bluuebunny/crossref_metadata_2025 huggingface dataset:
859. Same-Day HIV Pre-exposure Prophylaxis (PrEP) Initiation During Drop-in STD Clinic Appointments Is a Safe, Feasible, and Effective Method to Engage Patients at Risk for HIV in PrEP Care
Authors: Kamis Kevin , Scott Kenneth , Gardner Edward , Wendel Karen , Marx Grace , Scott Mia , Montgomery Angela , Rowan Sarah
Published: November 2018

Background

Patients at risk for HIV generally do not have immediate access to PrEP. We hypothesized that by offering free, 30-day PrEP starter packs and navigation support during drop-in STD clinic appointments, individuals would be likely to initiate and continue PrEP.

Methods

Individuals aged ≥18 years presenting for drop-in appointments in the Metro Denver STD Clinic and indicated for PrEP were eligible for the study. Exclusion criteria were history of renal dysfunction, chronic hepatitis B (HBV), HIV, pregnancy, and indications for postexposure prophylaxis. Eligible individuals were provided PrEP education and offered a free, 30-day PrEP starter pack and navigation support for cost assistance. Participants were tested for creatinine, HBV, HIV, and pregnancy at enrollment, and navigated to an appointment for ongoing PrEP care. Participants’ medical records were reviewed for a minimum of 4 months after enrollment. Descriptive statistics and logistic regression were used to characterize the study population and follow-up.

Results

From April to October 2017, 100 individuals filled a tenofovir–emtricitabine prescription (figure). Median participant age was 28 years, 98% were male, 53% were non-Hispanic White, 8% non-Hispanic Black, and 34% Hispanic. Median annual income was $24,000, 62% had health insurance, 26% had a primary care provider (PCP), and 50% had a recent bacterial STI. No participants had abnormal baseline creatinine or HBV. 77% completed ≥1 PrEP follow-up visit during the study period; 57% completed their first visit within 31 days. 56% completed a second follow-up visit. No HIV seroconversions were detected during follow-up. Factors significantly associated with attending ≥1 follow-up appointment were age ≥ 30 years, higher income, and having health insurance or a PCP at enrollment. In multivariate logistic regression, only higher income was associated with attending ≥1 follow-up appointment (median income for those with ≥1 follow-up visit vs. no follow-up: $24,960 vs. $14,000, P <0.01).

Conclusion

Providing immediate access to PrEP during drop-in STD clinic visits is a safe and feasible approach to initiation of PrEP care. Additional resources are needed to support PrEP continuity care, particularly for low-income individuals.

Disclosures

K. Kamis, Gilead Scienes: Research Coordinator, Research grant. S. Rowan, Gilead Sciences: Investigator, Research grant.
862. Spatial Distribution of HIV Transmission in Ethiopia and Characteristics of HIV Clusters
Authors: Ying Roger , Fekadu Lelisa , Schackman Bruce R , Verguet Stéphane
Published: November 2018

Background

HIV prevalence in Ethiopia has decreased by nearly 75% in the past 20 years with the implementation of antiretroviral therapy, but HIV transmission continues in certain high-risk regions around the country. Identification of the spatial and temporal trends of these transmission clusters, as well as their epidemiologic correlates, can lead to refinement of targeted interventions.

Methods

We used data from the 2005, 2011, and 2016 Ethiopia Demographic and Health Survey program (DHS). The spatial-temporal distribution of HIV was estimated using the Kuldorff spatial scan statistic, which determines the likelihood ratio of HIV within possible circular clusters across the country. Significant clusters (P < 0.05) were identified and compared based on known HIV risk factors using descriptive statistics to compare them to the noncluster area of the country. All analyses were conducted in SaTScan and R.

Results

Data from 11,383, 29,812, and 26,753 individuals with HIV were included in the 2005, 2011, and 2016 DHS, respectively. Four HIV clusters were identified consistently over the 3 time points, with the clusters representing 17% of the total population and 47% of all HIV cases. The 4 clusters were centered on the Addis Ababa, Afar, Dire Dawa/Harare, and Gambella regions, respectively. Cluster 1 is characterized by higher levels of unsafe injections (4.9% vs. 2.2%, P < 0.001) and high-risk occupations, such as truck drivers (5.7% vs. 1.7%, P < 0.001), when compared with noncluster regions, but by lower levels of transactional sex (18.6% vs. 23.0%, P < 0.001). Cluster 2 is also characterized by higher levels of high-risk occupations (2.8% vs. 1.7%, P < 0.01), whereas cluster 4 is characterized by a lower prevalence of circumcised men (59.1% vs. 91.3%, P < 0.01). No cluster had significantly higher levels of having more than one sexual partner in the last 12 months, although cluster 3 had a significantly lower level (0% vs. 1.7%, P < 0.001).

Conclusion

HIV in Ethiopia is composed of heterogeneous clusters of HIV transmission that appear to be driven by different risk factors. Further decreasing the HIV burden will likely require targeted and prioritized interventions in specific regions rather than uniform national policies.

