bluuebunny/crossref_metadata_2025_split huggingface dataset:
1351. How Do Infectious Diseases Clinicians Manage Patients with Suspected Ocular Tuberculosis? Results of an Emerging Infections Network Survey
Authors: Fraimow Henry S , Beekmann Susan E , Polgreen Philip M , Sunstrum James 
Published: October 2019

Abstract

Background
Ocular tuberculosis (OTb) is uncommon and many ID physicians (IDPs) have limited experience with OT. Ophthalmologists now include IGRAs in evaluating idiopathic uveitis, and some IDPs report increased referrals for possible OTb. Our goal was to understand how IDPs approach diagnosis, treatment, and reporting of OTb.

Methods
The Emerging Infections Network surveyed members treating adult ID patients in 2019 about referrals for suspected OTb. The survey used hypothetical case scenarios to evaluate factors influencing the management of possible OTb, and queried involvement of public health agencies.

Results
754 of 1,379 (55%) physicians responded. 141 (19%) reported ≥1 referral for possible OTb in the past 3 years; 35% of these reported increasing referrals over time. Most frequent indications for referral were uveitis and positive IGRA (60%) and idiopathic uveitis without positive IGRA or TST (33%). For a hypothetical case with uveitis, positive IGRA but no other symptoms, respondents were much more likely (79% vs. 29%) to treat as TB disease if TB risk factors were present. Respondents were more likely to require a positive eye culture or NAAT prior to treating a risk factor-negative patient (39% vs. 12%). 54% of respondents believed <10% of eye specimens were culture or NAAT-positive for suspected OTb. 94% would treat suspected OTb with INH, RIF, PZA ± EMB but duration of treatment varied with 27% stopping therapy for lack of clinical response and 59% continuing for at least 6 months regardless of response. 44% were unsure if improvement should be expected on therapy. One-third of respondents either did not report or reported only culture-confirmed OTb cases on treatment to public health agencies.

Conclusion
IDPs report increased referrals for possible OTb, mainly for idiopathic uveitis and positive IGRAs. There is considerable practice variation in management of possible OTb. The decision to treat as TB disease is heavily influenced by TB epidemiologic risk factors, and there is heterogeneity in treatment duration and in expectation of response to therapy. Prospective studies to assess treatment responses in OTb and improved collaboration with ophthalmologists are necessary to better manage this emerging syndrome. Treated OTb cases should be reported to public health agencies.

Disclosures
All authors: No reported disclosures.
1353. Effect of Implementing Xpert MTB/RIF Ultra Assay on Diagnosis of Tuberculosis in a Medical Center in Central Israel
Authors: Schwartz Orna , Yossepowitch Orit , Maor Yasmin 
Published: October 2019

Abstract

Background
Tuberculosis (TB) is a worldwide public health concern both in developing and developed countries. The new Xpert MTB/RIF Ultra assay (Ultra, Cepheid, Sunnyvale, USA) recently endorsed by the WHO has high sensitivity to TB detection. The aim of this study was to assess the impact of this assay on TB diagnosis in a medical center in Israel where the baseline prevalence of TB is low.

Methods
The Xpert MTB/RIF Ultra assay is a cartridge-based automated diagnostic test that can simultaneously identify Mycobacterium tuberculosis complex and resistance to Rifampicin. We began using this test in 1.1.2018. To assess the impact of this assay on the rate of TB diagnosis we compared TB tests and positive cases during two time periods: period I (1.1.2017-31.10.2017) when TB diagnosis was based on the Xpert MTB/RIF assay to period II (1.1.2018 to 31.10.2018) when TB diagnosis was based on Xpert MTB/RIF Ultra assay. Included were all TB tests performed on sputum, deep suction or bronchoalveolar lavage. Files of positive patients were reviewed.

Results
The study included 1034 samples from 717 patients. Results are presented in Table 1. During the second period, TB rates increased by 231%. During the entire study there was no change in the hospital’s guidelines regarding TB diagnosis policy and there was no epidemiological change in the population served by the hospital. Only three cases had rifampicin resistance. In 5 cases (20%) during period II the result was trace amounts, an entity that did not exist in the former assay and in 3 cases culture results were negative. In 2017, 6 patients (60%) were African born, 3 patients (30%) originated from Eastern Europe, and one patient (10%) was born in the Middle East region. In 2018, 9 patients (36%) were born in Africa, 9 patients (36%) were born in Eastern Europe, and 7 patients (28%) were born in the Middle East region. Mean age at diagnosis was 38 years for patients diagnosed during period I and 53 years for patients diagnosed during period II.

