bluuebunny/crossref_metadata_2025 huggingface dataset:
89. Efficacy and Tolerability of Voriconazole (VOR) vs. Isavuconazole (ISA) Prophylaxis (px) in Preventing Invasive Fungal Infections (IFI) in Lung Transplant Recipients (LTR)
Authors: Samanta Palash , Marini Rachel V , McCreary Erin K , Shields Ryan K , Falcione Bonnie A , Alex Viehman J , Sacha Lauren , Rivosecchi Ryan , Jeong Kwak Eun , Silveira Fernanda P , Clarke Lloyd , Clancy Cornelius J , Nguyen Minh-Hong
Published: October 2019

Background

IFI is a significant complication following lung transplant (LT). VOR was universal antifungal px in our LT program from 2004 to October 2015, at which time px was changed to ISA. We compared the efficacy and tolerability of VOR vs. ISA px in LTR.

Methods

We reviewed all LTR from September 2013 to February 2018 who received VOR or ISA Px. The standard duration of px was 3 or 4 months following basiliximab and alemtuzumab induction, respectively. All patients were followed for ≥1 years post-Tx. IFI was defined by revised EORTC/MSG criteria.

Results

In total, 310 LTR were included, 149 and 161 of whom received ISA and VOR px, respectively. There was no difference in demographics, underlying diseases, single vs. double LT, or induction therapy (alemtuzumab vs. basiliximab) between the 2 groups. At 1-year after LT, 9% (14) and 8% (13) of patients in ISA and VOR groups developed IFI, respectively (P = 0.5). 5% (7) and 3% (5) of patients developed breakthrough (BT) IFI during ISA and VOR px, respectively (P = 0.6; Figure 1, P = 0.4, Kaplan-–Meier). ISA BT included pneumonia (PNA, 2), endobronchial IFI (2), mediastinitis (1), chest wall IFI (1), and candidemia (1). ISA BT patients were infected with Aspergillus fumigatus (3; 2 with ISA MIC = 0.5 µg/mL, 1 MIC = 1 µg/mL), black mould (1), and yeasts (3; 2 C. glabrata, 1 C. albicans). VOR BT IFI included PNA (2), endobronchial IFI (1), empyema (1), and chest wall IFI (1). VOR BT IFIs were due to A. ustus, A. niger, A. lentulus, black mould, and Rhizopus spp (1 each). All Aspergillus VOR BT isolates exhibited VOR MIC ≥2 µg/mL. Patients with IFI were more likely to have positive pre-LT respiratory fungal culture (P = 0.01) and grade ≥3 ischemic reperfusion injury (IRI) post-LT (P = 0.01). VOR and ISA were prematurely discontinued in 53% (85) and 14% (21) of patients due to adverse events, respectively (P < 0.0001). Hepatotoxicity was more common with VOR (22%, 35) than ISA (5%, 7) (P < 0.0001). IFI was an independent risk factor for death at 1 year (Figure 2, P < 0.0001, Kaplan–Meier).

Conclusion

ISA was as effective as VOR in preventing IFI in LTR, and significantly better tolerated. Pre-LT fungal culture positivity and grade ≥3 IRI post-LT were risk factors for the development of IFI. IFI within 1-year post-LT had a significant impact on mortality

Disclosures

Fernanda P. Silveira, MD, MS, FIDSA, Ansun: Grant/Research Support; Qiagen: Grant/Research Support; Shire: Grant/Research Support; Whiscon: Grant/Research Support.
91. Differential Impact of Cytomegalovirus (CMV) Donor (D) Serostatus on Rates and Kinetics of CMV Viremia among CMV Seropositive Recipients (R+) of Ex vivo T-cell Depleted (TCD) and Unmodified (CONV) Hematopoietic Cell Transplants (HCT)
Authors: Stern Anat , Su Yiqi , Fang Jiaqi , Perales Miguel , Maloy Molly , Giralt Sergio , Papanicolaou Genovefa
Published: October 2019

Background

In unmodified (CONV) HCT, CMV donor seropositivity (D+) conveys partial protection against CMV disease mediated by the transfer of donor CMV T-cell immunity through the allograft. Ex vivo T-cell depletion by CD34 selection affords a stringent depletion of donor T cells, thus transfer of donor T-cell immunity to CMV would be negligible. We evaluate the impact of CMV D serostatus on rates and kinetics of CMV viremia by Day (D)100 post-HCT in a contemporary cohort of CONV and TCD recipients from a single center.

Methods

A retrospective cohort study of R+ adult recipients of first peripheral blood or marrow HCT for hematologic malignancies (excluding multiple myeloma) from June 2010 to December 2017 at MSKCC. Routine CMV monitoring by a quantitative PCR assay occurred weekly from D14 through D100. Patients were treated preemptively. CMV viral burden was assessed as the time-averaged area under the viremia curve over 100 days from HCT (AAUC) calculated as the sum of the area of trapezoids of AUC viral loads divided by the number of weeks of follow-up viremia. The median AAUC for all patients with CMV reactivation (AAUC50) was used to classify patients as CMV controllers (AAUC ≤ AAUC50) or noncontrollers (AAUC >AAUC50).

Results

Of 509 R+, 290 (57%) patients received CONV and 219 (43%) TCD HCT; from 300 (59%) D+ and 209 (41%) D− donors. In CONV, CMV viremia occurred with similar frequency in D+ (65%) and D− (62%), P = 0.6. In contrast, in TCD, CMV viremia occurred more frequently in D+ compared with D− (83% vs. 71%, P = 0.03). Among CONV, D+ was associated with lower CMV burden (median AAUC) compared with D− (0.791 vs. 1.13, respectively, P = 0.0004). In contrast, in TCD, AAUC was similar between D− and D+ (1.19 vs. 1.35; P = 0.86). Among CONV with CMV viremia, D− were more likely to be noncontrollers compared with D+ (56% vs. 31%, respectively, P = 0.001). In contrast, among TCD with CMV viremia the proportion of noncontrollers was similar between D− and D+ (61% vs. 60%, respectively; P = 1).

