Urinary Antigen Research Articles

A Community Outbreak of Legionnaires' Disease with Two Strains of L. pneumophila Serogroup 1 Linked to an Aquatic Therapy Centre.

An outbreak of Legionnaires’ disease affected 18 people in Montpellier, a town of the south of France, between December 2016 and July 2017. All cases were diagnosed by a positive urinary antigen test. No deaths were reported. Epidemiological, environmental and genomic investigations (nested Sequence-Based Typing (nSBT) and whole genome sequencing) were undertaken. For the cases for which we had information, four had a new isolate (ST2471), one had a different new isolate (ST2470), one had a genomic pattern compatible with the ST2471 identified by nSBT (flaA = 3), and one had a genomic pattern not compatible with two previous identified STs (pilE = 6). The analysis conducted on the pool of an aquatic therapy center revealed seven isolates of Legionella pneumophila. Whole genome analysis confirmed the link between the environmental and clinical isolates for both ST2470 and ST2471. As the outbreak occurred slowly, with several weeks between new cases, it was not possible to immediately identify a common source. The sixth case was the first to report having aquatic therapy care. Of the 18 cases, eight had attended the aquatic therapy center and the other 10 were inhabitants who lived, worked or walked close to the center. The main cause for this outbreak was the lack of facility maintenance. This investigation highlights the risk to public health of aquatic therapy centers for users and nearby populations, and emphasizes the need for risk reduction measures with specific guidelines to improve health and safety in aquatic facilities.

Co-Infection in COVID-19 Pneumonia: Discussion Continues.

Sixty-six patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and pneumonia on chest computer tomography were prospectively recruited. A combined respiratory swab for polymerase chain reaction (PCR), urine sample for pneumococcal and Legionella antigen, and sputum or endotracheal aspirate were collected. Urinary antigen and blood culture tests were negative in all cases as well as the PCR tests for other respiratory viruses and atypical bacterial pathogens. In total, 5 patients (7.5%) had co-infection. By PCR a high prevalence of colonization with bacterial pathogens was found. In conclusion, co-infection is rare in coronavirus disease 2019 patients, and additional examination to identify other pathogens should be performed only in selected cases.

Reliability of point-of-care circulating cathodic antigen assay for diagnosing schistosomiasis mansoni in urine samples from an endemic area of Brazil after one year of storage at -20 degrees Celsius.

ABSTRACTBackground The World Health Organization recommends reliable point-of-care (POC) diagnostic testing to eliminate schistosomiasis. Lateral flow immunoassay that detects schistosome circulating cathodic antigen (CCA) in urine to establish prevalence thresholds for intervention in endemic areas is recommended. Stored urine may be useful if surveying at-risk populations is delayed or interrupted by unforeseen circumstances, such as the current COVID-19 pandemic. This study evaluated the manufacturer’s claim that Schistosoma mansoni infection can be reliably diagnosed in urine samples stored at -20°C for one year. Methods Two-hundred-forty-two subjects from an endemic site in Brazil provided one urine sample each for testing with URINE CCA (SCHISTO) ECO TESTE® (POC-ECO) and one stool sample each for testing with Kato-Katz (KK) and Helmintex® (HTX) as a robust reference standard for infection status. At least 2 ml of urine from each participant was stored at -20°C; after one year, 76 samples were randomly selected for POC-ECO retesting. Results: The POC-ECO agreement between freshly collected and stored urine was inadequate considering trace results as positive (Cohen’s kappa coefficient κ = 0.08) and negative (κ = 0.36). POC-ECO accuracy was not significantly greater than that of routine KK (54%; 95% confidence interval: 42.1%-65.5%). Conclusions The precision and accuracy of POC-ECO have to be optimized in both freshly collected and stored urine before it can be recommended for use in control programs in Brazil.