Disclosures

All authors: No reported disclosures.
923. Rapid Emergence of Candida auris in the Chicago Region
Authors: Kerins Janna L , Tang Angela S , Forsberg Kaitlin , Jegede Olufemi , Ealy Michelle , Pacilli Massimo , Welsh Rory M , Murphy Elizabeth B , Fealy Amy , Walters Maroya Spalding , Raczniak Gregory , Vallabhaneni Snigdha , Black Stephanie R , Kemble Sarah K
Published: November 2018

Background

In 2016, Candida auris was first reported in the United States, with 2 Illinois patients among the first cases. In response, the state and 3 Chicago-area health departments (HDs) investigated clinical cases and performed point prevalence surveys (PPSs) to identify colonized cases.

Methods

Clinical cases had positive C. auris cultures obtained for clinical care; colonized cases had positive surveillance cultures during PPSs. In August 2016–January 2018, PPSs were performed in Chicago-area acute care hospital (ACH) intensive care units, long-term acute-care hospitals (LTACHs), and high-acuity floors of skilled nursing facilities (SNFs) and SNFs caring for ventilated patients (vSNFs). Facility and HD staff obtained composite axilla/groin swabs from assenting patients to detect colonization. Facilities with an epidemiologic link to a clinical case or a shared patient population with a facility housing a clinical case were prioritized for PPSs.

Results

During May 2016–January 2018, Chicago-area facilities reported 24 clinical cases, including 10 bloodstream infections. HDs performed 33 PPSs at 20 facilities (5 ACHs, 5 LTACHs, 3 SNFs, and 7 vSNFs) during August 2016–January 2018. Of 1,364 patients screened, 92 (6.7%) were colonized with C. auris; 10 (50%) facilities had ≥1 colonized patient. A significantly higher proportion screened positive from September 2017 to January 2018 (84/822, 10.2%) than in August 2016–August 2017 (8/542, 1.5%; z-test P < 0.01). Prevalence of C. auris colonization was highest in vSNFs (median: 7.7%; range: 0%–43.3%), compared with ACHs (0%; 0%–6.3%), LTACHs (0%; 0%–14.3%), and SNFs (0%, 0%–1.5%). PPSs in vSNFs identified 91% (84/92) of colonized cases. Among 5 vSNFs with repeat PPSs, 4 had higher prevalence on repeat screening (median: 26.1%; range: 0%–43.3%) than at baseline (1.2%; 0%–17.0%).

Conclusion

C. auris has rapidly emerged in the Chicago area. Increasing prevalence of C. auris colonization during repeat PPSs indicates transmission and amplification within vSNFs. To prevent spread, state and local HDs provided infection control recommendations, disseminated health alerts, and recommended placing vSNF patients from high-acuity floors on transmission-based precautions.

Disclosures

All authors: No reported disclosures.
933. Serum Albumin Is Associated With Higher Inflammation and Carotid Atherosclerosis in Treated HIV Infection
Authors: Dirajlal-Fargo Sahera , Kulkarni Manjusha , Sattar Abdus , Funderburg Nicholas , McComsey Grace A
Published: November 2018

Background

Lower serum albumin has recently been associated with cardiovascular disease and non-AIDS malignancies in HIV. This analysis explores the associations between serum albumin and markers of inflammation and atherosclerosis.

Methods

We conducted a nested study within in the SATURN-HIV trial in which 147 HIV+ adults on stable antiretroviral therapy (ART), were virally suppressed, and had an LDL-cholesterol level <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Measures of serum albumin, carotid intima media thickness (IMT, surrogate marker of atherosclerosis), inflammation, T-cell and monocyte immune activation were assessed at baseline, 24, 48, and 96 weeks later. Spearman correlations and linear-mixed effects models with random intercept and slope were conducted to assess associations with albumin.

Results

Mean age was 45 years, 80% were male, 69% were African American, and 46% were receiving protease inhibitors. Mean serum albumin was not significantly different between the groups at any time points (4.05–4.08 g/dL in statin arm vs. 4.01–4.11 g/dL in placebo arm, P = 0.08–0.35). Low serum albumin significantly correlated with elevated levels of interleukin-6 (IL6), d-dimer, fibrinogen, and high sensitivity C-reactive protein (hsCRP) at all time points (P ≤ 0.04). Low serum albumin also correlated with higher inflammatory monocytes (CD14+CD16+) at week 24 and week 96 (P ≤ 0.03) but not with markers of T-cell activation at any time point (P ≥ 0.10). Lower baseline albumin significantly predicted larger changes in IMT (P = 0.03), IL6, d-dimer, tumor necrosis factor-α receptor 1, fibrinogen, and hsCRP (P ≤ 0.02) over 96 weeks. After adjusting for age, gender, smoking, body mass index, vascular cell adhesion molecule and creatinine clearance, every 1 g/dL decrease in albumin remained associated with a 0.5 mm increase in IMT over 96 weeks (P = 0.05).

