bluuebunny/crossref_metadata_2025 huggingface dataset:
928. Major Decrease in Prevalence of Hepatitis C Viremia in Key Populations following the Second Year of Treatment as Prevention for Hepatitis C (TraP HepC) Program in Iceland
Authors: Gottfredsson Magnus , Tyrfingsson Thorarinn , Runarsdottir Valgerdur , Hansdottir Ingunn , Bergmann Ottar M , Bjornsson Einar S , Johannsson Birgir , Sigurdardottir Bryndis , Fridriksdottir Ragnheidur H , Löve Arthur , Löve Thorvardur J , Sigmundsdottir Gudrun , Hernandez Ubaldo , Heimisdottir Maria , Olafsson Sigurdur
Published: November 2018

Background

Hepatitis C Virus (HCV) commonly affects people who inject drugs (PWID) and/or with history of injection drug use (IDU). They are also disproportionately represented in addiction treatment centers and the penitentiary system. In order to curtail spread of HCV it is therefore important to approach these groups. PWID and prisoners have been prioritized in the TraP HepC program. The impact can thus be assessed by monitoring HCV prevalence at sentinel sites, such as addiction hospitals and prisons.

Methods

TraP HepC offers direct-acting antiviral agents (DAAs) to all HCV patients in Iceland, starting in January 2016. HCV PCR is performed at the end of treatment and 12 weeks later (SVR12). PWID and prisoners are monitored for reinfection and retreated if needed. We compared the prevalence of HCV viremia among PWID admitted for treatment at Vogur addiction hospital and inmates of the penitentiary system, before and after 2 years of TraP HepC.

Results

Two years into the program 667 patients had been evaluated of which 632 were initiated on their first course of DAAs and 7 were pending, representing 80% of the estimated total patient population. Of those who completed first treatment according to guidelines the SVR12 is 95.5%. Drop-out from first treatment was 8.2%; nevertheless, the SVR12 was >40% and most of the remaining viremic patients completed or are undergoing retreatment. In 2012–2015, prior to TraP HepC the prevalence of HCV viremia among actively injecting PWID admitted for addiction treatment was 47.9%, dropping to 39.8% in 2016 and 16.2% in 2017 (P < 0.001). Likewise, the prevalence of viremia among patients with history of IDU but not recently injecting fell from 27.4% (2012–2015) to 19.8% in 2016 and 4.1% in 2017 (P < 0.001). The prevalence of viremia among inmates of the penitentiary system was 29% prior to initiation of TraP HepC, dropping to 7% in 2017 (P < 0.01). These results are not explained by declining IDU in the community.

Conclusion

On a population level the domestic transmission of HCV can be reduced by DAAs when combined with other efforts. Two years into the TraP HepC program the prevalence of viremia among two of the most important drivers of the epidemic has been markedly reduced. The program is ongoing, with further emphasis on increased intensity of screening, retreatment and harm reduction.

Disclosures

All authors: No reported disclosures.
964. Impact of Doxycycline as Malaria Prophylaxis on Risk of Influenza Like Illness Among International Travelers
Authors: Lago Kathryn , Telu Kalyani , Tribble David R , Ganesan Anuradha , Kunz Anjali , Geist Charla , Fraser Jamie , Mitra Indrani , Yun Heather
Published: November 2018

Background

International travelers are often at risk for both influenza like illness (ILI) and malaria. Doxycycline is active against many pathogens causing ILI and is routinely used for malaria prophylaxis. We evaluated the incidence of and risk factors for ILI, and whether the choice of malaria prophylaxis was associated with ILI.

Methods

TravMil is a prospective observational study enrolling subjects presenting to 6 military travel clinics. We analyzed pre- and post-travel surveys from travelers to regions outside of the continental United States, Western or Northern Europe, Canada, or New Zealand between July 2010 and August 2018. ILI was defined as subjective fever associated with either a sore throat or cough. Characteristics of trip and traveler and the use of malaria prophylaxis were analyzed to determine association with development of ILI. Poisson regression models with robust error variance were used to estimate relative risk of ILI.

Results

A total of 3,227 travelers were enrolled: 62.1% male, median age of 39 (IQR 27, 59), median travel duration 19 days (IQR 12, 49). 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean, Mexico, and Central or South America. Military travel (46%) and vacation (40%) were most common reasons for travel. Twenty percent took doxycycline for malaria prophylaxis, 50% other prophylaxis (89% atovaquone–proguanil), and 30% took none. 8.7% developed ILI. Compared with those on no or other prophylaxis, doxycycline was associated with decreased risk of ILI [RR 0.65 (0.43–0.99), P = 0.046], as was military travel [RR 0.30 (0.21–0.43), P < 0.01]. Increased risk of ILI was associated with female gender [RR 1.57 (1.24–1.98), P < 0.01], travel to Asia [RR 1.37 (1.08–1.75), P = 0.01], cruises [RR 2.21 (1.73–2.83), P < 0.01], and longer duration of travel [RR 1.01 (1.00–1.01, P < 0.01].

Conclusion

The use of doxycycline is associated with a decreased risk of ILI compared with taking no or other malaria prophylaxis. The reasons for this are unclear but may be related to anti-inflammatory effects, activity against bacterial respiratory pathogens, effects on disease transmission in closed populations (e.g., military deploying groups), or other unmeasured factors. With few proven strategies for decreasing ILI risk in travelers, these findings bear further investigation.