Conclusion
The new assay enabled a significantly higher diagnosis rate for TB at our institution. We believe that this mainly reflects a higher diagnosis rate in patients with paucibacillary TB. Further study is needed to assess the relation between cultured confirmed diseases and the assay results, particularly in patients with trace results.

Disclosures
All authors: No reported disclosures.
1363. Does Genotypic Testing Improve Treatment Outcomes in Drug-Resistant Tuberculosis?
Authors: Thampy Anupa , Ninan Marilyn , Sarojini Michael Joy , Rupali Priscilla 
Published: October 2019

Abstract

Background
Treatment of drug-resistant tuberculosis (DR-TB) requires toxic and complex drug regimens. Dismal outcomes occur due to a delay in the report of susceptibility results. WHO endorses genotypic tests like line probe assay (Mtbdrsl) for an early diagnosis enabling start of robust treatment regimens. Data correlating Mtbdrsl and specific mutations with outcome are rare.

Methods
A concurrent cohort study was conducted on all patients diagnosed to have DR-TB between January 2016 and June 2017 in the departments of Pulmonary Medicine and Infectious Diseases at a tertiary care center in India. Patients aged >18 years with a positive Mtbdrsl (done on culture) or Mycobacterial culture were prospectively followed up till completion of therapy for assessment of outcomes. Patients were divided into 2 groups based on diagnostic method used: culture group and Mtbdrsl group. Risk factors for adverse outcomes were assessed.

Results
Total of 82 patients, of which 62.2% were males with a mean age of 32 years were included; 50 in the Mtbdrsl group and 32 in the culture group. Among these, 40.2% were multi-drug-resistant Tuberculosis (MDR-TB), 53.7% were Pre–XDR (pre-extensively drug resistant i.e, quinolone-resistant tuberculosis) and 6.1% were XDR (extensively drug-resistant TB). Isolated pulmonary involvement (46.3%) was common followed by disseminated TB (29.3%). Overall good outcome was seen in 39/82 (14.6% cured and 32.9% completed treatment) and bad outcome in 43/82 (41.5% lost to follow up, 7.3% treatment failure and 3.7% died). Good outcome was noted in Mtbdrsl group was 22/50 (44%) vs. 17/32 (53.1%) in the culture group. Mtbdrsl group had 140 days mean decrease in time to initiation of appropriate therapy but the odds of having a better outcome was 0.693 (CI: 0.284–1.690, P = 0.499). Among the 15 different types of mutations, FQ mutations gyrA 94Gly and gyrA 90Val comprised 15% each with gyrA 94Gly noted to have a poorer outcome [OR 2.5 (CI 0.471–13.265)]. All 5 patients with XDR TB (50 % had rrs 1401Gly mutation) had a poor outcome.

Conclusion
Contrary to what is expected, Mtbdrsl did not significantly contribute to better treatment outcomes. High-risk mutation gyrA 94Gly was prevalent and associated with poorer outcomes. Small sample size and a wide variety of mutations preclude generalizability of our results.

Disclosures
All authors: No reported disclosures.
1368. Tuberculosis in Older Patients in Cali, Colombia (2011–2016): A Hospital-Based Cohort Study
Authors: Fernando García-Goez Jose , Diego Velez Juan , Pino-Escobar Jessica , Lucía Mora Barbara , Parra-Lara Luis Gabriel , Caylà Joan A , Miró José M 
Published: October 2019

Abstract

Background
Tuberculosis (TB) in older adults is a public health concern worldwide. We aim to describe the outcomes of patients over 65 years old with a confirmed TB diagnosis. We furthermore assessed factors related to poor outcomes among this patient population.

Methods
This retrospective study included patients older than 65 years with a biological specimen positive by smear microscopy, culture, or GeneXpert. Clinical and microbiological data, information about drug-related side effects, adverse reactions, and TB treatment outcomes were reviewed. Patients were subsequently assigned to either the octogenarian group or non-octogenarian group, also the treatment success group or treatment nonsuccess group.