Conclusion

Lower serum albumin in controlled HIV is associated with higher markers of chronic inflammation, hypercoagulation, and monocyte activation, which could explain the prior observation that albumin predicts non-AIDS events in HIV. Our findings suggest that serum albumin may predict progression of carotid atherosclerosis independent of traditional risk factors.

Disclosures

G. A McComsey, Gilead: Consultant, Consulting fee and Research support. Merck: Consultant, Consulting fee and Research support. Viiv: Consultant, Consulting fee and Research support. Roche: Research Contractor, Research support. Astellas: Research Contractor, Research support.
934. Incidence of Skin and Soft-tissue Infection in People Living With HIV in a Large Urban Public Health Care System in Houston, Texas, 2009–2014
Authors: Hemmige Vagish , Arias Cesar , Pasalar Siavash , Giordano Thomas P
Published: November 2018

Background

Skin and soft-tissue infections (SSTIs) disproportionately impact patients with HIV. Recent declines have been noted in the incidence of SSTIs in the non-HIV population. We set out to study the epidemiology and microbiology of SSTIs in a population of 8,597 patients followed for HIV primary care in a large urban county system from January 1, 2009 to December 31, 2014.

Methods

SSTIs were identified from the electronic medical record (EMR) by the use of ICD-9 billing codes. Charts were reviewed to confirm the diagnosis of acute SSTI and abstract culture and susceptibility data. We calculated yearly SSTI incidence using Poisson regression with clustering by patient.

Results

2202 SSTIs were identified. Of 503 (22.8%) cultured SSTIs, 332 (66.0%) included S. aureus as a pathogen, of which 287/332 (86.4%) featured S. aureus as the sole pathogen. Of S. aureus isolates with susceptibilities, 231/331 (69.8%) were methicillin-resistant, and the proportion did not vary by year (P = NS).

The observed incidence of SSTI was 78.0 per 1,000 person-years (95% CI 72.9–83.4) and declined from 96.0 infections per 1,000 person-years in 2009 to 56.5 infections per 1,000 person years in 2014 (P < 0.001). Other significant predictors of SSTI incidence in both univariate as well as multivariate analysis included CD4 count, viral load, and being a Spanish-speaking Hispanic.

Conclusion

Although SSTI rates in a large urban HIV-infected outpatient cohort declined approximately 40% between 2009 and 2014, SSTIs remain a significant problem.

Disclosures

C. Arias, Merck & Co., Inc.: Grant Investigator, Research support. MeMed: Grant Investigator, Research support. Allergan: Grant Investigator, Research support
963. Whole Blood Transcriptome Analysis Reveals Differences in Erythropoiesis and Neurologically Relevant Pathways Between Cerebral Malaria and Severe Malarial Anemia
Authors: Nallandhighal Srinivas , Park Gregory , Ho Yen-Yi , Opoka Robert , John Chandy , Tran Tuan
Published: November 2018

Background

Plasmodium falciparum malaria can rapidly progress to severe disease that can lead to death if left untreated. Severe malaria cases commonly present as severe malarial anemia (SMA), defined in children as hemoglobin (Hb) <5 g/dL with parasitemia, or as cerebral malaria (CM), which manifests as parasitemia with acute neurological deficits and has an inpatient mortality rate of ~20%. The molecular and cellular processes that lead to CM and SMA are unclear.

Methods

In a cross-sectional study, we compared genome-wide transcription profiles of whole blood obtained from Ugandan children with acute CM (n = 17) or SMA (n = 17) and community children without P. falciparum infection (n = 12) who were enrolled in a parent cohort study of severe malaria. We determined the relationships between gene expression, hematological indices, and plasma biomarkers, including inflammatory cytokines.

Results

Both CM and SMA demonstrated enrichment of dendritic cell activation, inflammatory/TLR/chemokines, monocyte, and neutrophil modules but depletion of lymphocyte modules. Neurodegenerative disease and neuroinflammation pathways were enriched in CM. Increased Nrf2 pathway gene expression corresponded with increased plasma heme oxygenase-1 and the heme catabolite bilirubin in a manner specific to children with both SMA and sickle cell disease. Reticulocyte-specific gene expression was markedly decreased in CM relative to SMA despite higher Hb levels and appropriate increases in plasma erythropoietin. Viral sensing/interferon regulatory factor (IRF) 2 module (M111) expression and plasma IP-10 levels both negatively correlated with reticulocyte-specific signatures, but only M111 expression independently predicted decreased reticulocyte-specific gene expression after controlling for leukocyte count, Hb level, parasitemia, and clinical syndrome by multiple regression.

Conclusion

Differences in the blood transcriptome of CM and SMA relate to neurologically relevant pathways and erythropoiesis. Erythropoietic suppression during severe malaria is more pronounced during CM versus SMA and is positively associated with IRF2 blood signatures. Future studies are needed to validate these findings.