Disclosures

All authors: No reported disclosures.
966. Infectious Diseases among US Resident Student Travelers after Return to the United States: A GeoSentinel Analysis, 2007–2017
Authors: Angelo Kristina M , Haulman Jean , Terry Anne , Leung Daniel , Chen Lin H , Barnett Elizabeth , Hagmann Stefan , Hynes Noreen , Connor Bradley , Anderson Susan , Hamer Davidson
Published: November 2018

Background

The number of US students studying abroad has more than tripled over the past 20 years. As study abroad programs diversify their destinations, more students are traveling to developing regions, increasing their risk of infectious diseases. Few data exist describing infections acquired by US students while traveling internationally. We describe the spectrum of disease among students who have returned from international travel and suggest how to reduce illness among these travelers.

Methods

GeoSentinel is a global network of travel and tropical medicine providers that monitors travel-related morbidity. Records of US resident student travelers, 17–24 years old, who returned to the United States and were given a confirmed travel-related diagnosis at one of 15 US GeoSentinel sites during 2007–2017. Those without ascertainable exposure regions were excluded. Records were analyzed to describe demographic and travel characteristics and diagnoses.

Results

There were 432 students included. The median age was 21 years; 69% were female. Over 70% had a pretravel consultation with a healthcare provider. The most common exposure region was sub-Saharan Africa (112 travelers; 26%); the most common exposure countries were India (44 students; 11%), Ecuador (28; 7%), Ghana (25; 6%), and China (24; 6%). Students presented to a GeoSentinel site a median of 8 days (range: 0–181) after travel; 98% were outpatients. The most common diagnosis categories were gastrointestinal (45%) and dermatologic (17%). Of 581 confirmed diagnoses, diarrheal illnesses were most common (165; 28%). Thirty-one (7%) students had a vector-borne disease; 14 (41%) of these were diagnosed with malaria (13 had a pretravel consultation) and 11 (32%) with dengue. Two students were diagnosed with acute HIV. Three had a vaccine-preventable disease (two typhoid; one hepatitis A).

Conclusion

Students experienced travel-related infections despite a large proportion receiving pretravel consultations. Students (especially those traveling to a less developed region) should receive specific pretravel instructions (including suggestions for behavioral modification, vaccination, and medication prophylaxis when applicable) to prevent gastrointestinal, vector-borne, sexually transmitted, and vaccine-preventable diseases.

Disclosures

All authors: No reported disclosures.
968. Managing Invasive Aspergillosis in the Era of Diagnostic PCR and Increasing Triazole Resistance: A Modeling Study of Different Strategies
Authors: Van De Peppel Robert , Van Der Beek Martha , De Boer Mark , Wallinga Jacco
Published: November 2018

Background

Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive Aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance on a genetic level, which opened up new possibilities for targeted therapy. In the absence of clinical trials, a modeling study delivers estimates of the added value of resistance detection with PCR and which empiric therapy would be optimal when local resistance rates are known.

Methods

We performed a decision-analytic modeling study based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. We compared 6 clinical strategies that differ in the use of PCR diagnostics (A: not used, B: used) and in empiric therapeutic choice in case of unknown triazole susceptibility: Voriconazole (1, VOR), Liposomal Amphotericin B (2, LAmB), or both (3). Outcome measures were proportion of correct treatment, survival, and serious adverse events.

Results

Implementing Aspergillus PCR tests was projected to result in residual treatment susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using VOR). Empiric LAmB outperformed VOR at resistance rates higher than 5–20%, depending on PCR use and estimated survival benefits of VOR over LAmB (Figure 1). Combination therapy of VOR and LAmB performed best at all resistance rates but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events (Figure 2). The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole-resistance rates.

Conclusion

Introduction of current Aspergillus PCR tests on BAL-fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and of adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR, and individual patient characteristics.

Disclosures

All authors: No reported disclosures.
971. Breakthrough Invasive Fungal Infections (IFI) in Acute Leukemia (AL) Patients Receiving Antifungal Prophylaxis
Authors: Wasylyshyn Anastasia , Castillo Caroline , Linder Kathleen A , Zhou Shiwei , Kauffman Carol A , Miceli Marisa H
Published: November 2018

Background

A major challenge in patients with AL receiving chemotherapy is to decrease the risk of IFI during the prolonged neutropenic period. Even with antifungal prophylaxis, the incidence of breakthrough IFI can be as high as 14%. Our objectives were to determine the incidence of all IFI and breakthrough IFI, to define risk factors associated with IFI, and to assess outcomes.

Methods

Single-center retrospective cohort analysis of all adult patients admitted to the University of Michigan for AL from January 1, 2010 to December 31, 2013. Chart review determined co-morbidities, chemotherapy regimens, antifungal prophylaxis, occurrence of IFI as determined by EORTC/MSG criteria, and outcomes. Chi-square, Fischer’s, ANOVA, and binary logistic regression tests were performed when appropriate.

Results

Of 363 patients, all but 4 had acute myeloid leukemia (AML); 124 had a stem cell transplant (SCT). A total of 103 (28%) had proven (n = 13), probable (n = 22), or possible (n = 68) IFI. Considering only those 35 patients who had proven or probable IFI, the only risk factor for development of IFI by logistic regression analysis was IFLAG chemotherapy (P = .006). Mold infections occurred in 27 patients: Aspergillus (19), Mucorales (5), both Aspergillus and Mucorales (1), Alternaria (1), and Scedosporium (1). Additionally, 5 patients had invasive candidiasis and 3 had Pneumocystis. Eighteen of 35 patients (51%) had breakthrough IFI while on posaconazole suspension (6), fluconazole (5), micafungin (5) or voriconazole (2). Factors significantly associated with breakthrough IFI were SCT (P = .04), neutrophils <500, ≥10 days at diagnosis (P = .002) and prophylaxis with posaconazole suspension (P = .003). Twelve-week mortality in proven and probable IFI was 31% (11/35). Nine of 11 deceased patients had breakthrough IFI; 8 of whom (5 with mold IFI and 3 with invasive candidiasis) died of the fungal infection.

