bluuebunny/crossref_metadata_2025 huggingface dataset:
126. Robust and Persistent Vaginal Colonization with LACTIN-V Vaginal Lactobacillus crispatus Probiotic in a Double-Blind, Placebo-Controlled (DBPC) Phase 2b Trial to Prevent Recurrent UTI (rUTI)
Authors: Stapleton Ann , Silvestroni Aurelio , Roberts Pacita , Cox Marsha , Hayden Hillary , Brittnacher Mitchell , Miller Samuel , Hooton Thomas
Published: November 2018

Background

We investigated vaginal colonization using repetitive sequence PCR (repPCR) and 16S rRNA sequencing in a Phase 2b DBPC trial of a L. crispatus intravaginal suppository probiotic for prevention of rUTI in premenopausal women.

Methods

Twenty-four young women with a history of rUTI and current culture-confirmed symptomatic UTI were enrolled and treated (Visit 0), then randomized (Visit 1) to receive an intravaginal suppository containing L. crispatus CTV-05 (LACTIN-V®, Osel, Inc.) or placebo daily for 5 days, then once weekly for 2 months. Participants were followed up during the 2-month probiotic/placebo intervention (Visits 2 to 4; active intervention) and during 2 months following the intervention (Visits 5 and 6; post-intervention). At each visit, vaginal swabs were collected for repPCR to determine the presence or absence of the probiotic strain and the duration of its presence in the vagina and for 16S rRNA-based sequence analysis to determine relative abundance of any L. crispatus.

Results

LACTIN-V vaginal suppository induced selective and sustained colonization in the probiotic but not the placebo recipients, as follows. Pre-intervention: Probiotic lactobacillus strain, not found in vaginal specimens obtained from participants in either arm of study. Active intervention: (1) Probiotic lactobacillus strain, (a) Probiotic arm: 100% of participants positive at one or more visits and (b) Placebo arm: 0% of participants positive at any time. (2) L. crispatus relative abundance, (a) Probiotic arm: above 90%, all specimens, all visits and (b) Placebo arm: below 15%, all specimens, all visits. Post-intervention: (1) Probiotic lactobacillus strain, (a) Probiotic arm: 75% of participants positive at Visit 5, 58% at Visit 6 and (b) Placebo arm: 0% of participants positive at Visits 5 and 6. (2) L. crispatus relative abundance, (a) Probiotic arm: 70% to 100% and (b) Placebo arm: below 15%.

Conclusion

LACTIN-V L. crispatus vaginal probiotic achieved robust and persistent colonization throughout 2 months of weekly dosing and for 2 months after the last dose in most participants.

Disclosures

All authors: No reported disclosures.
157. Reducing Blood Culture Contamination Rates Through the Use of a Red Top Tube Discard
Authors: Ramlal Bharat , Renouf Rosemary , Aslanzadeh Jaber
Published: November 2018

Background

Septicemia is a major cause of death in the United States and accounts for up to $16.7 billion in annual health care expenses. Blood culture is the gold standard for laboratory diagnosis of bacteremia and resultant septicemia; however, false-positive blood cultures hinder the accurate determination of true bacteremia with often serious implications. The goal of this study was to determine the efficacy of collecting a 1 mL discard in a red tube prior to blood culture collection and to assess its effectiveness in reducing contamination rates in Hartford Hospital Emergency Department (HHED).

Methods

During the months of June to December 2017 blood cultures were collected by the phlebotomy team using ChloraPrep (chlorhexidine) as the sole disinfecting agent. Blood cultures consisted of BD BACTEC plus Aerobic/F and BD BACTEC Lytic/10 Anaerobic drawn at the same time and monitored on BD BACTEC FX instrument for 5 days. Prior to collecting blood cultures 1 mL of blood was collected in a red top tube and discarded. Monthly and overall contamination rates were then compared with 2016 in which a red top discard tube was not used.

Results

During June to December 2016, there were a total of 9,576 blood cultures collected with a total of 178 contaminants and an overall contamination rate of 1.9%. During June to December 2017, there were a total of 9,133 blood cultures collected with a total of 73 contaminants and an overall contamination rate of 0.8%. During both years, our contamination rates were well below the CLSI recommendation; however, a significant reduction in blood culture contamination was observed after the use of a Red Top discard tube (0.8% vs. 1.9%) (Figures 1–3).

Conclusion

The cost of a standard blood draw with Red Top tubes is minimal (few cents) while a single collection using an initial specimen diversion device (ISDD) can range from $15 to $18. During the course of this study, the use of a standard Red Top discard cost approximately $456 (2017); if an ISDD was used instead, this would have generated $136,995 in healthcare cost. At our institution, we were able to keep our contamination rates below 1% after the implementation of a standard Red Top discard tube. This suggests that the use of a Red Top discard prior to blood culture collection is an effective means for reducing and maintaining a low blood contamination rate.

Disclosures

All authors: No reported disclosures.
167. A Bordetella pertussis Human Challenge Model Induces Immunizing Colonization in the Absence of Symptoms
Authors: De Graaf Hans , Ibrahim Muktar , Hill Alison , Gbesemete Diane , Gorringe Andrew , Diavatopoulos Dimitri , Kester Kent , Berbers Guy , Faust Saul , Read Robert
Published: November 2018

Background

Bordetella pertussis is one of the leading causes of vaccine preventable death and morbidity globally. Over the last 20 years, pertussis has resurged worldwide, even in territories with high immunization coverage. To improve vaccine strategies, a greater understanding of human B. pertussis infection and immunity is required. This study aims to develop a safe controlled human B. pertussis infection model and to define natural immune responses against wild-type B. pertussis in order to facilitate the development of bioassays and next-generation pertussis vaccines.

