bluuebunny/crossref_metadata_2025_split huggingface dataset:
1370. Concurrent Anti-PD -1 and Anti-tubercular Therapy in a Patient with Refractory Lymphoma and Pulmonary Tuberculosis: A Case Report
Authors: Rajagopal Sumanth , Nguyen Vu 
Published: October 2019

Abstract

Background
safety and efficacy of concurrent treatment for tuberculosis and checkpoint inhibitor drugs are unknown.

Methods
case report.

Results
36-year-old gentleman presented with bulky adenopathy in December 2016. Work-up revealed classical Hodgkin’s lymphoma with extra-nodal sites of involvement including bone, lungs and skeletal muscle. After his disease proved refractory to the standard first and second-line treatments, complete remission was achieved with anti-CD 30 drug-toxin conjugate, brentuximab followed by consolidation with autologous stem cell transplant in February 2018. However, his lymphoma recurred in June 2018 with new bulky adenopathy and new bilateral nodular pulmonary infiltrates. PET imaging revealed multiple avid lymph nodes, liver and bone lesions. Biopsy of a neck node confirmed relapsed lymphoma. Cultures of sputa revealed drug-susceptible M. tuberculosis. Four drug treatment with Isoniazid, Rifampin, Ethambutol and Pyrazinamide was initiated in June 2018. Hospice enrollment was considered because of progressive lymphoma and poor functional status. In July 2018, patient elected for a trial of salvage treatment with Nivolumab, a PD-1 checkpoint inhibitor (CPI) while on anti-tubercular treatment. He was monitored for paradoxical worsening of symptoms. He tolerated the tuberculosis medications well for the entire 6-month course, follow-up sputa were culture negative. His lymphoma remains in remission on maintenance nivolumab as a donor search is underway.

Conclusion
Auto-immune reactions and immune-related adverse events are major side effects of CPI drugs. Our understanding of the interplay between checkpoint inhibitors and infectious risks continues to evolve. Among the few cases reported in the literature, patients on CPIs have experienced both reactivation of latent tuberculosis as well as severe, fatal paradoxical reactions during treatment of active tuberculosis. Despite the relatively uncomplicated course in our patient, tuberculosis in this group of patients poses many challenges in diagnosis and management and warrants close monitoring and follow-up.

Disclosures
All authors: No reported disclosures.
1373. Clinical Presentation, Demographics, and Outcomes of Cases of Tuberculosis (TB) at Princess Margaret Hospital, Nassau, The Bahamas 2014–2016
Authors: McIntosh Javardo , Forbes Nikkiah , Moss Kevin , Frankson M Anthony C 
Published: October 2019

Abstract

Background
Tuberculosis (TB) is one of the oldest diseases known to man, yet the world health organization reports that Tuberculosis is one of the top 10 causes of death worldwide. There are various factors that have made the eradication of tuberculosis in the Bahamas difficult such as high rates of HIV infection and immigrants migrating from countries with high TB prevalence. In understanding the epidemiology and risk factors of TB cases in the Bahamas, the development of protocols can improve screening procedures and decrease disease burden.

Methods
A retrospective chart review of cases of Tuberculosis diagnosed at the Princess Margaret Hospital, Nassau, Bahamas. 189 cases of active tuberculosis diagnosed between 2014–2016 and all cases were evaluated for demographics, risk factors, clinical manifestation, method of diagnosis, symptoms, and treatment outcomes.

Results
Of the 189 cases of notified tuberculosis between 2014 and 2016, 46 cases were reported in 2014, 60 cases in 2015 and 83 cases in 2016. The mean age was 37.96 (±18.20) years old. 164 (86.8%) presented with symptoms, 19 (10.1%) of cases were diagnosed by routine screening and 6 (3.2%) of cases were diagnosed by contact tracing. 109 (59.9%) were HIV negative and 73 (40.1%) were HIV positive. 144 (76.2%) presented with cough, 84 (44.7%) weight-loss, 80 (42.3%) fever, 44 (23.3%) night sweats, 43 (22.8%) chills, 32 (16.9%) fatigue, and 25 (13.2%) hemoptysis. 126(66.7%) completed the full course of antibiotic therapy, 29(15.3%) patients expired before completing treatment and 18(9.5%) of patients defaulted.