Conclusion

Patients receiving chemotherapy for AL remain at risk for IFI despite the the use of antifungal prophylaxis. In our study, prophylaxis with posaconazole suspension was found to be an independent risk factor for breakthrough IFI. Mortality was high among patients with breakthrough IFI.

Disclosures

All authors: No reported disclosures.
974. Impact of Mandatory Infectious Disease (ID) Specialist Approval on Hospital-Onset Clostridium difficile (HO-CDI) Testing and Infection Rates: Results of a Pilot Study
Authors: Lin Michael Y , Wiksten Tiffany , Tomich Alexander , Hayden Mary K , Segreti John
Published: November 2018

Background

The 2017 IDSA C. difficile guidelines recommend the use of nucleic acid amplification testing alone for detection of HO-CDI if appropriate stool specimens are collected (e.g., patients not receiving laxatives and ≥3 unformed stools in 24 hours). The potential role of ID specialists in enforcing appropriate C. difficile testing is unclear.

Methods

At a single academic hospital, we performed a pilot study of an ID specialist-led approval process for C. difficile testing. During the baseline period (January 2016 and November 2017), HO-CDI testing appropriateness was enforced using a computerized decision support tool that discouraged inappropriate testing based on detected laxative use and stool frequency criteria; however, clinicians frequently ignored the computer alerts. During the intervention period (December 2017 and March 2018), all HO-CDI testing on hospital day 4 or later triggered a computer alert requesting mandatory testing approval by an ID specialist. Approvals were provided via telephone consultation 7 days a week between 8 a.m. and 5 p.m. (in both periods, CDI testing was not performed overnight). We analyzed differences HO-CDI testing and infection rates (defined by CDC’s LabID event) per 10,000 patient days using Poisson models. We also analyzed the number of approval pager calls, rates of C. difficile testing approval, and time burden.

Results

Two infectious diseases specialists (M.Y.L.; J.S.) primarily answered C. difficile pager approval requests; the remainder of approvals were provided by ID specialists already consulted on the patients. During the intervention period, ordering providers made 159 calls to the approval pager; 119 (75%) received approval. HO-CDI testing and infection rates declined between the baseline and intervention periods (figure). There was a mean of 1.3 pager approval requests per day (range, 0–4) with an average of 3 minutes of time spent per request.

Conclusion

An ID specialist-led C. difficile testing approval process was feasible and associated with a significant decrease in HO-CDI testing and infection rates, due to enforcement of appropriate testing. ID specialists can provide a key role in enforcing appropriate C. difficile testing, but more experience is needed with respect to sustainability.

Disclosures

M. Y. Lin, Stryker (Sage Products): Research support in the form of contributed product, Research support. OpGen, Inc: Research support in the form of contributed products, Research support. CareFusion Foundation (now BD): Grant Investigator, Research grant.
979. Standardizing Medical Student Learning for Infectious Diseases Consult Electives: Prioritizing Content
Authors: Abdoler Emily , Hauer Karen , Schwartz Brian
Published: November 2018

Background

The goals of 4th-year medical student electives vary, and students’ learning during clinical electives may occur solely through the subspecialty cases that students encounter. We aim to standardize learning during electives by creating a toolkit to guide elective directors in the development of curricula that reinforce basic science principles, highlight areas for high-value care, and provide opportunities for further inquiry. The first step is to determine the core specialty topics applicable to students regardless of career choice. Here, we describe this content prioritization process within the context of an infectious diseases (ID) elective pilot curriculum.

Methods

We conducted a modified, 2-round Delphi process to develop consensus on ID topics that all graduating medical students should know. Through review of the literature for common diagnoses and high value care, and the medical school curriculum, the authors generated an initial list of 16 topics. An interdisciplinary group of 90 expert faculty educators from Internal Medicine, Family Medicine, Emergency Medicine, and Surgery rated these topics’ importance using a 5-point Likert scale, from 0 (absolutely do not include) to 4 (very important). We considered items rated at least 3 (important) by at least 80% of participants to have reached consensus.

Results

Sixty of 90 (67%) educators responded to the initial survey, and 48/60 (80%) completed both surveys. Nine additional topics were proposed by first-round participants. After the second round, 14 topics met the consensus criterion. Many common conditions, several dangerous infections, and infectious issues overrepresented in the local population met consensus. However, while many of the topics failing to meet consensus addressed rare conditions or those typically managed by subspecialists, some were also common conditions.

Conclusion

Standardizing medical student learning during elective rotations begins with identifying key topics. Our process included a diverse group of educators to determine key topics. We will use this list to guide the content of a new asynchronous, online ID elective curriculum, and we will describe our process as part of a curriculum development toolkit for other elective directors.

Disclosures

All authors: No reported disclosures.
1633. A Multifaceted Intervention to Improve Prescribing for Acute Respiratory Infection in Adults and Children in Emergency Department and Urgent Care Settings (MITIGATE Trial)
Authors: Yadav Kabir , Meeker Daniella , Mistry Rakesh , Doctor Jason , Fleming-Dutra Katherine , Fleischman Ross , Gaona Samuel , Stahmer Aubyn , May Larissa
Published: November 2018

Background

Antibiotics are prescribed in approximately half of emergency department (ED) and urgent care center (UCC) visits for antibiotic inappropriate or presumed viral acute respiratory infection (ARI). Unnecessary antibiotic use increases adverse events, antibiotic resistance, and healthcare costs. Antibiotic stewardship in the ED and UCC requires specific implementation tailored to these unique settings.

