bluuebunny/crossref_metadata_2025 huggingface dataset:
2403. Clostridium difficile ribotypes and human microbiota differ in Taiwan and the United States with respect to diarrheal patients
Authors: Motyka Jonathan , Cheng Hao-Tsai , Lin Cheng-Yu , Keidan Micah , Young Vincent B , Kao John , Rao Krishna
Published: October 2019

Background

Clostridium difficile infection (CDI) has high incidence in the United States, but less so in East Asian countries such as Taiwan. The reason for this is not understood, but microbial studies could reveal important epidemiologic insights. We hypothesized that the circulating strains of C. difficile and the gut microbiota differ between the United States and Taiwan.

Methods

Patients with diarrhea ± CDI from the University of Michigan and Chang Gung Memorial Hospital were included. CDI was defined by + enzyme immunoassay for the glutamate dehydrogenase gene and toxins A/B, with reflex to tcdB gene PCR for discordants. C. difficile was isolated by anaerobic culture and characterized by PCR ribotype. The fecal microbiota was assessed by sequence analysis of 16S rRNA-encoding gene amplicons targeting the V4 region. Amplicon sequences were processed using the mothur bioinformatics pipeline, with an operational taxonomic unit (OTU) defined by < = 3% sequence homology. Analysis was performed via logistic regression, principal coordinates (PCoA), and ANOVA.

Results

Community diversity by Shannon index of CDI- patients was lower (Figure 1); this difference was greater in Taiwan (P < .001, OR = 3.9 per unit Shannon). Taiwanese CDI- patients had lower Bacteroidetes relative abundance (RA) (Figure 2). The Taiwanese CDI- group also differed on PCoA and ANOVA (Figure 3, P < .001). OTU1 (genus Firmicutes) was depleted in CDI+ patients (P < .001, OR = 0.69 per 10% RA increase). Circulating ribotypes (Table 1) differ between countries, with no epidemic strains (R027/R078) present in Taiwan (P = .027). R027 and 014/020 comprised > 50% of US isolates while > 50% of Taiwanese isolates were R002.

Conclusion

Taiwan and US CDI+ patients differ in dominant ribotypes. It is overall difficult to differentiate diarrheal CDI+ and CDI- patients by the microbiome. Taiwanese CDI- patients are outliers, and possible reasons (e.g., differential burden of parasitic infection; diet) require further study. The increased diversity and lower Bacteroidetes in CDI+ vs. CDI- diarrheal patients contrast with prior studies that instead compared with CDI- non-diarrheal patients. Circulating strains in Taiwan include no epidemic variants; whether this explains the differential incidence needs further study.

Disclosures

All authors: No reported disclosures.
2405. Clinical Characteristics and Prognostic Factors for Extraintestinal Infection Caused by Clostridium difficile: An Analysis of 62 Consecutive Cases
Authors: Chung Hyemin , Cho Eunbeen , Bae Seongman , Jae Kim Min , Pil Chong Yong , Lee Sang-Oh , Soo Kim Yang , Hee Woo Jun , Kim Sung-Han , Choi Sang-Ho
Published: October 2019

Background

Whereas Clostridium difficile enterocolitis has been well studied, data regarding extraintestinal C. difficile infection remain scarce and anecdotal. We investigated characteristics and prognostic factors in patients with extraintestinal C. difficile infection at a large university hospital over a recent 20-year period.

Methods

We conducted a retrospective cohort study of patients at a 2,700-bed tertiary care hospital from January 1997 through December 2018 whose extraintestinal clinical specimen revealed C. difficile. Gastrointestinal (GI) disruption was defined as compromised integrity of the GI tract by abdominal surgery, perforation, malignancy, or bleeding. Patients were divided into 3 groups: group A (GI disruption with malignancy, n = 15); group B (GI disruption without malignancy, n = 23); group C (No GI disruption or malignancy, n = 24). The main outcome was 30-day all-cause mortality.

Results

A total of 62 patients were enrolled, and the incidence of extraintestinal C. difficile infection was 2.81 per 100,000 admissions. Median age was 56 years and 36 (58.1%) of the patients were men. Seven patients (11.3%) had confirmed C. difficile enterocolitis, and 38 patients (61.3%) had a polymicrobial infection. C. difficile bacteremia was identified in 22 patients (35.5%) and was significantly more common in group A (60.0% [9/15]) than groups B (43.5% [10/23]) or C (12.5% [3/24]) (P = 0.01). Thirty-day mortality rates were also significantly higher in group A than groups B or C (60.0% [9/15] vs. 13.0% [3/23] and 16.7% [4/24], respectively; P < 0.001) (Figure 1). C. difficile bacteremia (P = 0.16), polymicrobial infection (P = 0.91), and antimicrobial therapy for C. difficile (P = 0.48) were not significantly associated with 30-day mortality. In a multivariate analysis, group A was an independent risk factor for 30-day mortality. (adjusted odds ratio; 7.29 [95% confidence interval; 1.68–31.68], P = 0.01).

Conclusion

Extraintestinal C. difficile infection was not commonly associated with C. difficile enterocolitis. Extraintestinal C. difficile infection accompanied by GI disruption with malignancy was associated with significantly poorer outcomes.