Methods

In this first-in-human controlled infection model, healthy volunteers aged 18–45 years with an anti-pertussis toxin (PT) IgG level of <20 IU/mL were inoculated intranasally with B. pertussis strain B1917. Safety, colonization, and shedding were monitored over a 17-day inpatient period. Colonization was assessed by culture and qPCR of nasal washes and nasopharyngeal swabs. Azithromycin eradication therapy was commenced on day 14. The dose of inoculum was escalated to optimize colonization rate, expressed as the percentage of volunteers colonized at any sampling point between day 3 and 14. The immunological response is being assessed at various time points over 1 year.

Results

24 volunteers were challenged in groups of 4–5. The dose was gradually escalated from 103 colony forming units (cfu) to 105 cfu. Colonization rate ranged from 0% (dose 103 cfu) to 80% (105 cfu). Amongst this initial cohort, no significant safety concerns or symptoms attributed to B. pertussis disease were reported. Eradication was achieved by 48 hours in 100% of colonized volunteers. At least 4-fold rise in anti-PT IgG by day 28 in comparison to baseline was observed in 5 out of 8 volunteers who had >1,000 cfu/mL viable B. pertussis in the nasal wash and in one volunteer without detectable colonization. Nasal wash cultures were more sensitive in detecting colonization than nasopharyngeal swab cultures. No shedding of B. pertussis was detected in systematically collected environmental samples.

Conclusion

This is the first study to demonstrate safe deliberate induction of B. pertussis colonization. It shows that asymptomatic B. pertussis colonization occurs and causes a systemic immune response. The model that we have developed will be a valuable tool to further investigate B. pertussis colonization and vaccine development.

Disclosures

K. Kester, Sanofi: Employee, Salary. S. Faust, Pfizer, Merck, Sanofi, AstraZeneca/Medimmune: Scientific Advisor, all honoraria paid to institution with no personal payments of any kind.
168. Intradermal Immunization Drives Humoral and Cellular Immunity to the Lung and Protects Against Acute P. aeruginosa Pneumonia
Authors: Baker Sarah , Morici Lisa
Published: November 2018

Background

Pseudomonas aeruginosa is a leading cause of hospital-associated pneumonia, with 6,700 multidrug-resistant infections in the US annually. Evidence suggests that antibodies and CD4 Th1 and Th17 responses contribute to protection against P. aeruginosa infection. Recent work suggests that intradermal (ID) immunization with a vaccine adjuvanted with a double mutant of E. coli heat-labile toxin (dmLT) can direct protective immune responses to mucosal tissues such as the lungs. We sought to determine whether ID immunization with P. aeruginosa outer membrane proteins (OMPs) with dmLT could drive migration of CD4+ T cells and antibodies to the lungs and protect against P. aeruginosa pneumonia.

Methods

We immunized C57Bl/6 mice with 1 µg of OMPs with 1 µg dmLT. Control mice received OMPs or saline. Antibody and T-cell responses were assessed by ELISA and flow cytometry, respectively. We then evaluated the protective efficacy of the vaccine in a lethal acute pneumonia model. Immunized mice were challenged with 7 × 106 CFU of P. aeruginosa via oropharyngeal aspiration into the lungs. Finally, we examined whether memory CD4+ T cells was essential for protection by depleting immunized mice of vaccine-induced memory CD4+ T cells.

Results

Mice immunized with OMPs and dmLT had a significantly greater concentration of anti-pseudomonal IgG in the serum and lungs and a significantly greater proportion of CD4+ T cells in the lung producing IFN-γ or IL-17A than mice immunized with OMPs alone or saline. ID immunization provided significant protection against P. aeruginosa pneumonia, with 78% of immunized mice surviving compared with 100% mortality in saline immunized controls. Memory CD4+ T-cell–depleted mice displayed reduced survival (40%) compared with nondepleted mice (80%), confirming that memory CD4 T+ cells contribute to OMP-dmLT vaccine-mediated protection.

Conclusion

These results demonstrate that ID vaccination against P. aeruginosa protects against acute lethal P. aeruginosa pneumonia by stimulating antigen-specific IgG and Th1- and Th17-type CD4+ memory T cells in the pulmonary milieu. ID immunization with dmLT may reduce the global morbidity and mortality caused by multidrug-resistant respiratory pathogens.

Disclosures

All authors: No reported disclosures.
865. Acanthamoeba Disease Associated With the Practice of Nasal Rinsing in Immunocompromised Patients
Authors: Cope Jennifer , Roy Shantanu , Ali Ibne
Published: November 2018

Background

The genus Acanthamoeba are free-living amebae found worldwide in water, including tap water, and soil that can cause rare but severe infections of the eye, skin, and central nervous system. Acanthamoeba spp. generally cause disease in immunocompromised persons, including those with HIV, hematologic malignancies, and solid organ transplants. The route of transmission and incubation period are not well known in humans, but animal studies have shown that disease can be produced via the intranasal, intrathecal, and intravenous routes. We describe 5 cases of Acanthamoeba disease among immunocompromised patients who practiced nasal rinsing prior to becoming ill.

Methods

The Centers for Disease Control and Prevention (CDC) offers a clinical consultation service for free-living ameba infections and maintains a Free-living Ameba laboratory with confirmatory diagnostic testing capabilities. When an Acanthamoeba case is confirmed in the United States, details about the case are collected on a standardized case report form which includes questions about the case–patient’s water and soil exposure prior to becoming ill. Questions about nasal rinsing were added to the form in 2011.