Objective. To evaluate the comparative effectiveness of patient and provider education adapted for the acute care setting (adapted intervention) to an intervention with behavioral nudges and individual peer comparisons (enhanced intervention), on reducing inappropriate antibiotic use for ARI in EDs and UCCs.

Methods

Pragmatic, cluster randomized clinical trial conducted in 3 academic health systems (1 pediatric-only, 2 serving adults and children) that included 5 adult and pediatric EDs and 4 UCCs. Sites were block randomized by health system, and providers at each site assigned to receive the adapted or enhanced intervention. Implementation science strategies were employed to tailor interventions at each site. The main outcome was the proportion of antibiotic inappropriate ARI diagnosis visits that received an antibiotic. We estimated a hierarchical mixed effects logistic regression model for visits that occurred between November and February for 2016–2017 (baseline) and 2017–2018 (intervention), controlling for organization and provider fixed effects.

Results

Across all sites, there were 45,160 ARI visits among 534 providers, with overall antibiotic prescribing at 2.6%; the pediatric-only system had a lower baseline rate (1.6%) compared with the other 2 systems (5.0% and 7.1%), P < 0.001). Despite the unusually low rate, we found a significant reduction in inappropriate prescribing after adjusting for health-system and provider-level effects from 2.6% to 1.4 % (odds ratio 0.52; 0.38–0.72). Reductions in prescribing between the 2 interventions were in the expected direction, but not significantly different (P < 0.062).

Conclusion

Implementation of antimicrobial stewardship for ARI is feasible and effective in the ED and UCC settings. The enhanced behavioral nudging methods were not more effective in high-performance settings.

Disclosures

All authors: No reported disclosures.
1638. Tele-Infectious Disease Consultation Produces Equivalent Outcomes as In-Person Consultation
Authors: Younus Faheem , Girio-Herrera Leonardo , Barrueto Fermin , Ahmed Zaka , Zimand Paul
Published: November 2018

Background

Technology can extend Infection Disease Consultants (IDCs) into resource limited small community US hospitals. We compared in-person infectious disease (ID) consults with Tele-ID consults to determine whether length of stay, antibiotic usage, drug cost, or readmission rates will remain the same between both groups over a 3-month period.

Methods

University of Maryland Harford Memorial Hospital (UM-HMH) is a 95-bed hospital including a 6-bed ICU. From May to August 2017 (study period) there was no IDC at UM-HMH. During study period, IDCs from a regional UM hospital provided formal Tele-ID consults through an HIPAA compliant secured Skype Business account. Patient history and wound examination were done by the IDC via video monitor while a bedside nurse assisted in performing the physical examination. Laboratory and radiological data were reviewed in real time as both hospitals shared the same electronic medical record and IT infrastructure (Meditech 6.15). A formal consultation was dictated and computer orders were entered by the IDC within 24 hours of the consult request. Daily Tele-ID follow-up rounds were conducted. IDCs had the authority to transfer a patient to the regional hospital for in-person care if deemed necessary. Study period was compared with a baseline period (May–August 2016) when IDCs were providing in-person consults at UM-HMH.

Results

Baseline period had 148 inpatient stays and study period had 148 inpatient stays. Despite similar case mix index in both groups, there was no statistical difference between the clinical outcomes. Results are shown in Table 1.

Conclusion

Tele-ID at our hospitals was noninferior to in-person ID consults. An integrated computer system, nursing support, and daily follow-up are key components of a successful Tele-ID program.

Disclosures

All authors: No reported disclosures.
1639. Efficacy of Voriconazole Prophylaxis Followed by Therapeutic Liposomal Amphotericin B for the Treatment of Murine Pulmonary Aspergillosis Caused by Azole-Resistant Aspergillus fumigatus Strains
Authors: Olson Jon , Slarve Matthew , Adler-Moore Jill
Published: November 2018

Background

Antifungal treatment for pulmonary aspergillosis is more difficult if the fungal strain causing the infection is azole resistant. To investigate this problem, we used a murine model of pulmonary aspergillosis caused by azole-resistant Aspergillus fumigatus strains V29 and V45, and compared treatment with voriconazole (Vr, oral 40 mg/kg, bid) or liposomal amphotericin B (L-AmB, 5 mg/kg, IV) used alone or in combination.

Methods

Mice (n = 14/gp) were immunosuppressed with 24 mg/kg triamcinolone acetonide, IP, d-3, d-1, and d+1 relative to fungal challenge (d0). For 2 groups, Vr was given prophylactically (proph) d-3, d-2, d-1 followed by L-AmB or buffer, d+1, d+2, and d+3. The other groups were given Vr, L-AmB, Vr+L-AmB, or buffer d+1, d+2, and d+3. On d0, mice were given 1.3 to 1.6 × 107A. fumigatus spores intranasally (Vr MIC = 64 μg/mL, V29; Vr MIC = 8 μg/mL, V45). On d+3, lungs were collected from 7 mice/gp and fungal burden determined by plating for colony forming units; 7 mice/gp were then monitored for morbidity to d+21.