Conclusion

Donor CMV serostatus has a differential effect on rates and kinetics of CMV viremia in R+ TCD and CONV HCT recipients. D+ is associated with less CMV viremia and less CMV burden in CONV but not in TCD. Our findings, if confirmed, have implications for donor selection algorithms.

Disclosures

All Authors: No reported Disclosures.
93. Trends in the Laboratory Detection of Rotavirus Before and After Implementation of Routine Rotavirus Vaccination: the United States, 2000–2018
Authors: Hallowell Benjamin D , Parashar Umesh D , Curns Aaron , DeGroote Nicholas , Tate Jacqueline
Published: October 2019

Background

Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection was the leading cause of severe gastroenteritis among US children.

Methods

To evaluate the long-term impact of rotavirus vaccination on disease burden in the United States, CDC analyzed national laboratory testing data for rotavirus from laboratories participating in CDC’s National Respiratory and Enteric Viruses Surveillance System (NREVSS) during the pre- (2000–2006) and post-vaccine (2007–2018) periods.

Results

Nationally, the median annual percentage of positive rotavirus tests declined from 25.6% (range: 25.2–29.4%) in the pre-vaccine era to 6.1% (range: 2.6–11.1%) in the post-vaccine period. When comparing the pre- and post-vaccine era, the annual peak in rotavirus positivity declined from a median of 43.1% (range: 43.8–56.3%) to a median 14.0% (range: 4.8–27.3%) while the season duration was reduced from a median of 26 weeks (range: 23–27 weeks) to 9 weeks (range: 0–18 weeks). In the post-vaccine period, a biennial pattern emerged with alternating years of low and high rotavirus activity.

Conclusion

The implementation of rotavirus vaccine has dramatically reduced the disease burden and altered seasonal patterns of rotavirus in the United States; these changes have been sustained over 11 post-vaccine introduction seasons.

Disclosures

All Authors: No reported Disclosures.
94. Pneumonia Severity Scores Poorly Predict Severe Outcomes Among Adults Hospitalized with Influenza
Authors: Doyle Joshua , Garg Shikha , O’Halloran Alissa , Beacham Lauren , Cummings Charisse N , Herlihy Rachel , Yousey-Hindes Kim , Anderson Evan J , Monroe Maya , Kim Sue , Lynfield Ruth , Irizarry Lourdes , Spina Nancy , Bennett Nancy M , Hill Mary , Reed Carrie , Schaffner William , Talbot Keipp , Self Wesley , Williams Derek
Published: October 2019

Background

Influenza can lead to severe outcomes among adults hospitalized with influenza, and causes substantial annual morbidity and mortality. We evaluated the performance of validated pneumonia severity indices in predicting severe influenza-associated outcomes.

Methods

We conducted a multicenter study within CDC’s Influenza Hospitalization Surveillance Network (FluSurv-NET) which included adults (≥ 18 years) hospitalized with laboratory-confirmed influenza during the 2017–18 influenza season. Medical charts were abstracted to obtain data on vital signs and laboratory values at admission on a stratified random sample of cases at a subset of hospitals at 11 network sites. Estimates were weighted to reflect the probability of selection. Cases were assigned to low- and high-risk groups based on the CURB-65 (‘Confusion, Urea, Respiratory rate, Blood pressure, Age ≥65’) index (high-risk cutoff = score ≥ 3), and the Pneumonia Severity Index (PSI) (high-risk cutoff = category V). We calculated area under receiver operating characteristic curves (AUROC), sensitivity, and specificity to estimate the performance of each index in predicting severe outcome categories: (1) intensive care unit (ICU) admission, 2) noninvasive mechanical ventilation (NIMV), (3) mechanical ventilation (MV), vasopressors, extracorporeal membrane oxygenation (ECMO) and (4) death.

Results

Among 27,523 adults hospitalized with influenza, 8665 (31%) were sampled for inclusion in this analysis; median age was 70 years and 92% had ≥ 1 chronic condition. A total of 1,366 (16%) were classified as high-risk by CURB-65 and 1,249 (14%) by PSI. Both indices had low discrimination for severe outcomes; the AUROC for CURB-65 ranged from 0.55 for ICU admission to 0.65 for death, and for PSI ranged from 0.58 for ICU admission to 0.73 for death. Risk status by CURB-65 was less sensitive than PSI in predicting MV, vasopressor, or ECMO usage as well as death (figure). The specificity of CURB-65 and PSI was similar against all outcomes (figure).

Conclusion

The CURB-65 and PSI indices performed poorly in predicting severe outcomes other than death; PSI had the best discrimination overall. Alternative approaches are needed to predict severe influenza-related outcomes and optimize clinical care.

Disclosures

All Authors: No reported Disclosures.
95. Impact of Influenza-Like Illnesses on Academic and Work Performance on a College Campus
Authors: Emanuels Anne , Brandstetter Elisabeth , Newman Kira L , Wolf Caitlin , Logue Jennifer , Englund Janet A , Boeckh Michael , Chu Helen Y
Published: October 2019

Background

Influenza-like illnesses are estimated to cause 500,000 hospitalizations and 50,000 deaths each year in the United States. The high-contact environment of a college campus makes students, faculty, and staff especially prone to respiratory illness, but the impact of these illnesses on academic and work performance is not well understood.

