow-up time. Results Among the 13,363 allo-HCT patients, 3,878 (29%) were coded with CMV, 1,754 (13%) with BKV/EBV/JCV, 626 (5%) with AdV, and 561 (4%) with HHV-6. Further, 3,949 (30%) were coded with 1 virus, 1,069 (8%) with 2, 238 (2%) with ≥3, and 8,107 (61%) with none. The unadjusted mean reimbursements per patient group were: 1 virus, $431,614; 2, $639,097; ≥3, $964,378; none, $266,345 (Table 1). Adjusted reimbursements were significantly higher for each additional viral infection among patients with and without GVHD compared to patients with no viral infections (p< .0001) (Figure 1). HRU also increased as the number of viral infections increased. Patients with multiple viruses had longer lengths of stay (up to 2.5 weeks for index, 5 weeks for readmissions), ICU days (up to 1.5 weeks for index and readmissions) and higher readmission rates (up to 3 times) (Table 1). Table 1: Economic burden and health resource utilization in the first year after allo-HCT, stratified by number of dsDNA viral infections Figure 1: Adjusted total reimbursements in the first year after allo-HCT, stratified by number of dsDNA viral infections and GVHD Conclusion Allo-HCT patients with multiple dsDNA viral infections have significantly higher health care costs and HRU in the first year after allo-HCT, irrespective of the presence of GVHD. Improved dsDNA virus prevention strategies may reduce costs and improve outcomes. Disclosures Joshua A. Hill, MD, Allogene (Consultant)Allovir (Consultant)Gilead (Consultant)Karius (Grant/Research Support, Scientific Research Study Investigator)Takeda (Grant/Research Support, Scientific Research Study Investigator) Richard T. Maziarz, MD, AlloVir (Consultant)Artiva Biotherapeutics (Board Member)Athersys (Advisor or Review Panel member)BMS/ Celgene (Consultant, Grant/Research Support, Scientific Research Study Investigator)CRSPR (Consultant, Scientific Research Study Investigator)Fate Therapeutics (Scientific Research Study Investigator)Incyte (Consultant, Scientific Research Study Investigator)Kite Therapeutics (Consultant)Novartis (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)Omeros (Consultant, Grant/Research Support)PACT Pharma (Consultant) Seung Hyun Moon, MD, MPA, AlloVir (Employee, Shareholder) Aastha Chandak, PhD, AlloVir (Independent Contractor) Zhiji Zhang, MS, AlloVir (Independent Contractor) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)

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382. Vitamin D Supplementation and Covid 19: Results from the U.S. N3C Data Enclave

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.583 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S293-S293

Author(s):

Kim Murray ◽

Kathleen M Fairfield ◽

Clifford james Rosen ◽

Sally L Hodder ◽

Jeremy Harper

Keyword(s):

Vitamin D ◽

Viral Infections ◽

Panel Member ◽

Vitamin D Supplementation ◽

Research Support ◽

Review Panel ◽

Co Morbidity ◽

Vitamin D Supplements ◽

Morbidity Index ◽

The U.S

Abstract Background It is estimated that 18% of adults in the U.S. take Vitamin D supplements. Some observational studies suggest that vitamin D supplementation activates the innate immune system and reduces the incidence and severity of viral infections. During the SARS-CoV-2 pandemic, vitamin D supplements were touted as a potential therapy to prevent the disease and/or complications. However, supportive evidence is lacking. Methods The National COVID Cohort Collaborative (N3C) enclave is the largest COVID-19 data base with nearly 1.4 million positive patients at 56 sites in the U.S. We performed a retrospective analysis of vitamin D supplementation, either prescribed before or during hospitalization for SARS-CoV-2. Results 137,399 people took vitamin D supplements out of 1.4 million. Females prescribed vitamin D outnumbered males by almost 2:1, whereas in non-users there were no sex differences. Most supplement users were older than 50. African Americans constituted 13% of the non-users, but 23% of those prescribed vitamin D. Infected individuals with any vitamin D supplementation, pre-Covid, post-Covid or both, had a 6.66% mortality rate vs 2% mortality in non-users. Similarly, nearly a third of the supplement users were hospitalized compared to 11% in the non-users. The Charlson Co-Morbidity Index was 3.0±3 (SD) in users vs 1.0±2 (SD) in non-users. Conclusion 10% of SARS-CoV-2 infected patients were taking vitamin D. They tended to be older, more likely to be African American and have significant co-morbidities. Hospitalization and mortality were higher among those taking Vitamin D in this cohort. Vitamin D is widely used to prevent and treat SARS-CoV-2 but without evidence of efficacy. Disclosures Sally L. Hodder, M.D., Gilead (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member)