Urinary antigen testing for respiratory infection during COVID-19: The microbiologist as a diagnostic steward

The use of antimicrobials in the management of community-acquired COVID-19 is commonplace but evidence for coinfection with common bacterial pathogens to justify their use is lacking. We undertook a retrospective review of all respiratory cultures, blood cultures and urinary antigen tests in COVID-19 patients looking for co-infection with Streptococcus pneumoniae and Legionella pneumophila, and specifically to judge the utility of urinary antigen testing. 2674 GSTT patients were included who had a positive RT-PCR test for SARS-CoV-2 performed at GSTT between 03-March-2020 and 31-Jan-2021 and who had at least one other microbiology sample for review.

Clinical features of patients with Legionnaires disease showing initial clinical improvement but radiological deterioration: A retrospective single-center analysis.

Patients with Legionnaires disease occasionally experience initial clinical improvement but radiological progression. However, data on this issue are so far limited. The aim of this study was to investigate changes in chest radiograph findings in patients with Legionnaires disease who showed initial clinical improvement and to identify risk factors and outcomes in these patients.All patients diagnosed with Legionnaires disease at a tertiary hospital in South Korea between March 2011 and May 2020 were retrospectively enrolled. Legionnaires disease was defined as abnormal chest radiographs accompanied by a positive finding on at least one of the following tests: urinary antigen test, sputum Legionella polymerase chain reaction, and sputum Legionella culture. Clinical improvement was defined as defervescence and decreased C-reactive protein level. Clinical and radiological records were reviewed on treatment days 7 and 14 and at discharge. We describe the characteristics of patients with clinical improvement but radiological deterioration on treatment for Legionnaires disease and compared them with patients with initial clinical improvement and stable or resolving chest radiograph findings.Of 140 patients with Legionnaires disease, 33 (24%) showed initial clinical deterioration, while the remaining 107 (76%) showed initial clinical improvement on day 7. The latter 107 patients were analyzed in this study; 22 (21%) showed radiological progression despite the clinical improvement. Risk factors for these patients were a high pneumonia severity index score and the use of mechanical ventilation. Mortality did not significantly differ between those with initial clinical improvement but radiological deterioration and those with both initial clinical and radiological improvement (28% vs 12%, P = .49).About one-fifth of patients with Legionnaires disease, especially those who had a high pneumonia severity index score and underwent mechanical ventilation, showed radiological deterioration despite of clinical improvement 1 week after appropriate treatment, while outcomes were not significantly worse in these patients. Therefore, our findings support that close monitoring without modification of antibiotics use is warranted in those who have clinical improvement regardless of radiologic findings.

National survey of physicians in Japan regarding their use of diagnostic tests for legionellosis

IntroductionBacterial culture remains the gold standard for the diagnosis of legionellosis. However, past reports indicate that most physicians use the urinary antigen test (UAT) alone. Combining it with other tests is important, especially in patients with negative UAT results. The aim of this study was to investigate the current situation of legionellosis diagnostics and clarify the issues that need to be addressed. MethodsBetween March 1, 2021 and April 30, 2021, a questionnaire survey was conducted in an anonymous manner among physicians working in Japan. Questionnaires were generated on a website and asked questions in a multiple-choice format. ResultsValid responses were received from 309 physicians during the study period. Most (92.9%) physicians reported using UAT as the initial test for patients suspected of having legionellosis, and <10% reported using other tests (e.g., culture, nucleic acid amplification test [NAAT], Gimenez staining, and serum antibody titer measurement [ATM]). When the initial test result was negative, 63% of physicians reported not conducting additional tests. Even when they chose to run additional tests, at most 27.8%, 23.6%, 12.3%, and 10.4% of all physicians used NAAT, culture, Gimenez staining, and serum ATM, respectively. The major reasons for not using tests other than UAT were “unavailability in the medical facility,” “long turn-around time,” and “difficult to collect sputum.” ConclusionsThe present survey revealed that most physicians in Japan used UAT alone for diagnosing legionellosis. Eliminating barriers to creating a reasonable environment and edification of physicians are needed to improve the current situation.