Results
A total of 108 patients were included. 59% were male, and 26% of patients were 80 years old or older. 81% of the patients presented pulmonary TB. Diagnostic delay greater than 90 days was present in 36% of the cases. There was a statistically significant difference in the rates of diabetes (P = 0.004) and COPD (P = 0.017) between the octogenarian group and non-octogenarian group. One hundred six patients started anti-TB therapy, 34% of cases were lost to follow-up, and 18% died. Patients of 65–79 years of age and those older than 80 years had similar mortality, 19% vs. 18%, respectively. When comparing treatment success (n = 45) and nonsuccess (n = 22) groups, most of the variables were found not to be statistically significant as TB risk factors, except malignancy (P = 0.013). Overall, survival of the patients was 78. 23% at 5 years follow-up; there were no differences between age groups.

Conclusion
The presence of baseline comorbidities as diabetes, malignancies and COPD, diagnosis delay, adverse events during anti-TB treatment and drug–drug interactions (DDI) makes this age group a different population, hence care models need to be evaluated to improve the indicators of the success of TB programs. Furthermore, the significant losses to follow-up require strict management of these patients and optimal coordination among health centers.

Disclosures
All authors: No reported disclosures.
1372. Patient’s Perceptions of Barriers to Tuberculosis Care in Private Sector in India
Authors: Yerramilli Aparna , Narreddy Suneetha , Anisetti Ravinder N , Grace K Angileena , Rakuditti Sandhya 
Published: October 2019

Abstract

Background
In spite of ambitious plans of all the stakeholders involved there is still a long way to go before Tuberculosis (TB) is eliminated In India due to barriers to care and cure. About half of the population affected with TB gets treated in the private sectors. This study was aimed to assess the patient knowledge on Tuberculosis and identify the barriers perceived by them.

Methods
A prospective study was conducted in a tertiary care center for a period of 3 months after obtaining approval from the Institutional ethics committee. All adults >18years diagnosed with tuberculosis (pulmonary, extrapulmonary) and receiving treatment in the Infectious Diseases Department were included. Subjects enrolled in the study were fully informed and gave their consent. A questionnaire was used to gather data regarding patient demographics, location, household size, co-morbid conditions, treatment, adverse drug reactions and barriers faced for their treatment.

Results
A total of 50 patients enrolled in the study. The majority of subjects belonged to age groups of 31–50 years (38%) with postgraduates accounting for 30%. About half (48%) of them were not working and 36 (72%) were married. About 31 (62%) were residing locally. The household size was 3–5 members (72%). Diabetes (13, 26%) and hypertension (11, 22%) were the common comorbid conditions seen. Newly diagnosed cases comprised of 35 (70%). Extrapulmonary TB was seen in 30 cases (60%) with lymph node and spine TB being more common. Adherence to the treatment was seen in 34(68%). Awareness regarding treatment duration and importance of treatment completion was seen in 64% and 82% of the study population, respectively. About 62% had visited more than one doctor for diagnosis with 42% responded that there was a delay in diagnosis. Common Barriers faced were stigma, adverse drug reactions, and transportation in 40 %, 12%, and 6% cases. The other factors faced by the respondents were the cost of diagnosis and treatment, adherence issues and loss of income.

Conclusion
India has the world’s highest incidence of Tuberculosis. Multifaceted barriers worsen the burden of Tuberculosis. Private sectors treat the majority of the extrapulmonary disease. Intensified efforts by means of public awareness and education are required to prevent the delay in diagnosis and reducing stigma.

Disclosures
All authors: No reported disclosures.
1379. Comparison of Inpatient Tuberculosis Screening Methods and Their Effect on Patient Duration in Airborne Isolation
Authors: Katherine. Theoktisto Mary , Ford Delvina , Khan Omar , Reveles Kelly R , Cadena Jose 
Published: October 2019

Abstract

Background
Tuberculosis (TB) remains a significant public health concern, and exposure in healthcare settings is prevalent. Current guidelines recommend testing for TB by acid-fast bacilli (AFB) smear microscopy with 3 sputum samples and/or using nucleic acid amplification test (NAAT), and mycobacterium culture. The purpose of this project is to compare how different TB diagnostic tests affect the duration of stay in respiratory isolation.

Methods
This study was conducted at the Veteran Affairs South Texas hospital, which includes a total of 437 beds. Data were collected retrospectively from medical records. Eligibility included patients admitted to the hospital and placed in airborne isolation for TB screening and diagnosis, had 3 sputum samples collected 8 hours apart and/or had 2 PCR MTB/RIF. Patients were excluded if they had TB or were not undergoing evaluation for TB. Three time periods analyzed included, 3 AFB sputum samples analyzed in-house from December 2012 to January 2014 (Group A), 3 AFB sputum samples analyzed at outside facility during 2013 to 2014 as well as 2 months in 2012 (Group B), and 2 MTB PCR/RIF in house during 2017 and 2018 (Group C). Duration of isolation was compared between groups using the Kruskal–Wallis test. A total number of 815 patients were screened, leaving 105 patients for analysis after exclusion. There were 49 patients analyzed from Group A, 28 from Group B, and 28 from Group C.

