bluuebunny/crossref_metadata_2025_split huggingface dataset:
1731. Disseminated Metacestode Infection Due to an Unknown Versteria Species
Authors: Lehman Bethany , Leal Sixto , Procop Gary W , O’Connell Elise M , Nash Theodore , Jones Stephen , Braunthal Stephanie , Cruise Michael , Mukhopadhyay Sanjay , Banzon Jona 
Published: November 2018

Abstract

Background
A 68-year-old woman with hypogammaglobulinemia and prior treated lymphoma presented with fever and abdominal pain. Evaluation revealed numerous nodules in the lung, eye, brain, and liver (Figure 1). Initial lung and liver biopsies showed necrotizing granulomas with no organisms and negative serology and cultures. After progression while on broad-spectrum antibiotics for 4 months, an open liver biopsy revealed numerous nodular lesions and a mass made up of multifocal coalescing cystic lesions. The mass consisted of a degenerating 3-layered membrane without scoleces characterized by a wavy protuberant ciliated eosinophilic outer layer, subjacent degenerating cells with pyknotic nuclei, and loose connective tissue suggestive of a bladder wall and calcareous corpuscles in a matrix of granulomatous inflammation with areas of necrosis (Figure 2). This was diagnostic of disseminated metacestodes (larval stage) of a cestode (tapeworm). Treatment with praziquantel and albendazole led to improvement of symptoms and lesions. Disseminated cestode infections other than due to Echinococcus species are rare in humans. Sequencing was pursued due to the unusual findings.

Methods
DNA was extracted from liver tissue followed by targeted amplification of the cestode COX1 gene. PCR products confirmed to be 134 bp, as expected for a cestode COX1 gene, then inserted into a 2.1 Topo vector and cloned. Five separate isolates were sequenced, and 4 were interpretable. The 129-bp consensus sequence is shown in Figure 3. Basic Local Alignment Search Tool (NCBI BLAST) was used to find highly similar sequences.

Results
The sequence matched to Versteria sp. (T. mustelae) COX1 gene from a mink in Oregon (accession KT223034) with 98% identity.

Conclusion
Metacestodes have the propensity to proliferate and rarely disseminate. There is one reported case of Versteria sp. causing a lethal disseminated infection of an orangutan. This is the first report of a Versteria sp. disseminated infection in a human and is singular because the patient survived. The patient likely accidentally ingested ova shed from a tapeworm in a mink or similar mammalian host. Histopathologic assessment is crucial in diagnosing cestode infection. COX1 gene sequencing is useful for cestode identification.

Disclosures
All authors: No reported disclosures.
1733. 10 Years of DTAC Experience With Donor-Derived Cryptococcus Transmission in Solid-Organ Transplantation in the United States
Authors: Mehta Aneesh K , Malinis Maricar , Vece Gabriel , Danziger-Isakov Lara , Florescu Diana F , Michaels Marian , Wolfe Cameron R , Strasfeld Lynne , Tlusty Susan 
Published: November 2018

Abstract

Background
Cryptococcosis is an important fungal complication of solid organ transplantation (SOT); cases occurring within 6 months posttransplant are often severe and sometimes donor derived. Morbidity can be related to delayed recognition of clinical symptoms or lack of communications among the SOT recipient centers. To better understand transmission of Cryptococcus (Crypto) and to identify opportunities for improved identification and communication, all potential donor-derived transmission events (PDDTE) of Crypto reported to OPTN/UNOS ad hoc Disease Transmission Advisory Committee (DTAC) over 10 years were analyzed.

Methods
All Crypto cases reported to DTAC between January 2008 and December 2017 were reviewed retrospectively as potential donor-derived transmission events (PDDTE). Likelihood of donor-derivation was adjudicated based on recipient and donor data.

Results
Fourty-six cases of Crypto were reported to DTAC during this period, involving 145 SOT recipients. Of the Proven or Probable donor-derived Crypto cases (n = 9), transmission occurred in 15 recipients; 2 donors each transmitted Crypto to 3 different recipients. Of the Possible cases, 9 recipients were affected. Six recipients with PDDTE Crypto died. Eight recipients received antifungal medications that would prevent transmission of Crypto (classified as intervention without disease transmission).
UNOS Region 7 had the highest number donors with 10, with 6 and 7 from Regions 2 and 3, respectively. No cases C. gattii were reported; however, most of the reports to DTAC did not discriminate between C. neoformans and C. gattii.

