bluuebunny/crossref_metadata_2025 huggingface dataset:
224. Epidemiology of Bloodstream infections in a Cohort of Allogeneic Hematopoietic Stem Cell Transplant Patients from 2009 to 2018
Authors: Classen Annika , Jakob Carolin , Stecher Melanie , Tobys David , Piepenbrock Ellen , Holtick Udo , Scheid Christof , Cornely Oliver , Janne Vehreschild Jörg
Published: October 2019

Background

Due to severe immunosuppression, patients undergoing allogeneic hematopoietic stem cell transplantation (aSCT) are at increased risk of infection and especially bloodstream infections (BSI) remain a major cause of death. Knowledge of the specific epidemiology of pathogens and resistances is of utmost importance to optimize antimicrobial treatment strategies.

Methods

Based on the Cologne Cohort of Neutropenic Patients (CoCoNut) database, we conducted a retrospective analysis of blood cultures collected within 100 days following transplantation of patients undergoing aSCT between January 2009 and December 2018 at the University Hospital of Cologne, Germany. Contamination of coagulase-negative Staphylococci (CoNS) isolates (single positive isolate within 5 days) was considered within the analysis.

Results

In total, 843 aSCT patients were available for analysis (484/843 [57%] male). The median age was 53 (interquartile range [IQR] 43–62) years, predominant underlying diseases were acute myeloid leukemia (47%, 397/843), lymphoma (14%, 117/843), and acute lymphoblastic leukemia (11%, 89/843). Median inpatient stay was 39 (IQR 34–50) days, while 67/843 (8%) patients died. Antibacterial prophylaxis was administered in 289/843 (34%) and antifungal prophylaxis in 738/843 (88%) patients. BSI was diagnosed in 233/843 (28%) patients. In total, 5,489 pairs of blood cultures were taken (median 4 per patient, IQR 2–8), while a pathogen could only be detected in 922/5,489 (17%). Most frequent pathogens were CoNS (259/922, 28%), Enterococcus spp. (219/922, 24%), E. coli (132/922, 14%), Klebsiella spp. (44/922, 5%), P. aeruginosa (39/922, 4%), S. aureus (37/922, 4%), and Candida spp. (42/922, 5%). Polymicrobial infection was detected in 58/922 (6%) cases. Within Enterococci isolates, 24/219 (11%) were VRE. None of the Klebsiella, but 9/132 (7%) of E. coli isolates were ESBL positive. In 4/37 (11%) cases S. aureus isolates were MRSA.

Conclusion

Patients in the early phase after aSCT are at high risk of BSI with a predominantly gram-positive spectrum. Empirical antimicrobial treatment must consider pathogen epidemiology and resistance patterns while waiting for blood culture results.

Disclosures

All authors: No reported disclosures.
235. Next-Generation Sequencing for Investigation of Hospital Outbreak of Carbapenem--Resistant Klebsiella pneumoniae
Authors: Kholy Amani , Soliman May Mohamed Sherif , Ramadan Arwa , El-Kholy Jehan
Published: October 2019

Background

Carbapenem--resistant Enterobacteriaceae constitute an urgent public health problem worldwide. In 2018, carbapenem--resistant Klebsiella pneumoniae (CR-KP) caused outbreaks of infection in 4 intensive-care units (ICUs)in a tertiary-care hospital in Egypt. We aimed to identify the clonal relatedness of isolates by whole genome (WGS).

Methods

Identification and antibiotic susceptibility testing was done by VITEK-2. Eleven isolates showed identical resistance pattern (resistant to Amikacin, gentamicin, Imipenem, meropenem, levofloxacin, and Piperacillin/Tazobactam) and were susceptible only to colistin. Caba-NP test was positive for carbapenemase production. The 11 isolates were studied by WGS by Illumina Miseq in a reference lab in Cairo University Hospital.

Results

In only one ICU, WGS identified 4 outbreak isolates of CR-KP that group together as a tight clonal cluster, suggestive of intra-ward transmission event. The outbreak isolates belonged to MLST 147. All isolates carried blaCTXM-15, blaoxa-48, and blaNDM1 encoding ESBL and carbapenemase activity. Other identified resistance genes were Str, AadA, MsrE, Tet, and DfrA, encoding resistance to aminoglycosides, macrolide–lincosamide–streptogramin, tetracycline and trimethoprim/sulphonamides. Virulence genes included Yersiniabactin, aerobactin, rmpA, rmpA2 and wzi64, which has been associated with pathogenicity and hypervirulent K. pneumoniae lineages. No clonal relationships were identified between the isolates from other ICUs.

Conclusion

WGS is a powerful tool that goes beyond high-resolution tracking of transmission events into identifying the genetic basis of drug-resistance and virulence.

Disclosures

All authors: No reported disclosures.
238. Direct identification of Bacterial Species with MinION Nanopore Sequencer In Clinical Specimens Suspected of Polybacterial Infection
Authors: Il Jun Kang , Moon Jangsup , Soo Kim Taek , Kyung Kang Chang , Mi Moon Song , Song Kyoung-Ho , Gyun Choe Pyoeng , Hwan Bang Ji , Won Park Sang , Suk Kim Eu , Kim Nam-Joong , Oh Myoung-don , Chu Kon , Beom Park Wan
Published: October 2019

Background

Conventional culture tests usually identify only a few bacterial species, which can grow well in the culture system, in the cases of polybacterial infection. 16S rRNA gene nanopore sequencing enables semi-quantitative identification of bacterial genetic materials. We aimed to evaluate usefulness of 16s rRNA gene nanopore sequencing in the cases suspected of polybacterial infection.