Results
Crude analysis of the data showed numerical differences in the total number of days and hours in isolation between the 3 groups. The average (mean) days in isolation were 4.2 for Group A, 7.4 for Group B, and 5.5 for Group C. There was no statistically significant difference in either days or hours of airborne precautions by “rule out” method. Days of isolation in airborne precautions (median IQR) was 4 for all groups (P = 0.3313). Likewise, hours of airborne precautions had a median IQR of 96 for all groups P = 0.4347.

Conclusion
Although there was no statistical significance between the groups, crude analysis did show a numerical difference in the mean total airborne days and hours. Lack of statistical difference may be due to low number of patients, timing of order placement for in-house PCR, and longer than expected stay in airborne precautions.

Disclosures
All authors: No reported disclosures.
1380. Safety of Repurposed Drugs for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: An Analysis of Adverse Events Reported in the Literature
Authors: Stone Heather , Duggal Mili , Sacks Leonard , Ghosh Mayurika 
Published: October 2019

Abstract

Background
Multi and extensively drug-resistant (MDR and XDR) tuberculosis (TB) remains a treatment challenge due to drug adverse events (AEs) and long regimens. Our aim was to identify AEs which resulted from repurposing drugs for MDR and XDR-TB.

Methods
A PubMed search for case reports of repurposed drugs for MDR and XDR-TB from January 1, 2014 to October 23, 2018 identified 130 patients (78 MDR, 52 XDR) in 91 articles. There were 31 extrapulmonary, 81 pulmonary TB cases, and 18 with both. Drugs were regarded as repurposed if they were either not approved for TB by the FDA, or they were approved for TB but were used in novel populations, novel combinations, or nonstandard doses. Drug labels were reviewed for AEs.

Results
Linezolid (n = 65) and moxifloxacin (n = 48) were the most commonly repurposed drugs. The following were also frequently used: clofazimine (n = 47), levofloxacin (n = 45), amikacin (n = 43), amoxicillin-clavulanate (n = 40), kanamycin (n = 36), carbapenems (n = 22), and clarithromycin (n = 17). Of the drugs that are approved for TB, the following were repurposed in a novel population, dose, or combination: cycloserine (n = 20), bedaquiline (n = 13), capreomycin (n = 4), ethambutol (n = 3), and isoniazid (n = 3). Treatments were discontinued due to AEs in 41 patients. There were no discontinuations for amoxicillin-clavulanate and levofloxacin. Extended drug exposure is a unique treatment feature for MDR and XDR-TB, which often requires ~2 years of treatment. Approximately 87% of treatment discontinuations due to AEs occurred after >1 month of exposure. AEs leading to treatment discontinuation after > 6 months of drug exposure were seen in 15 cases, of which 12 were due to linezolid and cycloserine. Peripheral and optic neuropathy was the most common AE reported (linezolid n = 12, cycloserine n = 1). Most AEs were labeled events.

Conclusion
Several antimicrobials are being repurposed to treat MDR and XDR-TB. There were no AEs reported after prolonged use that was not described in drug labels. Physicians should review information in labeling if prescribing drugs in this manner. There is a need for comparative safety data for repurposed drugs assessed through clinical trials.

Disclosures
All authors: No reported disclosures.
1381. M.genavense in the ART Era: From Persistent Disseminated Disease to Severe Disease
Authors: Manion Maura , Lynn Niamh , Pei Luxin , Hammoud Dima , Laidlaw Elizabeth , Roby Gregg , Metzger Dorinda , Mejia Yolanda , Lisco Andrea , Bergin Colm , Sereti Irini 
Published: October 2019

Abstract

Background
Mycobacterium genavense is an opportunistic pathogen in HIV patients that is difficult to culture and difficult to manage clinically. Here we describe three cases of HIV patients with Mycobacterium genavense with courses representing the spectrum of M.genavense presentations in the current ART era complicated by differing divergent immune responses.