Disclosures

All authors: No reported disclosures.
973. Inter-facility Patient Sharing and Clostridium difficile Incidence in the Ontario Hospital Network: A 13-Year Longitudinal Cohort Study of 116 Hospitals
Authors: Brown Kevin , Daneman Nick , Schwartz Kevin , Langford Bradley , Johnstone Jennie , Adomako Kwaku , Etches Jacob , Garber Gary
Published: November 2018

Background

Inter-facility patient movement plays an important role in the dissemination of antimicrobial resistance and C. difficile infection (CDI) throughout healthcare systems. However, the relative performance of different patient sharing metrics for predicting CDI incidence is not known. We compared 3 different measures of inter-facility patient sharing as they relate to CDI incidence in Ontario facilities.

Methods

A retrospective cohort analysis was used to predict incident CDI (ICD-10 = A04.7 identified from Discharge Abstract Database records) across Ontario hospitals (Nhospitals = 116) between April 1, 2003 to March 31, 2016. Patients with a stay of <3 days and those with a history of CDI in the prior 90 days were excluded from the risk set but not from patient sharing metrics. Poisson regression models with facility-level random effects were used to predict facility CDI incidence (per 1,000 admissions) and measure the percent change in facility-level variance (PCV). The 3 metrics of inter-facility patient sharing included: (1) “importation”—the rate of patients with a discharge from another distinct facility in prior 90 days, (2) “incidence-weighted importation”—equal to importation weighted by the incidence of CDI in the previous facility, and (3) “case importation”—importation of patients with a history of CDI.

Results

Over the 13-year period, we observed 58,427 cases of healthcare-associated CDI among 12,750,000 admissions. Facility CDI incidence ranged from 2.9 to 19.6 per 1,000 admissions (6.8-fold range). Patient sharing metrics were strongly related to facility CDI incidence (figure). In models adjusting for facility risk factors, all 3 measures still explained an important portion of inter-facility variation in CDI incidence: importation (PCV = 5%, P = 0.01), incidence-weighted importation (PCV = 15%, P < 0.001), and “case importation” (PCV = 48%, P < 0.001).

Conclusion

We observed a substantial variation in facility CDI incidence that was explained by linkages between acute care facilities, especially linkage to other facilities with a high incidence of CDI. Facility infection prevention staff should consider incorporating the facility CDI incidence into risk stratification assessments of patient transfers.

Disclosures

All authors: No reported disclosures.
976. Clostridium difficile Colonization Molecular Epidemiology and Anti-toxin Serological Responses in Healthy Infants: A Prospective Cohort Study
Authors: Kociolek Larry , Kelly Ciaran P , Espinosa Robyn , Budz Maria , Balaji Aakash , Ozer Egon , Tanz Robert , Chen Xinhua , Gerding Dale N
Published: November 2018

Background

Infant C. difficile colonization is common, but the molecular epidemiology and immunologic consequences of colonization are poorly understood.

Methods

In this prospective cohort study of healthy infants, serial stools collected between 1–2 and 9–12 month olds were tested for glutamate dehydrogenase (detects nontoxigenic or toxigenic C. difficile [TCD]), tcdB PCR (detects TCD), and cultured for C. difficile. Isolates underwent whole genome sequencing and multilocus sequence typing (MLST). Clonal strains were identified by single nucleotide variant (SNV) analysis. TCD was confirmed by BLAST identification of tcdA/tcdB. Serum collected at 9–12 month olds underwent ELISA for measurement of IgA, IgG, and IgM against TCD toxins A and B. For comparison, anti-toxin IgG was measured in cord blood of 50 consecutive full-term deliveries (unrelated to study infants). Arbitrary ELISA units were compared by Wilcoxon rank-sum test.

Results

Among 32 infants, 16 (50%) had at least one TCD+ stool, 12 of whom were colonized at least 1 m prior to serology measurements (Figures 1 and 2). A variety of STs were identified, and evidence of putative in-home (enrolled siblings) and outpatient clinic transmission was identified (Figure 3). Infants with TCD colonization had significantly greater levels of anti-toxin IgA and IgG compared with non-colonized infants and IgG compared with unrelated cord blood (Table 1).

Conclusion

Infant C. difficile colonization is a dynamic process with variable strain types and duration. Outpatient clinics may be a C. difficile reservoir for some patients. TCD colonization is associated with a humoral immune response against toxins A and B, but whether natural TCD immunization protects against CDI later in life requires further investigation.

Disclosures

L. Kociolek, Alere/Techlab: Investigator, Research support. C. P. Kelly, Actelion: Consultant, Consulting fee. Artugen: Consultant, Consulting fee. Facile: Consultant, Consulting fee. GSK: Consultant, Consulting fee. MSD: Consultant, Consulting fee. Seres: Consultant, Consulting fee. Summit: Consultant, Consulting fee. Vedanta: Consultant, Consulting fee. D. N. Gerding, Merck: Scientific Advisor, Consulting fee. Actelion: Scientific Advisor, Consulting fee. DaVolterra: Scientific Advisor, Consulting fee. Summit: Scientific Advisor, Consulting fee. Rebiotix: Medical Officer and Scientific Advisor, Consulting fee. Pfizer: Consultant, Consulting fee. MGB Pharma: Consultant, Consulting fee. sanofi pasteur: Consultant, Consulting fee. Seres: Investigator, Research grant. CDC: Investigator, Research grant. US Dept VA: Investigator, Research grant. Treatment/Prevention of C. difficile: Patent Holder, no license or royalties.
1629. Targeted Antimicrobial Use Admission Provides an Actionable Denominator for Antimicrobial Stewardship Programs Evaluating Inpatient Length of Therapy
Authors: Dyer April , Ashley Elizabeth Dodds , Davis Angelina , Johnson Melissa , Jones Travis , Moehring Rebekah W
Published: November 2018