Conclusion
This DTAC case series highlights both donor and recipient-derived cryptococcal infections and their potential to have devastating clinical impact. These data also highlight important delays in recognizing Crypto in SOT and in communicating these results to other centers when a PDDTE is possible. Transplant teams should have a high level of suspicion for Crypto in SOT, particularly in those with fever of unknown etiology, pulmonary infiltrates, headaches, and mental status changes. In the future, it may be helpful for transplant center to perform specific testing to discriminate between Cryptococcus species to understand their differential impact in SOT.

Disclosures
D. F. Florescu, Astellas: Grant Investigator, Grant recipient. C. R. Wolfe, Merck: Scientific Advisor, Consulting fee.
1763. Estimating Median Survival Time to Central Line-Associated Bloodstream Infection (CLABSI) Among Patients in Intensive Care Units Reported to National Healthcare Safety Network (NHSN)
Authors: Soe Minn , Edwards Jonathan R 
Published: November 2018

Abstract

Background
Duration free of central line-associated bloodstream infection (CLABSI) in a hospital may vary by type of patient population. We estimated patients’ median time to CLABSI by intensive care unit (ICU) type among acute care hospitals.

Methods
The study population was ICU patients whose CLABSI data were reported to National Healthcare Safety Network (NHSN) in 2016 under the reporting requirement of the Centers for Medicare and Medicaid. The unit of analysis was ICU location, not an individual patient. We conducted counting process survival analysis method to compute time (day) to a CLABSI beginning from day 1 of first reporting month in 2016 in a given ICU location. Once a CLABSI occurred in a location, the start time of follow-up was reset to day 1 after the date of event. The Cox regression method was used to explore the hospital and location-level characteristics that are potentially associated with the daily hazard of CLABSI for an ICU. We also assessed the proportionality hazard assumption of these factors. Adjusting for the vector of means of covariates, we then estimated median time to CLABSI by ICU location type, which is defined as follow-up time (days) by which 50% of events have happened in a given ICU type.

Results
In 2016, 6,935 ICUs at 3,384 hospitals reported CLABSI data to NHSN, with a total of 10,985 CLABSIs and 2,449,361 follow-up time in days. Factors associated with an increased daily hazard of CLABSI were the following: admission to a hospital with a large bed size, major teaching status, and admission to a patient care location with a higher device utilization ratio (Table 1). Adjusted survival curves showed that median time to event (median CLABSI-free time) among ICUs ranged from 66 days (level III neonatal ICU), 90 days (burn units) to 275 days (oncology units), and 284 days (cardiothoracic units) (Table 2, Figure 1).

Conclusion
The study demonstrated that ICUs with level III care for neonatal patients and ICUs with burn patients were least likely to achieve the target of “zero” infection in a defined period and may warrant further targeted interventions. Similar research to investigate infection control performance through estimating median infection-free time is needed beyond ICUs and across multiple HAI types and facility settings.

Disclosures
All authors: No reported disclosures.
1766. Sustained Viral Suppression with Dolutegravir and Boosted Darunavir Dual Therapy Among Highly Treatment-Experienced Individuals
Authors: Hawkins Kellie , Montague Brian , Rowan Sarah , Mclees Margaret , Beum Robert , Johnson Steven C , Gardner Edward 
Published: November 2018

Abstract

Background
The use of antiretroviral (ARV) dual therapy for treatment of HIV is increasing; raltegravir with boosted darunavir (bDRV) is recommended in certain clinical situations in DHHS guidelines. Dolutegravir (DTG) with bDRV has not been widely studied. We sought to determine the effectiveness of DTG/bDRV in treatment experienced patients.

Methods
This retrospective cohort study evaluated viral suppression in patients prescribed DTG/bDRV dual therapy within a large urban health system. Data collected included demographics, cumulative ARV exposure, reasons for use, regimen start/stop dates, and viral suppression (HIV-RNA ≤200). Follow-up was defined as the number of days from start of regimen until last HIV-RNA determination on the study regimen.

Results
From January 1, 2013 to December 31, 2017, 60 patients received DTG/bDRV dual therapy: 15% were female, median age was 56, 83% were ≥3 class ARV-experienced, and median time since starting ARVs was 20 years. Median follow-up on DTG/bDRV was 444 days (IQR 273–808). Viral suppression was achieved by 59 of 60 (98%) patients at some point on DTG/bDRV. When stratified by baseline viral suppression, 46 of 46 (100%) who had baseline viral suppression maintained viral suppression in comparison to 11 of 14 (79%) without baseline viral suppression (table). The most common reasons for DTG/bDRV were simplification in setting of prior resistance (47%), toxicity reduction (39%), and virologic failure (15%). At study end, 53 of 60 (88%) were still on DTG/bDRV and the most common reason for stopping was drug interactions.