Results

Optimum treatment was observed when Vr was given proph, followed by L-AmB post-challenge (Vr/L-AmB), with better survival (100%) for both fungal strains vs. buffer or Vr post-challenge (P ≤ 0.04); for V29, significantly better survival was also seen with Vr/L-AmB vs. L-AmB or Vr+L-AmB post-challenge (P ≤ 0.01). For strain V45, lung fungal burden was significantly lower for Vr/L-AmB versus all other treatments (P ≤ 0.04), while for strain V29, fungal burden was lower for the Vf/L-AmB and L-AmB post-challenge groups versus the other groups, but the differences were not significant. Notably, although the lung fungal burden with Vr proph and Vr postchallenge were both similar to the buffer control, Vr proph yielded significantly better survival than Vr post-challenge (P ≤ 0.001).

Conclusion

These preclinical observations demonstrate that combining L-AmB with Vr for the postchallenge treatment of pulmonary aspergillosis caused by azole-resistant strains is not an effective therapeutic option. However, the results do show that Vr proph, but not Vr postchallenge, can have some limited antifungal activity, and can significantly enhance the antifungal effects of post-challenge L-AmB. This regimen could be considered in areas where there is a high incidence of azole-resistant A. fumigatus.

Disclosures

All authors: No reported disclosures.
1645. Exploring Clinical and Antiviral Efficacy of Baloxavir Marboxil in a Phase 3, Randomized, Double-Blind, Placebo- and Active-Controlled Study of Otherwise Healthy Adults/Adolescents in Seasonal Influenza: Impact on Regional Participants, Treatment Time and Influenza Type B Virus Infection (CAPSTONE-1 Study)
Authors: Kawaguchi Keiko , Portsmouth Simon , Shishido Takao , Uehara Takeki , Hayden Frederick
Published: November 2018

Background

Baloxavir marboxil (BXM), a selective cap-dependent endonuclease inhibitor, has demonstrated efficacy + safety for influenza in otherwise healthy patients. We present subgroup analyses for (i) United States vs. Japan (J), (ii) time (t) of treatment (early: ≥0 to ≤24 hours, vs. late: >24 to ≤48 hours), and (iii) influenza type B infections from the global Ph 3 trial (16/17 season).

Methods

A multicenter, randomized, double-blind, placebo (PLC)- and oseltamivir (OV)-controlled study recruited patients in Japan (n = 846) and United States (n = 590). Inclusion criteria: age 12–64 years, fever + flu symptoms, and ≤48 hours from symptom onset. Patients (20–64 years) randomized (2:2:1) to a single oral dose of BXM, PLC, or 75 mg OV BID for 5 days; patients 12–19 years were randomized (2:1) to receive BXM or PLC. BXM dose: 40/80 mg for BW </≥80 kg. Primary endpoint: time to alleviation of symptoms (TTAS) in ITTI population (pop). Viral titers measured from pre-/postdose nasal swabs.

Results

BXM reduced the median TTAS by 30.6 hours versus PLC (87.3 versus 117.9 hours, P = 0.1373) in the US pop and t to cessation of viral shedding: 24 versus 72 hours for PLC (P < .0001). Median TTAS in the United States versus J pop was longer, due to imbalances between groups. In both early/late treatments from symptom onset, BXM reduced TTAS versus PLC (Table 1). Regardless of the t to treatment from symptom onset, BXM reduced virus titer significantly from BL versus PLC and OV (Table 2). No significant reduction in TTAS was seen, while BXM reduced virus titer versus PLC and OV in type B virus infection.

Conclusion

Outcomes for United States were aligned with the Ph 3 Results. Early treatment with BXM leads to a significantly faster TTAS vs. PLC. BXM caused significant viral titer reduction regardless of treatment time versus OV. BXM reduced virus titer vs. PLC and OV in type B virus infection.

Disclosures

K. Kawaguchi, Shionogi & Co., Ltd.: Employee, Salary. S. Portsmouth, Shionogi Inc: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary.T. Uehara, Shionogi & Co., Ltd.: Employee, Salary. F. Hayden, Shionogi & Co., Ltd.: Scientific Advisor, Consulting fee (donated) and travel support for attending 6th ESWI meeting, 10–13 September 2017, Latvia, to present phase 3 OWH results.
1648. Incidence of Norovirus and Rotavirus From Multisite Active Surveillance in Veteran’s Affairs Hospitals, December 2016–February 2018: Results From the SUPERNOVA Network
Authors: Cardemil Cristina V , Kambhampati Anita , Grytdal Scott , Rodriguez-Barradas Maria C , Vargas Blanca , Beenhouwer David , Evangelista Karen , Marconi Vincent , Meagley Kathryn , Brown Sheldon , Perea Adrienne , Lucero Cynthia , Holodniy Mark , Browne Hannah , Gautam Rashi , Bowen Michael D , Vinje Jan , Parashar Umesh D , Hall Aron J
Published: November 2018

Background

Viruses are frequently implicated in acute gastroenteritis (AGE) outbreaks, yet the endemic burden of norovirus and rotavirus disease in adult populations is not well characterized. In 2016, we implemented a multisite AGE surveillance platform capturing cases and controls in 4 VA hospitals (Atlanta, Bronx, Houston, and Los Angeles), collectively serving >320,000 patients annually.

Methods

Inpatient AGE cases and age- and time-matched controls were identified through prospective screening of admissions via standardized case definitions. Outpatient cases were passively identified using stool samples submitted for routine clinical microbiological diagnostics. Samples were tested with the FilmArray Gastrointestinal Panel, followed by genotyping of virus positives. Incidence was estimated using population denominators of unique patients served annually by site.

