bluuebunny/crossref_metadata_2025 huggingface dataset:
1296. Should HIV Disclosure at ED Based on Preliminary Results?
Authors: Aguilera Elizabeth A , Del Bianco Gabriela P , Murphy Daniel , Rodriguez Gilhen , Heresi Gloria , Murphy James , Prater Samuel
Published: October 2019

Background

It is recommended that all adults presenting to Emergency Departments (ED) be offered opt out testing for HIV. There is evidence that detection of HIV infection, disclosure of infected status to the patient, and enrollment into HIV care are best accomplished during the ED visit. Any delay results in loss of patients. Among critical variables are capacities to conduct screening and confirmatory testing during the time the patient is a resident in the ED. We report on a facility where HIV screening is performed during ED patient dwell times but confirmatory results follow in ≥24h. The conundrum is whether patients found HIV positive by a screening test should be informed of the positive screening finding before confirmatory results are in hand.

Methods

Data obtained from a routine opt-out HIV screening program for the interval June 2017 to March 2019 conducted at the ED in Houston, Texas were evaluated. Patients between 18–65 years with Glasgow Score >9 were eligible for testing. HIV fourth-generation ADVIA Centaur™ Ag/Ab COMBO (Siemens) was used for screening. Positives screening tests were followed by Gennius™ HIV1/HIV2 confirmatory test.

Results

12,040 HIV fourth-generation tests were performed; 232 (1.9%) were positive; the specificity of the screening testing was 98.2%. Twenty-two (9.5%) of screening test positive individuals were found HIV false positive (Ag/Ab positive and Gennius negative). The population had a mean age of 43.8 years (21–64), was predominately female (63.6%) and white (40.9%). Further testing was completed for 14 of the 22 patients with false-positive screening tests. 13 had negative tests for HIV RNA and 1 had a second HIV Ag/Ab test with negative findings. 8 (36.3%) screening test false-positive patients could not be located after their departure from the ED.

Conclusion

If patients were disclosed of their HIV-positive status because of the screening test result, approximately 10% of these individuals would have been incorrectly categorized generating significant personal and social disruption while waiting for the confirmatory result.

Disclosures

All authors: No reported disclosures.
1318. Examining Multimorbidity as a Moderating Effect on the Relationship Between Substance Use and Viral Suppression Among People Living with HIV
Authors: Crawford Timothy N , Thornton Alice
Published: October 2019

Background

Substance use and multimorbidity (≥2 chronic conditions) are highly prevalent among people living with HIV (PLWH). However, their impact on achieving viral suppression are not well understood. The purpose of this study was to examine the relationship between substance use and viral suppression and the potential moderating effect of multimorbidity.

Methods

A retrospective cohort study was conducted at an academic Ryan White Funded clinic in central Kentucky. Individuals were included if they were diagnosed with HIV, seeking care between 2010 and 2014, had at least one year of follow-up, and did not have a chronic condition at the time they entered care. The primary independent variable was substance use which included alcohol, nicotine use, and/or illicit drug use; the moderating variable was multimorbidity (0, 1, ≥2 chronic conditions); and outcome was viral suppression (≤50 copies/mL). A logistic regression model was developed to examine the interaction between substance use and multimorbidity on achieving viral load suppression. The model controlled for medication adherence, insurance status, age, and CD4+ cell counts.

Results

A total of 941 individuals were included in the study, with an average age of 43.9 ± 11.7 years. Approximately 67.0% reported substance use; 54% had ≥2 chronic conditions diagnosed. The three most prevalent conditions diagnosed were hypertension (34.6%), mental health (33.9%), and diabetes (21.5%) Approximately 61.0% of substance users had ≥2 conditions. Those with viral suppression were less likely to be substance users, but were more likely to have ≥2 conditions compared with their counterparts. There was a significant interaction between substance use and multimorbidity (P = 0.037). Stratified by multimorbidity, substance use was associated with unsuppressed viral loads; among those with ≥2 chronic conditions substance users had lower odds of achieving viral suppression compared with nonusers (OR=0.24; 95% CI=0.10–0.55).

Conclusion

Substance use may impede the opportunity for PLWH to achieve viral suppression, increasing their risk of transmission and progression of disease. More research is needed to understand the role substance use plays in impacting viral load, specifically among those with multiple chronic conditions.

Disclosures

All authors: No reported disclosures.
1319. Events of Disengagement from HIV care and Subsequent Reengagement in a Kenyan Pastoralist Community: Frequency, Determinants, and Patient Views
Authors: Yonga Paul Otieno , Kalya Stephen Kiplimo , Lynen Lutgarde , Decroo Tom
Published: October 2019

Background

Regular follow-up HIV-infected patients on antiretroviral therapy (ART) is vital to ensure viral suppression, thus reducing HIV transmission, and HIV-related morbidity and mortality. However, some patients have been reported to have events of disengagement from care with subsequent re-engagement in care, though knowledge on the magnitude and determinants of this phenomenon, particularly in pastoralist communities is scarce.

Methods

A mixed-methods study was carried out among HIV-infected patients on antiretroviral therapy (ART) follow-up between January 2014 and June 2017 at the Baringo County Referral Hospital, Kabarnet, Kenya. Records on their clinic attendance and laboratory follow-up were extracted, and those noted to have a recent event of disengagement from care who later re-engaged in care, were then purposively sampled for in-depth interviews.