Methods

The research was conducted in a single university hospital for one year. Conventional bacterial culture identification and nanopore sequencing of 16s rRNA gene were carried out simultaneously for cases where polybacterial infection is strongly suspected. Blood agar plate was used for conventional culture, and Microscan (Beckman Coulter, United States) and Vitek 2 (Biomerieux, FR) automated systems were used for identification. For nanopore sequencing, 16S rRNA gene PCR was performed from the clinical specimens, and sequencing libraries were generated from the PCR products using the rapid barcoding sequencing kit (Oxford nanopore technologies, UK). MinION sequencing was performed for 1–3 hours and the generated reads were analyzed using the EPI2ME 16S BLAST workflow.

Results

Specimens were obtained from 15 patients; 6 liver abscess, 2 psoas abscess, 2 thigh abcess, 1 paraspinal abscess, 1 mycotic aneurysm, 1 necrotizing fasciitis, 1 fingertip gangrene and 1 abscess in coccyx area. 16s rRNA gene nanopore sequencing showed monobacterial organism in 8 (53.3%) specimens and polybacterial organisms in 7 (46.6%) specimens. In three (37.5%) cases of 8 cases with monobacterial infections identified by 16s rRNA gene sequencing, no organism was grown in conventional culture, possibly due to previous antibiotic administration. Notably, among 8 cases with polybacterial infection by 16s rRNA gene nanopore sequencing test, traditional culture test showed polybacterial infection in only two (25%) cases and single bacterial organism was identified in the other 6 (75%) cases.

Conclusion

Nanopore sequencing of 16s rRNA gene using the MinION sequencer may be useful for identification of causing microorganism and differentiation between monobacterial and polybacterial infection when polybacterial infection is suspected.

Disclosures

All authors: No reported disclosures.
245. Plasma and Respiratory Specimen Metagenomic Sequencing for the Diagnosis of Severe Pneumonia in Mechanically-Ventilated Patients
Authors: Kitsios Georgios , Yang Libing , Nettles Rachel , Haris Zia , Dunlap Daniel , Rapport Sarah , Haidar Ghady , Ho Carine , Hollemon Desiree D , Ahmed Asim A , Hong David K , Morris Alison , McVerry Bryan
Published: October 2019

Background

Metagenomic sequencing of respiratory microbial communities may overcome the limitations of culture-based pneumonia diagnostics. Nonetheless, respiratory metagenomics requires high-quality specimens, may miss deep-seated infections and cannot distinguish colonization from infection. Plasma microbial cell-free DNA (mcfDNA) sequencing may offer a noninvasive alternative for culture-independent diagnosis and help refine interpretations of respiratory metagenomics.

Methods

We obtained concurrent plasma and endo-tracheal aspirate (ETA) samples from 29 mechanically-ventilated patients (15 culture-positive, 11 culture-negative pneumonia, 3 uninfected control patients). We performed plasma mcfDNA sequencing (Karius®Test, Redwood City, CA) and ETA metagenomics (MiNION, Oxford Nanopore Technologies). We compared sequencing results with clinical microbiologic cultures for identified DNA pathogens.

Results

Uninfected control patients had a negative signal for mcfDNA in plasma and oral bacteria in ETA specimens. In culture-positive pneumonia samples, Karius testing identified a median of 2 pathogens per sample (range 0–10), which were concordant with clinical isolates in 11/15 (73%) cases (figure). In 5/11 (45%) of concordant cases, Karius and MiNION suggested polymicrobial infections with additional pathogens not identified by cultures. In culture-negative cases, Karius detected potential pathogens in 8/11 (73% cases), which matched the species identified in ETA specimens by MiNION. In cases of clinical aspiration, Karius detected more organisms (median 8, range 0–14) per sample mainly consisting of oral origin bacteria compared with cases without history of aspiration (median 1, range 0–6, P = 0.04).

Conclusion

Metagenomic sequencing in plasma and ETA samples showed good concordance between the blood and lung compartments as well as with culture results in pneumonia patients. Metagenomics revealed potential pathogens missed by cultures in ~75% of culture-negative pneumonias and suggested polymicrobial infections especially in cases with aspiration. Further research is needed to evaluate the clinical utility of real-time metagenomics for pneumonia diagnosis in mechanically ventilated patients.

Disclosures

All authors: No reported disclosures.
248. Thirty-Day Mortality Among Patients with Candidemia Diagnosed by T2Candida Assay Alone: Influence of Risk Factors and Candida Species
Authors: White Cameron , McCarty Todd , Lee Rachael A , Leal Sixto M , Pappas Peter
Published: October 2019

Background

Candidemia is a common cause of healthcare-associated bloodstream infection with high mortality rates despite antifungal therapy. Risk factors include prolonged ICU stay, immunosuppression, and exposure to broad-spectrum antibiotics. Blood cultures (BC) remain the gold standard for diagnosis but lack sensitivity and can take days to result. T2Candida (T2C) is a rapid diagnostic test utilizing PCR and magnetic resonance technology to detect five Candida species in whole blood in less than 6 hours. In this study we examined characteristics of patients with positive T2C assays in the absence of positive BC including risk factors and 30-day mortality rates.

Methods

We conducted a retrospective analysis of positive T2C cases at UAB Medical Center from 2016 to 2018 with either negative or no BC. For each patient we determined if clinical signs (e.g., hypotension, leukocytosis) and risk factors for candidemia were present at the time of collection. Our primary outcome of interest was 30-day mortality. Data were compared by multivariate analysis.