Background

Actionable, easy to interpret antibiotic use (AU) metrics provide antimicrobial stewardship programs (ASPs) with clear targets. Current aggregate AU metrics lack the ability to discriminate between long courses in a limited number of patients versus short courses in a large number of patients.

Methods

We developed a novel AU denominator termed “targeted antimicrobial use admission,” defined as an inpatient admission in which a selected agent or group of agents was administered. When used with length of therapy (LOT), it provides the average number of days patients receive the targeted agent(s) during inpatient hospital admissions. To demonstrate the added utility of this metric, we used descriptive statistics to compare it to LOT, LOT/1,000 patient days, LOT/1,000 admissions, and LOT/admission to quantify intravenous (IV) vancomycin use among 25 hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) for calendar year 2017. The metric was also used to compare hospitals to one another and track durations at an example hospital over time.

Results

Total LOT included 128,680 days of IV vancomycin (table). LOT/targeted antimicrobial use admission is the only metric that allows programs to quickly assess agent durations.

Conclusion

Stewardship programs seeking to shorten durations of therapy can track this metric over time to determine the impact of their ASP efforts (Figure 1). The metric can also be used to compare average durations of IV vancomycin by hospital to determine when and if agent-focused audit and feedback or antibiotic timeouts may be useful (Figure 2). The network mean provides a target for agent-specific de-escalations, in days, for facilities with longer durations. LOT/targeted antimicrobial use admission provides an actionable metric for quantifying antimicrobial durations. This metric is easy to interpret and can feasibly be captured through the electronic prescribing record to aid in selecting ASP strategy.

Disclosures

All authors: No reported disclosures.
1634. A 9-Point Risk Assessment for Patients Who Inject Drugs Requiring Intravenous Antibiotics May Allow Health Systems to Focus Inpatient Resources on Those at Greatest Risk of Ongoing Drug Use
Authors: Eaton Ellen , Mathews Ronald , Lane Peter S , Paddock Cayce S , Rodriguez J Martin , Taylor Benjamin B , Saag Michael , Kilgore Meredith , Lee Rachael
Published: November 2018

Background

We implemented an Intravenous Antibiotics and Addiction Team (IVAT) intervention to identify hospitalized persons with a history of injection drug use (IDU) that are safe for discharge with IV antibiotics based on a 9-point risk assessment. IVAT has been shown to reduce average length of stay (ALOS) without increasing readmissions. We analyzed the cost savings of the IVAT to the health system.

Methods

PWID at the University of Alabama at Birmingham (UAB) hospital with indications for prolonged IV antibiotics received IVAT to determine risk of continued IDU. “Low-risk” patients were discharged for outpatient antibiotics and addiction care; others continued inpatient antibiotics, group therapy, opioid agonist therapy (if applicable), and weekly assessment for discharge readiness. Cost of care was defined by direct costs and was obtained by querying financial accounts.

Results

A total of 37 pre-IVAT and 111 post-IVAT admissions (including 25 “low risk”) met study criteria. IVAT reduced ALOS by 20 days. Total direct costs per admission in the post-IVAT period were 33% lower: $26,014 versus $38,716 (Table 1). Because ALOS at UAB for all patients is 6.58 days, a 20-day ALOS reduction following IVAT creates capacity for an additional 333 patients (n = 20/6.58 × 111).

Conclusion

IVAT for PWID allows health systems to focus inpatient resources on those at greatest risk of ongoing IVDU, creates additional inpatient capacity, and may cut hospital direct costs by one-third.

Disclosures

J. M. Rodriguez, finch: Research Contractor, Research support. seres: Research Contractor, Research support.
1636. Variation in Clinical Practice Patterns Among Infectious Diseases Faculty at a Large Academic Institution
Authors: Phadke Varun K , Spicer Jennifer O
Published: November 2018

Background

Clinical practice patterns vary between providers, but few studies have examined this variation among infectious disease (ID) physicians. Characterizing these differences in practice can help identify areas where targeted educational interventions or further research are needed to improve clinical decision-making. We describe a faculty survey conducted at our institution designed to identify clinical practice variation within a large academic ID division.

Methods

In January 2017, an electronic survey was distributed to all clinical ID faculty at our institution. The survey collected baseline demographic information as well as responses to 28 common clinical dilemmas encountered in routine practice. Descriptive statistics were performed.