Results

342 patient records were analyzed, of which 48% (166/342) of the patients were noted to be active at the end of the study period, with 63.3% (105/166) of them noted to have one or more events of disengagement from care. Female patients, patients with baseline CD4 counts ≥200 cells/mm3, and patients with a low WHO stage category (I and II) were more likely to return to care after an experience of disengagement from HIV care (P < 0.05). Eight interviewee transcripts showed the following reported reasons for disengagement in care: long distances, stigma, work-related problems, medication side effects, competing priorities, perceived recovery of the health status, medication fatigue, and not being informed of their clinic return dates. Motivators for re-engagement in care included hospital admissions, fear of getting sick like their spouse, and phone reminders.

Conclusion

A vast majority of patients currently active in care experienced multiple events of disengagement from care. Thus, early identification of those who disengage from care is recommended, before they become lost to follow-up.

Disclosures

All authors: No reported disclosures.
1326. Comorbid Mental Health Disorders Are a Key But Manageable Barrier to Suppression of HIV Viral Load
Authors: Stivers Tiffany , Porterfield J Zachary , Collins Jana , Yang Justin , Parrish Robert , Thornton Alice
Published: October 2019

Background

Kentucky sits at the epicenter of the HIV epidemic in the United States and harbors 54 of the top 220 HIV/HCV outbreak vulnerable counties in the United States; 44 of which are served by the Bluegrass Care Clinic at the University of Kentucky. Understanding the barriers to care at the frontlines of the epidemic is of critical importance in the work toward the eventual elimination of HIV in the United States and elsewhere.

Methods

The Bluegrass Care Clinic has achieved viral suppression in 90% of the HIV-positive patients enrolled in care. Given the catchment area served by this clinic, however, the unsuppressed 10% of patients likely represent the tip of an iceberg of undiagnosed patients or those lost to care from remote and at-risk communities. We developed a quality improvement project to specifically review the barriers to achieving viral suppression in this subset of patients in our clinic. Additionally, we developed an outreach algorithm for patients identified as having comorbid mental health issues to increase engagement in both HIV and mental healthcare.

Results

We found that nearly 45% of virally unsuppressed patients in our clinic had comorbid mental health disease and 30% had substance use disorders. Female sex was associated with being unsuppressed (P = 0.003); however, age and race were not predictive. Of the patients identified as having mental health barriers to care, 58% were able to be contacted using our outreach algorithm and 58% of these patients accepted referral into a mental health service. In this first 12 months of this program 26% of these patients achieved viral suppression and an additional 18% had substantial decreases in their viral loads.

Conclusion

This preliminary report highlights the importance of identifying and addressing barriers to care. Comorbid mental disorders have consistently been associated with greater difficulties in achieving viral suppression. We present an effective and successful program for engaging patients in mental healthcare using an interdisciplinary outreach program that is designed to be generalizable. These data set the stage for reaching the missing subset of patients who are not currently engaged in HIV care, a critical next step for universal test and treat and 90/90/90 strategies.

Disclosures

All authors: No reported disclosures.
1337. Development, Maintenance, and Application of Opsonophagocytic Assays to Measure Functional Antibody Responses to Support a 20 Valent Pneumococcal Conjugate Vaccine
Authors: Scully Ingrid L , Cutler Mark W , Gangolli Seema , Belanger Todd , Cooper David , Jones Thomas , McKeen Andrew , Tan Charles , Watson Wendy , Anderson Annaliesa S , Jansen Kathrin U , Pride Michael W
Published: October 2019

Background

Opsonophagocytic assays (OPAs) are an important tool for assessing vaccine-induced functional antibody responses. OPAs are complex assays composed of many biological components (eg serum, complement sources, bacteria, and human phagocytes) which contribute to assay variability and may result in titer drift if not carefully controlled. Rigorous development and validation coupled with routine monitoring of assay performance are required to ensure that high-quality OPA serological data are consistently generated throughout the lifetime of existing and next-generation pneumococcal vaccines.

Methods

OPA specificity was demonstrated by competing functional antibody activity with pneumococcal polysaccharides. Assay qualification/validation assessed accuracy, precision, and sample linearity. Assay performance over time was assessed through the implementation of quality control serum data tracking systems and longterm serum proficiency panels that are routinely tested during assay performance. Human quality control sera are included on each assay plate to ensure that each plate meets pre-specified acceptance criteria. Proficiency serum panels are comprised of individual human serum samples derived from subjects immunized with pneumococcal vaccines and are used to monitor performance across a range of serological titers and over time.

Results

The OPAs were shown to be specific and reproducible. Monitoring of assay performance over time demonstrated that the assays are stable. For the 13 serotypes contained in 13vPnC reliable titers have been generated in over a decade of testing which is an essential prerequisite in the evaluation of next-generation pneumococcal conjugate vaccines such as 20vPnC, whose licensure depends on demonstration of non-inferiority to 13vPnC.

Conclusion

Maintenance and careful monitoring of high-quality assays to measure functional antibody responses, such as OPAs, is critical for the delivery of reliable serological data to support the advancement of pneumococcal vaccine programs. Pneumococcal OPAs must be rigorously maintained to ensure continuity of serological data over time and inform licensure decisions of next-generation vaccines as well as postmarketing and seroepidemiology studies.

Disclosures

All authors: No reported disclosures.
1338. Development of a Novel Application for Differential Diagnosis of Tick-borne Diseases
Authors: Meyer Corey , Sanjak Jaleal , Cerles Audrey , Garnier Christian , MacMillan Laurel
Published: October 2019

Background

Early diagnosis and treatment of tick-borne diseases (TBDs) is critical for mitigating their adverse health outcomes, but the differential diagnosis of TBDs is challenging because many symptoms are nonspecific and commonly used diagnostic assays have significant shortcomings. Furthermore, although the local incidence of TBDs is recognized as an important factor in diagnosis, tools to help clinicians formally consider surveillance data in their decision-making are not available. To address these gaps, Gryphon Scientific developed a differential diagnosis application (app) for TBDs that calculates a patient’s likelihood of infection with specific TBDs based on their symptoms, risk factors, and state of suspected tick exposure.