Disclosures

All authors: No reported disclosures.
2430. Comorbidity and Severity of Illness Risk Adjustment for Hospital-Onset Clostridioides difficile Infection
Authors: Cabral Stephanie , Nadimpalli Gita , Thom Kerri , Leekha Surbhi , Harris Lisa , Blanco Herrera Natalia , Harris Anthony
Published: October 2019

Background

Hospital-onset C. difficile infection (HO-CDI) rates are publicly reported. However, patient-level risk factors are not included in the current risk adjustment methodology, and the knowledge as to which risk factors to include is incomplete. This study aimed to determine whether electronically-available comorbidities and laboratory indicators of severity of illness are risk factors for HO-CDI.

Methods

We performed a retrospective cohort study of all adult patients admitted to three hospitals (one academic, two community) in Baltimore, Maryland between January 1, 2016 and January 1, 2018. Information extracted from electronic medical records included demographics, ICD-10 codes, laboratory results within 24 hours of admission (i.e., hematocrit, hemoglobin, platelet count, leukocytes, BUN, CO2, creatinine, glucose, sodium, and potassium), medication administration (i.e., antibiotic and antacid use), and C. difficile test result. Comorbid conditions were assessed by the Elixhauser Comorbidity Index components. HO-CDI was defined by positive laboratory test > 3 days after admission. Potential risk factors for HO-CDI were assessed using bivariate log binomial regression. Multivariable log binomial regression was conducted using significant (P < 0.1) covariates.

Results

At hospital 1 (academic), 314 of the 48,057 (0.65%) eligible patient admissions had HO- CDI; 41 of the 8,791 (0.47%) and 75 of the 29,211 (0.26%) of patient admissions at community hospitals 2 and 3, respectively, had HO-CDI. In multivariable analysis, Elixhauser Score was a significant risk factor for HO-CDI at all hospitals when controlling for antibiotic and antacid use; for every one-point increase in Elixhauser Score, there was an increased risk of HO-CDI of 1.27 (95% CI: 1.21, 1.32) at hospital 1, 1.38 (95% CI: 1.24, 1.54) at hospital 2, and 1.28 (95% CI: 1.10, 1.31) at hospital 3. Table 1 shows significant risk factors for HO-CDI for each hospital. When individual comorbidities were assessed in the regression analysis, fluid and electrolyte disorders were a significant risk factor for HO-CDI for all hospitals.

Conclusion

Laboratory values upon admission and electronically available patient comorbidities are important risk factors for HO-CDI and should be considered for future risk adjustment.

Disclosures

All authors: No reported disclosures.
2438. Using Artificial Neural Networks to Predict Intra-Abdominal Abscess Risk Post-Appendectomy
Authors: Al Khatib Hassan S , Alramadhan Morouge , Murphy James , Tsao KuoJen , Chang Michael L
Published: October 2019

Background

Applying Artificial Intelligence techniques to healthcare data are gaining momentum. Early identification of patients at risk of surgical site infections is a major clinical goal. Our objective for this study was to determine whether deep learning AI techniques could identify patients at risk of intra-abdominal abscess development post-appendectomy using clinical data for pediatric patients undergoing appendectomy.

Methods

A dataset of 1,574 patients classified by surgeons as negative (1,328) or positive (246) for Intra-Abdominal Abscess Post-Appendectomy for Appendicitis were selected from a database containing 6,127 patients less than 19 years-old who had appendectomy at our institution between 2009–2018. Demographic, clinical, and surgical information were extracted. 34 Independent variables were identified to be useful for the study. Using Random Forest methodology 12 variables with the highest influence on the outcome were selected for the final dataset. Data imputation (MICE algorithm) was used to replace missing data points. Two “Reproducible” Artificial Neural Networks with different architectures were developed to predict the risk of developing Intra-Abdominal Abscess Post- Appendectomy: Model (1) 12 Inputs, 3 hidden layers with 12 Neurons each, and 1 Output. Model (2) 12 Inputs, 2 hidden layers with 18 Neurons each, and 1 Output.

Results

For the 1,574 patients (80%-20% used as training and test sets), Model (1) achieved Accuracy of 89.84%, Sensitivity of ~ 70%, and Specificity of 93.61% on the test set while Model (2) achieved Accuracy of 84.13%, Sensitivity of 81.63%, and Specificity of 84.6%. The difference between the models is that in Model (2) we over sampled the minority class (using SMOTE algorithm) to balance both classes which helped the model to learn both classes without bias and improved sensitivity over Model (1).

Conclusion

Deep learning algorithms applied to enough clinical variables can identify patients with high probability for the risk of developing intra-abdominal abscess post-appendectomy. While further test sets are necessary to validate the models, Artificial Neural Networks can be an important addition to current post-surgical care guidelines to personalize and optimize care to reduce infections following appendectomy.

Disclosures

All authors: No reported disclosures.
2454. A Cluster of Gram-Negative Bloodstream Infections in Connecticut Hemodialysis Patients Associated with Contaminated Wall Boxes and Priming Buckets
Authors: Backman Lauren , Dumigan Diane G , Harizaj Adora , Oleksiw Marylee , Carusillo Evelyn , Malo Sue , Ransom Acacia , Patel Priti , Nguyen Duc , Moulton-Meissner Heather , Boyce John M
Published: October 2019

Background

Patients requiring maintenance hemodialysis (HD) are at increased risk of bloodstream infections. We investigated a cluster of infections due to unusual Gram-negative bacilli that affected patients undergoing HD at an outpatient unit with 19 stations (Clinic A).