Results

Five Acanthamoeba case patients in CDC’s free-living ameba database were reported to have performed nasal rinsing prior to becoming ill. The median age was 60 years (range 36–73 years) and 3 of 5 patients were female. Two were solid-organ transplant patients (heart and kidney), 2 had chronic lymphocytic leukemia, and 1 had HIV. Three patients presented only with encephalitis and died. The 2-organ transplant patients had a combination of rhinosinusitis, osteomyelitis, and skin lesions. One survived and the other died, the cause of which was unrelated to Acanthamoeba. All reported using tap water to perform nasal rinsing, most for sinus congestion using a neti pot or similar device and one for religious purposes.

Conclusion

Acanthamoeba is an inhabitant of water, including treated tap water. Immunocompromised patients, like those presented here, might be at risk for infections caused by Acanthamoeba transmitted via tap water used for nasal rinsing. Clinicians caring for immunocompromised patients should advise their patients not to use tap water for nasal or sinus rinsing.

Disclosures

All authors: No reported disclosures.
918. Typhoid Fever in the US Pediatric Population, 1999–2015, and the Potential Benefits of New Vaccines
Authors: McAteer Jarred , Derado Gordana , Hughes Michael , Bhatnagar Amelia , Medalla Felicita , Chatham-Stephens Kevin , Appiah Grace D , Mintz Eric D
Published: November 2018

Background

In the United States, typhoid fever is rare. About 300 typhoid cases are reported to CDC annually through the National Typhoid and Paratyphoid Fever Surveillance (NTPFS) system. Most are acquired during international travel and while visiting friends and relatives. CDC recommends pretravel vaccination of at-risk children with one of two currently available vaccines: oral (age ≥6 years) or injectable (age ≥2 years). In anticipation of licensure of new protein-conjugate typhoid vaccines that could be administered to children ≥6 months old, we characterized clinical, epidemiologic, and antimicrobial resistance data of pediatric typhoid fever cases reported to CDC.

Methods

We reviewed laboratory-confirmed Salmonella enterica serotype Typhi infections reported to NTPFS and antimicrobial resistance data on Typhi isolates in the National Antimicrobial Resistance Monitoring System (NARMS) from 1999 to 2015.

Results

Of 2,051 pediatric (≤18 years) cases of typhoid fever, 80% had traveled internationally within 30 days of illness onset (most frequently to South Asia [82%]), 81% were hospitalized (median duration 6 days; range 0–77 days), and none died. Eight hundred twenty-seven (40%) were <6 years old; 219 (26%) were 6 months–2 years old. While 76% of pediatric cases were vaccine eligible (travelers ≥2 years old), only 6% were known to be vaccinated. Of 2,020 isolates tested for antimicrobial susceptibility, 1,211 (60%) had decreased susceptibility or resistance to ciprofloxacin, of which 277 (23%) were also resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole (multidrug-resistant [MDR]). None were resistant to ceftriaxone or azithromycin. MDR isolates were more likely in children than adults (16% vs. 9%, P < 0.05) and in travel-associated than domestically acquired cases (16% vs. 6%, P < 0.05).

Conclusion

Among pediatric cases of typhoid fever, 94% of currently vaccine-eligible travelers were unvaccinated. Emphasis on current vaccine indications and an effective pretravel typhoid vaccine for children between 6 months and 2 years old available during routine immunization visits could begin to reduce the burden of disease, and help prevent drug-resistant infections, in this vulnerable age group.

Disclosures

All authors: No reported disclosures.
919. Clinical and Microbiologic Characteristics Associated With Long-Term Orthopedic Complications Following Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children
Authors: McNeil J Chase , Kok Eric , Sommer Lauren , Vallejo Jesus G , Hulten Kristina G , Kaplan Sheldon L
Published: November 2018

Background

Staphylococcus aureus is the most common cause of acute hematogenous osteoarticular infections (AHOAIs) in children. While the vast majority of patients do well, a small proportion experience significant morbidity, including chronic infection and pathologic fractures. We sought to describe clinical and microbiologic variables present on the index admission that may predict long-term orthopedic complications (OC).

Methods

Cases of S. aureus AHOAI were identified from 2011 to 2016 at Texas Children’s Hospital (TCH). All cases were reviewed for the development of OC until April 1, 2018. OC included chronic osteomyelitis (CO), growth arrest/limb length discrepancy, avascular necrosis, chronic dislocation, and pathologic fracture (PF) with or without angular deformity. All S. aureus isolates were characterized by PCR for Panton–Valentine Leukocidin (PVL) genes and agr group. Statistical Analyses were performed with STATA.

Results

A total of 252 cases were identified meeting inclusion criteria (figure). Twenty-four (9.5%) developed OC; of which, 50% were CO and 25% PF. Patients who developed CO more often had positive blood cultures during the index admission (P < 0.001), surgical drainage after hospital day 2 (33.3% vs. 8.8%, P = 0.02) as well as a longer time to 50% reduction in C-reactive protein (CRP, 9 vs. 7 days, P = 0.01). Patients who developed PF more often had infection due to PVL-positive organisms (83.3% vs. 38.6%, P = 0.03) and had a longer duration of fever after admission (9.5 vs. 2.5 days, P = 0.03). Overall, OC were associated with ICU admission (P = 0.04), a slower decline in CRP (P = 0.02) and a greater proportion of patients with surgery after hospital day 2 (P = 0.04) as well as infection secondary to agr III isolates (P = 0.03). There was no statistically significant relationship between OC and patient age, affected bone, time to initiation of effective antimicrobial therapy, duration of intravenous therapy, or final antibiotic choice.