Methods

A differential diagnosis model for TBDs was developed using data on: (1) TBD symptom and risk factor prevalence in TBD patient populations, collected from clinical studies; and (2) human TBD incidence data from notifiable disease surveillance systems and tick infection prevalence data from reports and public databases, which were combined to develop an environmental risk measure. These data were used to build a Bayesian Belief Network (BBN) model that predicts TBD infection probabilities based on a patient’s symptoms, risk factors, and state of suspected tick exposure. Performance of the model was validated using case studies from the biomedical literature. The model was incorporated into an app developed using R-shiny, called TBD-DDx (Figures 1 and 3).

Results

A pilot application was developed that includes 10 states (AR, CT, MA, ME, MN, MO, NH, RI, VT, and WI) and the 11 TBDs endemic to those states. The differential diagnosis model identified the patient’s true disease as the top-predicted disease in 56% of cases and within the top three predicted TBD in 84% of cases. The inclusion of incidence factors in the model improved performance (Figure 4).

Conclusion

These results demonstrate that the TBD-DDx app is a promising tool for informing clinical diagnoses of TBDs to guide selection of diagnostic testing and treatment. This study represents the first use of a BBN modeling approach that incorporates an environmental risk measure and could be adapted for differential diagnosis of other diseases with environmental or other exposure risks.

Disclosures

All authors: No reported disclosures.
1341. Development of a Series of High-Throughput Screens to Identify Leads for Nontuberculous Mycobacteria Drug Design
Authors: McGuffin Sarah , Mullen Steven , Early Julie , Parish Tanya
Published: October 2019

Background

Nontuberculous mycobacteria (NTM), particularly Mycobacterium avium complex and Mycobacterium abscessus complex, cause significant morbidity and mortality in patients with impaired host immunity or pre-existing structural lung conditions. NTM infections are increasing at an alarming rate worldwide and there is a dearth of progress in regard to the development of efficacious and tolerable drugs to treat such infections. Traditional drug discovery screens do not account for the diverse physiological conditions, microenvironments, and compartments that the bacilli encounter during human infection. In order to help populate the NTM drug pipeline, and explore the disconnect between in vitro activity, in vivo activity, and clinical outcomes, we are developing a high throughput in vitro assay platform that will more closely model the unique infection-relevant conditions encountered by NTM.

Methods

We are developing and validating a suite of in vitro assays that screen compounds for activity against extracellular planktonic bacteria, extracellular bacteria within biofilms, intracellular bacteria, and nutrient-starved non-replicating bacteria.

Results

We are using both the smooth and rough morphotypes of M. abscessus and M. avium. We have validated high throughput assays to pharmaceutical standards for replicating and non-replicating M. abscessus. We have also tested a panel of 18 known anti-mycobacterial compounds. Assay development is currently underway to test compounds for activity against NTM in biofilm and inside macrophages as well.

Conclusion

To enhance hit identification for scaffolds to use as starting points for NTM drug development, focused libraries of compounds that have undergone significant preclinical profiling and/or compounds with known activity against M. tuberculosis (TB) will be screened. Such a “piggyback” approach usurps advances made in TB drug development and leverages them for NTM drug discovery. This will help expedite novel drug development, reduce attrition rate, and offer a shorter route to clinical use as it exploits the prior investment in medicinal chemistry, pharmacology, and toxicology.

Disclosures

All authors: No reported disclosures.
1344. Interferon Gamma Release Assay (IGRA) Responses in HIV-Infected and -Uninfected Women in Pregnancy
Authors: Kaplan Samantha , Matemo Daniel , Mecha Jerphason O , Kinuthia John , John-Stewart Grace , LaCourse Sylvia
Published: October 2019

Background

Pregnancy and HIV-associated immunologic changes may affect latent TB infection (LTBI) interferon-gamma release assay (IGRA) QuantiFERON TB Gold Plus (QFT-Plus) diagnostic performance.

Methods

In this ongoing study, HIV-infected and -uninfected women 20–34 weeks gestation without TB in the past year are enrolled from antenatal clinics in western Kenya and tested with QFT-Plus. Mean quantitative IFN- γ responses to mitogen, and M. tuberculosis antigens (TB1 [primarily CD4+] and TB2 [addition of CD8+ response]) were compared using two-sample t-tests. Proportions for categorical variables were compared using univariate logistic regression.

Results

Among 306 women (HIV+ 127 [41.5%], HIV− 179 [58.5%]) enrolled between January 2018 and March 2019, median maternal and gestational age were 25 years (IQR 21–28) and 28 weeks (IQR 24–32), respectively. Among HIV-infected women at enrollment, 99.2% were on ART, median CD4 count was 440 cells/mm3 (IQR 235–703), 37.5% were virally suppressed, and 60.6% reported having received isoniazid preventive therapy (IPT). Overall, 95 (31.1%) women were QFT-Plus positive (HIV+ 38 [29.9%], HIV− 57 [31.8%], OR 0.90, 95% CI 0.54–1.48, P = 0.671); 190 (62.1%) were negative (HIV+ 81 [63.8%], HIV− 109 [60.9%]), and 21 had indeterminate results (HIV+ 8 [6.3%], HIV− 13 [7.3%], OR 0.83, 95% CI 0.33–2.09, P = 0.690). Mean response to mitogen was similar between HIV-infected and -uninfected women (6.0 vs. 6.1 IU/mL, P = 0.663]. Among QFT-Plus positive women, HIV+ women had significantly lower TB1 responses than HIV− women (HIV+ 2.7 vs. 4.2 IU/mL, P = 0.035). Mean TB2 responses had a similar pattern, but did not reach statistical significance (HIV+ 3.1 vs. 4.3 IU/mL, P = 0.107). Both TB1 and TB2 were positive for 82 women (86.3%), 4 women were only TB1 positive (4.2%), and 8 women were only TB2 positive (8.4%).