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. We also advise screening HIV-positive patients for TB. Screening other high-risk groups such as migrant populations would also benefit to reduce the amount of latent TB cases which may progress to active TB.

Disclosures
All authors: No reported disclosures.
1378. Clinical Characteristics of Tuberculosis Among Patients with Cancer in an Endemic Country
Authors: Buppanharun Jirawat , Vanichanan Jakapat 
Published: October 2019

Abstract

Background
Tuberculosis (TB) is an infection caused by reactivation of Mycobacterium tuberculosis. Decreasing host immune system plays an important role in pathophysiology especially in patients with human immunodeficiency virus (HIV) infection and transplant recipients. Exposure to immunosuppressive agents among patients with solid and hematologic malignancy is likely to increase risk of TB. However, characteristics of TB in this population remain scarce.

Methods
A single-center, retrospective descriptive study was conducted at King Chulalongkorn Memorial Hospital. Adult patients who developed TB between January 2008 and October 2018 after diagnosis of solid or hematologic malignancy were identified using ICD-10 code. Baseline, clinical characteristics, and treatment outcomes were collected.

Results
A total of 114 patients developed TB after diagnosis of malignancy including, 67 (58.8%) with solid tumor and 47 (41.2%) with hematologic malignancy. Lung cancer was the most common solid malignancy with TB (17.9%) followed by head and neck carcinoma (14.9%) and colorectal cancer (13.4%). For hematologic malignancies, non-Hodgkin’s lymphoma was the most common malignancy (53.2%) followed by leukemia (29.8%) and multiple myeloma (14.9%). Among patients who received immunosuppressive treatment, the mean onset of TB was 4.97 months (range 0.25 to 57 months) and 2.55 months (range 0.1 to 18 months) after treatment of solid and hematologic malignancies. Pulmonary and pleural involvement remained the most common site of infection in both groups. Mortality was highest among patients with hematologic malignancies (40.4%) while mortality in solid malignancies was 11.9%.

Conclusion
TB in patients with solid and hematologic malignancies contained substantial morbidity and mortality. Immunosuppressive agents and chemotherapy may play an important role especially in the endemic area.

Disclosures
All authors: No reported disclosures.
1393. Tuberculosis (TB) After Solid-organ Transplant (SOT) and Hematopoietic Stem Cell Transplant (HSCT)
Authors: Peña-Puga Cecilia F , Morado-Aramburo Oscar , Lambraño-Castillo Darwin , Cuellar-Rodríguez Jennifer 
Published: October 2019

Abstract

Background
Tuberculosis is an important opportunistic infection that affects transplant recipients; the risk of active infection increases significantly when compared with the general population. Most disease results from reactivation of latent infection, being extrapulmonary and disseminated disease the most common presentations. Most cases occur during the first year post-transplantation when immunosuppression is higher. We describe the clinical characteristics of patients diagnosed with TB after transplant.

Methods
Single-center, retrospective study of adult SOT and HSCT recipients in Mexico City, who developed active TB after transplant. We reviewed medical records, and collected demographic data, clinical characteristics, and outcome.