Pulmonary bacterial infections in adult patients hospitalized for COVID-19 in standard wards

ObjectivesDuring the COVID-19 pandemic, antibiotic use was very common. However, bacterial co-/secondary infections with coronaviruses remain largely unknown in standard wards. We aimed to investigate the characteristics of pulmonary bacterial infections associated with COVID-19 in hospitalized patients. MethodsA retrospective monocentric observational study was conducted in Bichat hospital, France, between February 26 and April 22, 2020. All patients hospitalized in standard wards with COVID-19 (positive nasopharyngeal PCR and/or typical aspect on CT-scan) and diagnosed with pulmonary bacterial infection (positive bacteriological samples) were included. Bacteriological and clinical data were collected from the microbiology laboratories and patient's medical records. ResultsTwenty-three bacteriological samples from 22 patients were positive out of 2075 screened samples (1.1%) from 784 patients (2.8%). Bacterial infection occurred within a median of 10 days after COVID-19 onset. Diagnosis of pulmonary bacterial infection was suspected on increase of oxygen requirements (20/22), productive cough or modification of sputum aspect (17/22), or fever (10/22). Positive samples included 13 sputum cultures, one FilmArray® assay on sputum samples, one bronchoalveolar lavage, six blood cultures, and two pneumococcal urinary antigen tests. The most frequent bacteria were Pseudomonas aeruginosa (6/23), Staphylococcus aureus (5/23), Streptococcus pneumoniae (4/23), Enterococcus faecalis (3/23), and Klebsiella aerogenes (3/23). No Legionella urinary antigen test was positive. Four out of 496 nasopharyngeal PCR tests (0.8%) were positive for intracellular bacteria (two Bordetella pertussis and two Mycoplasma pneumonia). ConclusionsPulmonary bacterial secondary infections and co-infections with SARS-CoV-2 are uncommon. Antibiotic use should remain limited in the management of COVID-19.

1298. Validation of Local Pseudomonas aeruginosa Risk Factors in Patients with Community-Onset Bacterial Pneumonia

BackgroundClinical guidelines for community-acquired pneumonia (CAP) encourage validation of local risk factors for multidrug-resistant organisms. This study aimed to validate previously derived, local risk factors for Pseudomonas aeruginosa in patients with community-onset bacterial pneumonia at Prisma Health-Midlands’ hospitals. MethodsIn this retrospective, observational cohort study, adult patients hospitalized with pneumonia MS-DRG codes from January 1, 2017 to March 31, 2020 were randomly screened. Enrolled subjects were admitted to 1 of 3 Prisma Health-Midlands’ hospitals with: diagnosis of pneumonia; receipt of inpatient antibiotics within 48 hours of symptom onset; receipt of over 48 hours of antibiotic therapy; and a causative bacterial pathogen identified via respiratory or blood culture, urinary antigen, or respiratory multiplex PCR panel. Performance of the locally derived score was compared to the Drug Resistance in Pneumonia (DRIP) Score, IDSA 2019 CAP guideline risk factors, and healthcare-associated pneumonia (HCAP) risk factors. Endpoints included sensitivity, specificity, positive and negative predictive value, overall accuracy, and over- and undertreatment rates. Overall accuracy was defined as a case in which the gram-negative antibiotic coverage recommended by the scoring schema would have been appropriate for the identified organism, i.e. neither overtreatment (overly broad-spectrum) nor undertreatment (inadequate spectrum). ResultsOf 713 patients screened, 36 patients met criteria and were enrolled. The most common bacterial pathogens identified were Pseudomonas aeruginosa (n = 10, 27.8%) and Streptococcus pneumoniae (n = 10, 27.8%). Performance characteristics for each scoring schema are summarized in Table 1.Table 1. Performance characteristics of risk scores predicting for Pseudomonas aeruginosa community-onset bacterial pneumonia. MDRO=multidrug-resistant organism; DRIP=Drug Resistance in Pneumonia Score; IDSA=Infectious Diseases Society of America 2019 Community-Acquired Pneumonia Guideline risk factors ; HCAP=healthcare-associated pneumonia risk factorsConclusionCompared to DRIP or IDSA 2019 CAP risk scores, the local risk score performed well at ruling out resistant gram-negatives given its higher specificity and lower overtreatment rate; yet, it did not perform as well at ruling in resistant gram-negatives given a lower sensitivity and undertreatment rate. All scores performed better than HCAP risk factors. Data from this study will be utilized to further refine the local risk score algorithm. Disclosures P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member) Hana Winders, PharmD, BCIDP, biomerieux (Grant/Research Support) Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder)