Methods

Between January 14 and April 3, 2019, the Seattle Flu Study enrolled participants with respiratory symptoms throughout the Seattle metropolitan area, including the University of Washington’s main campus. Individuals with at least two self-reported respiratory symptoms in the previous 7 days were eligible to enroll. Participants completed a questionnaire with questions about their medical history, current illness episode, and other behavioral characteristics; a corresponding mid-nasal swab was also collected. Influenza-like illness (ILI) was defined as self-reported fever with a cough and/or sore throat. Laboratory results are pending. Logistic regression was used to assess the association between ILI and work and academic outcomes, including missing class, missing work, performing poorly on an assignment or examination, and experiencing high interference on daily life.

Results

A total of 497 participants enrolled at the University of Washington. Participants had a median age of 22, and 61% were female. Of those with self-reported ILI, 27% reported smoking, 22% had traveled out of state, and 14% had traveled internationally in the month before enrollment. These characteristics did not differ between those with ILI and those with non-ILI. Having symptoms of ILI was associated with reports of missing work (OR 2.9; 95% CI: 1.9, 4.5), missing class (OR 3.4; 95% CI: 2.3, 5.2), performing poorly on assignments and exams (OR 1.8; 95% CI: 1.2, 2.6), and having high interference with daily life (OR 6.0; 95% CI: 3.8, 9.5) as compared with individuals with a non-ILI illness. These impacts were strongest during January and February.

Conclusion

A high prevalence of ILI was observed on campus. These symptoms were found to have a substantial impact on academic and occupational productivity. This demonstrates the need for greater illness prevention efforts on college campuses during influenza season.

Disclosures

All Authors: No reported Disclosures.
837. Prior Hospitalizations Among Cases of Community-Associated Clostridioides difficile Infection—10 US States, 2014–2015
Authors: Hatfield Kelly M , Baggs James , Winston Lisa Gail , Parker Erin , Johnston Helen , Brousseau Geoff , Olson Danyel M , Fridkin Scott , Wilson Lucy , Perlmuter Rebecca , Holzbauer Stacy , Phipps Erin C , Hancock Emily B , Dumyati Ghinwa , Ocampo Valerie , Kainer Marion A , Korhonen Lauren C , Jernigan John A , McDonald L Clifford , Guh Alice
Published: October 2019

Background

Despite overall progress in preventing Clostridioides difficile Infection (CDI), community-associated (CA) infections have been steadily increasing. Although the incubation period of CDI is thought to be relatively short, gastrointestinal microbial disruption from remote healthcare exposures (e.g., inpatient antibiotic use) may be associated with CA-CDI. To assess this potential association, we linked CA-CDI infections identified through CDC’s Emerging Infections Program (EIP) to Medicare claims data to describe prior healthcare utilization.

Methods

We defined an EIP CA-CDI case as a positive C. difficile test collected in 2014–2015 from an outpatient or inpatient within 3 days of hospital admission, provided there was no positive test in the prior 8 weeks and no admission to a healthcare facility in the prior 12 weeks. We linked EIP CA-CDI cases aged ≥65 years to a Medicare beneficiary using unique combinations of birthdate, sex, and zip code. Cases were included if they maintained continuous fee-for-service coverage for 1 year prior to the event date. To calculate exposure odds ratios for previous hospitalizations, each case was matched to 5 control beneficiaries on age, sex, and county of residence. We used logistic regression to calculate adjusted matched odds ratios (amOR) that controlled for chronic conditions.

Results

We successfully linked 2,287/3,367 (68%) EIP CA-CDI cases. Of these, 1,236 cases met inclusion criteria; the median age was 77 years and 63% were female. We identified 69 (5.6%) cases with misclassification of prior healthcare exposures, most of whom (48, 70%) were hospitalized in the 12 weeks prior to their event. Among the 1,167 true CA-CDI cases, 33% were hospitalized in the prior 12 weeks to 1 year. The median number of weeks from prior hospitalization to CDI was 27 (IQR 18–38, Figure 1). Cases had a higher risk of hospitalization than matched controls in the prior 3–6 months (amOR: 2.33, 95% CI: 1.87, 2.90) and 6–12 months (amOR: 1.43 95% CI: 1.18, 1.74).

Conclusion

Remote hospitalization in the previous year was a significant risk factor for CA-CDI, especially in the 3–6 months prior to CA-CDI. Long-lasting prevention strategies implemented at hospital discharge and enhanced inpatient antibiotic stewardship may prevent CA-CDI among older adults.

Disclosures

All Authors: No reported Disclosures.
838. Oral Vancomycin Prophylaxis Works!
Authors: Van Hise Nicholas W , Hines David , Didwania Vishal , Beezhold David , Chundi Vishnu , Fliegelman Robert , Han Alice , Van Hise Allyssa , Chundi Vaishali , Manian Farrin , Petrak Russell M
Published: October 2019

Background

Clostridium difficile infections (CDI) cause approximately 500,000 cases a year with an estimated cost that exceeds $4.8 billion. Despite interventions that addressed environmental disinfection, antibiotic stewardship, and infection control, many institutions continue to have a significant burden of disease. Public reporting and “pay for performance” have increased the impetus for better control of CDI. We describe the use of an unpublished scoring system to assess the risk of CDI with subsequent use of OVP to prevent exsporulation and infection in high-risk groups.

Methods

A large urban hospital in the Chicago area of approximately 400 beds, after following recommended guidelines for prevention of C. difficile, instituted an assessment tool to predict the risk of developing C. difficile infection.This is an observational, cohort study reviewing the pre- and post-implementation of OVP (oral Vancomycin prophylaxis) in hospitalized patients. From January 2017 to December 2017, eligible patients were assessed for risk of C. difficile. The intervention period, from January 2018 to December 2018, we prospectively gave eligible patients oral vancomycin (OVP) 125 mg twice daily if the risk score was 13 or above. No changes in environmental cleaning, antimicrobial stewardship, or restriction of testing were instituted during the periods of enrollment. The analysis was approved by the institutional review board.