Results

A total of 173 patients with T2C positivity alone were included in the analysis. The most common risk factor was the use of broad-spectrum antibiotics followed by CVC (Table 1). The mean number of risk factors per patient was 3.6 (Figure 1). Overall 30-day mortality was 41%. Patients with a T2C result of C. albicans/C. tropicalis were almost 2.5 times more likely to die at 30 days (aOR 2.401, CI 1.159–4.974) compared with those with other positive results. Increasing number of risk factors (aOR 1.457, CI 1.126–1.886) and increasing age (aOR 1.052, CI 1.026–1.079) were significantly associated with increased odds of death at 30 days (Table 2).

Conclusion

In this study we demonstrate a significant association between increasing number of risk factors, older age, and A/T result with higher odds of 30-day mortality among patients with T2C positivity alone. While concern for false-positives exists when using T2C, our data suggest that this is an acutely ill population which warrants early and aggressive antifungal therapy. The lower limit of detection of T2C (1 cfu/mL) as compared with BC may explain lack of paired positive cultures in these patients despite clinical signs of and risk factors for candidemia.

Disclosures

All authors: No reported disclosures.
252. Development and Evaluation of a Novel MultiCode Real-Time PCR Assay for the Detection of Pneumocystis jirovecii in Bronchoalveolar Lavage Fluid and Induced Sputum
Authors: Liu Baoming , Carroll Karen C , Zhang Sean
Published: October 2019

Background

Pneumocystis jirovecii is a medically important fungal pathogen responsible for opportunistic infections in immunocompromised hosts with high morbidity and mortality. Compared with standard microscopy based assays, home-brew nucleic acid amplification tests (NAAT) have emerged as sensitive tools for the diagnosis of P. jirovecii pneumonia, but their sensitivities vary depending upon selected genetic targets. Recent studies suggest that the mitochondrial small subunit (mtSSU) is a better NAAT target given its higher copy number and stable expression in the disease process. We aimed to develop and evaluate a mtSSU-targeted MultiCode real-time PCR assay that incorporates a sample processing control (SPC) and enables detection of P. jirovecii in bronchoalveolar lavage fluid (BALF) and induced sputum.

Methods

Firstly, we compared manual DNA extraction using Zymo Quick DNA kit with automated extraction using the NucliSENS easyMAG system after sample pretreatment with either FastPrep mechanical grinding or vortex-based bead beating. We then determined the mouse hepatitis virus SPC (Luminex) spike-in amount, and optimized the PCR conditions on the ABI 7500 PCR system. A new Pneumocystis mtSSU run control was generated by cloning and transforming mtSSU gene into a genetically engineered E. coli strain, and quantified with a home-brew quantitative TaqMan PCR. Lastly, the performance characteristics of the MultiCode PCR assay were determined.

Results

Mechanical grinding of BALF or sputum before the easyMAG based extraction was better than the other extraction protocols as evidenced by lower CT of mtSSU or SPC. Diluted SPC added to samples before DNA extraction made its CT within 31–34. With the mtSSU run control, the limit of detection of the new assay was 80 copies/mL. No cross-reactivity was found with 9 respiratory viruses, 8 bacteria or 11 fungi. The assay has high reproducibility for three-day detection of the same sample aliquots for mtSSU (CT: 30.0–30.3; CV%: 0.5–1.6) and SPC (CT: 32.1–32.2; CV%: 0.8–2.4).

Conclusion

We developed a novel MultiCode real-time PCR assay for detection of P. jirovecii in BALF and sputum, which demonstrated high analytical sensitivity, specificity and reproducibility and warrants further clinical validation.

Disclosures

All authors: No reported disclosures.
253. Evaluation of a Cryptococcal Antigen Lateral Flow Assay and the Burden of Cryptococcal Disease: A Cohort Study at Grady Memorial Hospital in Atlanta, Georgia
Authors: Harrington Kristin , Wang Yun , Rebolledo Paulina , Liu Zhiyong , Yang Qianting , Kempker Russell R
Published: October 2019

Background

While Cryptococcus neoformans is a major cause of morbidity and mortality among HIV-infected persons worldwide, there is scarce recent data on disease prevalence in the United States, including in Southeastern states, where HIV rates are high. We sought to determine the prevalence of cryptococcal disease and compare the performance of a cryptococcal antigen (CrAg) lateral flow assay (LFA) vs. latex agglutination (LA) test.

Methods

All patients from Grady Memorial Hospital in Atlanta, Georgia who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg LA testing as part of routine management from November 2017 to July 2018 were included. The LFA was performed on all samples by research staff; results were not available to clinicians. Rates of disease and agreement between the LA test and LFA were calculated.

Results

Among 467 patients, 570 LA tests were performed; 417 on serum and 153 on CSF (87 patients with multiple tests performed). Mean age was 44 years, and most were male (n = 322, 69%). Most patients had HIV (n = 371, 79%); median CD4 count was 73 cells/mm3 and 77% were not receiving ART. Among HIV-infected individuals, testing was performed equally in the inpatient and outpatient setting. Cryptococcal testing was done in 53 persons without apparent risk factors. Thirty-three (7%) patients had a positive serum or CSF test. Five (1%) patients had both a positive serum and CSF LA test and LFA. While the overall agreement between the LA test and LFA was substantial to high for CSF (κ = 0.71) and serum (κ = 0.93), respectively, there were important discrepancies. Four patients with a negative serum LA test had a positive serum LFA. Five patients had false-positive CSF LA tests, determined by negative CSF LFA testing, India ink, and CSF and fungal cultures. All were treated with amphotericin and flucytosine with one patient experiencing a severe anaphylactic reaction to amphotericin.