Methods

A case was defined as a HD patient at Clinic A with >1 blood or urine culture positive for Delftia acidovorans, Enterobacter absuriae, or Burkholderia cepacia during the period February 1 – April 30, 2018. An investigation included review of patient records, facility policies, practice observation, environmental cultures, and a 1:4 case–control study. Controls were patients without bloodstream infection (BSI) during the outbreak period.

Results

The cluster included 3 patients. Patient 1 had BSI due to D. acidovorans (2/08), E. absuriae (3/15) and B. cepacia (3/17). Patient 2 had BSI due to D. acidovorans (3/17 and 3/27) and S. maltophilia (4/5). Patient 3 had a urine culture positive for D. acidovorans and S. maltophilia (4/2). The case–control study showed that cases had been dialyzed more often than controls on the third shift (P < 0.0001) and at station 2 (P < 0.0001), where subsequently a wall box spent dialysate drain connection swab culture yielded D. acidovorans. E. absuriae was recovered from wall boxes and spent dialysate drain connection at two stations and from used prime buckets from two stations; one wall box culture grew S. maltophilia. D. acidovorans and E. absuriae patient isolates were not available for genomic analysis. Observations revealed that waste water was leaking onto the floor from several wall boxes, and that priming buckets were often rinsed with tap water after being disinfected with 1:100 bleach solution and not allowed to dry before reuse. Multiple deficiencies in hand hygiene and station disinfection were observed. No deficiencies in water treatment practices were identified. Multiple water cultures obtained in August were negative for the observed pathogens.

Conclusion

A cluster of unusual Gram-negative infections in outpatient HD patients was most likely due to exposures to contaminated wall boxes or priming buckets; poor hand hygiene and station disinfection can contribute to transmission to patients.

Disclosures

All authors: No reported disclosures.
2457. Data Science for Outbreak Investigation: Identifying Risk Factors, Tracing Contacts, and Eliciting Transmission Pathways in a Vancomycin-Resistant Enterococci (VRE) Outbreak
Authors: Zahnd Stefan , Hossmann Theus , Atkinson Andrew , Herbel Sabine , Salazar-Vizcaya Luisa , Dahlweid Michael , Marschall Jonas
Published: October 2019

Background

In 2018 we experienced a nosocomial outbreak due to vancomycin-resistant enterococci (VRE) in our hospital network. Our goals were to characterize risk factors for VRE acquisition, elicit potential hot spots of transmission, and delineate an optimized approach to tracing contacts.

Methods

We assembled diverse datasets of variable quality and covering different aspects of care from electronic medical records generated during the outbreak period (1/2018–9/2018). Patients who tested VRE-positive during this period were compared with controls with up to 3 negative screenings. First, we identified risk factors for VRE colonization by means of uni- and multivariate analyses. Next, we elicited transmission pathways by detecting commonalities between VRE cases, and determined whether patients with characteristics and connections similar to VRE cases were missed by our current contact tracing strategy.

Results

We compared 221 VRE patients to 33,624 controls. Independent predictors of VRE colonization were ICU admission (OR 4.9, with 95% confidence interval [3.7–6.5], P < 0.001)], number of records in the database (a proxy for severity-of-illness, OR 1.1 [1.1–1.1], P < 0.001), length of hospital stay (OR 2.7 [2.0–3.5], P < 0.001), age (OR 1.3 [1.2–1.4], P < 0.001), and weeks of antibiotics (OR 1.2 [1.1–1.3], P < 0.001). By using complex network analysis, we were able to establish three main pathways by which the 221 VRE cases are connected: healthcare personnel, medical devices, and patient rooms. This multi-dimensional network extends beyond our current contact tracing strategy, which captures inpatients based on geographical proximity (cf. figure).

Conclusion

In this outbreak investigation based on a large electronic healthcare data collection, we found three main risk factors for being a VRE carrier (ICU admission, length of hospital stay, antibiotic exposure), along with three important links between VRE cases (healthcare personnel, medical devices, patient rooms). Data science is likely to provide a better understanding of outbreaks, but interpretations should take data maturity, the scope of included sources, and potential confounding factors into account.

Disclosures

All authors: No reported disclosures.
2461. Community-Acquired in Name Only: A Cluster of Carbapenem-Resistant Acinetobacter baumannii in a Burn Intensive Care Unit
Authors: Shenoy Erica S , Pierce Virginia M , Sater Mohamad , Pangestu Febriana , Herriott Ian , Fred Hawkins , Suslak Dolores , West Lauren R , Huntley Miriam , Rosenberg David C
Published: October 2019

Background

Detection of nosocomial outbreaks often relies on epidemiological definitions of community and nosocomial acquisition. We report a cluster of three carbapenem-resistant Acinetobacter baumannii (CRAB) infections linked to a single source patient with infections occurring within 2 days of admission to a burn intensive care unit (ICU). The epidemiological investigation was supplemented by whole-genome sequencing (WGS) of clinical and environmental isolates.

Methods

Study participants included burn ICU patients identified with infections caused by CRAB. A detailed review of patient demographic and clinical data was conducted. Clinical A. baumannii isolates were assessed by antimicrobial susceptibility testing and WGS. Review of infection control practices on the affected unit was followed by environmental sampling. A. baumannii isolates obtained through environmental sampling were assessed for carbapenem resistance and then underwent WGS for comparison to the clinical isolates.

