1325. Recalibrating Estimates of Pneumococcal Disease in Hospitalized Canadian adults from 2010 to 2017 with Use of an Extended Spectrum Serotype-specific Urine Antigen Detection

Background Pneumococcal vaccine recommendations in Canada include both age- and risk-based guidance. This study aimed to describe the burden of vaccine-preventable pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) by age in hospitalized adults. Methods Active surveillance for all-cause CAP and IPD in hospitalized adults was performed from 2010 to 2017, including laboratory results, patient demographics, and outcomes. Streptococcus pneumoniae was detected using blood and sputum culture, or urine antigen detection (UAD). Serotype was assigned using Quellung reaction, PCR, or serotype-specific UADs spanning the 24 serotypes in PCV13 and PPV23 vaccines. Data were categorized by age (16-49, 50-64, 65+, and 50+ years) and over time. Results 11129 ACP cases and 216 cases of IPD (non-CAP) were identified. A laboratory test for S. pneumoniae was performed in 8912 of ACP cases, identifying 1264 (14.2%) as pCAP. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These serious outcomes, as well as mortality, were more prominent in bacteremic pCAP and IPD. Risk factors for death in pCAP included aged 75+ years, immune compromising conditions, and BMI < 18.5. When categorized by age, the proportion of individuals aged 65+ years for pCAP and IPD was 49.8% and 48.6%, and the 50-64 year age cohort represented 31.3% and 29.9%, respectively. The contributions of PCV13 and PPV23 serotypes remained relatively stable over time, and overall represented 57.6% and 90.9% for pCAP, and 35.0% and 72.0% for IPD, respectively. Conclusion Seven years following infant PCV13 immunization programs in Canada, PCV13 and PPV23 serotypes in pCAP and IPD remained predominant causes of pneumococcal disease. Serious outcomes were particularly evident in adults 50+, suggesting pneumococcal vaccines should be encouraged in this age group. Disclosures Jason J. LeBlanc, PhD, FCCM, D[ABMM], GSK (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support) Todd F Hatchette, MD, GSK (Grant/Research Support)Pfizer (Grant/Research Support) Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Allison McGeer, MSc,MD,FRCPC,FSHEA, GlaxoSmithKline (Advisor or Review Panel member)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Louis Valiquette, MD, M.Sc., Cubist (Consultant)GSK (Grant/Research Support)Merck (Consultant)Optimer (Consultant)Pfizer (Grant/Research Support) Shelly McNeil, FRCPC, MD, GSK (Grant/Research Support)Pfizer (Grant/Research Support)Sinofi Pasteur (Grant/Research Support)

711. A Unique Breath Secondary Metabolite Volatile Signature for the Diagnosis of Histoplasmosis

Background Histoplasmosis is a common endemic fungal infection in the Americas, causing significant morbidity and mortality, particularly in immunocompromised patients. Existing diagnostic methods are limited in their sensitivity (especially in pulmonary histoplasmosis) and turnaround time. Methods We examined prospectively collected breath samples from 84 patients with suspected histoplasmosis 3/2019 - 2/2020 at Hospital Roosevelt (HR; Guatemala City, Guatemala, n = 56) and suspected invasive fungal disease 1/2018 - 10/2019 at Brigham and Women’s Hospital (BWH; Boston, MA, USA, n = 28) using thermal desorption gas chromatography-tandem mass spectrometry (TDU-GC-MS/MS). Patients were evaluated for histoplasmosis and other infections according to the local standard of care – of note, 18/56 patients at HR did not have Histoplasma urine antigen testing. Results Median age was 44 years, 60 (71%) were male, 23 (27%) had HIV, 15 (18%) had hematologic malignancy. 7 patients were diagnosed with histoplasmosis over the study period (4 at HR, 5 at BWH), with a clinical syndrome + positive Histoplasma urine or serum antigen test, with some patients also having yeast forms on tissue biopsy. 3 patients had disseminated and 4 pulmonary histoplasmosis. 4 patients with histoplasmosis had co-infections – 2 tuberculosis (TB), 1 influenza, and 1 Pneumocystis jirovecii (PJP) pneumonia. 4 patients were receiving antifungal therapy active against Histoplasma at the time of their first breath sample. We found 3 sesquiterpenes: (A) cyperene, (B) 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene, and (C) viridiflorol in patients with histoplasmosis, that distinguished these patients from those with other pneumonia (TB, coccidioidomycosis, invasive aspergillosis, mucormycosis, PJP, bacterial pneumonia) with 100% sensitivity and 70% (95% CI 59, 80) specificity. Figure 1. TDU GC-MS/MS spectral comparison in histoplasmosis vs. the other invasive mycoses aspergillosis or mucormycosis. A: Cyperene; B: (1R,4aR,8aR)-2,5,5,8a Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene; C: viridiflorol; D: 1H-Indene, 2,3,3a,4-tetrahydro-3,3a,6-trimethyl-1-(1-methylethyl)-; E: β-funebrene; F: trans-α-bergamotene; G: eremophilene; H: spathulenol; I: cedrene; J: cedranoxide, 8,14- Conclusion Conclusion: Patients with histoplasmosis have a unique secondary metabolite breath signature that can be used for the noninvasive diagnosis of pulmonary and disseminated histoplasmosis. Many patients in this cohort did not undergo urine antigen testing or other diagnostic workup for histoplasmosis, which may have affected our specificity estimates. Disclosures Francisco M. Marty, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator)