Results

In 2017, 82 patients had a score of 13 or over. Of the 82 patients, 72 (87.8%) developed CDI. In 2018, 62 eligible patients had a score of 13 or over and were given OVP. Of the 62 patients, 5 (8%) developed CDI. The relative risk comparing C. difficile in ≥13 vs. <13 patients (RR = 19.2652; 95% CI = 7.3656, 50.3899). The tool is associated with a specificity of 88.54% and sensitivity of 94.67%, along with a negative predictive value of 95.51% and positive predictive value of 86.59%. Fisher’s exact test was performed between OVP and no OVP in relation to the development of CDI in high-risk patients (P < 0.01). VRE rates reported on the antibiogram remained consistent throughout the study period. No significant differences in baseline characteristics were noted.

Conclusion

In institutions where appropriate infection control measures and antibiotic stewardship have been implemented, the use of a prediction tool to guide OVP is effective in preventing C. difficile.

Disclosures

All Authors: No reported Disclosures.
839. Effect of Clostridioides difficile (C. difficile) Toxin Test Reporting on Clinical Treatment and Outcomes of Toxin-Negative PCR-Positive Patients at Five California Hospitals
Authors: Polage Christopher R , Grein Jonathan , Morgan Margie , Doernberg Sarah B , Miller Steve , Chinn Raymond , Woerle Cathy , Yim Jennifer , Bittencourt Cassiana , Krishna Sneha , Anne Ocampo Nicolle , Gibbs Laurel , Mabalot Shannon C , Quan Kathleen A , Khusbu Usme , Madey Keith M , Ganzon Czarina , Memar Fatemeh , Pascual Christian B , Cohen Stuart , Liu Catherine , Yokoe Deborah S , Huang Susan S
Published: October 2019

Background

Guidelines support the use of toxin tests after C. difficile antigen detection or nucleic acid amplification tests (e.g., PCR) to help clinicians distinguish colonization from infection and reduce overdiagnosis but the safety of toxin-based diagnostic approaches remains controversial.

Methods

Five California hospitals monitored hospitalized adults with C. difficile testing before and after operational changes to reduce test-related overdiagnosis (2016–2018). Four added a toxin test to an existing GDH antigen/PCR-based approach and/or changed reporting to encourage the use of toxin results for clinical decision-making (i.e.,“toxin-dominant reporting”). One used the same test (toxin only) and reporting strategy throughout. All used a standardized tool to document clinical outcomes and treatment four days after testing (i.e., Day 5).

Results

In total, 1,034 patients had a Day 5 assessment with PCR-dominant reporting (pre-operational changes); 2,511 patients had a Day 5 assessment with toxin-dominant reporting (post-operational changes and single facility with no test change). Fewer Toxin-negative/PCR-positive (Toxin−/PCR+) patients received treatment with toxin-dominant reporting (median change: −52.1% [interquartile range (IQR): −35.1%, −69.1%]; aggregate P < 0.001). Day 5 outcomes were similar or better with toxin-dominant reporting despite less treatment. Patient discharge rates and in hospital diarrheal recovery was greater in the subset of Toxin−/PCR+ patients during the toxin-dominant reporting period: median discharge rate change = 8.8% [IQR: 1.5%, 11.9%] (aggregate P = 0.04); median diarrheal recovery rate change = 11.8% [IQR: 8.8%, 18.2%] (aggregate P = 0.018).

Conclusion

In a 5-center study, toxin-dominant test result reporting decreased anti-C. difficile treatment and improved discharge rates and diarrheal recovery in Toxin−/PCR+ patients. More work is needed to determine the rate of C. difficile-related adverse events in Toxin−/PCR+ patients.

Disclosures

All Authors: No reported Disclosures.
847. The Effect of Antimicrobial Administration on Blood Culture Positivity in Patients with Severe Manifestations of Sepsis
Authors: Cheng Matthew P , Stenstrom Robert , Paquette Katryn , Stabler Sarah , Akhter Murtaza , Davidson Adam , Gavric Marko , Lawandi Alexander , Jinah Rehman , Saheed Zahid , Demir Koray , Huang Kelly , Mahpour Amirali , Shamatutu Chris , Caya Chelsea , Troquet Jean-Marc , Clark Greg , Yansouni Cedric , Sweet David
Published: October 2019

Background

Current guidelines recommend obtaining blood cultures prior to antimicrobial therapy in patients with sepsis. Administering antimicrobials immediately without waiting for blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear the degree to which this strategy impacts diagnostic yield.

Methods

We performed a patient-level, single-arm, diagnostic trial. Seven urban emergency departments affiliated with academic medical centers across Canada and the United States participated in the study. Adults ≥18 years of age presenting to the emergency department with evidence of severe manifestations of sepsis, including a systolic blood pressure <90 mmHg and/or a serum lactate ≥4 mmol/L were included. Study participants had 2 sets of blood cultures drawn prior to and immediately following antimicrobial administration. The primary outcome was the difference in blood culture pathogen recovery rates before and after administration of antimicrobial therapy.

Results

Of the 3,164 participants screened, 325 were included in the study (mean age, 65.6 years; 63.0% men) and had repeat blood cultures drawn after the initiation of antimicrobial therapy (median time of 70 minutes, IQR 50 to 110 minutes). Pre-antimicrobial blood cultures were positive for one or more microbial pathogens in 102/325 (31.4%) patients. Fifty-four participants (52.9%) had matching blood culture results after initiation of antimicrobial treatment. The absolute difference in pathogen recovery rates was 14.5% ([95% CI 8.0 to 21.0%]; P < 0.0001) between pre- and post-antimicrobial blood cultures. Results were consistent in an analysis of the per-protocol population (absolute difference, 13.3% [95% CI 6.1 to 20.4%]; P < 0.0001). Including the results of other microbiological cultures done as part of routine care, microbial pathogens were recovered in 69 of 102 (67.7%) participants (absolute difference, 10.2% [95% CI 3.4 to 16.8%]; P < 0.0001).

