bluuebunny/crossref_metadata_2025 huggingface dataset:
1269. Cohort Profile: The Translational Platform HIV (TP-HIV), a Multicenter Cohort Project in Germany
Authors: Stecher Melanie , Wasmuth Jan-Christian , Knops Elena , Eis-Hübinger Anna , Bogner Johannes , Spinner Christoph , Eberle Josef , Lehmann Clara , Degen Olaf , Rockstroh Jürgen , Altfeld Markus , Wolf Timo , Mueller Matthias C , Scholten Stefan , Wyen Christoph , Jessen Heiko , Postel Nils , Pauli Ramona , Wolf Eva , Eger Johanna , Schäfer Guido , Stellbrink Hans-Jürgen , Krsnaric Ivanka , Heger Eva , Kastenbauer Ulrich , Behrens Georg , Fätkenheuer Gerd , Vehreschild Jörg
Published: October 2019

Background

While Germany has a long tradition in HIV research with many well-established regional cohorts, there was a lack of collaborative efforts toward harmonized data collection and biobanking, both key strategies for efficient translational research projects. Key challenges are heterogeneity of data systems and privacy concepts, of existing study and data collection protocols, and sample collection, storage, and sharing.

Methods

In 2013, we established the Translational Platform HIV (TP-HIV) with support of the German Centre for Infection Research (DZIF) as a collaboration between university hospitals and specialized HIV care centers throughout Germany. After assessing the individual needs of all partner sites, we have taken comprehensive action to create a common platform for collaboration in all research stages. We developed protocols, rules of operation, biobanking strategies, and privacy concepts for all collaborating partner sites. Patients infected with HIV (PLWH) who sign the informed consent for the TP-HIV are pro- and retrospectively included in the cohort.

Results

To date, the TP-HIV infrastructure is implemented at 27 member sites from 11 cities, potentially extending to more than 20,000 patients currently treated for HIV across Germany. Facing the special needs in the German research environment, the TP-HIV established a unique data- and biomaterial collection allowing expedited translational research and reduce project overheads, regulatory burden, and data security regulations for investigators. By active surveillance, rapid access to individual patient groups such as patients with acute HIV infection, TP-HIV is an ideal platform for early phase clinical trials with new drug candidates. Researchers with clinical, biological, epidemiological, and statistical expertise have been brought together within the TP-HIV, which enables an effective translational chain from bench to bedside and back. New collaborations have been established with currently 23 active study protocols.

Conclusion

The TP-HIV has demonstrated to be a powerful tool for generating and testing research hypotheses in PLWH. In the future, we will work to further expand our network and address the pressing needs in the German research environment.

Disclosures

All authors: No reported disclosures.
1284. Pre-exposure Prophylaxis (PrEP) for HIV in Vermont: an Assessment of Prescribing in a Uniquely Rural State
Authors: DiMarco Daniela E , Kennedy Amanda , Tompkins Bradley , Read Jennifer , Pierce Kristen
Published: October 2019

Background

In the United States and Vermont, men who have sex with men (MSM) make up the majority of new human immunodeficiency virus (HIV) infections every year. Despite HIV prevention campaigns and approval of antiviral therapy for pharmacologic HIV pre-exposure prophylaxis (PrEP), HIV cases in Vermont—a predominantly rural state—are on the rise. The primary objective of this study was to assess prescribing practices and barriers surrounding PrEP for adult MSM in Vermont.

Methods

A web-based healthcare provider survey was deployed electronically over a 10 week period in 2019 to a convenience sample of licensed primary care, sexual health, and infectious disease providers in Vermont. Questions were designed to target factors thought to influence PrEP prescribing, with a focus on prescribing behaviors and perceived barriers.

Results

An estimated 500 providers received the survey. There were 137 survey respondents, 106 (77%) were physicians, primarily in internal medicine. Though only 47 (34%) providers had experience prescribing PrEP to MSM patients, over 89% identified as willing to prescribe PrEP to high-risk groups. Among PrEP prescribers, screening frequency for HIV and bacterial sexually transmitted infections (STIs) while on PrEP fell below the current guideline recommendations at 72% and 53%, respectively. Less than 70% of providers routinely obtain sexual history for male patients. Among providers willing to prescribe PrEP, concern regarding medication toxicity was the only statistically significant barrier (χ 2 = 5.5, P = 0.02). Concerns regarding risk compensation behavior and lack of knowledge or experience regarding prescribing PrEP also demonstrated an association with provider willingness to prescribe PrEP, however did not reach statistical significance.