Results
We identified 16 patients with post-transplant TB; 13 SOT, and 3 HSCT recipients. The majority of SOT recipients were women (53.8%); median age was 43 years, 9 were kidney and 4 liver transplant recipients. At TB diagnosis, 84.6% of patients were on 3 immunosuppressors. Latent TB was assessed before transplant in 5 patients (38.4%), of these 3 (60%) were tuberculin skin test+, and 2 received isoniazid. Extrapulmonary disease was most common (7, 53.8%). Predominant symptoms were fever (53.8%), chills (30.8%), and diaphoresis (38.5%); six were diagnosed during the 1st year (46.2%) post-transplant; the median of time to diagnosis was 24 months after transplant. The diagnosis was made by histopathology in most cases. Twelve patients received first-line anti-TB treatment. Overall mortality was 30.8%, directly attributable to TB in 2. In the HSCT group, 2 were women; median age was 22 years, 2 allogeneic and 1 autologous transplant. One patient had been treated for latent TB before transplantation. Two developed disseminated disease. Two patients presented within 6 months after the transplant, and the other within a year. Mortality was 100%, attributable to the infection in two patients.

Conclusion
In regions with intermediate to a high prevalence of TB; post-transplant TB could result from reactivation or post-transplant exposure. Most cases occur within the first year post-transplant; clinical symptoms are nonspecific, which lead to a delay in diagnosis. Morbidity and mortality remains high.

Disclosures
All authors: No reported disclosures.
1395. Comparison of Four Recommendations Guiding the Use of Neuroimaging in the Management of Bacterial Meningitis
Authors: Park Nicola , Hasbun Rodrigo 
Published: October 2019

Abstract

Background
Currently multiple sets of recommendations exist to guide the use of cranial imaging before lumbar puncture in adults with suspected meningitis. We aimed to compare the utility of the four main guidelines [Infectious Diseases Society of America (IDSA), European Society for Clinical Microbiology and Infectious Diseases (ESCMID), UK, and Swedish guidelines] in detecting major head CT scan findings that eventually impacted clinical management in adults with community-acquired bacterial meningitis.

Methods
A retrospective observational study of 111 adults (age > 17 years) with community-acquired bacterial meningitis admitted to 10 tertiary care hospitals in Houston TX, between December 2004 and March 2016. Major and minor CT findings were stratified based on their inclusion status within the four separate guidelines.

Results
A total of 38 (34%) patients had minor head CT scans (small ischemic white matter changes, lacunar strokes) and 17 (15%) patients had major CT findings (hydrocephalus, subarachnoid hemorrhage or interventricular hemorrhage, cerebral edema, pneumocephalus, ventriculomegaly, septic embolus, hindbrain herniation, and temporal lobe encephalitis). Of those 17 with major CT findings, 6 patients had a change in clinical management [External Ventricular Drainage (EVD) placement] as a direct result of their CT findings. The IDSA set of guidelines was the only one that included all of the major CT scan findings and all the cases in which the findings of a brain CT resulted in a change in management (EVD placement).

Conclusion
The IDSA was the most inclusive guideline in regards to (1) indications for cranial imaging that would have detected all major abnormal brain CT findings and 2) including cranial imaging that resulted in significant changes in clinical management in adults with community-acquired bacterial meningitis.

Disclosures
All authors: No reported disclosures.
1425. Treatment Outcomes in Patients with Pyogenic Vertebral Osteomyelitis Who Have Cirrhosis
Authors: Kim Tae-Hwan , Kim Jihye 
Published: October 2019

Abstract

Background
The mortality in liver cirrhosis was reported to be greater than that in the five major cancers. Infection further increases the mortality of patients with cirrhosis by four fold. Considering the greatly increased mortality from infection in patients with cirrhosis, early diagnosis and prompt treatments should be compulsory to save patients’ lives. However, adherence to such basic principle for patients with cirrhosis is not easy for clinicians engaged in the treatment of pyogenic vertebral osteomyelitis (PVO). Therefore, the mortality rate is expected to be high. However, no reports have described the mortality rate in this patient group.

Methods
A retrospective study was conducted to investigate the treatment outcome in PVO patients with cirrhosis, and to identify the predictors of their mortality. Mortality was divided into two categories, 30-day and 90-day mortality. A stepwise multivariate logistic regression model was used to identify predictors of mortality. Due to high mortality rate, the clinical outcome was investigated in patients with at least 90-day survival.