Conclusion

Among patients with severe manifestations of sepsis, the administration of empiric antimicrobial therapy significantly reduces the yield of pathogen recovery when blood cultures are drawn shortly after treatment initiation.

Disclosures

All Authors: No reported Disclosures.
887. High Rates of Virologic Suppression Achieved in HIV-1–Infected Adults Rapidly Starting Antiretroviral Therapy (ART) with the Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) 800/150/200/10 mg Regardless of Baseline Disease Characteristics: Week 48 Subgroup Analyses From the Phase 3 DIAMOND Trial
Authors: Huhn Gregory D , Ramgopal Moti , Crofoot Gordon , Gathe Joseph , Seyedkazemi Sareh , Cosler Patricia , Bruce Simonson Richard , Luo Donghan , Dunn Keith
Published: October 2019

Background

Rapid initiation of ART requires that clinicians start therapy prior to having baseline laboratory Results. High rates of virologic suppression and retention were reported in the DIAMOND trial. Efficacy and safety are presented, according to baseline disease characteristics.

Methods

DIAMOND (ClinicalTrials.gov: NCT03227861), a phase 3, single-arm, open-label, prospective, multicenter study, assessed efficacy/safety of D/C/F/TAF in rapid initiation. Adults enrolled within 14 days of diagnosis and started D/C/F/TAF without baseline laboratory results; investigators reviewed results as they became available. Primary endpoint was virologic suppression (HIV-1 RNA < 50 copies[c]/mL; intent-to-treat (ITT); Food and Drug Administration [FDA] snapshot) at Week 48. Virologic suppression <50 c/mL and <200 c/mL were also assessed via an observed analysis, excluding patients with missing data.

Results

Overall, 109 patients were enrolled; 25% had HIV-1 RNA ≥100,000 c/mL and 21% had CD4+ < 200 cells/μL (Table 1). 21% of patients started therapy within 24 hours of diagnosis. At Week 48, 84%, and 88% of patients had HIV-1 RNA <50 c/mL and <200 c/mL (FDA snapshot), respectively. In the observed analysis, 96% and 100% of patients had HIV-1 RNA <50 c/mL and <200 c/mL, respectively, at Week 48. Earlier ART initiation, HIV-1 RNA <100,000 c/mL, and CD4+ >200 cells/μLwere associated with numerically higher virologic suppression rates (ITT-FDA snapshot; Table 2). No patient discontinued due to lack of efficacy or met protocol-defined virologic failure (PDVF) criteria. In the observed analysis, virologic suppression rates were consistent across all subgroups; all patients were suppressed <200 c/mL at Week 48. One patient discontinued due to an adverse event (AE); incidences of grade 3/4 (10%) and serious (9%) AEs were low, with no serious AEs related to study drug and no deaths.

Conclusion

In the first phase 3 study of an STR in a rapid initiation model, no patients rapidly starting D/C/F/TAF discontinued therapy due to lack of efficacy or had PDVF through 48 weeks. High rates of virologic suppression were achieved and maintained with a variety of baseline characteristics, and treatment was safe and well tolerated, indicating D/C/F/TAF as a preferred ART option for patients rapidly starting treatment.

Disclosures

All Authors: No reported Disclosures.
896. A Safe, More Cost-Effective Protocol: Universal Decolonization vs. MRSA Screening and Contact Precautions
Authors: Whitaker Jacqueline , Kusha Barmak , Longcoy Joshua , Rutter Amanda H , Ferrier Sheryl , Marzi Caitlin R , Montalvo Gonzalez Leslie
Published: October 2019

Background

A trial of universal decolonization (alcohol-based nasal antiseptic plus chlorhexidine gluconate bathing) was instituted for 12 months, in a 536-bed short-term acute care hospital, as a replacement for nasal screening, contact precautions (CP) and decolonization of methicillin-resistant Staphylococcus aureus (MRSA)-colonized patients. The impact on the rate of MRSA bacteremia and costs associated with nasal screening tests, isolation, and gown use was assessed.

Methods

Prior to the universal decolonization trial, patients at high-risk for MRSA colonization were screened using a nasal polymerase chain reaction (PCR) test, and those that tested positive were decolonized with 5 days of mupirocin nasal ointment and daily CHG bathing, and were placed in CP. Starting in April 2018, a universal decolonization protocol was instituted for all hospitalized patients, with a twice-daily alcohol-based nasal antiseptic (in place of mupirocin), and daily bathing with CHG foam soap (in place of CHG cloths). Nasal screening of high-risk patients, targeted decolonization and CP for MRSA-colonized patients, was discontinued during the 12-month universal decolonization trial period. Outcome measures for the trial included MRSA bacteremia per National Healthcare Surveillance Network (NHSN) multi-drug-resistant organism (MDRO) Lab ID definition, isolation day count, utilization of gowns, and nasal screening tests with estimated costs associated. Measures for the 12-month trial period were compared with those of the prior 12-month period, i.e., April 2017–March 2018.

Results

Compared with prior 12-month period, during the universal decolonization trial, there was a 42% reduction in isolation days ($118/day), a 74% reduction in nasal PCR tests ($36/each), and an 11% decrease in the monthly use of gowns ($12/each). The total cost avoidance (after accounting for the cost of the alcohol-based nasal antiseptic and CHG soap) was $1,394,685. There was no statistical change in the MRSA bacteremia rate (0.067 to 0.070) per 1,000 patient-days.