Conclusion

The majority of Vermont providers sampled are willing to prescribe PrEP, suggesting there is great opportunity to increase prescribing and use, potentially having an impact on reducing HIV transmission among MSM in the state. Provider education targeted toward guidelines for STI and HIV screening on therapy, obtaining sexual histories, and minimal toxicity risk may serve to increase prescribing of PrEP among Vermont providers.

Disclosures

All authors: No reported disclosures.
1305. Use of a Clinical Pharmacist to Reduce Inpatient ART (Antiretroviral Therapy) Errors
Authors: Mitchner DeMaurian , Richey Lauren E
Published: October 2019

Background

Continuous antiretroviral therapy (ART) that results in viral suppression is the goal of therapy for people living with HIV (PLWH). This results in improved clinical outcomes and prevents transmission to partners. University Medical Center is an urban charity hospital that provides the majority of inpatient care to PLWH in the city of New Orleans. HIV care providers noticed many ART errors during transitions of care, particularly during inpatient admissions. Impartial regimens and interactions can occur when non-HIV providers manage patients in the hospital leading to resistance and viral failure.

Methods

A clinical pharmacist was hired to improve the quality of HIV care, both in the inpatient and outpatient setting. An electronic medical records alert was created for any patient with HIV who was admitted to the hospital. The clinical pharmacist then reviewed the ART orders Monday through Friday and provided recommendations to the inpatient teams. Data on the frequency and types of errors on the medication administration record (MAR) were recorded. Data were collected for 6 months, from October 2018 to March 2019. Three-month data from October 2018 to December 2018 was compared with three-month data from January 2019 to March 2019 for quality improvement purposes.

Results

One hundred forty-eight people living with HIV were admitted to the hospital during the specified time period. A minority of the patients (25%) had a consult to an HIV Specialist. Eight (5%) were omission of ART (no regimen or partial regimen), 19 (13%) had food or drug interactions, and 14 (10%) had the incorrect ART regimen ordered. The clinical pharmacist was able to contact the inpatient team and have these errors corrected. There was a 20% decrease in the patients with errors in their inpatient ART order on the MAR during the review period, due to physicians and pharmacists proactively contacting the pharmacist prior to orders being placed and processed.

Conclusion

Errors in ART in the inpatient setting are common. A clinical pharmacist intervention can successfully decrease ART errors as patients’ transition between inpatient and outpatient care.

Disclosures

All authors: No reported disclosures.
1308. The Association Between Refill History and Viral Load Suppression in HIV-infected Patients at a University-Based HIV Clinic in the Midwest
Authors: Havens Josh , New-Aaron Moses , Gao Yangyang , He Qingfeng , Bares Sara H , Nada Fadul
Published: October 2019

Background

Patients with HIV (PWH) with sustained virologic suppression (VS) on antiretroviral therapy (ART) achieve better health outcomes and pose effectively no risk of transmitting HIV to their sexual contacts. Adherence to ART is the main predictor of VS in PWH, yet no adherence benchmark has been identified. The clinical utility of ART pharmacy refill history collection is unknown. We hypothesize that pharmacy refill histories of ART represented as a percentage of days covered (PDC) will correlate with VS in PWH.

Methods

We conducted a single-center, retrospective cohort study of PWH ( ≥19 years) receiving care at a Midwestern HIV clinic between January 1, 2018 and December 31, 2018, with at least 1 HIV RNA reading during the study period. Refill histories were collected for each eligible study patient and a PDC was calculated as the “number of tablets dispensed / number of days within study period” to provide an ART coverage measure. ART regimen, sociodemographic, and clinical characteristics were abstracted from the HIV registry. An HIV RNA ≤ 50 copies/mL and a PDC of ≥80% were used as measures of VS and sufficient adherence, respectively. Pearson’s chi-square tests and binary logistic regression were used to determine the effect of PDC on VS.