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Current Status of a Medical Information System

Methods of Information in Medicine ◽

10.1055/s-0038-1636005 ◽

1970 ◽

Vol 09 (03) ◽

pp. 149-160 ◽

Cited By ~ 1

Author(s):

E. Van Brunt ◽

L. S. Davis ◽

J. F. Terdiman ◽

S. Singer ◽

E. Besag ◽

...

Keyword(s):

Information System ◽

Medical Records ◽

Medical Information ◽

Clinical Laboratory ◽

Development Program ◽

Medical Data ◽

Direct Access ◽

Medical Information System ◽

Current Status ◽

Central System

A pilot medical information system is being implemented and currently is providing services for limited categories of patient data. In one year, physicians’ diagnoses for 500,000 office visits, 300,000 drug prescriptions for outpatients, one million clinical laboratory tests, and 60,000 multiphasic screening examinations are being stored in and retrieved from integrated, direct access, patient computer medical records.This medical information system is a part of a long-term research and development program. Its major objective is the development of a multifacility computer-based system which will support eventually the medical data requirements of a population of one million persons and one thousand physicians. The strategy employed provides for modular development. The central system, the computer-stored medical records which are therein maintained, and a satellite pilot medical data system in one medical facility are described.

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1066. Immune Escape Mutant Detection Using Commercially Available Methods for Hepatitis B Surface Antigen Serological Testing

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1252 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S562-S562

Author(s):

Robert Gish ◽

Vincent Streva

Keyword(s):