Conclusion

Patients with S. aureus AHOAI with a delay in source control, slow decline in CRP, prolonged fever or ICU admission are at higher risk of OC. While nonspecific, these findings suggest that such patients may warrant especially cautious clinical follow-up to identify sequelae early. Large multicenter studies are needed to better predict OC in this setting.

Disclosures

All authors: No reported disclosures.
921. Antibiotic Prescribing for Children in Family Medicine Clinics Within a Practice Research Network
Authors: Poole Nicole , Kronman Matthew , Gerber Jeffrey S , Baldwin Laura-Mae , Zerr Danielle
Published: November 2018

Background

Family medicine clinics provide care for one-third of US children, yet comprehensive data about antibiotic prescribing in this patient population are lacking. We aimed to characterize antibiotic prescribing for children in family medicine clinics.

Methods

A retrospective cohort of patients aged 0–17 years with a visit to a family medicine clinic within the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) Region Practice and Research Network (WPRN) from January 1, 2014 to April 30, 2017 was studied. Patients with complex chronic conditions were excluded. We defined narrow-spectrum antibiotics as penicillin, amoxicillin, first-generation cephalosporins, sulfonamides, and nitrofurantoin; and broad-spectrum antibiotics otherwise. On the basis of national guideline recommendations and a previously published hierarchical classification system, we assigned diagnoses to one of the 3 tiers: diagnoses for which antibiotics were (1) almost always indicated (e.g., bacterial pneumonia), (2) may be indicated (e.g., pharyngitis), and (3) generally not indicated (e.g., bronchiolitis/bronchitis).

Results

We studied 20,779 pediatric patients with 97,228 clinic visits. Oral antibiotics were prescribed in 10,922 (11%) of all encounters. The median rate of antibiotic prescribing among providers was 14% (interquartile range: 4.9%–18.5%). Of all antibiotics prescribed, 51% were broad-spectrum agents. Acute respiratory tract infections (ARTIs) accounted for 67% of all antibiotics prescribed. Of the antibiotics prescribed for ARTI, 25% were for diagnoses where antibiotics are generally not indicated. First-line guideline-recommended antibiotics were prescribed in 80% of acute otitis media, 80% of sinusitis, 68% of pharyngitis, and 31% of community acquired pneumonia diagnoses. Azithromycin monotherapy was prescribed in 52% of community acquired pneumonia diagnoses.

Conclusion

Specific targets for improving antimicrobial prescribing within a family medicine practice research network include prescribing of broad-spectrum antibiotics (particularly azithromycin), prescribing for conditions where antibiotics are not indicated, and first-line guideline-recommended prescribing for pharyngitis and community acquired pneumonia.

Disclosures

All authors: No reported disclosures.
927. Tap Water Avoidance Decreases Rates of Nontuberculous Mycobacteria in Intensive Care Units
Authors: Baker Arthur W , Smith Becky , Sexton Daniel J , Huslage Kirk , Stout Jason E , Anderson Deverick J , Moehring Rebekah W , Hostler Christopher , Lewis Sarah S
Published: November 2018

Background

We recently investigated a clonal outbreak of Mycobacterium abscessus molecularly linked to a colonized water supply at a new hospital addition. Use of sterile water instead of tap water for patient care in ICUs successfully mitigated the respiratory phase of the outbreak. We hypothesized that avoidance of tap water would also be associated with decreased respiratory isolation of other nontuberculous mycobacteria (NTM).

Methods

We analyzed all positive cultures for NTM obtained at our hospital from August 2013 through December 2015. The pre-intervention outbreak period was defined as August 2013 through May 2014; the tap water avoidance intervention period was defined as June 2014 through December 2015. NTM isolation was defined as a positive culture from a respiratory specimen obtained from an ICU patient on day 3 or later of hospitalization. We also performed AFB cultures of biofilms obtained from ICU water sources.

Results

NTM were isolated from 137 patients during 70,168 patient-days (figure). NTM isolation decreased from 41.0 patients/10,000 patient-days in the outbreak period to 9.9 patients/10,000 patient-days in the intervention period (IRR, 0.24; 95% CI, 0.17–0.34; P < .0001) (table). Incidence rates of the 4 most common NTM (M. abscessus, M. chelonae/immunogenum, M. avium complex, and M. gordonae) also markedly decreased. Biofilm cultures were positive for at least 1 NTM isolate in 25 of 33 (76%) ICU water sources, including M. abscessus (n = 11, 33%), M. chelonae/immunogenum (n = 11, 33%), and M. gordonae (n = 11, 33%).

Conclusion

The use of sterile water for ICU patient care substantially decreased NTM isolation from patient respiratory specimens, presumably reducing risk of symptomatic infection. Hospitals with endemic NTM should consider tap water avoidance for high-risk patients.

Disclosures

All authors: No reported disclosures.
962. Cutaneous Leishmaniasis: Investigating Skin Drug Levels to Optimize Liposomal Amphotericin Dosing
Authors: Aronson Naomi E , Koles Nancy , Moran Sean , Zhang Aihong
Published: November 2018

Background

Liposomal amphotericin B (L-amB, AmBisome®) is popular for off-label use in the treatment of cutaneous leishmaniasis (CL) using dosing of 3 mg/kg/day for days 1–5, 8, 9, or days 1–5, 10 with reported clinical cure rates of 46–84%. In rodents, the skin concentration of L-amB is 40-fold less than that in visceral organs. We hypothesize that a specific L-amB regimen targeted to skin concentrations could maximize a beneficial treatment response in CL.