Conclusion
In a highly treatment-experienced cohort of patients, DTG/bDRV dual therapy demonstrated sustained rates of viral suppression, even in those who were failing therapy prior to initiating the regimen. Further study of this potent, simple, high-barrier dual class regimen is warranted.

Disclosures
S. Rowan, Gilead Sciences: Investigator, Research grant. S. C. Johnson, Viiv Healthcare: Scientific Advisor, Consulting fee.
1770. The Association of Unmet Needs With Subsequent Retention in Care and HIV Suppression Among Hospitalized Patients With HIV Who Are Out of Care
Authors: Dandachi Dima , May Sarah , Davila Jessica , Cully Jeffrey , Amico K Rivet , Kallen Michael A , Giordano Thomas P 
Published: November 2018

Abstract

Background
Unmet needs among hospitalized patients with HIV may prevent engagement in HIV care leading to worse clinical outcomes. Our aim was to examine the role of unmet subsistence needs (e.g., housing, transportation, food) and medical needs (e.g., mental health, substance abuse treatment) as barriers for retention in HIV care and viral load (VL) suppression.

Methods
We utilized data from the Mentor Approach for Promoting Patients’ Self-Care intervention study, the enrolled hospitalized HIV-patients at a large publicly funded hospital between 2010 and 2013, who were out-of-care. We examined the effect of unmet needs on retention in HIV care (attended HIV appointments within 0–30 days and 30–180 days) and viral load suppression, 6 months after discharge.

Results
A total of 417 participants were enrolled, 78% reported having ≥1 unmet need at baseline, most commonly dental care (55%), financial (43%), or housing needs (34%). Participants with unmet needs at baseline, compared with those with no needs, were more likely to be African American, have an existing HIV diagnosis, and be uninsured. Among participants who completed a baseline and 3-month survey (n = 320), 45% reported a need for dental care, 42% reported financial needs, and 32% reported housing needs that were unmet at either time point (Figure 1). Having a dental care need at baseline that was met was significantly associated with higher odds of VL improvements at 6-month follow-up (OR: 2.2; 95% CI: 1.04–4.50, P = 0.03) and higher odds for retention in care (OR: 2.06; 95% CI: 1.05–4.07, P = 0.04). An unmet need for transportation was associated with lower odds of retention in care (OR: 0.5; 95% CI: 0.34–0.94, P = 0.03), even after adjusting for other factors. Compared with participants with no need, those who reported ≥3 unmet subsistence needs were less likely to demonstrate viral load improvement (OR: 0.51; 95% CI: 0.28–0.92; P = 0.03) and to be retained in care (OR: 0.52; 95% CI: 0.28–0.95; P = 0.03).

Conclusion
An important and novel finding in our study is that the number of unmet subsistence needs had a significant effect on retention in care and VL suppression. Broader access to programs that can assist in meeting subsistence needs among hospitalized patients could have significant individual and public health benefits.

Disclosures
All authors: No reported disclosures.
2559. Incidence and Clinical Impact of Discordant Genotypic and Phenotypic Categorization of Methicillin Susceptibility in Staphylococcus aureus Bacteremia
Authors: Gulliver Jessica , Jung-Hynes Brittney , Chen Derrick 
Published: November 2018

Abstract

Background
Methicillin-susceptible/methicillin-resistant Staphylococcus aureus (MSSA/MRSA) can be directly identified from positive blood culture bottles using molecular methods. This provides faster results than traditional phenotypic testing, but discrepancies between the two are occasionally found. We sought to determine the incidence and clinical impact of such discrepancies.

Methods
Positive blood culture bottles are routinely tested in the hospital clinical laboratory for mecA via Xpert MRSA/SA BC (PCR), and antimicrobial susceptibility testing (AST) via MicroScan PC33 is performed on recovered S. aureus isolates; discrepancies between PCR and AST are resolved by repeat and supplemental (Kirby-Bauer) testing. A retrospective review of medical and laboratory data from January 2015 to December 2017 was performed on all patients that had discordant PCR and AST results.