Evaluation of qPCR on blood and skin microbiopsies, peripheral blood buffy coat smear, and urine antigen ELISA for diagnosis and test of cure for visceral leishmaniasis in HIV-coinfected patients in India: a prospective cohort study

IntroductionHIV coinfection presents a challenge for diagnosis of visceral leishmaniasis (VL). Invasive splenic or bone marrow aspiration with microscopic visualisation of Leishmania parasites remains the gold standard for diagnosis of VL in HIV-coinfected patients. Furthermore, a test of cure by splenic or bone marrow aspiration is required as patients with VL-HIV infection are at a high risk of treatment failure. However, there remain financial, implementation and safety costs to these invasive techniques which severely limit their use under field conditions.Methods and analysisWe aim to evaluate blood and skin qPCR, peripheral blood buffy coat smear microscopy and urine antigen ELISA as non-invasive or minimally invasive alternatives for diagnosis and post-treatment test of cure for VL in HIV-coinfected patients in India, using a sample of 91 patients with parasitologically confirmed symptomatic VL-HIV infection.Ethics and disseminationEthical approval for this study has been granted by The Liverpool School of Tropical Medicine, The Institute of Tropical Medicine in Antwerp, the University of Antwerp and the Rajendra Memorial Research Institute of Medical Science in Patna. Any future publications will be published in open access journals.Trial registration numberCTRI/2019/03/017908.

A Hospital-based Study on the Local Epidemiology of Pneumonia Including the Contribution of Legionella Pneumonia

Background: In real-life practice, only 20% of hospitalised pneumonia cases have an identified etiology. The usage of Legionella urine antigen test (LUAT) in developed nations revolutionised case detection rates. Accordingly, our objectives were to study the microbiological etiology for hospitalised pneumonia patients and the diagnosis of Legionella pneumonia. Methods: A prospective, observational single-centre study was conducted where all 504 cases that were consecutively admitted for pneumonia were enrolled. Blood and sputum samples obtained were used to identify pathogens using standard microbiological culture methods. The urine samples collected were tested using the ImmunocatchTM Legionella immunochromatographic (ICT) urine antigen test. Results: A microbiological diagnosis was only achieved in 104 cases (20.6%) and a Gram-negative infection predominance was observed. Culture-positive cases required longer hospitalisation (8.46 days versus 5.53 days; P < 0.001) and the higher usage of antipseudomonal antibiotics (23.1% versus 8.3%; P < 0.001). Only 3 cases (0.6%) were diagnosed with Legionella pneumonia. Conclusion: The local pathogen distribution is diverse compared to other regions. Culture-negative pneumonia is common and significantly differs from culture-positive pneumonia. Legionella pneumophila serotype 1 is not a common cause of pneumonia and LUAT did not help demystify the cause of culture-negative pneumonia.