Methods

SKH1 477 Elite hairless mice (Charles River), 5 per group, received intravenous L-amB at doses of (A) 3 mg/kg/day for days 1–5, 8, 9, (B) 5 mg/kg/day for 4 days, (C) 10 mg/kg load than 5 mg/kg/day for 3 days, (D)10 mg/kg/day for 2 days, (E) 15 mg/kg/day for 2 days. Serum and skin (back) punch biopsies were collected on day 0, 2, 5, 14, and 21. Nasal mucosa was biopsied on day 21. Tissue samples were homogenized and L-amB was extracted with methanol and acetonitrile. Liquid chromatography–mass spectrometry was performed using these extracted samples on an Agilent 1200 series HPLC and an AB Sciex Q-Trap 4000 mass spectrometer. Experiment conducted twice for confirmation.

Results

L-amB doses were well tolerated by the mice, except weight loss was seen in regimen E. Day 21 serum L-amB levels were 82 ± 3.2 (ng/mL) regimen A, 91 ± 4.2 in B, 89 ± 4 in C, 118 ± 3.7 in D, 98 ± 1.5 in E. Mean L-amB nasal tissue levels on day 21 were 1.33 + 3.2 (ng/mg tissue) regimen A and 6.5 ± 3 in D (P = 0.031). Mean L-amb skin levels on day 14 were 8.4 ± 5.6 (ng/mg tissue) in regimen A, 4.0 ± 1.7 in B, 6.2 ± 3.3 in C, 13.9 ± 7.1 in D, 33.9 ± 24.7 in E. Skin L-amB levels at day 21 were less than 5 (ng/mg tissue) except for regimen D 9.3 ± 4.2 and regimen E 7.8 ± 2.6. SKH1 477 Elite mice did not permit an adequate Leishmania major infection (very tiny lesions when compared with other murine species) to correlate these results clinically in this specific murine model.

Conclusion

While regimens A–D received similar total dosages of L-amB, the skin and nasal mucosal levels were significantly higher in the short, high daily dose regimens compared with the L-amB regimen that is currently used in CL patients. This suggests that better clinical results might be seen by using a L-amB dosing regimen for CL of 10 mg/kg for 2 days, a dose regularly used in the treatment of pediatric visceral leishmaniasis.

Disclosures

All authors: No reported disclosures.
965. Applying Clinical Prediction Tools to Patients with Lassa Fever
Authors: Chiosi John , Shaffer Jeffrey , Schieffelin John
Published: November 2018

Background

Clinical prediction tools such as the Quick Sequential Organ Failure Assessment (qSOFA) and the Modified Early Warning Score (MEWS) have been used to predict mortality from sepsis in high-income countries, but their application to low- and middle-income countries have been limited. Lassa fever is a viral hemorrhagic fever endemic to West Africa with a case fatality ratio for hospitalized patients of up to 69%. The purpose of this study was to evaluate existing clinical prediction tools for critical illness in predicting adverse outcomes in patients with Lassa fever.

Methods

We conducted a retrospective cohort study of patients admitted to the Kenema Government Hospital Lassa ward in Sierra Leone between 2012 and 2017. Patients were required to meet the World Health Organization case definition for suspected Lassa Fever to be admitted to the ward. We included patients who had laboratory-confirmed Lassa fever via ELISA tests for Lassa Ag or IgM. Control samples were included with negative ELISA tests for Lassa Ag and IgM. We compared criteria for qSOFA, MEWS, Systemic Inflammatory Response Syndrome (SIRS), and Universal Vital Assessment (UVA) among the Lassa Ag+ (patients with acute viremia), Ag-/IgM+ (patients who cleared the virus and developed an immune response), and Ag−/IgM− (control) groups.

Results

There were 157 patients included in this preliminary analysis. Of patients in the Ag+ group, the mean age was 20.2 years and 40.8% were female. Patient demographics were similar among all groups. Clinical outcomes significantly differed among the groups, with the highest in-hospital mortality at 62.5% in the Ag+ group. For each clinical prediction tool, mean scores significantly differed among groups (P < 0.05; see table). The highest scores were consistently seen in the Ag+ group.

Conclusion

Patients with acute viremia for Lassa fever had higher scores for clinical prediction tools compared with controls, which imply a higher risk of mortality. Additional research is needed on the sensitivity and specificity of these tools for mortality due to Lassa fever.

Disclosures

All authors: No reported disclosures.
969. GRP78 and Integrin β1/α3 Play Disparate Roles in Epithelium Invasion During Mucormycosis
Authors: Alqarihi Abdullah , Gebremariam Teclegiorgis , Alkhazraji Sondus , Uppuluri Priya , Edwards John E , Ibrahim Ashraf S
Published: November 2018

Background

Mucormycosis is a lethal fungal infection caused by Mucorales. Inhalation is the major route of entry resulting in rhino-orbital or pulmonary infections. Nasal and lung epithelial cells are among the first cells that encounter inhaled spores. We sought to identify the nasal and lung epithelial cell receptors interacting with Rhizopus during tissue invasion.

Methods

R. delemar-induced nasal (CCL30) or lung epithelial (A549) cell invasion was studied using Uvetix dye, while host cell injury was determined by 51Cr-release assay. Epithelial cell receptors were isolated by affinity purification of biotinylated host cell membrane proteins and then identified by LC-MS. Blocking antibodies were used to confirm the role of the receptor in the invasion/injury assays. For survival studies, ICR mice were immunosuppressed with cyclophosphamide and cortisone acetate on day-2, +3, and +8. Mice were infected with 2.5 × 105R. delemar spores intratracheally, and then treated with a single dose of 100 μg (i.p.) anti-β1 integrin antibody. Placebo mice received 100 µg of isotype-matching IgG.