Results
Eighty-five patients were identified after initial exclusion. The patients’ mean age was 60.5 years, and 50 patients were male. The early mortality rates within 30 and 90 days were 17.6% and 36.5%, respectively (Table 1). Multivariate analysis revealed that increased age, CTP class C, and bacteremia at the time of PVO diagnosis were predictors of 30-day mortality while higher MELD score, presence of combined infection, and multiple spinal lesions were predictors of 90-day mortality (Figure 1, Table 2). The duration of antibiotic treatment and the length of hospital stay (from the PVO diagnosis) were longer in CTP C patients; however, they were statistically insignificant (Table 3). Recurrence of PVO was more common in CTP C patients (P = 0.028) (Table 3).

Conclusion
Attention should be paid to the high mortality between 30 and 90 days after PVO diagnosis (18.8%), which was higher than the 30-day mortality. Liver function was consistently strong predictor of mortality in PVO patients with cirrhosis. The high-risk patients should be targeted for an aggressive diagnostic approach using spinal MRI and intensive medicosurgical treatment.

Disclosures
All authors: No reported disclosures.
1430. The Hidden Costs of Vancomycin Use During the Treatment of Staphylococcus aureus Bacteremia Concurrent with Acute Hematogenous Osteomyelitis
Authors: Ashley. Copley Lawson , Sanchez Maria J , Sue Paul K , Lindsay Eduardo A , Patel Karisma , Tareen Naureen G 
Published: October 2019

Abstract

Background
Current guidelines recommend the use of parenteral vancomycin for children with acute hematogenous osteomyelitis and concurrent Staphylococcus aureus bacteremia (SAB) due to Methicillin-Resistant Staphylococcus aureus (MRSA), despite vancomycin’s slow bactericidal activity. This study explores the hidden costs of this approach.

Methods
Children with AHO and concurrent SAB, treated from 2009 to 2018, who had received vancomycin at some point during their treatment course were studied. Data collected included antibiotic susceptibilities; duration of bacteremia, blood culture results, duration of vancomycin; number of dose/interval changes; vancomycin trough and creatinine levels; rate of achieving target trough; use of other nephrotoxic agents; occurrence of acute kidney injury (AKI); and length of stay.

Results
130 children diagnosed with AHO and concurrent SAB received vancomycin. Isolates were CR MSSA (3 or 2.3%), CR MRSA (5 or 3.8%), CS MSSA (35 or 26.9%), and CS MRSA (87 or 66.9%). Mean LOS was 14.6 days. 1,312 blood cultures were obtained (503 positive cultures and 809 negative cultures). Bacteremia persisted an average of 3.6 days. Target trough level (15–20 µg/mL) was achieved in 65 children (50%) within an average of 3.4 days of initial dosing. Attempts to reach therapeutic levels were abandoned in 32 children (24.6%) as MSSA was isolated before the trough. There were 319 vancomycin dose and/or interval changes, 1,192 serum creatinine levels, and 689 vancomycin trough levels obtained. Fourteen children (10.8%) experienced AKI. Additional nephrotoxicity exposure included: NSAIDs (127), IV contrast (100), loop diuretics (37), and aminoglycosides (11).

Conclusion
This study exposes and quantifies a substantial amount of resources devoted to dosing adjustments and serum level monitoring for vancomycin use in children with AHO and concurrent SAB. The cost differential in comparison to that of newer antibiotic alternatives is undermined by the effort to attain therapeutic target levels, resolve bacteremia, and address episodic AKI. If vancomycin is utilized, a deliberate approach should be taken to minimize risk of toxicity, including AUC/MIC ratio calculation, as opposed to therapeutic level monitoring, and avoid the concurrent use of other nephrotoxic agents.