Conclusion

Replacement of nasal screening, decolonization, and CP for colonized MRSA patients with universal decolonization, using twice daily alcohol-based nasal antiseptic paired with daily CHG bathing, was found to be a safe and cost-saving protocol.

Disclosures

All Authors: No reported Disclosures.
963. Extragenital Chlamydia and Gonorrhea Among Females Visiting an STD Clinic
Authors: Maynard Michaela , Nunez Hector R , Tao Jun , Montgomery Madeline , Almonte Alexi , Sowemimo-Coker Genoviva , Chu Christina , Sosnowy Collette , Chan Philip , Chan Philip
Published: October 2019

Background

Rates of chlamydia (CT) and gonorrhea (GC) are increasing in the United States. Annual screening for urogenital infection is recommended for sexually active females less than 25 years and older females at risk. CT and GC can be detected at pharyngeal and rectal sites and are commonly asymptomatic. Currently, extragenital screening is only recommended in men who have sex with men (MSM). Data among females on extragenital CT and GC are limited.

Methods

We reviewed all females presenting to a sexually transmitted diseases (STD) clinic in Providence, Rhode Island from May 2014 to December 2018. During this time, urogenital, pharyngeal, and rectal screenings were offered to all females presenting for care. We evaluated demographics, behaviors, and laboratory data on urogenital, pharyngeal and rectal CT/GC. Univariate and bivariate analyses were performed to determine the characteristics of demographic and behavioral variables associated with extragenital infection.

Results

During the study period, 2,672 females presented for STD screening. Median age was 26 years (interquartile range [IQR]: 33–22). Most patients (95%) reported engaging in sex with male partners. More than half (59%) had at least one extragenital (pharyngeal or rectal) test performed (77% pharyngeal only, 0.4% rectal only, 23% both). During the study period, there were 334 CT and 66 GC infections identified across all three anatomical sites. Of individuals with a positive CT result (N = 273), 85% (N = 233) had a positive urogenital, 19% (N = 53) a positive pharyngeal, and 18% (N = 48) a positive rectal specimen. Of individuals with a positive GC result (N = 50), 62% (N = 31) had a positive urogenital, 54% (N = 27) a positive pharyngeal, and 16% (N = 8) a positive rectal specimen. Among individuals with a positive CT or GC result, (N = 315), 17% (N = 55) had an extragenital infection in the absence of a positive urogenital result. No single risk factor was statistically associated with an extragenital CT or GC infection. Most individuals (82%) were asymptomatic at presentation.

Conclusion

In an STD clinic setting, a significant number of pharyngeal and rectal CT/GC infections may be missed in the absence of extragenital screening. Settings which engage at-risk females should consider implementation of routine CT/GC extragenital screening.

Disclosures

All Authors: No reported Disclosures.
967. Concordance of Antibiotic Prescribing with the Proposed American Dental Association Acute Oral Infection Guidelines within Veterans Affairs (VA) Dentistry
Authors: Carlsen Daniel , Suda Katie J , Patel Ursula C , Gibson Gretchen , Jurasic Marianne M , Poggensee Linda , Fitzpatrick Margaret A , Echevarria Kelly , Durkin Michael , McGregor Jessina C , Evans Charlesnika T
Published: October 2019

Background

US dentists prescribe 10% of outpatient antibiotics. However, assessing the appropriateness of dental antibiotic prescribing has been challenging due to a lack of guidelines for common infections. In 2019, the American Dental Association proposed clinical practice guidelines (CPG) on the management of common acute oral infections for the first time. Our objective was to describe national baseline antibiotic prescribing for the treatment of irreversible pulpitis, apical periodontitis, and acute apical abscess prior to the release of the proposed CPG.

Methods

We performed a cross-sectional analysis of national VA data from January 1, 2017 to December 31, 2017. We identified cases of irreversible pulpitis, apical periodontitis, and acute apical abscess using ICD-10-CM codes. Patient demographics, facility location, medical conditions, dental procedure codes (“CDTs”), and diagnostic (ICD-10-CM) codes were extracted from the VA Corporate Data Warehouse. Antibiotics prescribed by a dentist within 7 days of a visit were included. Multivariable logistic regression identified variables associated with antibiotic prescribing for each infection.

Results

Of the 470,039 VA dental visits with oral infections coded, 25% of irreversible pulpitis, 41% of apical periodontitis, and 61% of acute apical abscess visits received antibiotics. Amoxicillin was prescribed most frequently. Although the median days’ supply was 7 days, prolonged use of antibiotics was frequent (9.2% of irreversible pulpitis, 17.8% of apical periodontitis, 28.7% of acute apical abscess received antibiotics for ≥8 days). Of the irreversible pulpitis visits with antibiotics prescribed, 20.0% received ≥2 antibiotics. Patients with high-risk cardiac conditions, prosthetic joints, and certain dental procedures were associated with receipt of antibiotics (table).

Conclusion

Prior to the release of the ADA guidelines, 75.8% and 59.4% of irreversible pulpitis and apical periodontitis were concordant with proposed recommendations. These data identify opportunities to improve prescribing and serve as a benchmark for future outpatient antimicrobial stewardship efforts. Future work should assess definitive dental treatment and populations without access to oral health care.

Disclosures

All Authors: No reported Disclosures.
979. BMI and ASCVD Risk Score Changes in Virologically Suppressed Patients with HIV Switching from TDF to TAF Containing ART
Authors: Schafer Jason J , Sassa Kaitlin , O’Connor Jaclyn , Shimada Ayako , Keith Scott , DeSimone Joseph
Published: October 2019

Background

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) containing antiretroviral therapy (ART) can preserve or improve renal function as well as bone mineral density in patients living with HIV infection (PLWH). The switch can also negatively influence cholesterol, but potential changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown.