Conclusion

We found a moderately high rate of cryptococcal disease and important discrepancies between the LA test and LFA. The LFA appeared to be more sensitive for cryptococcemia and more specific for meningitis. Clinical implications of these findings include earlier detection and treatment of cryptococcemia, and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.

Disclosures

All authors: No reported disclosures.
259. Racial Differences in Clinical Phenotype and Hospitalization of Blastomycosis Patients
Authors: Anderson Jennifer L , Frost Holly M , King Jennifer P , Meece Jennifer K
Published: October 2019

Background

Dimorphic fungal infections, such as blastomycosis, cause significant morbidity and mortality. Most studies describing blastomycosis have focused on non-Hispanic Caucasians and our understanding of the clinical presentation and outcomes for patients of other race/ethnicities is limited. We evaluated whether clinical presentation and disease severity varied across racial/ethnic groups.

Methods

Blastomycosis patients were identified from Marshfield Clinic Health System and patient data were abstracted from electronic medical records. Blastomyces genotyping was performed for cases with available isolates. Univariate analyses using χ 2 tests and multivariate logistic regression modeling were used to determine the association of race/ethnicity with clinical presentation. Significance was defined as P ≤ 0.05.

Results

In total 477 patients were included.Age differences were observed across race/ethnicity categories (P < 0.0001). Non-Hispanic, Caucasians were oldest (47 years, SD 20) and Asians were the youngest (30 years, SD 18). Underlying medical conditions were more common in non-Hispanic Caucasians (55%) and African Americans (AA) (52%) than Hispanic Caucasians (27%) and Asians (29%, P = 0.0002). Risk for hospitalization was highest for Hispanic Caucasian (aOR 2.9, 95% CI 1.2–1.7), American Indian Alaskan Native (AIAN) (aOR = 2.4; 95% CI 1.0–5.5), and Asian (aOR = 1.9; 95% CI 1.0–3.6) patients when compared with non-Hispanic Caucasian patients. Ninety percent of B. dermatitidis infections occurred in non-Hispanic Caucasians whereas blastomycosis in Hispanic Caucasian, AIAN, and Asian patients was frequently caused by B. gilchristii (P < 0.0001).

Conclusion

Hispanic Caucasian, AIAN, and Asian blastomycosis patients were younger and healthier, but more frequently hospitalized. Patients in these racial/ethnic groups may need more aggressive treatment and closer therapeutic monitoring. Underlying host factors along with organism virulence likely play a role in these differences.

Disclosures

All authors: No reported disclosures.
276. Detection of Rhizopus oryzae-Specific Antigen (RSA) in Serum and Bronchial Alveolar Lavage Is a Potential Early Diagnostic Marker in Mucormycosis by R. oryzae
Authors: Shibata Wataru , Yamada Koichi , Niki Mamiko , Yamagoe Satoshi , Miyazaki Yoshitsugu , Kaneko Yukihiro , Kakeya Hiroshi
Published: October 2019

Background

The diagnosis of mucormycosis was made by the identification of an organism in the histopathology with culture confirmation. However, culture often yields no growth, and histopathological identification of organism with typical of mucorales is sometimes difficult. Therefore, a reliable new diagnostic tool is expected. We reported a novel Rhisopus-specific antigen (23kDa, named protein RSA) by screening with a signal sequence trap was detected at significantly higher concentrations in serum and in lung homogenates in the infected mice on day 4. And the results were suggested RSA was a possible diagnostic marker of mucormycosis (Sato K, et al. Medical Mycology, 2017, 55,713–719). Here, we examined whether the RSA was detected on early stage in sera and bronchial alveolar lavage (BAL) of infected mice.

Methods

We developed the ELISA Kit using monoclonal antibody for RSA. The mice were injected with cortisone acetate and cyclophosphamide, and R. oryzae was infected intratracheally. Mice sera and BAL was obtained from infected mice on day 1, 2, 3, and 4. Then the concentration of RSA in sera and BAL was evaluated using the ELISA Kit for RSA.

Results

The RSA was detected in sera and BAL on day 1, 2, 3, and 4. The concentration of RSA in sera and BAL were significantly higher on day 1 as compared with uninfected mice. And the concentration of RSA in sera was the upward trend through day 1 to 4. However, the concentration of RSA in BAL was stable through day 1 to 4.

Conclusion

The RSA is a potential early diagnostic marker in mucormycosis by R. oryzae.

Disclosures

All authors: No reported disclosures.
291. Using Individualized Provider Feedback to Improve HCV Screening in a High-Volume Emergency Department
Authors: Zucker Jason , Sani Fereshteh , Ruperto Kenneth , Slowkowski Jacek , Purpura Lawrence , Schluger Aaron , Olender Susan , Scherer Matt , Gordon Peter
Published: October 2019

Background

Ending the Hepatitis C Virus (HCV) epidemic requires HCV testing as the critical first step. Busy urban Emergency Rooms are uniquely suited for HCV screening programs but numerous barriers to effective program implementation exist. We describe an emergency room physician champion model that utilizes the feedback intervention theory (FIT) to providers to increase HCV screening rates.

Methods

Due to the changing epidemiology of HCV in 2017 New York Presbyterian supported one-time universal HCV screening. In September 2018, our physician champion provided an educational session to ED providers about the importance of HCV screening and the proposed study. From the end of September to the end of March 2019, providers received a monthly e-mail from the ED champion and an automated text message with their individual and peer HCV screening rates. The number of HCV tests and percent of individuals with documented HCV testing in the ED was compared pre and post this intervention and to HCV testing in the inpatient and outpatient setting where feedback was not provided.