Results

Twenty-four (44%) of 54 active clinical ID faculty (12 assistant professors, 6 associate professors, and 6 professors) completed the survey. Examples of clinical dilemmas with >80% agreement among faculty included: (1) S. aureus bacteremia should be a mandatory ID consult (88%) and (2) lumbar puncture should be performed for all patients with suspected ocular syphilis (88%). The majority of clinical dilemmas had less than 80% agreement, and these spanned the range of routine ID practice. Examples included: (1) use of ceftriaxone for outpatient antibiotic therapy for nonbacteremic invasive methicillin-susceptible S. aureus infections (58% agree), (2) length of treatment for guideline-defined uncomplicated S. aureus bacteremia (50% 2 weeks, 50% 4 weeks), (3) use of fixed-dose dolutegravir/abacavir/lamivudine as a single-drug regimen for an HIV-infected patient with an M184V mutation (42% agree), and (4) benefit of routine anal Pap smears among HIV-infected men who have sex with men (50% agree).

Conclusion

Practice patterns vary between ID physicians within our institution, particularly for clinical dilemmas for which there is insufficient or conflicting published data. Further studies to examine practice pattern variation among ID physicians across institutions and geographic regions could identify areas where further research or educational interventions are needed to enhance clinical care.

Disclosures

All authors: No reported disclosures.
1640. Toward New Anti-Biofilm Therapies: High Mobility Group Box 1 (HMGB1) Protein and Its Structural Variants Can Be Used to Disrupt Bacterial Biofilms (BBs)
Authors: Katragkou Aspasia , Warren Lauren , Buzzo John , Goodman Steven
Published: November 2018

Background

BB-related infections are a major public health problem, as they are notoriously refractory to current treatments. One of the defining characteristics of BBs is the extracellular polymeric substance (EPS). Extracellular DNA and the bacterial DNABII family of proteins are key components of EPS and are crucial for BBs structural integrity. It is known that targeting DNABII proteins disrupts BBs. We hypothesized that HMGB1, a DNA-binding eukaryotic protein, could affect BBs as it binds to the same DNA structures as the DNABII proteins. HMGB1 is comprised of 3 domains, A Box, B Box, and C tail, all of which have different functions. We aimed to determine in vitro the effects of HMGB1 and its individual domains against BBs.

Methods

Klebsiella pneumoniae (KP), a common cause of nosocomial infections, was used for all BBs disruption assays. Human recombinant full-length HMGB1 (rHMGB1; 1–215), a C45S mutation variant (mHMGB1) and the HMGB1 domains A Box (1–89), B Box (90–176), AB Boxes (1–176), B-linker Box (80–179), and B-linker Box C106S were expressed (in E. coli) and purified to >95%. To evaluate the effect of rHMGB1 and the various domains on established BBs, each protein species (200 nM) was added to preformed BBs at 24 hours. At 40 hours the BBs were washed, stained with LIVE/DEAD®, visualized via confocal laser scanning microscopy and images were analyzed by COMSTAT to calculate average thickness and biomass.

Results

Exogenous rHMGB1 and its individual domains, with the exception of A Box caused a significant reduction (P < 0.05) in average thickness (AT) and biomass (BM) of KP biofilms when compared with untreated KP biofilms (% reduction mean ± SE in AT: 44% ± 0.33, 75% ± 0.04, 63% ± 0.1, 77% ± 0.03, 64% ± 0.08, 54% ± 0.15 and in BM: 61% ± 0.01, 80% ± 0.01, 68% ± 0.02, 67% ± 0.01, 73% ± 0.02, 56% ± 0.02 induced by rHMGB1, mHMGB1, B-Box, B-linker Box, AB Boxes, and B-linker Box C106S, respectively).

Conclusion

Full-length recombinant HMGB1 was able to significantly disrupt established KP biofilms as were all truncated HMGB1 forms containing the B Box domain and could potentially be used as a therapeutic treatment for BB-related infections.

Disclosures

J. Buzzo, ProclaRx: Collaborator, Research support. S. Goodman, ProclaRx: Collaborator and Scientific Advisor, Research support.
1663. Marked Improvement in Pandemic H1N1 Component Shedding and Immunogenicity in 2017–2018 Russian-Backbone Live Attenuated Influenza Vaccine (LAIV) in Gambian Children
Authors: Lindsey Benjamin , Jankey Jagne , Armitage Edwin , Jeffries David , Mohammed Nuredin , Drammeh Sainabou , Senghore Elina , Sallah Hadi , Tregoning John , Hoschler Katja , Dong Tao , Clarke Ed , Kampmann Beate , De Silva Thushan
Published: November 2018

Background

Recent observational studies in the United States have reported reduced effectiveness of the Ann Arbor-backbone live attenuated influenza vaccine (LAIV), coinciding with emergence of 2009 pandemic H1N1 (pH1N1). A recent RCT in Senegal of the Russian-backbone LAIV also showed no efficacy, with pH1N1 the predominant vaccine-matched strain circulating during the study. The reasons for this reduced effectiveness and efficacy are unclear but may involve pre-existing immunity or pH1N1 virus-specific factors. We explore these underlying reasons through an LAIV immunogenicity study in Gambian children across 2 influenza seasons.