349. Diagnostic Testing and Antibiotic Utilization in Patients with COVID-19

BackgroundPatients with COVID-19 receive high rates of antibiotic therapy, despite viral origin of infection. Reports of bacterial coinfection range from 3.5 to 8% in the early phase of infection. This study aimed to evaluate the relationship between diagnostic tests and antibiotic utilization in patients admitted with COVID-19 at the University of Maryland Medical Center to better inform future prescribing practices.MethodsRetrospective cohort study of adult patients with a positive SARS-CoV-2 PCR on admission from March 2020 through June 2020. Associations between diagnostic tests employed and antibiotic initiation and duration were explored using bivariate analysis (SPSS®). ResultsBaseline characteristics of 224 included patients are reported in Table 1. Excluding SARS-CoV-2 PCRs, most frequently performed diagnostic tests included blood cultures (65.6%), MRSA nasal surveillance (45.1%), respiratory cultures (36.2%), respiratory viral panel (RVP) (33.0%), and Legionella (28.6%) and pneumococcal (26.3%) urine antigens. Positivity of RVP, Legionella, pneumococcus, blood, and respiratory tests were low (1.3%, 0.4%, 0.9%, 1.8%, and 6.7%, respectively). A total of 62% of patients were initiated on antibacterial therapy with a median cumulative antibiotic duration of 77.9 hours (IQR 41.4, 111.8). History of chronic respiratory disease (76% vs. 58.6%; P=0.025), any degree of oxygen requirement on admission (72% vs. 42.6%; P=0.006), and performance of blood cultures (70.7% vs. 46.8%, P< 0.0001) were associated with antibiotic initiation. Positive bacterial diagnostic respiratory culture (median duration 72.8h [IQR 46.7, 96.6] vs. 97.3h [IQR 79.8, 194.1]; P=0.027) and positive blood culture (median duration 80.1h [IQR 42.1, 111.7] vs. 97.5h [IQR 71.8, 164.8]; P=0.046) were associated with longer antibiotic duration. Patients who did not have respiratory cultures performed had similar antibiotic durations as those with negative respiratory cultures.Table 1. Baseline Characteristics ConclusionDespite low coinfection rates, negative diagnostic tests did not result in shorter empiric antibacterial duration. These findings highlight the ongoing need for both diagnostic and antimicrobial stewardship in COVID-19. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

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

BackgroundHistoplasmosis 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. MethodsWe 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.ResultsMedian 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)

68. Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients with Community-Acquired Pneumonia Admitted within a Large Academic Medical System