Conclusion

Among pregnant women, HIV-infection was not associated with increased prevalence of QFT+ responses. However, among QFT-positive women, TB1 responses were lower in HIV-positive women with a similar trend observed for TB2 responses. These findings suggest that HIV-associated immunologic changes may influence QFT test performance.

Disclosures

All authors: No reported disclosures.
1367. Tele-TB: Using TeleMedicine to Increase Access to Directly Observed Therapy for Latent Tuberculosis Infections
Authors: Donahue Megan L , Eberly Matthew , Stagliano David , Rajnik Michael
Published: October 2019

Background

Otherwise healthy patients with latent tuberculosis infection (LTBI) have a 10 percent lifetime risk of progression to active TB disease. This risk is higher in recently exposed persons, young children, and the immunocompromised. Treatment of LTBI decreases the risk of progression. However, traditional treatment regimens required either daily isoniazid (INH) for 9 months, with historically poor compliance, or 12-week directly-observed therapy (DOT) with INH and rifapentine (RPT), with improved compliance but challenges of coordinating weekly clinic visits, further complicated if patients must travel a great distance for care and/or miss considerable amounts of time from work or school to attend encounters.

Methods

Our referral area is complicated by congested traffic often resulting in one-way commutes in excess of 2 hours. These travel times would be prohibitive for conducting traditional weekly in-clinic DOT. In an effort to improve access to DOT, we implemented TeleMedicine LTBI DOT within a military pediatric infectious diseases clinic. Local providers were requested to refer patients aged two and older diagnosed with LTBI to our DOT TeleMedicine clinic. All patients without absolute contraindications for receiving INH and/or RPT were offered LTBI treatment via weekly TeleMedicine DOT or daily INH. If the family opted for TeleMedicine DOT, the first visit was performed in person to discuss treatment options, demonstrate use of the TeleMedicine software, and to ensure the patient was able to take the medications. Baseline information about patient travel time to our facility for patients enrolled in the LTBI DOT clinic was determined.

Results

To date, seven patients have completed LTBI treatment via TeleMedicine DOT. Average one-way travel time to our facility for patients participating in the TeleMedicine DOT was 72 minutes. Actual time spent in the TeleMedicine DOT encounters was less than 10 minutes. Appointments were arranged to take place outside usual school and work hours so patients could complete DOT with minimal interruptions to daily life, resulting in 100% treatment compliance and completion.

Conclusion

Conducting DOT using TeleMedicine is a viable and time-saving measure that still allows for high levels of patient compliance and treatment completion while minimizing interruptions to academic and work schedules.

Disclosures

All authors: No reported disclosures.
1371. Tuberculosis and HIV Coinfection in the Bahamas: A Retrospective Review of Cases Diagnosed Between 2014 and 2016
Authors: McIntosh Javardo , Moss Kevin , Forbes Nikkiah , Frankson M Anthony C
Published: October 2019

Background

Tuberculosis (TB) is one of the oldest diseases known to man, yet the world health organization reports that TB is one of the top 10 causes of death worldwide. HIV infection is the most potent biologic risk factor for developing tuberculosis. The HIV epidemic has been responsible for increasing the burden of TB worldwide and The Bahamas has been no exception. The aim of this study was to determine the HIV testing rate as well as prevalence of TB-HIV coinfection for The Bahamas and compare cases of TB based on HIV status for clinical presentation, radiologic findings, TST results and Smear and Culture results. We also evaluated cases of TB-HIV for degree of immunosuppression and compliance to antiretroviral therapy.

Methods

A retrospective chart review of cases of Tuberculosis diagnosed at the Princess Margaret Hospital, Nassau, Bahamas. 189 cases of active tuberculosis diagnosed between 2014 and 2016 and all cases were evaluated for demographics, risk factors, HIV status, clinical manifestation, radiologic findings, and smear and culture results.

Results

Of the 189 cases of notified tuberculosis between 2014 and 2016, 109 (59.9%) were HIV negative and 73 (40.1%) were HIV positive. For patients who were HIV positive, 54(74%) were previously diagnosed with HIV and 19(26%) were newly diagnosed. Of the patients who were previously diagnosed with HIV, 14(25.9%) were on antiretroviral (ARV) medications and compliant, 34(63.0%) were on ARVs and noncompliant and 6(11.1%) were not on ARVs. 4(8.2%) patient had a CD4 count ≥500, 8(16.3%) patients had a CD4 count between 499–200 and 37(75.5%) had a CD4 counts 1000.

Conclusion

HIV is a major risk factor for Tuberculosis in the Bahamas and it is advised that all patients diagnosed with TB be tested for HIV. Routine screening of HIV patients for TB is recommended. Noncompliance with antiretroviral therapy remains a public health issue as it increases susceptibility to TB infection.