Methods
Two patients were in a longitudinal study at NIAID enrolling patients with HIV and suspected IRIS (PANDORA) (NCT02147405) and one was seen at St. James’s hospital in Dublin. Frozen peripheral blood mononuclear cells were collected at the time of presentation and were used for in vitro stimulation with irradiated M. genavenese in cases 1 and 2 to detect production of cytokines by CD4 T cells.

Results
Pt 1: 27-year old male with M. genavense presenting as diarrhea, abdominal pain, skin nodules, hepatosplenomegaly, and lymphadenopathy (LAN) that persisted on one year of anti-mycobacterial therapy and ART. No CD4 T-cell cytokine response to M. genevense genavense was detected (Fig 1). He received interferon-g and optimization of his antimycobacterial regimen with improvement of symptoms and decreased pathogen burden on repeated biopsies. Pt 2: 55-year old female with M. genavense IRIS manifesting as fevers and abdominal pain that persisted for 10 months on ART (CD4 109 cells/µmL) requiring intermittent corticosteroid use complicated by adrenal insufficiency. She had evidence of CD4 T-cell response to M. genavense in vitro and improved with optimization of her anti-mycobacterial and corticosteroid regimen. Pt 3: 39-year-old male with M. genavense IRIS presenting as fevers, LAN, pleuritic chest pain, and abdominal pain on ART (CD4 19 c/mµL) persisting despite immunologic response to ARV therapy (CD4 recovery to 419 c/mL), appropriate anti-mycobacterial therapy and corticosteroids. He required 4 doses of infliximab (5 mg/kg IV) that facilitated tapering of prednisone.

Conclusion
The clinical presentation of Mycobacterium genavense in HIV patients in the ARV era range from disseminated disease with poor immune reconstitution to persistent or severe IRIS requiring immune suppression. Effective clinical outcomes relied on appropriate anti-mycobacterial and either immune-boosting or immune-suppressive therapies.

Disclosures
All authors: No reported disclosures.
1402. Long-Term Mortality and Epilepsy in Patients After Brain Abscess: A Nationwide Population-based Matched Cohort Study
Authors: Bodilsen Jacob , Dalager-Pedersen Michael , van de Beek Diederik , Brouwer Matthijs C , Nielsen Henrik 
Published: October 2019

Abstract

Background
The long-term outcome of brain abscess is unclear.

Methods
We used medical registries to conduct a nationwide population-based matched cohort study to examine the long-term risks of mortality and new-onset epilepsy in patients hospitalized with brain abscess in Denmark from 1982 through 2016. Comparison cohorts from the same population individually matched on age, sex, and residence were identified, as were siblings of all study participants (Figure 1). We computed cumulative incidences and hazard rate ratios (HRRs) for mortality and new-onset epilepsy among brain abscess patients, comparison cohorts and siblings. Population and appendicitis controls had similar characteristics and prognosis why only comparisons between brain abscess patients and population controls are detailed here.

Results
We identified 1,384 brain abscess patients with a median follow-up time of 5.9 years (IQR 1.1–14.2). The 1-year, 2–5 year, and 6–30-year mortality of patients after brain abscess was 21%, 16% and 27% when compared with 1%, 6% and 20% for matched population controls (Figure 2). Cox regression analyses adjusted for Charlson comorbidity index score showed 1-year, 2–5 year, and 6- to 30-year HRRs of 17.5 (95% CI 13.9–22.2), 2.61 (95% CI 2.16–3.16) and 1.94 (95% CI 1.62–2.31). The mortality in brain abscess patients compared with population controls was significantly increased regardless of sex or age group except among subjects 80 years or older, and in both previously healthy individuals and immuno-compromised persons. Among the 30-day survivors of brain abscess (median follow-up 7.6 years [IQR 2.2–15.5]), new-onset epilepsy occurred in 32% compared with 2% in matched population controls. Cause-specific Cox regression analysis adjusted for stroke, head trauma, alcohol abuse, and cancer showed 1-year, 2–5-year, and 6–30-year HRRs for new-onset epilepsy of 155 (95% CI 78.8–304), 37.7 (95% CI 23.0–59.9), and 8.93 (95% CI 5.62–14.2) (Figure 3). Comparisons between sibling cohorts suggested no substantial effect of family-related factors on the long-term risk of death or epilepsy after brain abscess (Figure 4).

Conclusion
Brain abscess is associated with an increased long-term risk of mortality and new-onset epilepsy for several years after the acute infection.

Disclosures
All authors: No reported disclosures.