Results

On average ED providers evaluated approximately 14,000 patients per month. HCV testing increased 1,600% from an average of 40 tests per month in the 18 months prior to the intervention to an average of 640 tests sent per month during the intervention. tests sent in December. This was compared with stable inpatient and outpatient HCV screening during the same time period.

Conclusion

Individualized provider feedback paired with an ED physician champion can lead to a significant increase in HCV testing. Ongoing studies will determine if this intervention can lead to long-term behavior change.

Disclosures

All authors: No reported disclosures.
293. Hepatitis C is now a Millennial Disease in Response to the Opioid Crisis: A Demographic Shift in Hepatitis C Infection
Authors: Rose Michelle , Allen Myers John , Ryan Nicholas , Prince Alissa , Talbot Morgan , Espinosa Claudia M
Published: October 2019

Background

Previous research has shown millennials represent the fastest growing generation for those infected with the hepatitis C virus (HCV). Millennials are also a key driver in the opioid crisis, particularly in states of the Appalachian region including Kentucky. Despite research demonstrating a change in prevalence from baby boomers (born 1945–1965) to millennials (born 1980–1995), large representative studies providing evidence of the magnitude of this demographic shift are lacking in the United States. Our objective was to assess trends of HCV infection since 2016 in a large healthcare system located in an area of high prevalence of opioid use and HCV infection.

Methods

All individuals were screened for HCV infection in 2016, 2017, and 2018 within Norton Healthcare per standard risk-based criteria (e.g., injection drug users, baby boomers, etc.) as recommended by CDC, except for pregnant women who were universally screened since 2016. We tested for demographic shifts over time using longitudinal and time series analyses techniques

Results

A total of 86,243 individuals were screened for HCV infection from 2016 to 2018. Of those, 2,615 (3.0%) individuals screened positive for chronic HCV. The average age of those infected significantly decreased by an average of 3.7 years annually (from 47.3 years in 2016 to 39.9 years in 2018, P < 0.001). We forecast a plateau near the age of 28 years will be observed in just over 7 years. In addition, the proportion of millennials increased over time (33.6% in 2016, 42.4% in 2017 and 51.4% in 2018, P < 0.001), while baby boomers significantly decreased over time (44.0% in 2016, 38.8% in 2017, and 29.3% in 2018, P < 0.001). Lastly, over time, those with chronic HCV were more likely to be male (increasing from 49.6% to 54.4%, P = 0.008) and Hispanic (increasing from 1.6% to 17.7%, P < 0.001)

Conclusion

Our results suggest that HCV infection has become a predominately millennial disease, skipping a generation. These results correlate with trends seen with the opioid epidemic, which is driven by millennials. We conclude that the opioid crisis has led to a drastic demographic shift, and currently the typical HCV-infected individual is a younger male. Without interventions, this trend will continue for over seven years, plateauing near the demarcation of millennials and generation Z

Disclosures

All authors: No reported disclosures.
307. Overcoming Hepatitis C Elimination Challenges in the Coachella Valley through the Collaboration of Linkage to Care, a Managed Care Organization, and a Federally Qualified Health Center
Authors: Duong Nicolette , Valenzuela Lindsey , Singh Tulika , Morris David , Hodgkins Brian , Le Jade , Kerkar Shubha J
Published: October 2019

Background

Per the Centers for Disease Control and Prevention, 2.4 million Americans have the hepatitis C virus (HCV). New cases increased by 14% from 2014 to 2016 in California with 400,000 infections, 4,000 infections in the Coachella Valley and about 50% unaware of their diagnosis. A barrier to elimination is the lack of rapid screenings and linkage to care (LTC) of infected individuals into an integrated system. Thus, we developed a program at the Hepatitis Center of Excellence (HCE) where pharmacists in a managed care organization (MCO) provide opportunities to overcome these boundaries. The partnership of the MCO and federally qualified health center (FQHC) was established in 2017 to expand access to care to the HCV community. We anticipate that our program will eliminate HCV in the Coachella Valley by modeling past success in human immunodeficiency virus (HIV) testing and LTC at the FQHC through an interdisciplinary approach.

Methods

A single-center, retrospective analysis from January 2017 to December 2018 of HCV individuals was conducted at the pharmacist-led HCE in Palm Springs, California. The LTC team approached barriers through prompt free screenings and major advocacy. Pharmacists and specialty physicians collaborated to ensure rapid assessment, treatment initiation and completion, and sustained virologic response (SVR). The HCE has adapted the HIV testing and LTC model in hopes of achieving similar feats. From 2014 to 2018, 92,947 total HIV tests were performed with 90.2% of HIV-positive patients linked to care. HCV testing was then added to HIV screening and expanded to other testing sites.

Results

The first visit with a clinical pharmacist consists of education, reviewing lab tests, cost assistance, and providing treatment options. From 2017 to 2018, 169 of 172 HCV positive individuals (98.2%) achieved SVR by treatment completion. The HCV LTC program demonstrated a 3.8% increase in HCV testing from 2017 to 2018.

Conclusion

Pharmacist-led care for a large volume of HCV patients allows time for specialty physicians to manage more complex cases. The collaboration between the FQHC, MCO, and LTC team showed HCV elimination is possible based on high SVR rates. HCE is projecting successful linkages to care and continuous campaigning for individuals to be treated for HCV in the Coachella Valley.