Disclosures

All authors: No reported disclosures.
1387. Women Living with HIV (WLWH) Lose IFNγ Responses Diagnostic of Latent TB Infection (LTBI) during Pregnancy and after INH Prophylactic Treatment (IPT)
Authors: Weinberg Adriana , Aaron Lisa , Montepiedra Grace , Sterling Timothy , Chaktoura Nahida , Browning Renee , Mmbaga Blandina T , Vhembo Tichaona , Nandkumar. Naik Shilpa , Pahwa Savita , Mathad Jyoti S , LaCourse Sylvia , McCarthy Katie S , Bradford Sarah , Costello Diane G , Zimmer Bonnie , Flore Pierre Marie , Gupta Amita , Theron Gerhard B
Published: October 2019

Background

TB is the most common opportunistic infection in PLWH. IPT is recommended for PLWH in endemic areas and for those with LTBI diagnosed by Quantiferon gold-in-tube (QGIT) or tuberculin skin test (TST) in other areas. We report on the performance of QGIT and TST in pregnant WLWH who received IPT antepartum (AP) or postpartum (PP).

Methods

WLWH participating in IMPAACT P1078, a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT AP vs. PP, were tested by QGIT at entry (14–34 weeks gestation) and by QGIT and TST at delivery (L&D) and 44 weeks PP. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations.

Results

Among 944 women with study entry mean (SD) of 29 (6) years of age, 521 (245) CD4+ cells/µL, on ART, including 63% with undetectable HIV plasma RNA, 284/944 (30%) were QGIT+ AP, 215/862 (25%) at L&D and 246/764 (32%) PP (P < 0.001), while 127 (15%) were TST+ at L&D and 126 (17%) PP. QGIT was more likely positive than TST at L&D (Odds ratio = 4.3; 95% CI = 2.8–6.8) and PP (6.4; 3.9–10.7; P < 0.001). QGIT and TST agreement coefficients (95% CI) were 0.4 (0.3–0.5) at L&D and 0.5 (0.4–0.5) PP. Among women QGIT+ AP, 59 (24%) reverted to QGIT- or indeterminate at L&D. However, 37 (63%) reverters recovered QGIT+ results PP, suggesting transient suppression of IFNg responses during pregnancy. Responses to the mitogen-positive QGIT kit control were absent in 60 (7%) women AP, 116 (16%) at L&D, but only 3 (0.4%) PP (P < 0.01), supporting the notion of transient immune suppression during pregnancy. Among women QGIT- AP, 33 (7%) converted to QGIT+ PP. Among AP QGIT+ women, 24 (11%) reverted to QGIT- PP after finishing IPT. None of the results differed between treatment arms (P ≥ 0.13).

Conclusion

In WLWH on ART, the loss of IFNγ responses to TB antigen and mitogen in pregnancy decreased the diagnostic value of QGIT. TST was similar at L&D and PP but was less sensitive than QGIT. QGIT conversions likely resulted from a combination of PP immune reconstitution and new TB infections. QGIT reversions might represent a change in TB-specific immunity in response to IPT. Reversions have been reported in adults without HIV after treatment of active TB. The clinical significance of QGIT reversions in PLWH needs further investigation.

Disclosures

All authors: No reported disclosures.
1394. Clinicopathologic Features of Infectious and Noninfectious Tissue Granulomas in Transplant Patients
Authors: Zachary Nussbaum Eliezer , Abi Raad Rita , Malinis Maricar , Azar Marwan M
Published: October 2019

Background

There is a paucity of literature about the implications of granulomatous disease in hematopoietic stem cell transplant (HSCT) and solid-organ transplant (SOT) patients. Given the broad range of infectious and noninfectious etiologies as well as the heightened risk for severe infection, it is important to characterize the clinicopathologic features of granulomas in this population and to develop a framework to guide further evaluation.

Methods

We performed chart reviews of 1,280 transplant recipients (791 SOT and 489 HSCT) at Yale-New Haven Hospital from 2009 to 2019 to identify patients with granulomas in pathologic specimens obtained peri-transplantation. Data on histopathology, microbiology, indication for biopsy, patient characteristics, and clinical presentation were recorded. Morbidity and mortality were noted at 1, 3, and 12 months after granuloma diagnosis.

Results

We identified 28 patients with granulomas (9 SOT, 19 HSCT); an incidence of 2.2%. None had explicit risk factors for MTB. Most granulomas (93%) were non-necrotizing. Common sources were lung (n = 9) and lymph node (n = 5). Most were found post-transplant (n = 19) and biopsies were prompted mostly by symptoms (n = 13) or incidental imaging findings (n = 9). Most granulomas were not associated with an infectious process (n = 20). Among infectious granulomas, bacterial soft-tissue infection (n = 2), bartonellosis (n = 2), and fungal infection (1 Cryptococcus and 1 Blastomyces) were most common. MTB PCR was negative in 4 specimens. Among granulomas discovered in SOT patients, 44% were infectious compared with 21% in HSCT recipients. Most infectious granulomas were found in symptomatic patients (75%). One granuloma-related adverse outcome occurred in a case of cryptogenic organizing pneumonia discovered pre-HSCT that worsened with tapering of immunosuppression post-HSCT.

Conclusion

Granulomas were uncommon in a large transplant population. Most were deemed noninfectious and their presence alone was not associated with adverse outcomes post-transplant or with increased immunosuppression. Granulomas were more likely to be infectious in SOT recipients and those with symptoms. Symptoms should guide the extent of microbiologic evaluation and reflexive MTB PCR testing is not warranted if risk factors are absent.