Disclosures
All authors: No reported disclosures.
1436. Comparison of Ceftazidime–Avibactam, Ceftolozane–Tazobactam, Piperacillin–Tazobactam, and Meropenem Activities When Tested Against Gram-Negative Organisms Isolated From Complicated Urinary Tract Infections
Authors: Sader Helio S , Flamm Robert K , Castanheira Mariana , Mendes Rodrigo E 
Published: October 2019

Abstract

Background
Complicated urinary tract infections (cUTIs) represent a major cause of healthcare-associated infection and a major source of gram-negative (GN) bacteremia. We evaluated the antimicrobial activities of recently approved β-lactamase inhibitor combinations and comparators against GN bacteria isolated from patients with cUTIs in the US hospitals in 2018.

Methods
Unique patient isolates were consecutively collected from patients with cUTIs in 65 hospitals in 2018, and the GN organisms (n = 4,371) were susceptibility (S) tested by reference broth microdilution methods. Enterobacterales (ENT) with elevated cephalosporin MICs were screened for β-lactamase-encoding genes by whole-genome sequencing.

Results
The most common GN organisms were E. coli (44.5%), K. pneumoniae (19.6%), P. mirabilis (6.7%), and P. aeruginosa (PSA; 5.3%). The most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.7%S), and meropenem (MEM; 99.4%S; table). Extended-spectrum β-lactamase (ESBL) genes were identified in 315 ENT (7.6%; excluding carbapenemase co-producers), including CTX-M-15 (63% of ESBL producers), other CTX-M types (25%), OXA-1/OXA-30 (39%), and SHV type (30%); approximately 50% of ESBL producers had ≥2 ESBL genes, mainly a CTX-M-type and an OXA-type (37% of isolates). The most active agents against ESBL producers were CAZ-AVI (100.0%S), AMK (99.7%S), and MEM (99.4%S); whereas ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) were active against 90.6% and 84.8% of ESBL producers, respectively. Only CAZ-AVI (87.0%S), colistin (COL; 87.0%S), and tigecycline (95.7%S) exhibited good activity against carbapenem-resistant ENT (CRE). Only 3 ENT isolates (0.07%) were CAZ-AVI resistant and all had a metallo-β-lactamase gene (2 VIM-1 and 1 NDM-1). CAZ-AVI (97.0%S) and C-T (99.1%S) were the most active β-lactams tested against PSA; other compounds with > 90%S for PSA were COL (99.6%), AMK (97.8%), tobramycin (93.5%), and CAZ (90.4%).

Conclusion
CAZ-AVI was highly active against a large collection of contemporary GN bacteria isolated from patients with cUTIs in US hospitals and provided greater coverage than the agents currently available in the US to treat cUTIs.

Disclosures
All authors: No reported disclosures.
1447. Ex Vivo Human Bladder Tissue Model to Evaluate Lactobacillus-Containing Formulations as Preventative Treatment Against Common Urogenital Pathogens
Authors: Nicklas Danielle , Finnegan Patrick , Siler Zach , Peterson Marnie , Sarangapani Shantha 
Published: October 2019

Abstract

Background
Urinary tract infections (UTIs) are common bacterial infections in adults, and catheter-associated UTIs are the most common nosocomial infection. The rise of multidrug-resistant organisms and an increased focus on antibiotic stewardship has influenced the development of novel treatments against such infections, and there is growing interest in the use of probiotics for antimicrobial therapy. We used an ex vivo human bladder tissue (HBT) model to evaluate the antimicrobial efficacy and biocompatibility of lactobacillus-based developmental formulations (created and supplied by ICET, Inc.) for preventative treatment against common UTI pathogens.

Methods
To assess antimicrobial efficacy, lactobacillus-based formulations (live and attenuated) were spiked with five prevalent UTI organisms (5 × 103 CFU/mL). Ex vivo HBT explants were treated with 300 μL of spiked formulation for 6 and 24 h at 37°C, then processed and plated on selective agars. Biocompatibility studies assessed ex vivo HBT tissue viability and inflammatory response (IL-8) to lactobacillus-containing formulations with MTT assay and ELISA at 2 h post-treatment.