Results

From December 1, 2016 to February 28, 2018, 875 cases (496 inpatients, 379 outpatients), and 374 controls were enrolled. Norovirus and rotavirus prevalence was highest among outpatient AGE cases (11.6% and 2.9%, respectively) followed by inpatient cases (3.4% and 1.6%, respectively); few controls were positive (norovirus, 1.3%; rotavirus, 0%). Norovirus-associated inpatient incidence was 15.2 per 100,000 population (range by site: 10.7–19.9/100,000) and rotavirus-associated inpatient incidence was 7.5 per 100,000 population (range by site: 0–12.8/100,000). The predominant norovirus genotype was GII.P16-GII.4 Sydney (50%), and rotavirus genotype was G12P[8] (83%). Norovirus was detected every calendar month and peaked in December–January, while rotavirus peaked in April. Nine deaths were documented among AGE inpatient cases, including one norovirus-associated death.

Conclusion

Implementation of a multisite AGE surveillance platform captured a wide spectrum of illness for norovirus and rotavirus in US Veterans including outpatient visits, inpatient hospitalizations, and one norovirus-associated death. Norovirus was the leading viral pathogen and was detected year-round. Ongoing surveillance using this platform will allow for further characterization of the pathogen distribution and associated AGE disease burden in adults.

Disclosures

V. Marconi, ViiV: Investigator, Research support and Salary. Bayer: Investigator, Research support. Gilead: Investigator, Research support.
1722. The Changing Epidemiology of Candidemia in the United States: Injection Drug Use as an Emerging Risk Factor for Candidemia
Authors: Zhang Alexia Y , Shrum Sarah , Williams Sabrina , Vonbank Brittany , Hillis Sherry , Barter Devra , Petnic Sarah , Harrison Lee H , Dumyati Ghinwa , Phipps Erin C , Pierce Rebecca , Schaffner William , Farley Monica M , Mody Rajal K , Chiller Tom , Jackson Brendan R , Vallabhaneni Snigdha
Published: November 2018

Background

Known risk factors for candidemia include diabetes, malignancy, antibiotics, total parenteral nutrition (TPN), prolonged hospitalization, abdominal surgery, and central venous catheters. Injection drug use (IDU) is not a common risk factor. We used data from CDC Emerging Infections Program’s candidemia surveillance to assess prevalence of IDU among candidemia cases and compare IDU and non-IDU cases.

Methods

Active, population-based candidemia surveillance was conducted in 45 counties in 9 states during January–December 2017. Data from 2014 to 2016 were available from 4 states and were used to look for trends. A case was defined as blood culture with Candida in a surveillance area resident. We collected clinical information, including IDU in the past 12 months. Differences between IDU and non-IDU cases were tested using logistic regression.

Results

Of 1,018 candidemia cases in 2017, 123 (12%) occurred in the context of recent IDU (1% in Minnesota and 27% in New Mexico) (Figure 1). In the 4 states with pre-2017 data, the proportion of IDU cases increased from 7% in 2014 to 15% in 2017, with the proportion in Tennessee nearly tripling from 7% to 18% (Figure 2). IDU cases were younger than non-IDU cases (median 34 vs. 62 years, P < 0.001). Compared with non-IDU cases, IDU cases were less likely to have diabetes (16% vs. 35%; OR 0.4, CI 0.2–0.6), malignancies (7% vs. 30%; OR 0.2, CI 0.1–0.3), abdominal surgery (6% vs. 19%; OR 0.3, CI 0.1–0.6), receive TPN (6% vs. 27%; OR 0.2, CI 0.1–0.4) and were more likely to have hepatitis C (96% vs. 47%; OR 16.1, CI 10.4–24.9), be homeless (13% vs. 1%; OR 17.8, CI 7.1–44.6), and have polymicrobial blood cultures (33% vs. 17%; OR 2.4, CI 1.6–3.6). Median time from admission to candidemia was 0.5 vs. 3 days and in-hospital mortality was 7% vs. 28% for IDU and non-IDU cases, respectively.

Conclusion

In 2017, 1 in 8 candidemia cases had a history of IDU, including a quarter of cases in some sites. The proportion of such cases increased since 2014. IDU cases lacked many of the typical risk factors for candidemia, suggesting that IDU may be an independent risk factor. Given the growing opioid epidemic, further study is necessary to elucidate how people who inject drugs acquire candidemia and design effective interventions for prevention.

Disclosures

All authors: No reported disclosures.
1723. Mumps Attack Rates Following Administration of a Third Dose of MMR Vaccine to School-Aged Children, Arkansas, 2016–2017
Authors: Guo Angela , Ayers Tracy , Leung Jessica , Fields Virgie , Va Puthiery , Safi Haytham , Waters Catherine , Wheeler J Gary , Marin Mona , Patel Manisha , Routh Janell , Haselow Dirk
Published: November 2018

Background

During the 2016–2017 school year, the largest mumps outbreak in the United States since 2006 occurred in Arkansas with nearly 3,000 cases. As part of outbreak response, a third dose of measles–mumps–rubella vaccine (MMR3) was offered at 27 schools with mumps attack rates ≥5 cases/1,000 students. We compared attack rates after vaccination clinics among students who received MMR3 and students with 2 MMR vaccine doses.

Methods

We obtained information on school enrollment and student immunization status from school registries, and mumps case status from Arkansas’s National Electronic Disease Surveillance System database. We included students aged 6–21 years who had previously received ≥2 doses of MMR vaccine. We used Arkansas’s Immunization Information System to identify students who received MMR3.