Methods

Gambian children aged 24–59 months (n = 118) were given 2016–17 northern hemisphere Russian-backbone trivalent LAIV. Vaccine shedding, haemagglutinin inhibition (HAI) titre, influenza-specific T-cell responses, and mucosal IgA were measured using RT-PCR, HAI assay, flow cytometry, and ELISA, respectively. The following year, a further 127 children were given 2017–2018 formulation LAIV, where the pH1N1 strain was updated.

Results

In 2016–2017, significantly less pH1N1 shedding (13.6% children) was seen compared with H3N2 (45.8%) and B/Victoria (80.5%). Similarly, poor pH1N1-specific HAI (5.1% seroconversion), mucosal IgA (18.6% responders) and T-cell responses (<10% responses to pH1N1 HA) were seen, whereas significantly greater responses in ≥1 immune compartments were seen to H3N2 and B/Victoria. pH1N1 shedding was not related to pre-existing immunity in 2016–2017. Vaccination with 2017–2018 LAIV showed improvement in pH1N1 shedding with no significant difference between strains: 67.7%, 63.2%, and 68.4% children shedding pH1N1, H3N2, and B/Victoria at day 2 post-LAIV (see Figure 1). This was matched by enhanced pH1N1 HA-specific T-cell responses, with 47.1% children showing a CD4+IFNg+ and 54.4% a CD4+IL2+ response (see Figure 2). HAI and mucosal IgA data for 2017–2018 are currently being generated and will be presented, as well as key interactions between the parameters measured.

Conclusion

Our data suggest that poor pH1N1 A/California strain replication in vivo may explain recent suboptimal LAIV performance and suggest that an improvement can be expected with new pH1N1 strains included in current LAIV formulations.

Disclosures

All authors: No reported disclosures.
1716. Results of the Respiratory Protection Effectiveness Clinical Trial (ResPECT)
Authors: Radonovich Lewis , Simberkoff Michael S , Bessesen Mary , Brown Alexandria C , Cummings Derek , Gaydos Charlotte , Los Jenna , Krosche Amanda , Gibert Cynthia , Gorse Geoffrey , Nyquist Ann-Christine , Reich Nicholas , Rodriguez-Barradas Maria , Price Connie , Perl Trish
Published: November 2018

Results of the Respiratory Protection Effectiveness Clinical Trial (ResPECT)

Background

Respiratory protection (RP) for healthcare personnel (HCP) is controversial and clinical studies are inconclusive about the effectiveness of N95 respirators (N95) and medical masks (MM) for protecting HCP from workplace viral respiratory infections and illnesses (VRII).

Methods

We conducted a cluster-randomized, investigator-blinded, multisite effectiveness study comparing N95 to MM in geographically diverse, high exposure outpatient settings between 2011 and 2016. Each year during VRII season, participants wore assigned devices when within 6 feet of patients with known or suspected respiratory illness. Respiratory swabs were collected from symptomatic and asymptomatic participants. Diaries detailed VRII exposures, influenza vaccination, adherence to RP and hand hygiene, and manifestations of illness. The primary and secondary outcomes were the incidence of laboratory-confirmed influenza (LCI) using polymerase chain reaction (PCR) and hemagglutinin inhibition assays (HAI), and acute respiratory illness (ARI), influenza-like illness (ILI), laboratory-confirmed respiratory illness (LCRI), and laboratory-detected respiratory infection (LDRI) (figure). Intervention protective effects were estimated using unadjusted odds and incidence rate ratios.

Results

5,180 HCP seasons enrolled and randomized (2,243 to N95 and 2,446 to MM), with 4,689 (91%) completing the study. In the intention-to-treat cohort (ITT), among participants in the N95 and MM groups, respectively, 207 (8.2%) and 193 (7.2%) were diagnosed with LCI (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.93–1.40); 1,556 (61.9%) and 1711 (64.1%) were diagnosed with ARI (relative risk (RR) 0.99, CI 0.92–1.06); 128 (5.1%) and 166 (6.2%) were diagnosed with ILI (RR 0.87, CI 0.68–1.10), 371 (14.8%) and 417 (15.6%) were diagnosed with LCRI (RR 0.97, CI 0.84–1.12); and 679 (27.0%) and 745 (27.9%) were diagnosed with LDRI (RR 0.99, CI 0.89–1.09). The adjusted ITT and per-protocol analyses yielded similar results.

Conclusion

In this outpatient-based, cluster-randomized, controlled trial, neither N95 nor MM resulted in superior protection from LCI or VRII.