Results
At 6 h, live lactobacillus-containing formulations (29–124, 29-124C) were bacteriostatic (90.00–99.89% log CFU/mL reduction) against Escherichia coli and Klebsiella pneumoniae and bactericidal (≥99.90% log CFU/mL reduction) against Candida albicans, Enterococcus faecalis, and Proteus mirabilis. By 24 h, live formulations were bactericidal against all five organisms tested. Attenuated formulation 29–125 achieved bacteriostatic efficacy against E. coli, K. pneumoniae, and P. mirabilis and bactericidal efficacy against C. albicans and E. faecalis at 24 h. Biocompatibility assessments following 2 h exposure to lactobacillus-based formulations revealed exposed explants were fully viable, with no significant changes in IL-8 production compared with PBS-treated controls.

Conclusion
This study suggests lactobacillus-based formulations are effective and safe options for UTI prevention. While this static ex vivo human bladder mucosalmodel does not fully replicate the dynamic and diluting conditions that occur in vivo, we anticipate that our findings will be confirmed by future in vivo studies.

Disclosures
All authors: No reported disclosures.
1465. Resistance to Oral Antibiotics Among Urinary Tract Infection Isolates of Escherichia coli from the United States and Europe in 2017
Authors: Critchley Ian A , Cotroneo Nicole , Sulham Kate , Melnick David , Mendes Rodrigo E 
Published: October 2019

Abstract

Background
Clinical guidelines have recommended oral antibiotics such as the cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of urinary tract infections (UTI’s) caused by Escherichia coli (EC). The utility of these agents continues to be eroded by increased prevalence of expanded spectrum β-lactamase (ESBL) genes and concomitant resistance determinants to other antimicrobial classes. This study assessed the prevalence of ESBL phenotypes among EC from UTIs in the United States and 11 countries in Europe (EU) in 2017 and the impact of co-resistance to oral agents used to treat UTIs.

Methods
2422 unique EC from UTIs in the United States and EU in the SENTRY Surveillance program were evaluated for susceptibility to various agents. All isolates were consecutively collected and centrally tested by CLSI methods and interpretive criteria. Isolates that met ESBL MIC screening criteria were characterized for the presence of β-lactamase genes.

Results
Among the 2422 isolates of EC from UTI’s in the United States and EU the resistance (R) rates for cefuroxime (CEF), levofloxacin (LEV) and TMP-SMX were 17.9%, 25.6% and 33.2%, respectively. The overall prevalence of ESBL phenotypes was 18.2% (18.7% in the United States and 21.0% in EU). Among the 411 ESBL phenotypes, R to CEF, LEV and TMP-SMX were: 94.3%, 70.6%, and 61.6%, respectively. In contrast, <0.1% of all EC or 0.2% of ESBL EC were meropenem (MER)-R. Only two carbapenemase-producing organisms were identified, an NDM-5- and a KPC-2-producing EC from Turkey and Greece, respectively. The CTX-M-15 was the most prevalent ESBL and identified among 167 isolates; with co-resistance to CEF, LEV and TMP-SMX noted in 100%, 82.6% and 70.7%, respectively. All CTX-M-15 isolates were susceptible to MER.

Conclusion
Oral agents such as CEF, LEV, and TMP-SMX exhibit R rates ≥17.9%. Co-resistance to CEF, LEV, and TMP-SMX were considerably higher among ESBL phenotypes (>61.1%) and confirmed blaCTX-M-15 genotypes (70.7%). In contrast, the carbapenems remained active against ESBL phenotypes and genotypes, such as blaCTX-M-15. New oral agents with the spectrum and potency of the carbapenems would address an unmet need for new options to treat multi-drug-resistant EC UTIs.

Disclosures
All authors: No reported disclosures.