Disclosures

All authors: No reported disclosures.
310. Disparities in Hepatitis C Linkage to Care in the DAA Era: Findings from a Referral Clinic with an Embedded Nurse Navigator Model
Authors: Sherbuk Jacqueline , McManus Kathleen , Knick Terry , Dillingham Rebecca
Published: October 2019

Background

Direct-acting antivirals (DAAs) have simplified and expanded access to Hepatitis C virus (HCV) treatment. Only 17% of the estimated 2.4 million Americans currently infected with HCV have linked to HCV specialty care. We evaluated linkage to care (LTC) in a non-urban hepatitis C referral clinic with a nurse navigator model of care and identified disparities in LTC during the DAA era.

Methods

A single-center retrospective cohort analysis was performed among all patients referred to an infectious diseases HCV clinic between 2014 and 2018. The primary outcome was LTC, defined as attendance at a clinic appointment. A multivariable Poisson regression model estimated associations of patient characteristics with LTC.

Results

Among 824 referred patients, 624 (76%) successfully linked to care and 369 (45%) achieved sustained virologic response. The mean age was 48.5 years (SD 13.5 years) and 46% (382 of 824) were uninsured. Common reasons for failure of LTC included no-shows (26.5%), could not be contacted (20.5%) and incarceration (10%). On multivariable analysis, LTC rates were higher among women (incidence rate ratio (IRR) 1.11, 95% CI 1.03–1.20, P = 0.01) and those with cirrhosis (IRR 1.20, 95% CI 1.11–1.30, P < 0.001). Lower rates of LTC were seen for young people (< 40 years old) (IRR 0.88, 95% CI 0.79–0.98, P = 0.02) and uninsured people (IRR 0.85, 95% CI 0.77–0.94, P = 0.002). Race, proximity to care, substance use, and HIV status were not associated with differences in LTC rates.

Conclusion

In an embedded nurse navigator model of care, a high rate of LTC was achieved despite the prevalence of barriers, including a high uninsured rate. LTC was the biggest drop-off in the cascade. Disparities in LTC based on age, sex, and insurance status are present. Substance use was not associated with differences in LTC, supporting current recommendations to provide treatment to all patients with HCV. No-shows were common, potentially due to lack of reliable contact information or lack of transportation. Qualitative work exploring patients’ experiences leading to failure of LTC would be helpful. Future interventions to improve care could include expanded access to insurance, affordable medical tests, and programs bridging care for incarcerated populations.

Disclosures

All authors: No reported disclosures.
331. Five Cases of Hemophagocytic Lymphohistiocytosis in Patients with HIV: A Fulminant and Lethal Combination
Authors: Bhatt Isha , Khan Zeb , Lam Paul , Quale John M
Published: October 2019

Background

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that can be either primary (genetic) or secondary (reactive) in etiology. Diagnosis can be elusive, especially in patients with HIV infection.

Methods

Medical records were reviewed for 5 patients with HIV infection and the diagnosis of HLH. Standard and alternative criteria were utilized to establish the diagnosis.

Results

Five patients with HIV infection had clinical criteria for the diagnosis of HLH. Ages ranged from 33–70 years and 4 were males. All five presented with fevers, cytopenias, and markedly elevated ferritin levels (table). All of the patients had CD4 levels of < 200 cells/µL. Evidence of hemophagocytosis was found on bone marrow examination in 3 patients. Inciting conditions included Pneumocystis jiroveci infection, EBV infection, lymphoma, and multiple myeloma. All patients received broad-spectrum antimicrobial as well as immunosuppressive therapy. Despite aggressive treatments, all patients died within one month of presentation.

Conclusion

In patients with underlying HIV infection, HLH can be a difficult diagnosis to establish. Mortality rates can be high, even with prompt recognition and therapy. The finding of fever and cytopenia in a patient with HIV infection should prompt the clinician to determine a ferritin level. If markedly elevated, the diagnosis of HLH should be aggressively pursued.

Disclosures

All authors: No reported disclosures.
337. Switching from TDF to TAF: Missed Opportunities for Statin Use in HIV
Authors: Mallon Patrick , Brunet Laurence , Fusco Jennifer S , Prajapati Girish , Beyer Andrew P , Wohlfeiler Michael , Fusco Gregory
Published: October 2019

Background

People living with HIV (PLWH) have been observed to have twice the risk for atherosclerotic cardiovascular disease (ASCVD) as the general population. Increases in total and low-density lipoprotein cholesterol have been observed in PLWH switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Changes in regimens represent an opportunity for healthcare providers to assess health markers and address clinical concerns. Current guidelines recommend initiating statin therapy in individuals with an elevated ASCVD risk. Failure to initiate statins in PLWH with an ASCVD ≥ 7.5% at switch represents a missed opportunity for statin initiation. We aimed to assess missed opportunities for statin therapy in PLWH switching from TDF to TAF-containing antiretroviral therapy.

Methods

Adults switching from TDF to TAF with ≥1 lipid measure on TDF ≤6 months prior to switch and ≥1 lipid measure ≥7 days after switch to TAF were identified in the OPERA® cohort (84 clinics in 18 US states/territories). The proportion of PLWH prescribed statins pre- and post-switch was stratified by ASCVD risk (recommended threshold: ASCVD ≥ 7.5%). The ASCVD score was imputed using the limit value for components out of the pre-specified range.