Results

R. delemar invades and damages both cells in a time-dependent manner. Nasal Grp78 and alveolar β1α3 integrin were isolated as putative receptors. Polyclonal antibodies targeting Grp78 or β1 integrin blocked R. delemar-mediated endocytosis of nasal and lung cells by ~70%. Also, anti-Grp78 and anti-β1 integrin antibodies blocked R. delemar-induced nasal and lung cell injury by ~60% (P < 0.001). Elevated glucose, iron, or BHB increased the expression of nasal Grp78 by 2- to 6-fold which resulted in enhanced R. delemar-mediated invasion and injury of host cells, while having no effect on β1α3 integrin expression. Finally, β1 antibodies protected mice from mucormycosis with median survival time of 16 days for treated mice versus 11 days for placebo and an overall survival of 30% versus 0% for placebo mice (P = 0.0006).

Conclusion

The upregulation of Grp78 on nasal epithelial cells in response to physiological elevated concentrations of glucose, iron, and BHB and subsequent enhanced invasion likely to provide insights into why diabetics in ketoacidosis are infected with the rhino-orbital mucormycosis rather than pulmonary disease. Our studies also provide a foundation for therapeutic interventions against mucormycosis.

Disclosures

All authors: No reported disclosures.
982. Summer Outbreak of Severe RSV-B Disease, Minnesota, 2017
Authors: Thielen Beth , Bye Erica , Wang Xiong , Friedlander Hannah , Maroushek Stacene , Shilts Meghan , Strain Anna , Como-Sabetti Kathryn , Ferrieri Patricia , Lynfield Ruth
Published: November 2018

Background

Respiratory syncytial virus (RSV) causes seasonal outbreaks peaking from October to April in the United States. While symptoms are typically mild and limited to the upper respiratory tract in older children and adults, RSV can cause severe lower respiratory disease, hospitalization and death, particularly among younger children, the immunocompromised and the elderly. During summer 2017, the Minnesota Department of Health (MDH) received a report of a cluster of severe respiratory illness in children with RSV-B infection admitted at an urban county hospital.

Methods

MDH conducts surveillance for RSV in Minneapolis-St. Paul with collection of respiratory specimens and clinical and demographic data. We compared characteristics of cases reported in summer 2017 with the previous 4 summer seasons. To understand the genetic relatedness among viruses, we performed complete genome sequencing from primary specimens using an Illumina MiSeq platform employing both a sequence-independent sequencing method and an RSV-specific, overlapping PCR-based approach.

Results

From May to September 2017, 58 cases of RSV (48 RSV-B) were reported to MDH compared with 18 (7 RSV-B) during the same period in 2016, 27 in 2015, and 29 in 2014. The median age and frequency of co-morbidities were similar across years; however, 50% required ICU admission in 2017 compared with 12% in preceding 3 years. The RSV-B genome was sequenced from 10 specimens from March to May 2016, 20 specimens from May to September 2017 and 30 specimens from October 2017-January 2018. Phylogenic analysis revealed that 15 cases from May to September. 2017 formed a unique clade distinct from the lineage encompassing 2016 cases from Minnesota and 35 representative complete RSV genomes in GenBank isolated from 6 continents over 13 years. From October 2017 to January 2018, we detected co-circulation of viruses from both lineages among older adults and children.

Conclusion

We identified an outbreak of RSV-B associated with severe disease among urban Minnesota children during a time of expected low RSV circulation. Complete genome sequencing data suggested emergence of a new lineage distinct from viruses circulating in Minnesota during the previous season. Genomic characterization can provide useful insights into epidemiologic variations.

Disclosures

All authors: No reported disclosures.
1632. Non-Visit-Based and Non-Infection-Related Ambulatory Antibiotic Prescribing
Authors: Linder Jeffrey A , Brown Tiffany , Lee Ji Young , Chua Kao-Ping , Fischer Michael A
Published: November 2018

Background

Many studies have examined or intervened on ambulatory antibiotic prescribing based on infection-related diagnosis codes. However, clinicians may prescribe antibiotics without seeing patients face-to-face or without documenting an infection-related diagnosis.

Methods

We measured the prevalence of non-visit-based and non-infection-related oral, antibacterial–antibiotic prescribing between November 2015 and October 2017 using the EHR of an integrated health delivery system. We examined the visit type (in-person vs. other) and classified prescriptions into 3 mutually exclusive groups based on same-day diagnosis codes: (1) infection-related for prescriptions associated with at least one of 21,730 ICD-10 codes that may signify infection; (2) non-infection-related for prescriptions only associated with the 72,519 ICD-10 codes that do not signify infections; and (3) associated with no diagnosis.

Results

There were 509,534 antibiotic prescriptions made to 279,169 unique patients by 2,413 clinicians in 514 clinics. Patients had a mean age of 43 years old, were 60% women, and 75% white. Clinicians were 54% women; were 63% attending physicians, 18% residents/fellows, 10% nurse practitioners, and 7% physician assistants; and were 41% medical specialists, 21% primary care clinicians, and 7% surgical specialists. The most common antibiotic classes were penicillins (30%), macrolides (23%), cephalosporins (14%), fluoroquinolones (11%), tetracyclines (10%), and sulfonamides (6%). Clinicians prescribed 20% of antibiotics outside of an in-person visit; prescription encounters were in-person (80%), telephone (10%), order-only (4%), refill (4%), and online portal (1%). Clinicians prescribed 46% of antibiotics without an infection-related diagnosis: 54% of antibiotic prescriptions were infection-related, 29% were non-infection-related, and 17% were associated with no diagnosis. Various look-back and look-forward durations for diagnosis codes changed the results only slightly.