Results

Three cases of CRAB infection in the affected unit spanning a period of 3 months were linked to a preceding source patient, with CRAB isolates from the four patients differing by 5–7 single nucleotide variations. All case patients had been admitted to the same room within 2 days before development of CRAB infection. Environmental sampling performed while the third case patient occupied the room identified highly contaminated areas, and environmental CRAB isolates linked the patient isolates. The contaminated areas were subsequently re-sampled after enhanced terminal cleaning of the room. No additional CRAB was isolated, but other pathogenic organisms were recovered.

Conclusion

We report a cluster of three infections caused by highly resistant A. baumannii that occurred in a burn intensive care unit over a period of 3 months, linked to a single source patient. Three case patients developed infections classified as community-acquired using standard epidemiological definitions, however, whole-genome sequencing revealed clonality. An extensive investigation identified the role of environmental reservoirs. Burn patients may be particularly vulnerable to early-onset nosocomial infection from environmental contamination.

Disclosures

All authors: No reported disclosures.
2478. Surveillance of antibacterial resistance among clinical isolates from hospitals in Shanghai: results of 2018
Authors: Yang Yang , Guo Yan , Zhu Demei , Hu Fupin
Published: October 2019

Background

To investigate the current state of antibacterial resistance of clinical isolates from hospitals in Shanghai, China.

Methods

Antimicrobial susceptibility testing (AST) was carried out for the clinical isolates from 50 hospitals (including 30 grade A tertiary hospitals and 20 grade B tertiary hospitals/grade A secondary hospitals, and there were 3 children hospitals among them) according to a unified protocol using Kirby–Bauer(KB) method or automated AST systems. Results were analyzed according to CLSI 2018 breakpoints.

Results

Of the 144373 clinical isolates, Gram-positive cocci and Gram-negative bacilli accounted for 29.6% and 70.4%, respectively. The overall prevalence of MRSA in Staphylococcus aureus was 45.9% and 78.4% for MRCNS in coagulase-negative Staphylococcus. No strains were found resistant to vancomycin in Staphylococcus spp. 84.1% of the 1204 strains of non-meningitis S. pneumoniae isolated from children were penicillin-susceptible (PSSP), 15.9% were penicillin-nonsusceptible, including penicillin-intermediate (PISP, 10.5%) and penicillin-resistant (PRSP, 5.4%) strains. Of the 361 strains isolated from adults, 94.5%, 3.0% and 2.5% were PSSP, PISP, and PRSP, respectively. Vacomycin-resistance E. feacium was 0.7% and no vacomycin-resistant E. feacalis were identified. According to PCR results, most of these resistant strains were vanA genotype. The prevalence linezolid-nonsusceptible E. faecalis was about 1.6%, few E. feacium was resistant to Linezolid. The overall prevalence of ESBL-producing strains was 54.0% in E. coli, 35.0% in Klebsiella pneumoniae and 47.1% in Proteus mirabilis. Enterobacteriaceae isolates were still mainly susceptible to carbapenems. Overall, 11.7% and 11.2% of the Enterobacteriaceae isolates were resistant to imipenem and meropenem, respectively. The predominant organism of CRE isolates was K. pneumoniae. The prevalence of CRAB and CRPA were 62.5% and 28.7%, respectively.

Conclusion

Antimicrobial resistance remains to be a problematic issue in healthcare settings, especially in Gram-negative bacilli, effective infection-control measures should be promoted to tackle this critical threat.

Disclosures

All authors: No reported disclosures.
142. Mean Platelet Volume Is Associated with Embolic Events of Infectious Endocarditis
Authors: Barnes Erin W
Published: October 2019

Background

Increased mean platelet volume (MPV) is a marker of more active and rapidly aggregating platelets. There is limited evidence that increased MPV is associated with more embolic disease in infectious endocarditis (IE). This study seeks to validate this relationship and assess for effect modification by injection drug use.

Methods

Records of all patients aged ≥18 admitted to Wake Forest Baptist Medical Center (WFBMC) from January 1, 2004 to September 30, 2015 with an ICD-9 code for IE and without a simultaneous ICD-9 code indicating”mechanical complication of cardiac device, implant and graft’ were reviewed. Inclusion criteria consisted of possible or definite IE by modified Duke criteria and labs drawn within 24 hours of presentation. Univariate analyses were assessed by Chi-square, Fisher’s exact test, Mann–Whitney U, and Student’s t-test. Multiple logistic regression assessed the association between MPV and embolic phenomena while controlling for potential confounders.

Results

A total of 237 cases (80 IDU-IE and 157 non-IDU IE) met criteria for analysis suffering 115 (48.5%) embolic events to the brain and/or lungs (41.4% in non-IDU vs. 62.5% in IDU-IE, P = 0.002). MPV (P < 0.0001) and drug use (P = 0.002) were significantly associated with embolic disease. S aureus involvement (P = 0.0002), vegetation ≥1 cm (P = 0.009), atrial fibrillation (P = 0.05), hypertension (P = 0.05), age (P = 0.0008), presenting hospital location (P = 0.001), total platelets (P < 0.0001), age-unadjusted Charleson comorbidity score (P = 0.001), and left-sided valve vegetation (P = 0.006) were also significantly associated while gender, white blood cell count, creatinine and albumin were not. MPV remained significantly associated with embolic disease in the fully adjusted model with OR 1.4, 95% CI [1.1–1.7]. Vegetation ≥1 cm (OR 2.4, 95% CI [1.2–4.7]), left-sided valve vegetation (OR 0.4, 95% CI [0.2–0.8]) and direct presentation rather than transfer to WFBMC (OR 0.4, 95% CI [0.2–0.8]) also remained significant. There was no evidence of an interaction between MPV and drug use nor evidence of effect modification when the analysis was stratified by drug use status.