Results

A total of 1019 patients were included in the study. 705 (69%) patients had a PDC ≥80% and 314 (31%) had a PDC <80%. VS between groups was 96% (PDC ≥80%) vs. 74% (PDC < 80%). A significant association was observed between VS and PDC (P < 0.0001) [HJP1]. Patients with a PDC ≥80% were 9.5 times more likely to attain VS as compared with patients with PDC < 80% (95% CI, 5.89–15.17). After adjusting for ART regimen, sociodemographic, and other clinical characteristics, the likelihood of VS remained higher for patients with a PDC ≥ 80% (aOR: 6.3; 95% CI, 3.7–11.0). Factors found to be negatively associated with VS were single marital status (aOR: 0.49; 95% CI, 0.24–0.95), current or historical opportunistic infection (aOR: 0.51; 95% CI, 0.26–0.99), and usage of a multiclass or dual ART regimen (aOR: 0.40; 95% CI, 0.16–0.98).

Conclusion

The utilization of PDC as an ART adherence benchmark was significantly associated with VS. PDC is an easy measure to calculate and could be useful in the clinical care of PWH. Future prospective studies are needed to confirm these findings.

Disclosures

All authors: No reported disclosures.
1346. Ruling out TB in New York City: Are Two NAATs (Nucleic Acid Amplification Testing) Enough?
Authors: Greendyke William G , Pike Janett , Andrada Lilibeth V , Balzer Krystal , Gray Thelesha , Russell Patrice M , Sharma Manu , Steinberg Ari , Whittier Susan , Furuya E Yoko
Published: October 2019

Background

Prompt diagnosis of pulmonary Mycobacterium tuberculosis (TB) infection can prevent nosocomial exposure. However, sputum smears are insensitive, and turnaround time for cultures can take weeks. Rapid diagnostics, such as nucleic acid amplification testing (NAAT), on respiratory specimens of patients suspected to have TB can improve diagnostic accuracy. Current practice at our institution is to obtain ≥ 3 NAATs in high-risk patients prior to discontinuing airborne isolation, but some studies have suggested that 2 negative NAATs may be sufficient. We conducted a retrospective study of patients at our institution diagnosed with TB.

Methods

The study was conducted at an academic adult hospital, an academic pediatric hospital, and a community hospital in New York City. Line lists of positive cultures for TB and positive NAATs from 2014 to mid-2018 were obtained from microbiology. Chart review was performed. Patient demographics, comorbidities, and radiographic findings were collected. Concordance between culture results and NAATs was evaluated. Incidence of inpatient TB exposure was noted.

Results

82 cases of TB were found in the study period (see Figure 1). 45 cases were new inpatient diagnoses of pulmonary TB. The most common presenting symptoms were cough (69%), weight loss (49%), and fever (42%, see Table 1). 38/45 (84%) of patients were originally from a country other than the United States. 43/45 (96%) of patients had abnormal lung imaging. Cavitary disease was seen in 29%; other upper lobe disease was seen in 42%. Among smear-negative pulmonary TB cases, NAAT was positive in 11/16 (69%) of patients. Within this subgroup, the sensitivity of one NAAT was 41% when compared with culture. In smear-negative, NAAT-positive patients, NAATs were fully concordant with cultures in 4/11 patients (36%, see Table 2). The median number of positive NAATs was 1; the median number of positive cultures was 2. Five patients with pulmonary TB had negative NAATs altogether (median = 3); 2/5 resulted in TB exposure investigations after airborne precautions were discontinued following NAAT results. Overall, 13/45 (28%) of new diagnoses resulted in an exposure investigation.

Conclusion

Obtaining ≥ 3 NAATs in patients suspected of pulmonary TB improved diagnostic accuracy compared with obtaining 2 or fewer.

Disclosures

All authors: No reported disclosures.
1354. Nocardia bejingensis: A Novel Isolate Affecting Immunocompromised Patients in the United States
Authors: Moore-Pardo Shylah M , Asquith Johonna , Aslam Sadaf , Mayer Cynthia , Greene John , Alrabaa Sally
Published: October 2019

Background

Nocardia species can cause localized or disseminated disease in humans. Infection results from direct inoculation or inhalation. In recent years, several new species have been identified via molecular methods. Further speciation is crucial as each organism has its own spectrum of disease and unique antibiotic susceptibility patterns. Immunosuppression, alcoholism, and certain lung diseases are well-established risk factors for nocardiosis. In fact, cases have incremented in association with increasing population of immunocompromised hosts as well as improved methods for detection and identification. Thus, Nocardia species may be considered opportunistic pathogens.