Disclosures

All authors: No reported disclosures.
1405. Infectious Causes of Chronic Meningitis in HIV-Negative Patients: A Case Series
Authors: Rivera Jose E , Bae Eunice H , Crissinger Tyler , Baldwin Kelly
Published: October 2019

Background

Chronic meningitis can be defined as inflammation of the cerebrospinal fluid (CSF) with the presence of >5 white blood cells/mm3 of CSF for 4 weeks. There is little literature available on defining the infectious causes or risk factors of chronic meningitis, and there are no studies that have looked at mortality in this group of patients. Our aim for this study was to evaluate the epidemiology, risk factors, and mortality of infectious causes of chronic meningitis within our healthcare system.

Methods

A total of 59 cases were identified through a systematic retrospective review from our electronic medical record database from 2004 to 2018 and were identified by having the presence of two consecutive lumbar punctures with a white blood cell count in CSF >5 WBC/mL3 in a 4-week period, or by having 4 weeks of meningeal symptoms with one lumbar puncture with >5 WBC/mL3. All cases were manually reviewed. We excluded patients with diagnosis of human immunodeficiency virus (HIV) infection. We included a review of comorbidities that could impair the immune system such as diabetes mellitus, alcohol use, chronic kidney disease (CKD) stage III or greater use of chemotherapy, immunotherapy, or chronic use of steroids and previous transplant recipients. The study was approved by the institutional review board

Results

59 cases of chronic meningitis attributable to an infectious etiology were identified. The most common pathogens were Borrelia burgdorferi (37%), Cryptococcus sp. (27%), and Candida sp. (10%). Other etiologies which were less common included viral etiologies (13%). Finally, there were two cases secondary to Streptococcus pneumonia. Regarding the total number of patients with the comorbidities studied, 13 (22%) had diabetes, 12 (20%) had CKD, 12 (20%) were under some form of chemo/immunotherapy including chronic steroid use and 3 (5%) of patients were transplant recipients.

Conclusion

Our study identified common infectious pathogens causing chronic meningitis in a rural, HIV-negative population. Our findings indicate that cryptococcus should be considered even within HIV-negative individuals, and Lyme disease should be considered in all endemic areas. Mortality was significant among patient with cryptococcal meningitis, where patients with Lyme meningitis did very well.

Disclosures

All authors: No reported disclosures.
1410. Serious Cryptococcal Infections with Ruxolitinib Use: A Case of Meningitis and a Review of the Literature
Authors: Harvey Jeremy , Tran Ly , Sampath Rahul , White Chris , Campanile Teresa
Published: October 2019

Background

Ruxolitinib is an inhibitor of Janus kinase (JAK) 1 and 2 and is approved for the treatment of myelofibrosis and polycythemia vera. Infectious complications associated with its use include reactivation of herpes simplex, zoster, hepatitis B, and tuberculosis, mucormycosis, and progressive multifocal leukoencephalopathy.

Methods

Seven cases of ruxolitinib-associated cryptococcal infections have been reported: three cases of meningitis, two cases of pulmonary disease, and two cases of disseminated disease (Table 1).

Results

We present a 72-year-old male with a history of JAK-2-positive polycythemia vera with secondary myelofibrosis, and concurrent multiple myeloma who presented with 3 weeks of chronic cough and 3 days of fever with severe bifrontal headache after remodeling a large birdcage in his backyard. The patient was on ruxolitinib, ixazomib, and weekly dexamethasone. Cerebrospinal fluid (CSF) analysis showed an elevated opening pressure of 29 cm of CSF, 173 leucocytes with a predominance of lymphocytes, protein of 87 mg/dL and a normal glucose level. BioFire FilmArray® Meningitis/Encephalitis panel detected targets for Cryptococcus in the CSF, and CSF cryptococcal antigen was positive at 1:4. CSF fungal cultures were subsequently positive for Cryptococcus neoformans, susceptible to liposomal amphotericin B (LAMB) and fluconazole. Ruxolitinib was discontinued, treatment with LAMB and flucytosine (5-FC) was associated with significant improvement of headache over the next week. Repeat CSF analysis in 2 weeks was culture negative with a negative cryptococcal antigen test. The patient completed 3 weeks of LAMB and 5-FC and then transitioned to oral fluconazole for a year.

Conclusion

Ruloxitinib and other JAK inhibitors suppress host immunity through impaired T-cell activation and downregulation of cytokines. The JAK-Signal Transducer and Activator of Transcription pathway is one of the most active pathways in host defense against cryptococcus, and use of JAK inhibitors like ruxolitinib may predispose to severe cryptococcal infections. Bird exposure is a risk factor, making environmental contact counseling for patients on ruxolitinib important. Fluconazole prophylaxis needs to be considered in select cases.

Disclosures

All authors: No reported disclosures.
1422. Evaluation of Diabetic Foot Infections and Osteomyelitis in a Veteran Population: Targets for Improved Outcomes
Authors: Carter Michael T , Trivedi Grishma , Fodero Kristen , Wattengel Bethany A , Sellick John , Mergenhagen Kari A
Published: October 2019

Background

Diabetic foot infections (DFI) complicated with osteomyelitis are a difficult infection to treat often resulting in poor outcomes. DFIs often require amputations, including serial amputations due to inadequate initial intervention and infection progression. This study examines various diagnostic and treatment strategies aimed to improve outcomes.

Methods

This retrospective cohort study included patients greater than or equal to 18 years of age with a DFI as identified via ICD 9 and ICD 10 codes from January 2005 to December 2018. Outcomes were analyzed to measure the impact of baseline characteristics on outcomes. The severity of infection was defined by PEDIS score (perfusion, extent, depth, infection, and sensation). Descriptive statistics were used to report differences.