Conclusion

Increased MPV is significantly associated with embolic disease of IE even when additional covariates are taken into consideration.

Disclosures

All authors: No reported disclosures.
2497. Women’s Perspectives on and Experiences with Long-acting Injectable Anti-retroviral Therapy in the United States and Spain: the Potential Role of Gender in Patient Preferences
Authors: Mantsios Andrea R , Murray Miranda , Karver Tahilin Sanchez , Davis Wendy , Margolis David , Kumar Princy , Swindells Susan , Bredeek Fritz , Deltoro Miguel García , García Rafael Rubio , Antela Antonio , Garris Cindy , Shaefer Mark S , Gomis Santiago Cenoz , Bernaldez Miguel Pascual , Kerrigan Deanna
Published: October 2019

Background

Adherence to antiretroviral therapy (ART) to treat HIV remains a critical global health challenge given its relationship with individual health outcomes and population-level transmission. Given barriers associated with oral ART adherence, and considerations of patients’ preferences, long-acting injectable (LA) ART (cabotegravir + rilpivirine) is under development and has been shown to be non-inferior to daily oral ART in Phase III trials. While most of the trial participants have been men, as LA ART gets closer to becoming available for routine clinical use, it is critical to understand how this option is perceived by women.

Methods

We conducted in-depth interviews with 67 individuals, 53 people living with HIV (PLHIV) and 14 healthcare providers, in 11 sites in the United States and Spain participating in Phase III LA ART trials (ATLAS, ATLAS 2-M and FLAIR). Twenty percent (10/53) of trial participants interviewed were women. Interviews explored patient and provider perspectives and experiences with LA ART, and appropriate candidates and recommendations to support use. Interviews were audio-recorded, transcribed and coded using thematic content analysis.

Results

Overall, several salient themes emerged regarding participant’s generally positive experiences transitioning from daily oral ART to injectable ART including: the importance of the clinical efficacy of LA ART, the ability to learn to manage injection side-effects over time, and the “freedom” reportedly afforded by LA ART logistically and psychosocially. Women interviewed shared many of the aforementioned positive perceptions of LA ART but also had some unique perspectives. Female participants discussed how LA ART was easier to integrate into their daily lives including managing their multiple roles and responsibilities, which often involved working full-time and taking care of themselves as well as their family and children.

Conclusion

Similar to all participants, female participants had generally positive views of LA ART. However, the gendered nature of their daily lives also led to some unique perspectives on why and how they were satisfied with LA ART that merits further exploration in future research.

Disclosures

All authors: No reported disclosures.
2501. CCR5 Targeted ARV Loaded Nanoparticle: Dual Protection for HIV Functional Cure
Authors: Destache Christopher J , Prathipati Pavan , Velagaputi Manasa , Mandal Subhra
Published: October 2019

Background

One of the NIH high-priority HIV/AIDS research objectives is to discover novel therapeutics aimed at developing safe, tolerable, strategies that targets cellular protein to induce long-term antiviral suppression. This current research aims at designing a novel targeted nano-formulation combining cell targeting and antiretroviral therapy to provide double protection against HIV-1.

Methods

CCR5 targeted combination antiretroviral drugs (cARV) loaded nanoparticles (NPs) were synthesized based on water-in-oil-in-water (W-O-W) emulsion methodology. For targeting CCR5+ T cells, a modified high affinity CCR5 monoclonal Ab (XFCCR5 mAb), was isolated from XF-CCR5 hybridoma cells. The XFCCR5 mAbs were covalently conjugated through their C-terminus by replacing the NHS group on FTC+DTG NPs with covalent amide bond. The CCR5 mAb binding was evaluated by SDS–PAGE methods. The CCR5-specific binding affinity of XFCCR5-FTC+DTG NP in compared with XFCCR5 monoclonal antibody (mAb) was evaluated by flow cytometry using CD4+CCR5+ TZM-bl cell line and PBMCs. The intracellular pharmacokinetic (PK) profile in TZMbl cells was evaluated by LC-MS/MS analysis, whereas in vitro efficacy was evaluated based on Steady-Glo® Luciferase Assay System using TZM-bl cells.

Results

XFCCR5-FTC+DTG NPs obtained averaged 173 ± 23 nm (mean ± SEM, n = 3) with 2.2 ± 0.47 mg XFCCR5 mAb bound per mg cARV NP. The formulation % entrapment efficiency of DTG and FTC respectively, to be 55 ± 1.6% and 42.6 ± 5.6%. The specific binding affinity (Km) of XFCCR5-FTC+DTG NP and XFCCR5 mAb were estimated to be 0.0057 and 0.0377, higher compared with wild-type anti-CCR5 mAb with higher Km value 0.303. Finally, the 4-day HIV-infection protection study result illustrates IC50 in case of XFCCR5-FTC+DTG NP and XFCCR5 NP to be as low as 0.0069 and 0.0031 µg/mL, respectively, compared with 1.771 µg/mL for XFCCR5 mAb (Figure 1, TZM-bl and Figure 2, PBMCs).

Conclusion

This nano-formulation aimed at duel protection by preventing HIV binding to CCR5+CD4+T cell due to CCR5 receptor blocking. These result support protection against HIV and maintenance of cARV drug levels. This novel formulation could be supportive of immune-alternative to achieve functional-cure against HIV.