Nocardia bejingensis was first isolated in 2001 by Wang et al from sewage soil in China. The first human infections were reported in Asia. Subsequently, cases were reported in Europe and a few cases have been described in the United States but it has been infrequently cited in the literature. Thus, not much is known about its spectrum of disease.

Methods

The primary objective of this study was to determine the risk factors and clinical manifestations of Nocardia bejingensis infection via retrospective chart review of 6 cases identified in Tampa General Hospital and Moffitt Cancer Center within a 5-year period. We aimed to evaluate the treatment used and the antibiotic susceptibility patterns of the isolates.

Results

All patients were immunocompromised (1/3 HIV/AIDS, 1/3 hematologic malignancy, 1/3 solid-organ transplant). Most were male (67%) and mean age of 48. The majority had lung involvement (67%). Thecal sac infection and femur osteomyelitis (OM) were atypical manifestations. Localized disease predominated. Combination therapy was preferred. Trimethoprim-sulfamethoxazole (TMP-SMX), Ceftriaxone, and carbapenems were mostly used. All isolates were susceptible to TMP-SMX. See Table 1.

Conclusion

This case series depicts clinical features, risk factors, and epidemiology of Nocardia bejingensis infections. Our observations suggest that it is a novel pathogen in the United States, affecting mainly immunocompromised hosts. Early detection, appropriate antibiotics, and surgery were keys in successful management. However, further studies are needed to further elucidate its pathogenesis.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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

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

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.
1467. Antimicrobial Susceptibility and Molecular Characterization of Extended-Spectrum β-Lactamase of Escherichia coli and Klebsiella pneumoniae of Urine Samples Isolated from Community Patients in South Brazil
Authors: Naomi Tano Zuleica , Vespero Eliana Carolina , Dias Juliana , Mestre Tejo Alexandre , Candido Evelyn P , Andrekowicz Andreia , Ramos Ana , Kobayashi Renata , Pavanelli Wander
Published: October 2019

Background

Enterobacteriaceae is the main pathogens of UTI. It is important to be aware the local epidemiological data for an appropriate initial treatment. Resistance to antimicrobial agents has increased, especially to first-choice antibiotics in the treatment of cystitis. Our objective is to asses the antimicrobial susceptibility profile from uropathogens isolated in community and evaluated the dissemination of extended-spectrum ß lactamase (ESBL), in E. coli and K. pneumoniae in south of Brazil.

Methods

From June 2016 to June 2017, all urine samples collected in the Basic Health Units and Emergency Departments were sent to a Central Laboratory. Identification and susceptibility tests were performed on the VITEK® 2 (bioMérieux, France) system. Clinical Laboratory Standards Institute (CLSI) breakpoints were used for the interpretation of susceptibility. Positive cultures were defined as those demonstrating ≥105 CFU / mL (colony-forming units). The presence of ESBL was also subjected to the Chrom ID BLEE® agar plate test (bioMérieux- Marcyl’Etoile, France). PCR technique uses specific primers for genes blaTEM and blaSHV. Detection of the blaCTX-M genes was performed by multiplex PCR.

Results

A total of 56,555 microbiologic tests were performed, 8189 were positive. Women were responsible for 89.4%, and 10% were pregnant. Table 1 shows uropathogens isolated. Graphic 1 shows antimicrobial susceptibility. Extended-spectrum ß lactamase production was present in 6.7% (n = 489). People older than 60 years had ESBL more frequent (P <0.05) as well as being pregnant is not related to ESBL (P <0.05). Table 2 shows the distribution of the bla genotypes.

Table 3: Distribution of blaCTX-M. Among blaCTX-M1 genotype, blaCTX-M15 was the most frequent.

Conclusion

In this study, the most frequent uropathogen isolated was E. coli followed by K. pneumoniae. Cotrimoxazol had high rates of resistance and nitrofurantoin the lowest. Quinolone resistance is more than 10%. Sensitivity to aminoglycosides and carbapenems remains high.We found relevant frequency of ESBL, CTX-M-1-group most commonly found. Among CTX-M-1, blaCTX-M15 was the most isolated.