Results

6,451 PLWH switched from TDF to TAF (Figure 1); over 90% had ASCVD scores available pre- (n = 5801) and post-switch (n = 5881). High ASCVD risk (≥7.5%) was more likely post-switch (34.1) than pre-switch (32.1%, P = 0.02; Figure 2). Of those with high ASCVD risk, only 31% and 41% were prescribed statins pre- vs. post-switch, respectively (Figure 3), representing a considerable missed opportunity for ASCVD prevention, with 59% of PLWH with an elevated risk of ASCVD not prescribed statins after switch from TDF to TAF. ASCVD scores were imputed for those outside the range of the score (e.g., patients < 40 years of age) to evaluate the entire population. Comparable results were obtained when the analysis was limited to PLWH who did not require ASCVD score imputation.

Conclusion

Despite a switch from TDF to TAF being associated with higher numbers of PLWH with elevated ASCVD risk, most did not receive a statin, representing considerable missed opportunities to reduce risk of cardiovascular disease in this at-risk population.

Disclosures

All authors: No reported disclosures.
359. TLR7 Gene Polymorphisms Influence Development of Hepatic Fibrosis in HCV/HIV Coinfection
Authors: Sherman Kenneth , Meeds Heidi L , Abdel-hameed Enass A , Rouster Susan D , M. Shata M Tarek
Published: October 2019

Background

Hepatic fibrosis in individuals with HCV/HIV coinfection or HCV mono-infection may be modulated by a variety of host factors. In this study, we investigated the role of gene polymorphisms of putative genes that might influence fibrosis progression including MICA (rs2596542), interferon-stimulated gene OAS2 (rs1293762) and the pathogen recognition receptors TLR7 (rs179009) and TLR9 (rs187084). Effect on a cytokine panel was evaluated.

Methods

Longitudinal samples were obtained from subjects enrolled in the NCI Multicenter Hemophilia Cohort Study. Within the cohort, a subset of subjects were included based upon presence or absence of the CCR5 delta-32 mutation which was previously shown to influence the rate of fibrosis progression. Hepatic fibrosis change was determined using the serum-derived Enhanced Liver Fibrosis (ELF) Index. Four putative genes with polymorphisms that have been previously associated with the development or progression of hepatic fibrosis were evaluated using Taqman SNP genotyping assays. Cytokine assays were performed using Luminex chipsets. Samples were analyzed using Statistix 10.0 using ANOVA and least square regression models.

Results

58 unique subjects were evaluated. The mean age was 38 years, and all were male. 74% were HIV infected and 97% were HCV infected (76.8% coinfection). Controlling for the effect of CCR5, only the TLR7 A -> G polymorphism was predictive of change in the ELF Index. There was no statistically significant predictive difference between genotypes in the other three polymorphisms. Subjects with the TLR7 A allele (n = 47) had an average increase in ELF of 0.79 units, while the G allele (n = 11) had an increase in ELF of 2.1 units (P = 0.008). A regression model identified TLR7 as a key factor in ELF change, as well as HCV/HIV coinfection. Interferon alfa-2 levels were highly associated (increased, P = 0.0007) with the TLR7 A -> G polymorphism, while RANTES levels were inversely associated (decreased, P = 0.0443) with it.

Conclusion

Of the gene polymorphisms investigated, only TLR7 (rs179009) is an independent predictor of development of hepatic fibrosis in HCV/HIV coinfected subjects. The mechanism may involve modulation of inflammatory response pathways.

Disclosures

All authors: No reported disclosures.
384. Denosumab-Related Osteonecrosis of the Jaw: an Emergent and Potentially Complex Bone and Joint Infection
Authors: Bricca Romain , Valour Florent , Anne Conrad , Braun Evelyne , Jaby Philippe , Bachelet Jean-Thomas , Breton Pierre , Gleizal Arnaud , Laurent Frederic , Chidiac Christian , Ferry Tristan
Published: October 2019

Background

Osteonecrosis of the jaw is a known complication of antiresorptive treatment, like bisphosphonate. More recently, denosumab was validated as a treatment in the osteoporosis and bone metastasis. Its mechanism is different from bisphosphonate but induces also a decrease of bone resorption and a risk of osteonecrosis of the jaw. In case of treatment failure by a dental surgeon or in complex cases, patients could be addressed to a bone and joint infection (BJI) reference center. The aim of this study was to analyze microbiology, as well as surgical and medical care of patients who present denosumab-related osteonecrosis of the jaw (DRONJ) and who were treated in a bone and join reference center.

Methods

All patients managed in our BJI reference center between January 2013 and December 2018 for a DRONJ were included in our retrospective observational monocentric cohort.

Results

Twelve patients (median age 71; ratio M/W 0.7) with a DRONJ (metastatic cancer, n = 10 (83%)) in grade 3 (n = 5), 2 (n = 4), 1 (n = 3) were included. Only 3 patients (25%) had a dental health control before initiating the treatment by denosumab and 7 patients (58%) had a dental surgical procedure done before the DRONJ. Eleven patients had a bone exposure, treated at least with a scaling and mucosal closure at the same time. All infections with bacterial cultures (n = 11 (91%)) were polymicrobial, including 8 (72%) with Streptococcus spp; 8 (72%) with anaerobia including 2 (18%) with Actinomyces; 5 (45%) with Staphylococcus spp; 5 (45%) with enterobacteria; 3 (27%) with Candida spp; 2 (17%) with a non-fermentative Gram-negative bacilli and 7 (64%) with others bacteria. All patients (n = 12) received a betalactam, 8 (66%) a lincosamide or a synergistin, 5 (41%) an antifungal, 5 (41%) metronidazole, 4 (33%) a fluoroquinolone, 3 (25%) a glycopeptide and 2 (17%) other antibiotics. The median follow-up was 6 months. Eight patients were cured after a medico-surgical care and a median duration of antibiotics of 97 days (including 28.5 days in intravenous). 2 patients required a suppressive antibiotic treatment, 1 relapsed at a distance of the treatment and 1 died from some other causes.