Disclosures

All authors: No reported disclosures.
2508. Virologic Suppression in Patients Switched to BIC/TAF/FTC with Baseline NRTI and/or INSTI Resistance
Authors: Natali Kayla M , Tilani Rahul , Slim Jihad
Published: October 2019

Background

BIC/TAF/FTC is the first fixed-dose combination tablet to contain both a second-generation INSTI and TAF and has therefore become a popular treatment option for HIV. Historically, patients with NRTI mutations were placed on four-drug, NRTI-retaining regimens or two-drug, NRTI-sparing regimens. Recently, data have emerged supporting the use of second-generation INSTIs with tenofovir/FTC in the setting of the M184V mutation alone. There is a paucity of data, however, evaluating the use of BIC/TAF/FTC in the setting of NRTI and/or INSTI mutations. This study assessed the role of BIC/TAF/FTC in patients with baseline NRTI and/or INSTI mutations.

Methods

This was an observational retrospective study conducted at an inner city HIV clinic. Patients were eligible if they were switched to BIC/TAF/FTC with confirmed adherence and had either the M184V mutation alone, M184V plus another NRTI mutation(s), an INSTI mutation alone, or both NRTI and INSTI mutation(s) at the time of ART switch. We evaluated virologic response (HIV RNA < 200 copies/mL) and duration of BIC/TAF/FTC therapy.

Results

There were 16 patients eligible for analysis. Among the patients, 69% were male and 31% were female. The majority of patients were Black (81%). The mean age was 63 years (SD ± 8.6). Thirteen patients were virologically suppressed (HIV RNA < 200 copies/mL) at baseline. The mean CD4 count at baseline was 630.4 cells/mm3 (SD ± 297.1). Mutations at baseline were as follows: M184V alone (25%), M184V plus another NRTI mutation(s) (56.25%), INSTI mutation alone (12.5%), NRTI and INSTI mutation(s) (6.25%). BIC/TAF/FTC mean duration of therapy was 10.5 months (range 6–14 months). The mean CD4 count of the patients switched to BIC/TAF/FTC was 687 cells/mm3 (SD ± 20.7). All patients switched to BIC/TAF/FTC achieved or maintained virologic suppression (HIV RNA < 200 copies/mL) with a mean HIV RNA of 26.25 copies/mL (SD ± 14.1). Fifteen of those switched to BIC/TAF/FTC had an undetectable HIV RNA level (HIV RNA < 50 copies/mL).

Conclusion

While a larger cohort and longer follow-up period is needed, BIC/TAF/FTC may maintain virologic suppression in patients with select baseline NRTI and/or INSTI mutations.

Disclosures

All authors: No reported disclosures.
2509. Pooled Resistance Analyses of Darunavir (DRV) Once Daily (QD) Regimens and Formulations Across 10 Clinical Studies of Treatment-Naïve (TN) and Treatment-Experienced (TE) Patients with Human Immunodeficiency Virus (HIV)-1 Infection
Authors: Lathouwers Erkki , Seyedkazemi Sareh , Luo Donghan , Brown Kimberley , De Meyer Sandra , Wong Eric Y
Published: October 2019

Background

DRV has demonstrated high efficacy and barrier to resistance development across diverse populations, from TN to heavily TE patients. We evaluated resistance data from 10 clinical studies of different DRV 800 mg QD–based antiretroviral regimens and formulations.

Methods

The analysis included patients from 10 phase 2/3 studies (48–192 weeks in duration) of ritonavir- and cobicistat-boosted DRV 800 mg QD–based regimens in TN and virologically failing or suppressed TE patients with HIV-1 (table). Three were phase 3 studies of the DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen (STR). Post-baseline resistance was evaluated in patients experiencing protocol-defined virologic failure (PDVF); definitions and criteria for resistance testing varied slightly among studies. Resistance-associated mutations (RAMs) were based on respective International Antiviral Society–USA mutation lists over time.

Results

Of the 3,635 patients evaluated, 250 met PDVF criteria and 205 had post-baseline genotypes/phenotypes. Overall, 4 (0.1%) patients developed (or had identified [switch studies]) ≥1 DRV and/or primary protease inhibitor (PI) RAM (table), and only 1 (< 0.1%, ODIN) patient lost DRV phenotypic susceptibility; this TE patient had prior VF with lopinavir. Among those who used a nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone (mostly emtricitabine [FTC] + tenofovir [TFV]), 12 (0.4%) patients had ≥1 NRTI RAM, including 10 with M184I/V associated with FTC resistance. No TFV RAMs were observed. Among patients receiving D/C/F/TAF (n = 1,949), none had post-baseline DRV, primary PI, or TFV RAMs; only 2 (0.1%) patients developed an FTC RAM.

Conclusion

Across a large, diverse population using DRV 800 mg QD–based regimens and formulations, resistance development remains rare; 0.1% of patients had ≥1 DRV and/or primary PI RAM post-baseline. Among 3 trials of the D/C/F/TAF STR, no patients developed a DRV or primary PI RAM. After > 10 years of investigating DRV 800 mg QD–based regimens in clinical trials, loss of phenotypic susceptibility to DRV has never been observed in TN or TE virologically suppressed patients and was only once observed in a TE patient with prior VF on multiple antiretrovirals, including a PI.