Results
Approximately 1,200 PCR assays were performed from January 2015 to December 2017, and there were 5 (0.4%) cases with discordant AST Results. Four cases were classified as MSSA by PCR but MRSA by AST, and 1 case was classified as MRSA by PCR but MSSA by AST. For the former group, antimicrobial therapy was changed in 2 patients to cover MRSA and 1 patient was readmitted, while the remaining 2 patients were already being treated for MRSA; for the latter case, this patient was treated for MRSA during the initial hospitalization, but was readmitted with disseminated MSSA and subsequently deceased. Based on genetic targets identified by PCR and cefoxitin and oxacillin AST, discrepancies were likely due to borderline oxacillin resistance (BORSA) (n = 1), presence of an SCCmec variant not detected by PCR (n = 1), or undetermined (n = 3).

Conclusion
Rapid identification of MRSA bacteremia via PCR provides actionable information to direct empiric treatment. While highly accurate, PCR results are infrequently not corroborated by AST. This rare possibility should be considered when modifying therapy based on initial PCR results, and there should be close communication between the clinical team and laboratory for these challenging cases.

Disclosures
All authors: No reported disclosures.
2560. Multispecies Outbreak of KPC-2 Producing Enterobacteriaceae in a Chilean Pediatric Hospital
Authors: Rojas Laura J , Marshall Steven H , Rivas Lina M , Spencer Maria , Rutter Joseph , Jacobs Michael R , Perez Federico , Coria Paulina , Valdivieso Francisca , Bralic Rafael Araos , Munita Jose M , Bonomo Robert A 
Published: November 2018

Abstract

Background
Carbapenem-resistant Enterobacteriaceae (CRE) are a critical global health problem. We detected a surge of CRE cases in a pediatric hospital in Chile, a country with a low endemicity of KPC-producing organisms. Herein, we describe the molecular epidemiology of this outbreak.

Methods
CRE isolates from clinical specimens and surveillance rectal swabs (obtained using chromID CARBA SMART agar, BioMerieux) of pediatric patients were collected from July 2015 to January 2017. Species identity was confirmed by MALDI-TOF. Carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like) were detected by multiplex PCR, followed by amplification and sequencing of the blaKPC allele. Conjugation experiments were conducted with representative species as donors and sodium azide-resistant E. coli J53 as recipient. PCR-based plasmid typing (PBRT Diatheva kit) was then performed on donors and recipients. For K. pneumoniae, genetic relatedness was investigated by PFGE, multilocus sequence typing and wzi typing.

Results
Sixty-one CRE clinical and surveillance isolates were obtained from 49 patients aged 17 days to 16 years. blaKPC-2 was present in 57/62 isolates; no other carbapenemases were found. For 11 patients, multiple cultures were obtained; 4/11 had more than one KPC-harboring species. KPC-harboring isolates displayed ertapenem MICs ranging from 1 to &gt;8 mg/L. Preliminary analyses suggest that blaKPC-2 is contained within a nonclassical Tn4401 structure (lacking the upstream promoter). Mating experiments indicate that blaKPC-2 is carried by a conjugative IncN backbone plasmid. Interestingly, K. pneumoniae isolates were nonclonal by PFGE and belonged to multiple STs unrelated to CG258 (ST34, ST36, among others) and different wzi types (37, 154, among others).

Conclusion
We report a multispecies outbreak of KPC-2 producing CRE in children mainly driven by horizontal dissemination of a promiscuous IncN plasmid. The nonclonal, multispecies nature of this outbreak provides insights into the complex dynamics of KPC dissemination in countries like Chile, where the clonal spread of highly successful clones like CG258 is not the predominant dissemination vehicle, and instead HGT-related spread could be playing a more important role.

Disclosures
All authors: No reported disclosures.
2565. A Novel Prognostic Gene Set for the Prediction of Severe Dengue
Authors: Robinson Makeda L , Sweeney Timothy E , Barouch-Bentov Rina , Sahoo Malaya K , Sanz Ana Maria , Pu Szu-Yuan , Ortiz Eliana , Albornoz Luis , Suarez Fernando Rosso , Montoya Jose G , Pinsky Benjamin , Khatri Purvesh , Einav Shirit 
Published: November 2018

Abstract

Background
There is an urgent need for the identification of biomarkers predictive of severe dengue. Single cohort transcriptomic studies have not yielded a parsimonious gene set predictive of severe dengue. We hypothesized that integration of gene expression data from heterogeneous patient populations with dengue infection would yield a set of conserved genes that is predictive of severe dengue and generalizable across cohorts.