Conclusion

Clinicians prescribed 20% of antibiotics outside of in-person visits and 46% of antibiotics without an infection-related diagnosis. Interventions that target visit-based, diagnosis-specific prescriptions miss a large share of antibiotic prescribing.

Disclosures

All authors: No reported disclosures.
1637. Improving Transitions of Care in the Division of Infectious Diseases
Authors: Paim Ana , Vijayvargiya Prakhar , Garrigos Zerelda Esquer , Tan Eugene , O’Horo John
Published: November 2018

Background

Patients dismissed from the hospital on oral or intravenous antibiotics frequently need follow-up appointments with the Division of Infectious Diseases (ID). Follow-up appointments may be inappropriately scheduled with respect to timing and indication. Suboptimal transitions of care may lead to increased no-shows and ultimately poor patient outcomes.

Methods

The baseline sample included 102 patients seen by the inpatient ID services at Mayo Clinic’s Rochester Methodist and Saint Mary’s Hospitals between January 1, 2017 and June 30, 2017. Defects in transitions of care were categorized as those pertaining to sign-off templates, sign-off labels, follow-up priority, and timing. The current transfer of care system from our institution is outlined in Figure 1.

Results

Out of 102 patients, 75 (74%) had at least one defect identified. Root cause analysis revealed multiple factors contributing to this performance gap (Figure 2). Patients often have variable health literacy and social or financial difficulties. There are often multiple ID providers with inadequate time to properly orchestrate follow-up. There are undefined checkpoints and triaging in the department’s scheduling policies. Interventions involved reformatting the ID sign-off template and clarifying the roles of providers in the transitions-of-care process. Analysis after 6 months of implementation revealed improvement of communication among teams, decline in improper sign off by 13% and decrease in antibiotic prescription errors by 2%.

Conclusion

This study demonstrates that well-designed sign-off templates can help with effective communication of the final treatment plan among providers and possibly improve patient outcomes. The target goal is to reduce the number of improper sign-offs by 50% within 1 year.

Disclosures

All authors: No reported disclosures.
1646. Combined Resistance Analyses From Phase 2b Studies of Presatovir Treatment in RSV-Infected Adults
Authors: Porter Danielle , Guo Ying , Perry Jason , Gossage David , Watkins Timothy , Chien Jason , Jordan Robert
Published: November 2018

Background

Presatovir is an oral respiratory syncytial virus (RSV) fusion inhibitor in development for the treatment of RSV infection. Results from a healthy volunteer challenge study show that presatovir significantly reduced RSV viral load and clinical signs and symptoms. Here we present combined resistance analyses from 4 phase 2b studies in naturally RSV-infected adults.

Methods

RSV RNA was isolated from nasal swabs collected at baseline and postbaseline in studies GS-US-218-0108, GS-US-218–1502, GS-US-218–1227, and GS-US-218–1797. Full-length RSV fusion (F) gene was PCR amplified and population sequencing was performed.

Results

Of 233 presatovir-treated adults in the efficacy analyses, post-baseline resistance-associated substitutions were detected in 18 (7.7%) subjects. Frequencies of resistance development varied by study (Table 1). Resistance substitutions known to confer high-level (>200 fold) reduced susceptibility to presatovir detected in >1 subject were: T400I (n = 6), S398L (n = 3), L141F (n = 2), and F140I (n = 2) in F. Subjects with resistant virus had less viral load reduction than presatovir-treated subjects without resistant virus. Resistance development did not impact clinical outcomes. In study GS-US-218-0108, subjects with lymphopenia (<200 cells/μL) at baseline were significantly more likely to develop resistance substitutions.

Conclusion

Presatovir treatment resulted in varying rates of resistance development across 4 phase 2b studies. Resistance development impacted virologic response without affecting clinical outcomes. Differences among study populations and dosing regimens may have influenced rates of resistance development.

Disclosures

D. Porter, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. Y. Guo, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. J. Perry, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. D. Gossage, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. T. Watkins, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. R. Jordan, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks.
1659. Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Clinical Data and Impact on Hospital Outcome Comparisons
Authors: Rhee Chanu , Jentzsch Maximilian , Kadri Sameer S , Seymour Christopher , Angus Derek , Murphy David , Martin Greg , Dantes Raymund , Epstein Lauren , Fiore Anthony E , Jernigan John A , Danner Robert L , Warren David K , Septimus Edward , Hickok Jason , Poland Russell , Jin Robert , Fram David , Schaaf Richard , Wang Rui , Klompas Michael
Published: November 2018

Background

Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices may confound efforts to benchmark hospital sepsis outcomes using claims data.

Methods

We evaluated the sensitivity of claims data for sepsis and organ dysfunction relative to clinical data from the electronic health records of 193 US hospitals. Sepsis was defined clinically using markers of presumed infection (blood cultures and antibiotic administrations) and concurrent organ dysfunction. Organ dysfunction was measured using laboratory data (acute kidney injury, thrombocytopenia, hepatic injury), vasopressor administrations (shock), or mechanical ventilation (respiratory failure). Correlations between hospitals’ sepsis incidence and mortality rates by claims (using “explicit” ICD-9-CM codes for severe sepsis or septic shock) versus clinical data were measured by the Pearson correlation coefficient (r) and relative hospital rankings using either data source were compared. All estimates were reliability-adjusted to account for random variation using hierarchical logistic regression modeling.