Hepatitis B ◽

Immune Escape ◽

Hepatitis B Surface Antigen ◽

Panel Member ◽

The United States ◽

Hbv Infection ◽

Hepatitis B Vaccination ◽

Review Panel ◽

B Virus ◽

Escape Mutants

Abstract Background Although overall infection rates of Hepatitis B virus (HBV) in the United States (US) remain stable, as many as 2.2 million persons are still chronically infected with Hepatitis B Virus (HBV)1. Persons who inject drugs (PWID) are at a higher risk of HBV infection and since 2009 three states (KY, TN, WV) have reported up to a 114% increase in cases of acute HBV infection due to higher infection rates among a non-Hispanic white populations (30–39 years), and injection drug users2. Hepatitis B vaccination is recommended as primary prevention for adults who are at increased risk for HBV infection, including PWID. However, data from the National Health Interview Survey indicate that hepatitis B vaccination coverage is low among adults in the general population3, and it is likely to be lower among injection drug users. Hepatitis B Surface Antigen (HBsAg) is the first serological marker to appear after HBV exposure and infection; this marker is included in the recommended panel for acute hepatitis diagnosis and accurate detection is necessary for early and accurate diagnosis. Serological testing challenges exist for HBsAg due to the high degree of genetic variability which can further be exacerbated by endogenous and exogenous pressures. The immuno-dominant region may have one or more mutations described as immune escape mutations which can decrease or abrogate HBsAg binding to antibodies used in immunoassays. Although the prevalence of these mutations is not well documented in the United States, international studies have shown that up to 79% of HBV-reactivated patients (vs 3.1% of control patients; p< 0.001) carry HBsAg mutations localized in immune-active HBsAg regions4. Methods A study was conducted using a panel of 10 unique recombinant HBsAg immune escape mutants. Panel members were tested by commercially available HBsAg serological immunoassays. Results It was found that although commercially available HBsAg immunoassays are the primary diagnostic tool for HBV diagnosis, not all HBsAg immune escape mutants are detected, with some method detecting as few as 5 out of 10 of these mutant samples. Figure 1 Conclusion Improvement is needed in commercially available methods for the accurate detection of HBsAg. Disclosures Robert Gish, MD, Abbott (Consultant)AbbVie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Access Biologicals (Consultant)Antios (Consultant)Arrowhead (Consultant)Bayer (Consultant, Speaker’s Bureau)Bristol Myers (Consultant, Speaker’s Bureau)Dova (Consultant, Speaker’s Bureau)Dynavax (Consultant)Eiger (Consultant, Advisor or Review Panel member)Eisai (Consultant, Speaker’s Bureau)Enyo (Consultant)eStudySite (Consultant, Advisor or Review Panel member)Exelixis (Consultant)Fujifilm/Wako (Consultant)Genentech (Consultant)Genlantis (Consultant)Gilead (Consultant, Advisor or Review Panel member, Speaker’s Bureau)GLG (Consultant)HepaTX (Consultant, Advisor or Review Panel member)HepQuant (Consultant, Advisor or Review Panel member)Intercept (Consultant, Speaker’s Bureau)Ionis (Consultant)Janssen (Consultant)Laboratory for Advanced Medicine (Consultant)Lilly (Consultant)Merck (Consultant)Salix (Consultant, Speaker’s Bureau)Shionogi (Consultant, Speaker’s Bureau)Viking (Consultant)

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1157. Clinical Safety, Efficacy, and Pharmacokinetics of Fosmanogepix, a Novel First-in-class Antifungal, in Patients with Renal Insufficiency: Subset Analysis from a Phase 2 Candidemia Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

Abstract Background Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, and broad-spectrum activity against yeasts and molds, including fungi resistant to other antifungal agents. Patients with candidemia often have underlying renal insufficiency or are receiving medications that affect renal function. This analysis evaluated outcomes in patients with varying degrees of renal insufficiency. Methods This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp within 96 hrs prior to study entry with ≤ 2 days of prior antifungal treatment were eligible, including those with renal insufficiency. Patients with neutropenia, C. krusei infection, deep-seated Candida infections or receiving hemodialysis were excluded. Subjects were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Patients requiring antifungal treatment beyond 14 days received fluconazole. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee. Successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment. Results 14/21 (66%) subjects had some degree of renal insufficiency: 7 had mild renal insufficiency (GFR:60-89), 5 had moderate renal insufficiency (GFR:30-59), and 2 had severe renal insufficiency (GFR:15-29). 12/14 (86%) completed study treatment, and treatment was successful at EOST in 12/14 (86%) subjects. Decline in renal function was not observed at EOST. 4 had worsening of renal function during the follow-up period; none required dialysis. Renal impairment did not increase exposure of FMGX. There were no treatment-related adverse events. Conclusion FMGX demonstrated high level treatment success with no evidence of drug-related nephrotoxicity, with no dose adjustments required. These preliminary data support the continued evaluation of FMGX in patients with candidemia and renal dysfunction as an alternative to potentially nephrotoxic antifungal agents. Disclosures Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

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1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1788 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S798-S799

Author(s):

Nicolo Cabrera ◽

Truc T Tran ◽

Travis J Carlson ◽

Faris Alnezary ◽

William R Miller ◽

...

Keyword(s):

Research Study ◽

Clinical Success ◽

Significant Proportion ◽

Scientific Research ◽

Panel Member ◽

Multidrug Resistant ◽

Outcome Data ◽

Research Support ◽

Gram Negative ◽

Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

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