Results

One hundred and thirty patients were included, 72% with osteomyelitis. The median PEDIS score was 3 (interquartile range 2–3). Magnetic resonance imaging was used to evaluate 38% of the population. Osteomyelitis patients who had an MRI performed were noted to have a higher rate of appropriate treatment and cure (56%) when compared with a similar group of patients who did not receive an MRI (25%) (P = 0.005). Comparing prolonged (> 4 weeks) therapy to short therapy, there was a significantly higher proportion of cures noted (62.71% vs. 36.62%, P < 0.0001). Failure was associated with less than 4 weeks of therapy (66.7%, P = 0.03) and presence of residual inflammation/infection after amputation (58.3%, P < 0.0001). Route of antibiotic had no impact on failure rates. However, patients with an initial drug-bug mismatch were more likely to fail. Sixty-six percent of patients with decreased ankle brachial index failed (P = 0.02).

Conclusion

Diabetic foot infections have serious consequences. Over a third of patients required further amputation or additional antibiotic therapy. Risk of failure was associated with short durations of therapy, poor perfusion, and residual inflammation after amputation. However, a higher rate of cures was noted with use of an MRI and prolonged therapy in patients. Stewardship initiatives may wish to focus on ensuring prolonged treatment courses and appropriate surgical intervention rather than on route of antibiotic therapy as there was no difference in failure rates.

Disclosures

All authors: No reported disclosures.
1429. Diagnosis and Management of Osteomyelitis Associated with Stage IV Pressure Ulcers: Report of a Query to the Emerging Infections Network of the Infectious Diseases Society of America
Authors: Kaka Anjum S , Beekmann Susan E , Gravely Amy , Polgreen Philip M , Johnson James R
Published: October 2019

Background

Despite the high prevalence and morbidity of stage IV pressure ulcers, there are few clinical studies to guide diagnosis and treatment of osteomyelitis in such patients.

Methods

The Emerging Infections Network conducted an electronic survey of adult ID physicians in 2018 to determine their approach to managing patients with stage IV pressure ulcers (exposed bone, tendon, or muscle) and osteomyelitis.

Results

The overall response rate was 42% (558/1,332). Of the respondents, 94/558 (17%) had not seen such patients in the last year, so opted out. Of the remaining 464 respondents, 276 (60%) usually felt confident in diagnosing osteomyelitis by physical examination, and laboratory or imaging test results; the strongest indicator of osteomyelitis was thought to be palpable or visible bone at the ulcer base (Figure 1). Approaches to diagnosing osteomyelitis in patients with visible and palpable bone varied: 41% would assume osteomyelitis was present, 27% would try local wound care and pressure-offloading before doing tests, 22% would do diagnostic tests immediately, and 10% would follow another strategy. The preferred tests for osteomyelitis were bone biopsy (for culture or histopathology) and MRI (Figure 2). Regarding treatment, respondents differed widely regarding favored route(s) of antimicrobial therapy (all IV, partly IV and partly oral, or all oral), regardless of presumed pathogen (Figure 3). Respondents also differed widely regarding preferred duration of antimicrobial therapy, but generally would treat longer in the absence of full surgical debridement (P < 0.001 overall) (Figure 4). Overall, 62% of respondents believed that osteomyelitis under stage IV pressure ulcers usually or almost always is treated excessively. Most respondents (59%) had multiple suggestions for future research, primarily regarding the duration and utility of antimicrobial therapy in this context.

Conclusion

ID physicians (i) report significant practice variability in their approach to diagnosing and treating osteomyelitis underlying stage IV pressure ulcers, (ii) are concerned about excessive antibiotic use in such patients, and (iii) perceive a critical need for additional research in this area.

Disclosures

All authors: No reported disclosures.
1458. Burden of Illness in Patients with Urinary Tract Infections With or Without Bacteremia Caused by Carbapenem-Resistant Gram-Negative Pathogens in US Hospitals (2014 to 2018)
Authors: Shields Ryan K , Kanakamedala Hemanth , Zhou Yun , Cai Bin
Published: October 2019

Background

Urinary tract infections (UTIs) are the most frequent infections caused by Gram-negative (GNB) bacteria in the USA. We aimed to characterize the burden of UTIs caused by carbapenem-resistant (CR) or -susceptible (CS) GNB in hospitalized patients with or without bacteremia.

Methods

Data from the Premier Healthcare Database of adult patients hospitalized between January 1, 2014 and June 30, 2018 with UTIs (defined as positive urine culture and receipt of GN antibiotics within −2 to 3 days of the index urine culture) with bacteremia (defined as positive blood culture with the same pathogen from the urine) or without bacteremia caused by CR or CS GNB were analyzed retrospectively. Stenotrophomonas maltophilia were presumed to be CR but rarely tested. Patient characteristics and outcomes (mortality, different types of length of hospital stay [LOS], ICU admission, discharge status and hospitalization charges) were compared.

Results

A total of 46,076 UTI patients were included. 11,212 patients with bacteremia were significantly more likely to have UTI index culture on the day of the admission vs. 34,864 patients without bacteremia (82.0% vs. 65.9%, P < 0.001, respectively). The same results were seen when stratified by CR status (CR: 68.59% vs. 61.23%, P < 0.047; CS: 82.29% vs. 66.19%, P < 0.001, respectively). UTI patients with bacteremia were also more likely to have a positive blood culture for the same pathogen on the same day of index urine culture (CR: 85.86%; CS: 95.45%). Pseudomonas aeruginosa was the most frequent CR pathogen (50.03%), followed by K. pneumoniae (14.28%) and Stenotrophomonas maltophilia (10.76%), and CR patients with bacteremia were more likely to die in the hospital and less likely to be discharged home than other groups. They also had longer median overall and infection-associated LOS, were more likely to be admitted to the ICU and had higher hospitalization charges (table).