BackgroundLimited data support the use of pneumococcal urinary antigen testing (PUAT) for patients admitted with community-acquired pneumonia (CAP) as a stewardship tool to curtail the use of broad-spectrum antimicrobials. At NYULH, CAP guidelines and admission order set were developed to standardize diagnostic testing, including PUAT. In this study we describe patients with positive versus negative PUAT and evaluate de-escalation and patients’ outcomes. MethodsThis was a retrospective study of adults admitted with diagnosis of CAP between January-December 2019 who had a PUAT performed. The primary outcome was incidence and timing of de-escalation of antimicrobials following PUAT result. Among patients with a positive PUAT we compared hospital length of stay (LOS), incidence of Clostridioides difficile infection (CDI), infection-related readmission within 30 days, and in-hospital mortality among those who were de-escalated versus those who were not de-escalated/required escalation. ResultsWe evaluated 910 patients, of which 121 (13.3%) were PUAT positive. No difference in baseline characteristics, including severity of illness as represented by the Pneumonia Severity Index (97 [IQR 76-117] vs 89 [IQR 67-115], p=0.083) and Charlson Comorbidity Index, were observed between PUAT positive and negative groups. Time to PUAT testing occurred shortly after presentation to the hospital in both cohorts (16h [IQR 16-27] vs 13h [IQR 8-22], p=0.140). Initial de-escalation occurred in 97/117 (82.9%) and 629/775 (81.2%) of PUAT positive and negative patients, respectively (p = 0.749). Median time to de-escalation was shorter in the PUAT positive cohort (1 [IQR 0-2] vs 1 [IQR 1-2] day, p = 0.01). Among the PUAT positive group, hospital LOS stay was shorter in patients who were de-escalated compared to those who were not de-escalated/required escalation (6 days [IQR 4-10] vs 8 days [IQR 7-12], p=0.0005) with no difference in the incidence of CDI (2 [2.1%] vs 1 [3.7%], p=0.535), in-hospital mortality (4 [4.3%] vs 3 [11.1%], p=0.185), or 30-day infection-related readmission (2 [2.1%] vs 1 [3.7%], p=0.535). ConclusionPUAT positivity resulted in quicker time to targeted therapy for CAP. Among patients with a positive PUAT, initial de-escalation of antimicrobials did not lead to worse patient outcomes. Disclosures All Authors: No reported disclosures

327. Assessment of Bacterial Co-infection Rates and Antibiotic Exposure in COVID-19 Patients

BackgroundCOVID-19 pandemic data suggest risk for bacterial co-infection upon hospital presentation remain extremely low. Despite low co-infection rates, antibiotics are prescribed for most patients. Current data are limited regarding institutional-specific change in antibiotic use over the course of the pandemic. Given the low rates of co-infections, Saint Luke’s Health System’s COVID-19 Treatment Taskforce developed a COVID-19 evaluation and treatment order set which included procalcitonin (PCT) . As co-infection literature emerged, active education was provided, and order sets were modified to provide passive education regarding co-infection rates. We aimed to assess antibiotic practice changes as data and strategies to influence use evolved during the pandemic.MethodsThis was a multi-center, single health-system retrospective cohort study. Ten community hospitals and 1 academic medical center were included in analysis. Inclusion criteria were age ≥18 years, admitted during April or September 2020 and had a positive COVID-19 result on admission. Patients were excluded if they were readmitted for COVID-19 related issues. Both primary and secondary outcomes were analyzed from the first 7 days after admission. The primary outcome was rate of respiratory bacterial co-infections. This was determined through sputum and blood cultures, urinary antigens including Streptococcus pneumoniae and Legionella, and PCT. Secondary outcomes included rate of antibiotic use, antibiotic days of therapy (DOT), length of therapy, and antibiotic use trends.Baseline Characteristics ResultsA total of 294 patients were included with 69 patients in April 2020 and 225 in September 2020. Primary and secondary results are shown in Table 2. Rate of culture-confirmed bacterial co-infection when examining April 2020 was 4.38% and 4.44 % in September 2020. Antibiotic uses, antibiotic DOT, and length of therapy were all significantly lower in September 2020 compared to April 2020. ConclusionOur results show bacterial co-infections were extremely low in our health system. Despite positive trends in antibiotic use, prescribing remained high. More targeted interventions to decrease antibiotic exposure in COVID-19 patients are needed. Disclosures All Authors: No reported disclosures