Disclosures

All authors: No reported disclosures.
2515. Clinical Relevance of Immune Non-Response Among Virally Suppressed Adults Living with HIV in Africa and the United States
Authors: Noiman Adi , Wang Xun , Esber Allahna L , Crowell Trevor A , Ganesan Anuradha , Polyak Christina , Ake Julie A , Agan Brian
Published: October 2019

Background

Immune non-response (INR) for people living with HIV (PLWH) is the inability to regain healthy CD4 counts despite viral suppression (VS) on antiretroviral therapy (ART). We identified factors associated with INR in two methodologically similar but demographically diverse cohorts with open access to care and assessed the relationship between INR and incident serious non-AIDS event (SNAE).

Methods

The US Military HIV Natural History Study (NHS) and the African Cohort Study (AFRICOS) are multisite, open cohort studies enrolling PLWH. Participants with 2 years of VS < 400 copies/mL on ART were evaluated for INR, defined as CD4 < 350 cells/µL at 2 years VS. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHR) and 95% CIs for factors associated with incident SNAE (first non-AIDS cancer, cardiovascular, gastrointestinal, genitourinary, liver, musculoskeletal or respiratory event) after 2 years of VS.

Results

10.8% of the 1,784 NHS and 25.8% of the 984 AFRICOS subjects had INR. The AFRICOS cohort was older and had a higher proportion of females. In both cohorts, immune non-responders were significantly older and had a significantly lower CD4 at ART initiation. Those with INR also took longer to reach 2 years of VS since starting ART. Odds of INR decreased by over 60% for every 100 cell increase in baseline CD4 in both cohorts (NHS aOR = 0.31 [95% CI 0.26, 0.37]; AFRICOS aOR = 0.36 [95% CI 0.21, 0.86]). In the NHS, hazard of incident SNAE was 61% higher for those with INR (aHR = 1.61 [95% CI 1.12, 2.33]). Probability of SNAE-free survival at 15 years since 2 years of VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups.

Conclusion

INR was common in two diverse cohorts with open access to care and treatment. The association with SNAEs suggests early identification of and interventions to prevent or reverse INR may improve clinical outcomes, but further study is needed. The clinical relevance of INR highlights the value of early HIV identification and treatment, and suggests CD4 monitoring at ART initiation and post-VS is important in settings where INR is prevalent.

Disclosures

All authors: No reported disclosures.
2531. Using Peer-to-Peer Education to Increase Awareness and Uptake of HPV Vaccine Among Chinese International Students
Authors: Esaggoff Aaron , Cohen, Samuel , Chang Guoxuan , Equils Ozlem , Orman Sarah Van , Burnett Alicia
Published: October 2019

Background

There are more than one million international college students in the United States. The University of Southern California hosts about 5,000 Chinese International Students (CIS). HPV-related cancers are common in China and the HPV vaccine was only recently introduced to the Chinese population. CIS in the United States have low HPV vaccination rates upon arrival. Once these students become aware of the affordability and the accessibility of the vaccine, they often contact a provider to start the vaccination series. The HPV vaccine is available to all eligible students at the USC student health center and is free of charge to students with Aetna Student Health Insurance. We examined the impact of a peer-to-peer education program about HPV disease and vaccination amongst CIS and assessed the impact of the program via an analysis of HPV immunization rates amongst CIS.

Methods

The study was IRB approved. Mandarin-speaking USC students volunteered to serve as peer educators in response to an inquiry from academic advisors. 18 CIS were trained by MiOra as Immunization Community Health Educators (ICHE) on HPV disease and vaccination as well as sexually transmitted infections and prevention. CIS educated peers at tables set up throughout USC.

Results

Initial data from 100 CIS students who were surveyed and educated in April 2019 were analyzed. 59 out of 99 (59.6%) students reported that they have either received or are in the process of receiving the HPV vaccine. 93 out of 99 (93.9%) indicated “no knowledge” or “some knowledge” about HPV and HPV vaccine while only 6 students (6.1%) reported “a great deal of knowledge.” 56 out of 99 (56.6%) thought that it is “unlikely” or “impossible” for them to acquire HPV. 92 out of 97 (94.9%) said they would be interested in getting vaccinated if it were free.

Conclusion

Many CIS have limited understanding of HPV risk factors and HPV vaccine; however, when informed, the majority of students indicated they would likely vaccinate if it was covered by insurance. Peer-to-peer education was very effective. Of the first 400 students educated, 80 visited the student health center. This is an ongoing project. We will continue to collect and report data on the impact of the peer-to-peer education and factors influencing.

Disclosures

All authors: No reported disclosures.
2544. An Exploratory Study of Resource Utilization by Practitioners when Managing Infections
Authors: Abdoler Emily , Gruenberg Katherine , Schwartz Brian , Schwartz Brian , MacDougall Conan
Published: October 2019

Background

Antimicrobial prescribing mistakes are common and adherence to guidelines for treatment of infections is poor. Effective use of clinical resources could help ameliorate these issues, but little is known about the use of such resources by physicians and pharmacists. We thus aimed to explore how practitioners utilize clinical resources in the management of infections.

Methods

We conducted individual interviews with a purposeful sample of eight Hospitalists, eight ID attendings, four ID pharmacists, and six non-ID pharmacists. As part of a larger, semi-structured interview exploring ID practice patterns, we asked respondents how they utilize resources when managing infections. We describe the resources mentioned by the different practitioners, as well as the frequency of their reported use.