753. Performance Characteristics of Diagnostic Assays in Blastomycosis

Background Blastomycosis has historically been a difficult diagnosis to establish, often initially misdiagnosed as bacterial pneumonia. Serologic assays and polymerase chain reaction (PCR) tests are available, but their performance is not well defined. The objective of this study was to characterize their performance. Methods Subjects were identified via chart review of patients diagnosed with blastomycosis from 2005 to 2020. A definitive diagnosis was based on fungal culture, histopathology, or cytology. Performance characteristics of the Blastomyces antibody enzyme linked immunosorbent assay (ELISA), immunodiffusion (ID), complement fixation (CF), urine and serum antigen ELISAs, and PCR were evaluated in patients with confirmed blastomycosis. Data on patient demographics, location of disease, and mortality was also collected. Results We identified 193 patients with blastomycosis. The mean age was 51.8 years (range, 11-84) and 73.6% of patients were male. 42.5% resided in Minnesota, 18.1% in Wisconsin, and 12.9% in Iowa. Diagnosis was based on culture in 142 (73.2%) or histopathology/cytology in 67 (34.7%) patients. Granulomatous inflammation was present in 73.1% (38/52) while 21.2% (41/193) had evidence of extrapulmonary dissemination. The antibody, ID, and CF assays were positive in 43.5% (37/85), 35.1% (33/94) and 20.5% (8/39) of patients, respectively. Sensitivity of Blastomyces PCR was 40% (4/10) in sputum and 75% (21/28) in bronchoalveolar lavage (BAL) fluid. Blastomyces urine and serum antigen tests were positive in 68% (34/50) and 50% (9/18) of cases, respectively, while the urine antigen was positive in 63.6% (7/11) of disseminated cases. Patients had a positive Histoplasma urine antigen test in 54.1% (20/37) and Aspergillus galactomannan in BAL in 34.8% (8/23) of cases. Serum beta-D-glucan test was positive in 16.7% (2/12). 90-day mortality was 21/193 (10.9%) and median time from diagnosis to death was 18 days. Conclusion In this cohort, Blastomyces urine antigen was the most sensitive noninvasive test, with similar performance in pulmonary and disseminated disease. However, its utility is limited by poor specificity due to cross-reactivity. Blastomyces PCR from BAL fluid demonstrated the highest sensitivity. Blastomyces antibody, ID, and CF had poor sensitivity. Disclosures All Authors: No reported disclosures

642. Trends and cost burden of Legionella urine antigen test

Background Legionella urine antigen (LUAg) testing is used to identify the pathogen Legionella pneumophila serotype 1 which accounts for 50 to 70% of Legionella pneumonia and has 80% sensitivity and 95% specificity. The 2019 ATS/IDSA CAP guidelines recommend against routinely testing urine for LUAg except when indicated by epidemiological factors or severe cases of CAP; however, the recommendation is based on a low quality of evidence. In 2014 & 2015 there were 32 and 39 cases, respectively in the state of Mississippi. The purpose of this study was to evaluate the trends of ordering LUAg, positive results and estimate the cost burden at the University of Mississippi Medical Center (UMMC). Methods We performed a retrospective study of all patients who received the LUAg test at UMMC from January 3, 2013 to December 31, 2019. Patient Cohort Explorer was used to obtain de-identified patient data from EPIC. We obtained the number of encounters and patients on whom the LUAg test was performed during their inpatient hospitalization. Coding and billing offices provided the cost per LUAg test. Results LUAg test was ordered 2,642 times on 2350 patients between 2013 and 2019. 22 LUAg test results were positive in 21 patients. 2,627 tests were done on patients admitted in the hospital. Of the 1,181 tests ordered in female patients, 11 were positive and of the 1461 tests done in male patients, 11 were positive. The minimum age for ordered test was under 1 year while the oldest patient is 89 years old with a median age of 57 years. The youngest patient to be positive is 21 and the oldest patient was 72 years. 1,471 tests were done in African American patients and 1084 tests in Caucasian patients. At the end of study period 1901 were alive and 741 deceased. The median length of stay for the patient receiving the test was 7 days with 1726 patients discharged within 10 days. 174, 255, 301, 433, 467, 395, 613 tests were ordered respectively from 2013 to 2019. At self pay cost of $132.82 in 2019 USD, the total cost of 2642 tests was $350,910.44. About $15,950.47 was spent for each positive LUAg test during the study period. Conclusion Incidence of pneumonia from Legionella in Mississippi is low. Based on our study, we recommend to follow the current ATS/IDSA guidelines and order the test in select patients as recommended, in efforts to reduce diagnostic costs. Disclosures All Authors: No reported disclosures