Methods
Ten dengue gene expression datasets were identified in publicly available microarray repositories. A novel integrated multicohort platform was used to detect differentially expressed gene transcripts between uncomplicated and severe dengue patients and validate the identified putative signature in silico and prospectively in a new cohort of 34 dengue patients in Colombia. Dengue diagnosis was made by NS1 antigen and anti-DENV IgM antibody and confirmed by RT-PCR assays, ELISA, and IgG avidity measurements. The expression level of the signature genes was measured via microfluidic qRT-PCR assays in blood samples collected longitudinally during the course of illness.

Results
Using the multicohort analysis to analyze 446 peripheral blood samples of patients with dengue infection from 7 publicly available gene expression datasets, we identified a 20 gene set that predicts the development of severe dengue. We in silico validated the diagnostic power of this gene set to separate severe dengue from dengue with or without warning signs in 3 independent datasets composed of 84 samples with a global area under the ROC curve (AUC) of 0.80 [95% CI 0.68–0.88]. We prospectively validated the gene set in a new cohort composed of 34 dengue patients from Colombia with an AUC of 0.89 [95% CI 0.81–0.97]. The severity scores measured in patients with severe dengue progressively declined in longitudinal samples.

Conclusion
Our data indicate that the identified 20 gene signature predicts the development of severe dengue in patients prior to its onset and suggest that dengue infection itself triggers this host response. These findings may provide new insight into the pathogenesis of severe dengue and have implications for the development of a prognostic molecular assay to identify patients at risk to develop severe dengue.

Disclosures
T. E. Sweeney, Inflammatix, Inc.: Employee and Shareholder, Salary. P. Khatri, Inflammatix, Inc: Scientific Advisor and Shareholder, Licensing agreement or royalty.
2572. Decreased T-Cell Response, but Appropriate Antibody Production to Tetanus Vaccine Among HIV-Exposed Uninfected Infants in Botswana
Authors: Smith Christiana , Moraka Natasha , Ibrahim Maryanne , Moyo Sikhulile , Mayondi Gloria , Kammerer Betsy , Leidner Jean , Gaseitsiwe Simani , Shapiro Roger , Lockman Shahin , Weinberg Adriana 
Published: November 2018

Abstract

Background
In Botswana, more than 10% of HIV-exposed, uninfected infants (HEU) are hospitalized or die in the first 6 months of life, largely due to infectious causes. Vaccine responses can act as a marker of the immune response to infectious antigens. Previous studies of vaccine responses in HEU have had conflicting results. We compared T-cell responses to tetanus and purified protein derivative (PPD), and antibody titers to tetanus, between HEU and HIV-unexposed infants (HUU).

Methods
A total of 443 HIV-infected and 451 HIV-uninfected mothers and their 453 HEU/457 HUU live-born infants were followed from pregnancy/delivery through 24 months postpartum in a prospective observational study in Botswana (“Tshipidi”). T-cell expression of interferon (IFN)-γ and interleukin (IL)-2 were measured at 6 months using FluoroSpot after stimulation with tetanus toxoid or PPD. Quantitative tetanus toxoid IgG was measured in plasma at 18 months using ELISA. Mean spot-forming units (sfu) per 105 cells and geometric mean antibody titers were compared between HEU and HUU infants who had received 3 doses of tetanus and 1 dose of Bacille Calmette–Guérin (BCG) vaccines by 6 months, and 3 or 4 doses of tetanus vaccine by 18 months.
Results. Peripheral blood mononuclear cells were available at 6 months for 63 HEU and 18 HUU. Plasma was available at 18 months for 39 HEU and 42 HUU. HEU infants had significantly lower IL-2 expression after tetanus stimulation than HUU infants (4.4 vs. 16.1 sfu/105 cells, P = 0.004; figure), but no difference in IFNγ expression. There were no differences in T-cell responses to PPD between HEU and HUU. There were no differences in tetanus geometric mean antibody titers between HEU and HUU.
Conclusion. In this cohort of infants from Botswana, we found decreased T-cell responses, but not antibody responses, to tetanus toxoid and no differences in T-cell responses to PPD. Cell-mediated immune defects may play a greater role than humoral immune defects in the increased susceptibility to infection among HEU. BCG vaccine produces robust T-helper 1 responses, which may overcome cell-mediated immune defects in HEU.

Disclosures
All authors: No reported disclosures.