Disclosures

All authors: No reported disclosures.
1474. Epidemiology and Outcomes of Hospitalized Patients with Urinary Tract Infections (UTI) Due to Multidrug-Resistant Organisms (MDRO)
Authors: Lahrman Frances J , Olsen Margaret A , Stwalley Dustin , Burnham Jason P , Kwon Jennie H
Published: October 2019

Background

MDROs are a threat to public health, and UTIs are the most common type of MDRO infection. The objective of this study was to describe risk factors and outcomes associated with MDRO UTIs.

Methods

A retrospective cohort study with IRB approval from Barnes-Jewish Hospital, January 1, 2006–November 8, 2017. Demographics, comorbidities, procedures, outcomes, and culture data were collected from the BJC Healthcare Informatics database for hospitalized patients with MDRO UTIs. MDROs were defined according to European and US CDC standards.

Results

A total of 7,945 hospitalized patients with MDRO UTI were identified. Demographics and comorbidities are described in Table 1. Notably, 69% of patients were female, 23% had underlying urinary system disease, and at least 20% had a foley catheter in place. Of these patients, 18% required an intensive care unit (ICU) stay within 48 hours before/after the positive urine culture, and 7% died during their hospitalization (Table 2). The most frequent cause of UTIs was MDR Enterobacteriaceae (Table 3).

Conclusion

Patients who are hospitalized with MDRO UTIs frequently have underlying urinary system disease and/or foley catheter. MDRO UTIs are a significant cause of morbidity and mortality in hospitalized patients, with 18% requiring an ICU stay, and death in 7% during the hospitalization. Further research is needed regarding risk factors and interventions to prevent, detect, and treat MDRO UTIs.

Disclosures

All authors: No reported disclosures.
1476. The Role of Empirical Antibiotics Determined by Pre-procedural Urinalysis and Urine Cultures in Elective Urological Interventions
Authors: Smith Georgia , Chung Kay Patrick , Catterwell Rick , Nelson Renjy , Warner Morgyn
Published: October 2019

Background

At a urology center in Australia, patients undergoing elective nonurgent urological surgery routinely receive empirical antibiotic treatment based on urinalysis (UA) prior to intervention to treat presumptive bacteriuria. Sterilization of urine with empirical antibiotics in procedures involving stone manipulation and mucosal disruption in the genitourinary system has been shown to reduce infection risks but whether this translates to low-risk urological interventions is not clear.

Methods

Patients undergoing outpatient elective urological procedures during a 3-month period between September and November 2017 were retrospectively reviewed. Patient demographics, results of urinalyses, empirical antibiotic use, and data surrounding post-intervention complications were collected and reviewed. Results were analyzed using SPSS v 25.

Results

Of 119 patients, 111 underwent a pre-procedure urinalysis. Fifty-eight percent (n = 64) of patients were treated with empiric antibiotics pre-operatively based on a positive UA (defined as the presence of urinary leukocytes or nitrites). Fifty-five percent (n = 41) of patients who received empirical antibiotics returned a positive urine culture, and only 49 percent (n = 20) of those receiving antibiotics cultured organisms susceptible to initial antibiotics prescribed. 1 Death, 3 incidences of bacteremia, and 10 incidences of bacteriuria up to 2 weeks occurred post-intervention in this cohort. There was no discernible risk of adverse events based on a composite of post-intervention death, bacteremia and bacteriuria in patients with a positive pre-procedural UA (n = 67/111, RR0.67 CI 0.49–0.91, P = 0.10). Pre-procedural sterilized urine similarly did not demonstrated any reduced risk of post-intervention adverse outcomes (n = 77/119, RR1.02 CI 0.64–1.63, P = 0.94).

Conclusion

This study demonstrated no increased risk of post-operative infection in patients with a positive urinalysis or urine culture with bacteriuria prior to intervention. There was a high use of broad-spectrum antibiotic as a reflex to positive urinalyses alone highlighting an avenue for improved anti-microbial stewardship. More research is needed to guide clinicians on the role of urine cultures and antibiotics prior to non-urgent urological procedures.

Disclosures

All authors: No reported disclosures.