Conclusion

UTIs complicated by bacteremia exacerbates the burden of illness in patients hospitalized with UTIs, increasing mortality, LOS, and hospitalization charges. The presence of CR pathogens further exacerbates this burden.

Disclosures

All authors: No reported disclosures.
1470. Linezolid for Treatment of Urinary Tract Infections Caused by Vancomycin-resistant Enterococci
Authors: Pontefract Benjamin , Madaras-Kelly Karl
Published: October 2019

Background

Urinary tract infections (UTI) caused by vancomycin-resistant enterococcus (VRE) are difficult to manage due to lack of effective oral treatment options. Linezolid is an antibiotic with activity against VRE that is available orally, but only 30% of each dose is excreted in the urine. Data on the efficacy of linezolid in the treatment of UTI is limited. The purpose of this analysis was to assess the comparative efficacy of linezolid to other VRE-active antibiotics in the treatment of UTI.

Methods

A national retrospective cohort of inpatient veterans with a positive urine culture for VRE during years 2013 through 2018 was developed. Patient demographics, vital signs, urinary symptoms, antibiotics prescribed, and 14-day post-treatment outcomes were collected. Patients without UTI symptoms, urine cultures with < 105 CFU/mL (<103 CFU/mL for catheterized patients), or patients not treated with VRE-active antibiotics were excluded. Odds ratios were used to compare linezolid and non-linezolid antibiotics for 14-day VRE bacteriuria, UTI retreatment, and death endpoints.

Results

Of 3,846 urine cultures identified with VRE, 624 (16%) patients were eligible for evaluation of UTI symptoms. Of these, 92/624 (15%) met study criteria. The primary reason for exclusion was asymptomatic bacteriuria [339/532 (64%)]. Linezolid was prescribed in 54/92 (59%) of cases. Comparators included penicillin’s [12/92 (13%)], nitrofurantoin [11/92 (12%)], daptomycin [7/92 (8%)], tetracycline’s [6/92 (7%)], and others [2/92 (2%)]. Between linezolid and comparator groups, mean (+S.D.) patient age [70 (12) vs. 68 (13) years, P = 0.45] and Charlson Comorbidity Index [8.9 (3.1) vs. 8.3 (3.5), P = 0.39] were similar. Negative outcomes were uncommon: 7% VRE bacteriuria, 8% UTI re-treatment, 4% death. No difference in [(OR) +95% CI] between linezolid and comparators was observed: positive VRE bacteriuria [0.3 (0.1, 1.9), P = 0.20], UTI retreatment [1.8 (0.3, 10.0), P = 0.49], death [1.4 (0.1, 16.1), P = 0.79].

Conclusion

Most patients with a VRE positive urine culture who received antibiotics did not meet diagnostic criteria for UTI, and negative outcomes were uncommon. Linezolid and comparator regimens with VRE activity were effective for treating mild VRE UTI.

Disclosures

All authors: No reported disclosures.
1486. Evaluation of the Impact of Homelessness on Presentation and Outcomes of Gram-Negative Sepsis
Authors: An Chiu Chiao , Werge Dominique A , Arab Niki , Palafox Miguel , Minejima Emi
Published: October 2019

Background

Low socioeconomic status has been shown to contribute to an increase in mortality and intensive care unit (ICU) admission in patients with sepsis. The role of homelessness on outcomes of gram-negative sepsis is currently unknown. The primary objective was to evaluate the impact of homelessness on presentation and outcomes compared with low socio-economic status patients with housing.

Methods

Single-center, retrospective cohort study of hospitalized adults with Enterobacteriaceae infections between 2015 and 2017. Medical charts were reviewed for pertinent data. Patients were grouped as homeless (H) vs. non-homeless (NH) and compared for patient characteristics, clinical presentation, and course. Primary outcome was 30-day mortality. Secondary outcomes were 30-day re-admission and hospital length of stay (LOS).

Results

198 patients were included; 68 in H group vs. 130 in NH group. H group were younger (mean 51 years vs. 57 years, P = 0.01), more likely to be male (71% vs. 37%, P < 0.01) and non-Hispanic White (57% vs. 21%, P < 0.01). Two groups had similar comorbidities, except H group had more liver dysfunction (16% vs. 7%, P = 0.05); however, less heart failure (7% vs. 18%, P = 0.03). H group had a more severe presentation with higher rate of ICU admission (57% vs. 41%, P = 0.04) although initial SOFA score (median 6 vs. 4, P = 0.14) and need for vasopressors (16% vs. 18%, P = 0.19) were similar. Urinary tract infection (37% vs. 45%, P = 0.36) and bacteremia (38% vs. 42%, P = 0.76) were the most common sources. Total antibiotic duration was similar (median 7d, P = 0.61); H group received more empirical vancomycin (16% vs. 7%, P = 0.05) and fluoroquinolones as definitive therapy (13% vs. 8%, P = 0.05). 30d mortality was similar (13% vs. 8%, P = 0.21); however, H group had significantly prolonged LOS by 4d (median 9 days vs. 5 days, P < 0.01) and higher 30 days re-admission (41% vs. 18%, P < 0.01).

Conclusion

Within a medically underserved population, homeless patients with gram-negative sepsis were younger and had more liver disease compared with patients with housing. As this group had increased utilization of healthcare resources including need for ICU-level care, prolonged LOS, and 30-day re-admission, additional targeted interventions to prevent and optimally treat Enterobacteriaceae infections in homeless patients may be needed.

Disclosures

All authors: No reported disclosures.