Results

All respondents reported using at least one resource to help manage infections, with a mean of 5.6 resources each. The majority of respondents use resources daily, although some ID practitioners use resources more frequently and some general practitioners less frequently (Figure 1). The types of resources utilized by respondents fell into six main categories: local ID resources, outside ID resources, primary literature, guidelines, colleagues, and pharmacy resources (Figure 2). In general, local resources are utilized more frequently by non-ID practitioners, while guidelines and the primary literature are utilized more frequently by ID practitioners. ID physicians use pharmacy resources more frequently than non-ID physicians. Six respondents spontaneously reported being motivated to review resources for their own interest or learning. Several also commented that accessibility was important in choosing resources.

Conclusion

Providers report use of resources to manage infections, although the type of resource and frequency of use varies. ID practitioners utilize more detailed resources than nonspecialists. Accessibility seems to influence resource utilization, which may explain the popularity of local ID resources. As such, efforts to make local ID resources as accessible and clear as possible may have an impact on appropriate antibiotic use. Future quantitative studies could help illuminate rates and perceived advantages of specific resource utilization.

Disclosures

All authors: No reported disclosures.
2547. Prioritizing Antimicrobial Resistance Learning Objectives Through a Modified, Two-Round, One-Day Delphi at a Multidisciplinary Conference
Authors: Budak Jehan , Kpokiri Eneyi E , Abdoler Emily , Tucker Joseph , Schwartz Brian , Schwartz Brian
Published: October 2019

Background

Antimicrobial resistance (AMR) is a global public health problem, but the learning needs of the medical profession on this topic are not well understood. The World Health Organization has called for better educational resources on AMR. Thus, we aimed to identify AMR learning objectives for physicians and medical trainees.

Methods

We designed a modified, two-round Delphi process to build consensus around these objectives, recruiting attendees at a one-day, multidisciplinary, international AMR symposium. Through review of the literature and discussion with experts in AMR, we generated an initial list of 17 objectives. We asked participants to rate the importance of including each objective in an AMR curriculum for physicians on a 5-point Likert scale, which ranged from “do not include” (1) to “very important to include” (5). Consensus for inclusion was predefined as ≥ 80% of participants rating the objective ≥ 4.

Results

The first round was completed by 30 participants, and the second by 21. Nobody declined to participate, but several people had to leave between rounds. Participants included physicians, researchers, graduate students, and a pharmacist, foundation manager, patient advocate, leader of an international financial institution, health administrator, and biomedical scientist. After the first round, 16 objectives met the consensus criteria, and participants suggested five additional topics. After the second round, 12 objectives met the consensus criteria (see Table 1). Objectives related to treatment of AMR most frequently met consensus criteria. Specific objectives with the highest consensus ratings were related to identifying infections not requiring antibiotics and recognizing the importance of using the narrowest spectrum antibiotic for the shortest period of time.

Conclusion

We successfully employed a modified, one-day Delphi process at an international, multidisciplinary AMR symposium to build consensus among experts and stakeholders regarding key learning objectives for AMR. This technique may be useful for guideline committees and other taskforces in the Infectious Diseases community. Our generated list may be useful for those developing AMR training materials for medical students and physicians.

Disclosures

All authors: No reported disclosures.
2550. A Meeting of the Minds Over Matters of the Heart: Using Interdisciplinary Education to Build Consensus in Managing Cardiac Implantable Electronic Device (CIED) Infections
Authors: Azim Ahmed Abdul , Zimetbaum Peter , Kramer Daniel B , Karchmer Adolf W , Stead Wendy
Published: October 2019

Background

CIED infections carry significant morbidity and mortality. Guidelines differ in management recommendations for CIED infections, which can result in a lack of consensus amongst Infectious Disease (ID) and Cardiology providers caring for these patients. We sought to identify areas of disagreement and consensus in the care of CIED infections amongst ID and Cardiology providers at an academic medical center. We used these data as a needs assessment to develop an interdisciplinary educational intervention focused on standardizing our institutional approach toward CIED infections, to create an internal guideline and to develop a new multidisciplinary team (MDT) for assistance managing complex patients hospitalized with CIED infections.

Methods

A pre-intervention survey was delivered to advanced practitioner providers, fellows and faculty of the divisions of Cardiology, Electrophysiology (EP) and ID to assess content knowledge in the diagnosis and management of CIED infections, attitudes toward the formation of a MDT, and perception of the degree of consensus amongst these specialty providers.

Results

The survey was sent to 206 providers, 40 (19.4%) participated. Only 16/40 (40%) agreed that there was consensus within the ID division in managing patients with CIED infections, and only 8/40 (20%) agreed that there was consensus amongst Cardiology and EP providers. 37/40 (92.5%) agreed that a MDT approach would be beneficial. Some survey responses diverged significantly from guideline recommended management strategies, including only 50% of respondents recommending CIED extraction for devices eroding through the skin. For patients with CIED-related endocarditis, 35% recommended delaying reimplantation of a new CIED until completion of a full course of antibiotics, despite guideline recommendations of significantly shorter delays.

Conclusion

Our survey revealed a striking lack of consensus amongst ID and Cardiology providers in the appropriate diagnosis and management of CIED infections, along with divergence from guideline recommendations in key areas. An interdisciplinary educational intervention to update provider content knowledge and unify interspecialty approaches could improve collaborative efforts and, ultimately, care of patients with CIED infections.

Disclosures

All authors: No reported disclosures.