1085. Epidemiology and Outcomes of Histoplasmosis in Transplant Recipients

Background Histoplasmosis in transplant recipients is understudied. We reviewed a large cohort of histoplasmosis in patients with solid organ and stem cell transplants in an endemic area to describe the epidemiology, clinical findings and outcomes. Methods We performed a single-center retrospective cohort study of patients diagnosed with histoplasmosis between 2002 and 2017. Demographic data, clinical findings, diagnostic methods, treatment, and mortality were collected. We compared the characteristics of patients with history of transplant to non-transplant (NT) patients. Results We identified 261 patients with histoplasmosis. Of those, 28(11%) were transplant recipients; 8(29%) liver, 8(29%) lung, 6(21%) kidney, 3(11%) heart, and 3(11%) stem cell. Median time from symptom onset to diagnosis was 6 vs 34 days in transplant vs NT groups (p=0.001). Lung was the most common organ involvement (89% in transplants vs 78% in NT, p=0.168). Spleen involvement was more commonly found in transplant patients (29 vs 14%, p=0.039). In patients with disseminated disease, urine antigen was 100% sensitive in transplant patients compared to 78% in the NT group (p=0.038). Duration of treatment was 13 vs 6 months in transplant vs NT patients (p= 0.003). Mortality was comparable between groups (14 vs 15% in transplant vs NT, p=0.918). Median time from transplant to diagnosis was 4.21 years. However, five patients (18%) developed histoplasmosis within 6 months. For these early diagnosed patients, ICU admission rate was 80 vs 30% (p=0.04) and rate of mechanical ventilator use was 80 vs 22% (p=0.011) compared to patients diagnosed later. Table 1: Patient characteristics Table 2: Organ involvement Table 3: Diagnostic test positivity Conclusion Transplant recipients with histoplasmosis are likely to be diagnosed early and be treated longer. Urine antigen is highly sensitive for diagnosis of disseminated disease. Histoplasmosis that occurs within the first 6 months after transplantation tends to be more severe. Disclosures Andrej Spec, MD, MSCI, Astellas (Grant/Research Support)Mayne (Consultant)Scynexis (Consultant)

111. Impact of Microbiology Laboratory Result Presentation on Antibiotic Stewardship: Process Use Evaluation

Background Advancements in laboratory diagnostics are constantly occurring and accuracy in interpreting results directly affects optimal patient care. The purpose of this process use evaluation was to assess the efficacy of our current presentation of microbiology results in facilitating appropriate clinical decisions and antibiotic stewardship. Methods A six question multiple choice survey was sent to prescribers and pharmacists. Each question used our healthcare system’s current presentation of microbiology results. The recipients were asked to make a clinical decision based on patient history and results presented. The topics surveyed included de-escalation of antibiotics based on polymerase chain reaction (PCR) for positive blood cultures (Image 1), evaluation of C. difficile PCR and enzyme immunoassays (Image 2), impact of recent immunization on results of S. pneumoniae urine antigen (Image 3), susceptibilities of Group C Streptococcus and H. influenzae (Images 4 and 5), and understanding of minimum inhibitory concentrations (MIC, Image 6). The anonymous surveys were collected either electronically or by paper. Image 1 Image 2 Results Several trends were seen in the 64 responses received (n, %). Questions with lab results containing detailed comments with guidance on how to interpret the results had the highest percentage of correct responses. This included our C. difficile (59, 92%) and S. pneumoniae urine antigen (61, 95%) results. Culture results with presumed susceptibilities and/or lack of guidance (H. influenzae (55, 86%); Group C Streptococcus (46, 72%)) had lower rates of correct interpretation and resulted in provider reluctance to de-escalate antibiotics. A similar trend was seen with the word “presumptive” on blood culture results by PCR (37, 58%). MICs were frequently misinterpreted as being able to compare activity between antibiotics (46, 72%). Image 3 Image 4 Image 5 Conclusion This study highlights that stewardship programs should focus on how lab results are reported and interpreted and should work with their microbiology lab to determine the presentation of results. Additions of detailed interpretations to Microbiology results may lead to improved de-escalation and antibiotic selection. Image 6 Disclosures All Authors: No reported disclosures