We included schools with at least 1 mumps case after their vaccination clinic. We calculated mumps attack rates by 2- and 3-dose MMR vaccine recipients. Observation time started 14 days after each clinic to allow for development of an immune response to MMR3, and continued to the end of the 2016–2017 school year. Observation time varied by school as schools held clinics on different dates.

Results

A total of 18 schools (10 elementary, 8 middle/junior high) with 10,275 students who had previously received ≥2 doses of MMR (85% of total enrolled) met inclusion criteria. Median number of students per school was 553. Median student age was 11 years (range, 6–18) and 1,525 students received MMR3. MMR3 uptake varied by school (median, 12%; range, 2–33%; interquartile range, 7–22%). A total of 12 mumps cases occurred among MMR3 recipients and 122 cases among 2-dose recipients. School-specific attack rates ranged from 0 to 23 cases/1,000 students among 3-dose recipients, and 2–41 cases/1,000 students among 2-dose recipients. Mumps attack rates within each school were lower for 3-dose recipients vs. 2-dose recipients in all but one school (P < .05). The differences in attack rates between 2- and 2-dose recipients ranged from −5 to 23 cases/1,000 students (median, 5/1,000).

Conclusion

Mumps attack rates were lower in 3-dose vs. 2-dose MMR vaccine recipients after MMR3 vaccination clinics, supporting a benefit of MMR3 for persons in outbreak settings. Further analysis is needed to determine impact of MMR3 on duration and size of mumps outbreaks.

Disclosures

All authors: No reported disclosures.
1725. Addressing Presenteeism: Variability in Facility Healthcare Personnel Work Restriction Policy Monitoring and Enforcement
Authors: Babcock Hilary , Beekmann Susan E , Polgreen Philip M
Published: November 2018

Background

Presenteeism, or working while ill by healthcare personnel (HCP) experiencing influenza-like illness (ILI), increases the likelihood of illness transmission to coworkers and patients. The CDC recommends that HCP with ILI not work until they are afebrile for at least 24 hours. Operationally, hospital policies and practices may not facilitate HCP staying home when ill.

Methods

In March 2018, the Emerging Infections Network surveyed their national network of infectious diseases physicians with hospital epidemiology responsibilities or interests to describe institutional experiences with and policies for HCP working with ILI.

Results

Of the 715 (51%) ID physicians, 367 responded. Of the 367, 135 were not aware of institutional policies and opted out of the rest of the survey. Of the remaining 232 respondents, 206 (89%) reported that their inpatient facility had institutional policies regarding work restrictions for HCP with influenza or ILI, but only 63% said that this policy was communicated to staff at least annually. Work restrictions were most often enforced for staff by sending ill HCP home and by encouragement to call in sick if necessary, while work restrictions for physicians-in-training and attending physicians were most often not enforced or variably enforced. A majority of respondents (53%) reported that adherence to work restrictions was not monitored. Ninety-six percent reported that lab confirmed influenza in patients was tracked by their facility, while 37% reported tracking patient ILI. For employees, 47% reported tracking of laboratory-confirmed influenza and 23% reported tracking ILI. For independent physicians, 13% reported tracking laboratory-confirmed influenza and 5% reported tracking ILI. Sixty-three percent reported that antiviral prophylaxis was provided to at least some employees after occupational exposures, while 9% reported provision of antiviral prophylaxis after nonoccupational (e.g., household) exposures.

Conclusion

Most institutions have policies to prevent HCP from working while ill. However, the dissemination, monitoring, and enforcement of these policies is highly variable. Improving communication about work restriction policies, as well as monitoring and enforcement of these policies, may help prevent the spread of infections from HCP to patients.

Disclosures

All authors: No reported disclosures.
1726. A Random Forest Prediction Model Accurately Identifies Periods at Increased Risk for Positive Legionella Cultures in a Hospital Water Distribution System
Authors: Decker Brooke K , Kelly Monique B , Mikolic Joseph , Walker Jon D , Clancy Cornelius J
Published: November 2018

Background

Hospitals devote considerable resources to water distribution system (WS) surveillance and remediation for Legionella in an effort to reduce risk of transmitting Legionnaires disease (LD). There are no models that accurately predict periods of greatest risk for Legionella culture positivity (cx +) within a WS. Our goal was to build and validate a model based on weather and water parameters that predicted Legionella cx+ in our hospital WS.

Methods

One liter water samples from fixtures at 2 campuses were cultured for Legionella on BCYE plates with cysteine as part of infection prevention protocols. Logistic regression (LR) and random forest (RF) models included daily hospital WS measurements and Pittsburgh FAA weather observation station data. Training and validation used 2014–2015 and 2016–2017 data, respectively. Models predicted a first +cx within 14 day windows.

Results

Cxs were defined as + by loop-day, if any cx from within a unique WS loop was + for Legionella on a given day. Of the 7,272 water samples, 5,304 were collected from 16 buildings on 2 campuses in which ≥1 cx + was obtained. A total of 1,262 WS loop-days were collected over 339 unique days from these buildings. Details on training and validation data sets appear in figure. Overall, water was Legionella cx + on 3% of loop-days. Models predicted positivity if risk was >6%. The LR model comprised of independent predictors of cx + had sensitivity/specificity of 44%/80% (AUC: 0.715; misclassification error: 0.21), and PPV/NPV of 9%/97% in the validation data set. The RF model comprised of the same predictors had sensitivity/specificity of 100%/98% (AUC: 1.0; misclassification error: 0.02), and PPV/NPV of 67%/100%. The most important RF variables in the validation data set were WS temperature and minimum pH over the 7 days prior to cx.