Methods

This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PLWH who switched from TDF to TAF without switching any other ART regimen components. Adult patients on TDF for ≥1 year with two consecutive HIV viral loads <200 copies/mL in the year prior to a TAF switch were included. Bodyweight, BMI, cholesterol, ASCVD risk score, and other variables were collected for the year prior to and following the switch. The unadjusted distributions of pre- and post-switch values were compared with the Wilcoxon signed-rank test. Repeated-measures generalized estimating equations were constructed to evaluate changes in BMI and ASCVD risk scores associated with TDF to TAF switches. These were adjusted for predictors retained in the model if their P-values were <0.05. ASCVD risk scores were skewed right, so those data were log-transformed prior to modeling.

Results

A total of 110 patients met the criteria and were included for analysis (Table 1). In unadjusted analyses, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD score in the year after switching from TDF to TAF (each P ≤ 0.01, Table 2). Only gender was retained in the adjusted BMI model, which suggested switching from TDF to TAF lead to an increase of 0.45 kg/m2 in the expected mean for BMI (95% CI: 0.14, 0.76). Age, gender, race, concomitant medications that can cause weight gain, and time since HIV diagnosis were retained as covariates in the adjusted ASCVD model. This model suggested that switching from TDF to TAF was associated with a 13% increase in the expected mean for ASCVD risk score (95% CI: 4%, 23%).

Conclusion

We observed significant increases in BMI and ASCVD risk in PLWH 1 year following a switch from TDF to TAF without changes in other ART regimen components. The mechanism of these metabolic changes is unclear and requires further study.

Disclosures

All Authors: No reported Disclosures.
1827. Genetic Characterization of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates Associated with the Development of Reduced Susceptibility to Vancomycin from Latin America
Authors: Liliana Vargas Ardila Monica , Castro-Cardozo Betsy E , Rios Rafael , Hernandez Angie K , Millan Lina V , Carvajal Lina P , Seas Carlos , Seas Carlos , Munita Jose M , Arias Cesar A , Reyes Jinnethe , Diaz Lorena
Published: October 2019

Background

Vancomycin (VAN) is a first-line therapeutic option for severe MRSA infections, especially in Latin America where other options are limited. However, reduced susceptibility to VAN may lead to therapeutic failures. The molecular mechanisms leading the development of VAN-intermediate S. aureus (VISA) and heterogeneous-VISA (hVISA) phenotypes are still unclear. We explored genetic signatures associated with hVISA phenotype in MRSA isolates recovered from bacteremic patients in 9 Latin American countries (2011–2014) in order to develop a genomic platform to identify these isolates.

Methods

From 538 VAN-susceptible MRSA (MIC90 = 1 µg/mL) we identified 30 hVISA isolates using GRD and macromethod E-tests; from these, 3 were confirmed by PAP-AUC. Whole-genome sequencing was performed in all 30 isolates using Illumina platform. Based on previous studies, we selected 46 genes involved in hVISA development. Multiple Blast alignments were performed using genomes of ATCC29213 and N315 (VAN-susceptible), Mu3 (hVISA) and Mu50 (VISA) as references.

Results

A total of 130 changes in 46 predicted proteins belonging to 8 functional categories were determined: 48 changes related to cell wall biogenesis, 22 to DNA/RNA processing, 17 to regulatory systems, 12 to cofactors and enzymes, 11 to membrane biosynthesis, 9 to virulence, 6 to amino acid metabolism, and 5 to transport of nitrogen and putrescine/spermidine. The most common changes identified in all the hVISA were: Y38H in Atl, N16S in PBP4, S160A in RpoB, L14I in WalK and E156G in YvqF, compared with VSSA strains. The proteins with the highest number of changes detected in the isolates confirmed by PAP-AUC were: CapP, DltA, Pbp4, TcaA, LytM (Cell wall biogenesis); MutL, RpoB (DNA/RNA processing); GraS (Regulatory systems); and PgsA (Membrane biosynthesis).

Conclusion

Changes in genes associated with cell wall biogenesis, DNA/RNA processing, regulatory systems, and membrane biosynthesis were the most prevalent in Latin American hVISA strains. Genetic signatures in genes encoding GraR (N197S), RpoB (H481Y, H481N), VraS (I5N), WalK (L14F, R222K) and MrsR (E146K) are potentially associated with this phenotype. These changes could be used to develop a platform for possible identification of hVISA isolates.

Disclosures

All Authors: No reported Disclosures.
1830. Single-cell Transcriptional Profiling Reveals an Immune Cell State Signature of Bacterial Sepsis
Authors: Reyes Miguel , Bhattacharyya Roby P , Filbin Michael , Billman Kianna , Eisenhaure Thomas , Hung Deborah T , Levy Bruce , Baron Rebecca , Blainey Paul , Goldberg Marcia B , Hacohen Nir
Published: October 2019

Background

Despite intense efforts to understand the immunopathology of sepsis, no clinically reliable diagnostic biomarkers exist. Multiple whole-blood gene expression studies have sought sepsis-associated molecular signatures, but these have not yet resolved immune phenomena at the cellular level. Using single-cell RNA sequencing (scRNA-Seq) to profile peripheral blood mononuclear cells (PBMCs), we identified a novel cellular state enriched in patients with sepsis.

Methods

We performed scRNA-Seq on PBMCs from 26 patients with sepsis and 47 controls at two hospitals (mean age 57.5 years, SD 16.6; 54% male; 82% white), analyzing >200,000 single cells in total on a 10× Genomics platform. We identified immune cell states by stepwise clustering, first to identify the major immune cell types, then clustering each cell type into substates. Substate abundances were compared between cases and controls using the Wilcoxon rank-sum test.