Conclusion

DRONJ is a potential complex BJI, for which some patients could benefit from medical care in a BJI reference center.

Disclosures

All authors: No reported disclosures.
386. Blue Light Reduces Cutibacterium (Propionibacterium) Acnes Bacterial Burden: Orthopedic Shoulder Infection Prevention Strategy?
Authors: Bhargava Swati , Boyle Kathleen , Diletti Sara , Nodzo Scott , Crane John , Duquin Thomas
Published: October 2019

Background

Cutibacterium acnes (C. acnes) is a common shoulder periprosthetic joint infection (PJI). Blue light (BL) is effectively used in the dermatologic clinical setting against acne vulgaris caused by C. acnes. Photodynamic therapy (PDT) is the use of light source and photosensitizer (PS) to enhance antimicrobial activity. We studied the effect of PDT using BL and PS in vitro on shoulder PJI isolates of C. acnes.

Methods

19 strains were grown in thioglycollate medium and diluted in sterile normal saline (NS) to a turbidity of 0.5 McFarland standard; OD600 of 0.1 to 0.15. 250 µL with PS added were placed in 96-well plates at 37ºC, exposed to BL (415 nm) placed 1 cm above for 0 to 60 minutes at 15-minute intervals. Susceptibility to BL alone, and BL with PSs such as riboflavin (R, Vit B2), fluorescein (F) or demeclocycline (tetracycline antibiotic, “D”) were studied. After serial 10-fold dilution with NS, 3 µL of each well were spotted onto Brucella Blood Agar plates and incubated anaerobically for 48 hours. Eradication was defined as below the limit of detection. Definitions include Sensitive (S) if 3-log decrease in bacterial density or eradication at any time point, Weakly Sensitive (WS) with 1- to 3-log decrease and Resistant (R) with no decrease.

Results

Based on BL alone, (n = 19). 68% strains were S, 32% were resistant. BL+ R (10 μg/mL) effect in 25% (n = 3) and exerted a protective effect against 33% (n = 4). BL+ F (1 μg/mL) potentiated in 67%. BL+ D (0.1–1.5 μg/mL) in 83% of strains tested. The most resistant strain was eradicated using BL + D at an increased concentration of demeclocycline (2.5 μg/mL).

Conclusion

F and D enhanced the potential for eradication compared with BL exposure alone. R was a photo-protectant to BL for select strains. Prior studies have hypothesized endogenous intracellular porphyrins excited by BL causing energy transfer and production of highly cytotoxic reactive oxygen species causing bacterial death. Future clinical research evaluating the use of preoperative PS and surgical site exposure to BL as a preventative PJI strategy are needed. Our research shows that BL with the addition of PS significantly reduces the bacterial burden of clinically relevant PJI shoulder isolates of C. acnes in an in vitro model.

Disclosures

All authors: No reported disclosures.
393. Changing Trends, Risk Factors, and Treatment Challenges in Staphylococcus aureus Septic Arthritis
Authors: Gobao Valerie , Alfishawy Mostafa , Shah Neel , Byers Karin , Yassin Mohamed , Urish Kenneth
Published: October 2019

Background

Staphylococcus aureus is a common organism in native septic arthritis. It is traditionally believed to be self-limited with rapid and aggressive debridement and appropriate antibiotic selection. The incidence of S. aureus septic arthritis is increasing, and further characterization is needed to improve diagnosis and treatment. For patients presenting with native S. aureus septic arthritis, we evaluated the reliability of methicillin-resistant S. aureus (MRSA) screening as a predictor to rule out MRSA septic arthritis, the risk factors associated with this disease, and the treatment and surgical outcomes.

Methods

A retrospective case–control study of patients diagnosed with septic arthritis in the UPMC health system (Pittsburgh, PA) between 2012 and 2016 was completed. The primary outcomes of interest were surgical intervention and the need to alter antibiotic treatment. Patient demographics, characteristics, and outcomes were recorded.

Results

A total of 215 cases of septic arthritis were identified, and 64% (n = 138) had S. aureus cultured. In this set, 36% (50/138) of these patients were identified with MRSA. Of the patients diagnosed with MRSA septic arthritis, 50% screened prior to admission had a positive result (8/16) and 48% screened during admission had a positive result (14/29). Compared with septic arthritis with other organisms, risk factors associated with S. aureus included history of intravenous drug use (OR: 4.3, CI: 1.7 to 10.8, P = 0.002) and being immunocompetent (OR: 0.3, CI: 0.1 to 0.6, P = 0.002). These infections were associated with concurrent infections of the spine (OR: 5.7, CI: 2.1 to 15.1, P = 0.0005). As compared with other organisms, there was a high probability of switching antibiotics during treatment (OR: 3.7, CI: 1.1 to 13.0, P = 0.04) and relapse of infection (OR: 4.2, CI: 1.2 to 14.6, P = 0.02).

Conclusion

S. aureus septic arthritis is associated with intravenous drug use, and not with immunosuppression. A negative MRSA screen does not rule out this organism. Concurrent spine infections are common. There is a high likelihood of infection relapse and that antibiotics will need to be altered during treatment. With the opioid epidemic, the incidence is likely to increase further. More work is needed to improve diagnosis and overcome treatment challenges.

Disclosures

All authors: No reported disclosures.