Conclusion

An RF model using water and weather data was validated as an accurate predictor of new Legionella cx+ within a hospital WS. Most importantly, NPV for the model was 100%, meaning that no positive Legionella cxs were recovered during periods identified as low-risk. The RF model is a powerful tool for most efficiently directing resources to Legionella surveillance and LD prevention.

Disclosures

All authors: No reported disclosures.
1756. Prediction of Bloodstream Infection Prior to Onset of Symptoms by Plasma Metagenomic Sequencing in Pediatric Patients With Relapsed or Refractory Malignancy (PREDSEQ)
Authors: Goggin Kathryn , Inaba Yuki , Gonzalez-Pena Veronica , Allison Kim J , Chan Ka Lok , Hollemon Desiree , Ahmed Asim , Hong David , Maron Gabriela , Hayden Randall , Choi John , Rubnitz Jeffrey , Gawad Charles , Wolf Joshua
Published: November 2018

Background

Patients undergoing treatment for relapsed or refractory malignancies are at high risk of life-threatening bloodstream infection (BSI). A predictive screening test for BSI might allow pre-emptive therapy, but no validated test is currently available. We tested the hypothesis that plasma metagenomic next generation pathogen sequencing (NGS) would predict BSI before the onset of attributable symptoms.

Methods

We enrolled 31 pediatric patients receiving for treatment relapsed or refractory malignancy in an IRB-approved prospective cohort study (PREDSEQ) of predictive sequencing. Episodes of febrile neutropenia or documented infection were collected prospectively from the medical record. BSI was defined according to NHSN criteria. Control Samples were defined as samples collected ≥7 clear days before or after any fever or documented infection. Residual clinical samples were stored for NGS; after filtering human sequences, reads were aligned to a curated pathogen database, and organisms above a predefined threshold were reported (Karius Inc., Redwood City, CA). Only bacteria and fungi were included in this analysis.

Results

A total of 11 BSI episodes occurred in 9 participants (Table 1) during the study period. Predictive sensitivity of NGS in the 2 days before onset of infection (n = 9) was 78% (95% CI 45–94%), and diagnostic sensitivity on the day of infection (n = 11) was 82% (95% CI 52–95%). Specificity of NGS for development of fever or infection within 7 days (n = 16) was 81% (95% CI 57–93%). NGS was positive up to 6 days prior to onset of BSI. In samples collected before or during documented infections, NGS also identified additional bacteria and fungi that were not detected by standard clinical testing.

Conclusion

Plasma NGS shows promise for the detection of BSI prior to onset of symptoms in high-risk patients.

Disclosures

K. Goggin, Karius Inc.: Investigator, Research support. K. L. Chan, Karius Inc.: Employee, Salary. D. Hollemon, Karius Inc.: Employee, Salary. A. Ahmed, Karius, Inc.: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. R. Hayden, Roche Molecular: Scientific Advisor, Consulting fee. Abbott Molecular: Scientific Advisor, Consulting fee. Quidel: Scientific Advisor, Consulting fee. C. Gawad, Karius Inc.: Investigator, Research support. J. Wolf, Karius Inc.: Investigator, Research support.
1769. Viral Suppression Among Participants of the Patient-Centered HIV Care Model Project—A Collaboration Between Community-Based Pharmacists and HIV Clinical Providers
Authors: Byrd Kathy , Hou John , Clay Patrick , Bush Tim , Delpino Ambrose , Shankle Michael , Camp Nasima , Kirkham Heather , Hazen Ronald , Weidle Paul
Published: November 2018

Background

The patient-centered HIV care model was developed to integrate community pharmacists with HIV clinical providers to deliver patient-centered HIV care. The project required 10 clinics to share, with their partnered community-based pharmacists, patients’ medical histories, laboratory results, and medications. Pharmacists reviewed the clinic data and worked directly with participants and/or their partnered clinics to make recommendations and discuss potential intervention strategies for identified therapy-related problems.

Methods

We calculated the proportion of persons virally suppressed (<200 copies/mL at the last test in each of two 12-month measurement periods), pre- and post-model implementation. Included in the analysis were persons with ≥1 HIV viral load in each measurement period. McNemar’s test was used to compare the proportion virally suppressed, pre- and postimplementation. Multivariable logistic regression was used to determine factors associated with viral suppression, postimplementation. Participant demographics and the proportion of days covered (PDC; a measure used to calculate adherence to medication therapy) were used as explanatory variables in the model. The PDC was modified to account for the time to the last viral load in the measurement period, and was stratified into 4 categories: ≥90%, <90–80%, <80–50%, and <50%.

Results

With 765 persons enrolled, the plurality of those included in the analysis (n = 648) were non-Hispanic black (n = 286), male (n = 470), and had a median age of 49 years (IQR=38–56). Viral suppression improved 16.3% from 73.9% to 85.9%, pre- to postimplementation (P < 0.001). Persons who had higher modified PDC (OR 1.9 per category level; 95% CI 1.4–2.6), were currently employed (OR 4.1; 1.6–12.8), or age >50 years (OR 4.7; 2.1–11.8), had greater odds of being suppressed. Non-Hispanic black persons were less likely to be suppressed (OR 0.2; 0.1–0.6); however, viral suppression among this group improved from 62.5% to 77.6%, pre- to postimplementation (P < 0.001).

Conclusion

Collaborations between community pharmacists and HIV clinic providers that seek to identify and address HIV therapy-related problems can lead to improved viral suppression among persons living with HIV.

Disclosures

P. Clay, Jaguar Health, Inc.: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Merck & Co., Inc.: Investigator, Research grant. A. Delpino, Walgreens: Employee and Shareholder, Salary.