Results

The study cohort included 4.3 million adult hospitalizations in 2013 or 2014. The sensitivity of hospitals’ claims data for sepsis and organ dysfunction was low and variable: median sensitivity 30% (range 5–54%) for sepsis, 66% (range 26–84%) for acute kidney injury, 39% (range 16–60%) for thrombocytopenia, 36% (range 29–44%) for hepatic injury, and 66% (range 29–84%) for shock (Figure 1). There was only moderate correlation between claims and clinical data for hospitals’ sepsis incidence (r = 0.64) and mortality rates (r = 0.61), and relative hospital rankings for sepsis mortality differed substantially using either method (Figure 2). Of 48 (46%) hospitals, 22 ranked in the lowest sepsis mortality quartile by claims shifted to higher mortality quartiles using clinical data.

Conclusion

Variation in the completeness and accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospital sepsis rates and outcomes. Sepsis surveillance using objective clinical data may facilitate more meaningful hospital comparisons.

Disclosures

All authors: No reported disclosures.
1727. Sustained Antimicrobial Activity of a Novel Disinfectant Against Healthcare Pathogens
Authors: Rutala William , Gergen Maria , Sickbert-Bennett Emily , Anderson Deverick J , Weber David
Published: November 2018

Background

Environmental contamination plays an important role in the transmission of MRSA, VRE, and C. difficile. Suboptimal compliance with hand hygiene or inappropriate glove use can result in indirect transfer of these pathogens to patients. This study evaluates a novel disinfectant that claims to kill microbes on surfaces for ≥24 hours.

Methods

We investigated the persistent antimicrobial activity of a novel disinfectant using an EPA protocol for sustained disinfecting activity. In brief, surfaces are inoculated, treated with the novel disinfectant, allowed to dry, and then abraded using a standardized abrasion machine under multiple alternating wet and dry wipe conditions (N = 12) interspersed with 6 re-inoculations. After 24 hours, the surface was re-inoculated a final time and ability of the disinfectant to kill ≥99.9% of 9 test microbes within 5 minutes was measured on 3 test surfaces (glass, formica, and stainless steel).

Results

The novel disinfectant demonstrated a 3–5 log10 reduction in 5 minutes when testing S. aureus, VRE, C. auris, CRE E. coli and antibiotic-sensitive strains of E. coli, and Enterobacter sp. (table). The disinfectant demonstrated lower killing for CRE isolates of Enterobacter sp. and K. pneumoniae, and for antibiotic-sensitive K. pneumoniae (~2 log10 reduction in 5 minutes). When the novel disinfectant was compared with 3 other commonly used disinfectants using the same methodology with S. aureus, the mean log10 reductions were: 4.4 (novel disinfectant); 0.9 (quat-alcohol); 0.2 (improved hydrogen peroxide); and 0.1 (chlorine).

Conclusion

Persistent disinfectants may reduce or eliminate the problem of recontamination and minimize the role of environmental surfaces in transmission of healthcare pathogens.

Disclosures

W. Rutala, PDI: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. D. Weber, PDI: Consultant, Consulting fee
1760. Interferon Gamma Release Assay for Diagnosis of Lyme disease
Authors: Hefter Yosefa , D’Arco Christina , Shute Travis , Dattwyler Raymond , Arnaboldi Paul , Nolan Sheila
Published: November 2018

Background

The sensitivity of current antibody detection assays against Borrelia burgdorferi in the early stage of Lyme disease is very low. In children especially, who commonly have febrile viral illnesses, manifestations of early Lyme disease can be misdiagnosed. We previously demonstrated that IFNγ secretion could be detected in whole blood collected from Lyme disease patients at first clinical presentation following overnight incubation of the blood with peptides derived from B. burgdorferi. In the present study, we further evaluated the utility of IFNγ release for the laboratory diagnosis of Lyme disease in children with varying stages of the illness.

Methods

Children ages 2–18 years with no prior history of Lyme disease and with manifestations of Lyme disease at any stage were enrolled in the study. Sick and healthy controls were enrolled for comparison. We collected history and physical examination data and blood samples at the time of enrollment, at 1 month, and at 6 months. Standard 2-tier testing with ELISA (whole cell sonicate [WCS] and C6) and western blot were run in parallel to the IFNγ release assay for all blood samples. Sensitivity and specificity of the study assay were determined for presentation at all stages of Lyme disease. Clinical data were summarized.

Results

Blood samples from 22 patients with Lyme disease and 7 controls (4 sick, 3 healthy) were obtained at the first visit. The IFNγ release assay detected early and early disseminated Lyme disease with 78% sensitivity compared with 59% sensitivity of 2-tier testing in our study. For patients presenting with a single erythema migrans (EM) lesion, the IFNγ release assay detected Lyme disease with 63% sensitivity compared with 14% sensitivity with 2-tier testing. The IFNγ release assay had only 25% sensitivity for detecting late disease. A single control patient was positive for both the IFNγ release assay and 2-tier serology.

Conclusion

A novel IFNγ release assay demonstrated significantly increased sensitivity when compared with 2-tier testing in the laboratory diagnosis of Lyme disease in patients presenting with a single EM lesion. Future study is needed to determine its utility in detecting early Lyme disease in patients with nonspecific febrile illness in the absence of erythema migrans.

Disclosures

R. Dattwyler, Qiagen: Collaborator, Research support. P. Arnaboldi, Qiagen: Collaborator, research materials.