Results

We identified 18 immune cell substates (Figure 1a), including a novel CD14+ monocyte substate (MS1) that is enriched in patients with sepsis (Figure 1b). The fractional abundance of the MS1 substate alone (ROC AUC 0.88) outperformed published bulk transcriptional signatures in identifying sepsis (AUC 0.68–0.82) across our clinical cohorts. Deconvolution of publicly available bulk transcriptional data to infer the abundance of the MS1 substate externally validated its accuracy in predicting sepsis of various etiologies across diverse geographic locations (Figure 1c), matching the best previously identified bulk signatures. Flow cytometry using cell surface markers unique to MS1 confirmed its marked expansion in sepsis, facilitating quantitation and isolation of this substate for further study.

Conclusion

This study demonstrates the utility of scRNA-Seq in discovering disease-associated cytologic signatures in blood and identifies a cell state signature for sepsis in patients with bacterial infections. This novel monocyte substate matched the performance of the best bulk transcriptional signatures in classifying patients as septic, and pointed to a specific cell state for further molecular and functional characterization of sepsis immunopathogenesis.

Disclosures

All Authors: No reported Disclosures.
1833. Measuring Influenza HA Stem-Specific ADCC in Human Sera Using Novel Stabilized Stem Nanoparticle Probes
Authors: Smatti Maria K , Nasrallah Gheyath , Althani Asmaa , Yassine Hadi
Published: October 2019

Background

Generating a vaccine that confers complete protection and overcomes the high variability among influenza viruses is the major goal in designing a universal influenza vaccine. Currently, there is considerable interest in the broadly neutralizing antibodies (bNAb) targeting the conserved HA stem region. These antibodies have been shown to activate cellular immune responses, such as antibody-dependent cellular cytotoxisity (ADCC), in addition to their neutralization activity. We had previously demonstrated that immunization with H1-based stabilized stem (SS) nanoparticles (np) protects against heterosubtypic lethal challenge with H5N1 influenza virus, despite the absence of detectable H5N1 neutralizing activity. Here, we utilized these novel SS np probes to develop a new protocol to assess the ADCC activity mediated by stem-directed antibodies in human sera.

Methods

Human sera samples were initially screened for binding reactivity to H1 SS trimer using ELISA procedure. Of these, selected samples representing high, moderate, and low binders were further characterized for binding to H1 and H5 SS their corresponding Δstem (Ile45Arg/Thr49Arg) probes, and were analyzed for ADCC activity using a reporter bioassay.

Results

The initial screening revealed 82% (73/90) seroprevalence of anti-HA (H1) stem epitope antibodies, as determined by the differential binding to HA SS and it corresponding epitope-mutant probe. Using equimolar amounts, the multivalent presentation of HA SS on np probes induced significantly higher ADCC activity compared with the monovalent SS probes (2- to 6-fold increase). Further, ADCC activity was similarly reported against different influenza group 1 subtypes: H1, H2, and H5. Importantly, ADCC was mediated mainly by antibodies targeting the bNAb-epitope on the HA stem. In conclusion, we developed an assay to measure stem-specific ADCC activity using SS np probes.

Conclusion

Our results indicate a high prevalence of HA-stem antibodies with cross-reactive ADCC activity. Such assay could be utilized in the assessment of next-generation influenza vaccines.

Disclosures

All Authors: No reported Disclosures.
1839. Contact Precautions’ Effects on MRSA Transmission in Department of Veterans Affairs Hospitals
Authors: Khader Karim , Thomas Alun , Visnovsky Lindsay D , Toth Damon , Keegan Lindsay T , Jones Makoto M , Rubin Michael , Samore Matthew H
Published: October 2019

Background

In 2007, the Department of Veterans Affairs (VA) implemented the methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative nationally in acute care facilities (ACFs). The initiative included universal nasal surveillance for MRSA colonization and implementation of contact precautions (CP) for identified carriers for the duration of their stay. Despite subsequent declines in MRSA infection rates in the VA, debate on CP efficacy continues, due to limited and inconclusive direct evidence. This study estimated CP impact on MRSA transmission in the VA.

Methods

We analyzed 1 year of data from 36 VA ACFs in 2014 using a Bayesian transmission model. The data included admission, discharge, and surveillance and clinical test results for MRSA. Per the MRSA Prevention Initiative protocol that placed known carriers on CP, we assumed patients were on CP starting 12 hours after a positive surveillance test, 24 hours after a positive clinical culture, or at admission if the patient had a positive test within 365 days prior to admission. Our model produced estimates of ward-specific transmission rate, surveillance test sensitivity, importation probability, and the CP effect parameter (CPe). For CPe < 1, CP reduced transmission. Additionally, we combined the estimates of CPe using a random-effects model with inverse variance weights to derive pooled estimates and corresponding standard errors.

Results

Facility size varied with a median daily census of 70 patients per day (range: 44–111). During the study period, 144,386 individuals were admitted into one of 36 ACFs, for 215,207 total admissions. The median percentage of admissions requiring contact precautions was 11.0% (range: 6.4%–16.1%). The estimated CPe was less than one in each of the 36 facilities with a median of 0.43 (range: 0.25–0.68). Our pooled estimate of CPe across all facilities was 0.47 (95% CI; 0.40, 0.55).

Conclusion

We found evidence of reduced MRSA transmission from patients on CP. This result was statistically significant in 5 of the 36 facilities and our pooled estimate suggests contact precautions could reduce the transmission rate by half. Further work is needed to account for imperfect compliance with CP, and for patients on CP for other reasons.

Disclosures

All Authors: No reported Disclosures.