Disclosures

C. Gaydos, BioFire: Consultant, Consulting fee. Cepheid: Speaker’s Bureau, Speaker honorarium. Becton Dickinson: Speaker’s Bureau, Speaker honorarium.
1728. Effectiveness and Healthcare Personnel (HCP) Perceptions of a Multi-Site Personal Protective Equipment (PPE) Free Zone Intervention
Authors: Visnovsky Lindsay , Mulvey Diane , Zhang Yue , Leecaster Molly , Donskey Curtis J , Krein Sarah L , Safdar Nasia , Alhmidi Heba , Barko Lauren , Haroldsen Candace , Ide Emma , Nevers McKenna , Shaughnessy Catherine , Stratford Kristina , Drews Frank , Samore Matthew , Mayer Jeanmarie
Published: November 2018

Background

CDC provides guidelines for using contact precautions (CP) when caring for patients with antibiotic-resistant bacteria or Clostridium difficile. However, HCP frequently report discomfort, difficulty of use, and interrupted workflow with CP. Modifying CP guidelines to balance these issues requires testing to assess benefits and maintenance of safe practices. A promising approach using a “PPE Free Zone” strategy within rooms of patients in CP has not been well-studied.

Methods

The PPE Free Zone comprised a 3–6 foot area inside door thresholds of CP patient rooms denoted by red tape placed on the floor. Within the zone, HCP were not required to don PPE. HCP were considered compliant if they performed hand hygiene (HH) and donned appropriate PPE before crossing the zone. Observers at 6 acute care facilities (ACF) were trained on observing HCP HH and use of PPE with CP. Observations were made before and after implementation of a PPE Free Zone. Intervention ACF conducted observations on 8 intervention units and 6 nonintervention units. Models of overall compliance and entry HH compliance were constructed using a generalized linear-mixed effects model with a logistic link function. Pre-intervention observations from all 6 ACF and intervention phase observations from the 3 intervention ACF were used in models.

Results

We observed 4,510 room entries. HH adherence declined over time in both intervention and control units but declined less among intervention units from pre to post intervention (β: 0.71, P = 0.007, Figure 1). Stratified by precautions type, the effect of the PPE Free Zone on HH was only significant for rooms in enteric precautions (P < 0.001). Compliance with PPE use was not significantly different pre- versus postintervention (P = 0.133). When surveyed, HCP had positive views of the PPE Free Zone: 65% (n = 172) agreed or strongly agreed the zone facilitates communication with patients, permits checking on patients more frequently, and saves time [n = 169] (Figure 2).

Conclusion

Although HCP viewed the zone positively and it had a significant effect on HH in enteric precautions rooms, the zone did not improve PPE compliance. Future interventions in the ACF setting should consider the complex sociotechnical system factors influencing behavior change.

Disclosures

All authors: No reported disclosures.
1729. Effect of Glove Disinfection on Bacterial Contamination of Healthcare Worker Hands
Authors: Robinson Gwen , Kpadeh Zegbeh Z , Alserehi Haleema , Morgan Daniel , Harris Anthony D , Johnson J Kristie , Leekha Surbhi
Published: November 2018

Background

Disinfection of gloves and gowns was recommended to decrease healthcare worker (HCW) self-contamination during doffing of gloves and gowns in the Ebola epidemic. To understand the potential role of this practice in preventing bacterial transmission, we examined the effect of disinfectants on bacterial contamination of HCW hands following glove removal.

Methods

A laboratory simulation study was conducted using methicillin-susceptible Staphylococcus aureus and antibiotic-sensitive Klebsiella pneumoniae among volunteer HCWs (n = 10 per organism). For each experiment, the volunteer donned 2 pairs of gloves with the “under glove” simulating HCW hands and “top glove” simulating actual glove use in the clinical setting. The top-glove was inoculated with 108 CFU bacteria for each step. Top gloves were sampled directly after inoculation (Arm A), and after disinfection with alcohol gel, bleach wipes, and quaternary ammonium (quat) wipes, in separate steps (Arm B). Under gloves were sampled after top glove removal without disinfection (Arm C), and top glove removal post disinfection (Arm D). Quantitative bacterial load reduction was compared for glove use (Arm C − Arm A), and for disinfectant use in addition to glove use (Arm D − Arm C). Qualitative detection of any bacterial load (present/absent) on under glove in the setting of disinfection prior to top glove removal was also assessed.

Results

Of 108 CFU inoculated, the median recovery was 1.2 × 104 CFU (both bacteria combined). After glove removal (no disinfection), the median recovery from the under glove was 2.7 × 102 CFU, for a reduction of 98% (1.6 log) in bacterial load. After top glove disinfection and removal, the median bacterial recovery from the under glove was 1.4 × 102, 0, and 0 CFU for alcohol, quat, and bleach (47% or 0.3 log reduction for alcohol; 99% or 2 log reduction for quat and bleach) (Figure 1). Regardless of quantity, bacteria were recovered from under gloves even after top glove disinfection in 70%, 40%, and 35% cases for alcohol, quat, and bleach, respectively (Figure 2).

Conclusion

Glove disinfection prior to glove removal is effective at reducing bacterial contamination of HCW hands. However, despite disinfection, some level of hand contamination occurs frequently.

Disclosures

J. K. Johnson, Q-Linea: Investigator, Research grant. Applied Biocode: Investigator, Research grant
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

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

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.