33. Evaluating the Safety and Effectiveness of a Non-Severe Community-Acquired Pneumonia Pharmacist Pathway

BackgroundOne of the main roles of the SSM Health WI Regional Antimicrobial Stewardship Program is to create infection treatment pathways based on the Infectious Diseases Society of America (IDSA) practice guidelines. Treatment pathways are used to guide provider prescribing of antimicrobials for disease states such as community-acquired pneumonia (CAP). The objective of this study was to evaluate the safety and effectiveness of a non-severe CAP pharmacist pathway based on the updated IDSA and American Thoracic Society 2019 CAP practice guideline.MethodsA retrospective chart review was performed on all patients placed on the non-severe CAP pharmacist pathway at SSM Health St. Mary’s Hospital in Madison, WI from September 2020 through April 2021. Patients who initially started on the pathway were removed if they met prespecified criteria (Table 1). The primary outcome in this study was 30-day respiratory-related readmission rate. Secondary outcomes included average total length of antibiotic therapy, pharmacist interventions [intravenous (IV) to oral (PO) conversion, antibiotic de-escalation (including discontinuation of azithromycin with negative legionella urinary antigen), duration of therapy], and 30-day all-cause readmission rate. Table 1. Criteria for Removal from the Pathway Figure 1. Pharmacist Interventions ResultsA total of 119 patients were initiated on the non-severe CAP pharmacist pathway, of which 47 patients (40%) completed the pathway and 72 patients (60%) were removed from the pathway. Of the 47 patients who completed the pathway, there were no respiratory-related readmissions with a 30-day all-cause readmission rate of 6.4% (N=3/47). The average total duration of beta-lactam therapy was 6.8 days and the average total duration of macrolide therapy was 1 day due to de-escalation with a negative legionella urinary antigen result. A total of 61 pharmacist-driven interventions were completed [IV to PO conversion (N=15), de-escalation (N=27), and duration of therapy (N=19)]. Table 2. Summary of Results ConclusionThe findings of this study suggest that implementation of a non-severe CAP pharmacist pathway is safe and effective. No readmissions were related to non-severe CAP management and pharmacists completed guideline-driven interventions related to antimicrobial de-escalation, IV to PO conversion, and duration of therapy. Disclosures All Authors: No reported disclosures

942. Pulmonary Infections in Intestinal Transplant Recipients with Preexisting Pulmonary Nodules

BackgroundPulmonary nodules in asymptomatic patients could represent latent pulmonary infections. Intestinal transplant (ITx) recipients with preexisting pulmonary nodules might be at higher risk for pulmonary infections. However, data is lacking. MethodsThis retrospective study included adult patients that underwent intestinal transplantation (ITx) from 5/2016 to 5/2020. Chest computed tomography (CT) scans performed within 12 months prior of ITx were obtained to evaluate for preexisting pulmonary nodules. Screening for endemic mycoses, Aspergillus, Cryptococcus and latent tuberculosis infection (LTBI) performed within 12 months prior ITx was obtained. We assessed for worsening pulmonary nodules, and fungal and mycobacterial infections during the 1st year post-transplant. Survival at one year post-transplant was also assessed. ResultsForty-three patients underwent ITx. Twenty-three (53%) were Female. Median age was 46 years (range: 18-67). Chest CT scans were performed in 36(84%) patients prior to ITx. Preexisting pulmonary nodules were found in 30 (83%) of the patients. All were asymptomatic. Nodules were not calcified in 10 (33%) patients, calcified in 4 (13%), some calcified and some not calcified in 4 (13%) and unclear in 12 (40%). All the patients screened negative for fungi [Coccidioides antibody (Ab) was done in 15 (50%) patients, Blastomyces Ab and Histoplasma Ab in 7 (23%) each, Histoplasma urine antigen (Ag) and Aspergillus serum galactomannan in 3 (10%) each, and Cryptococcus serum Ag in 10 (33%) patients]. QuantiFERON-TB (QFT) was negative in 35 (81%) patients, positive in 2 (5%) and indeterminate in 6 patients (14%). QFT-Gold In-Tube was replaced to QFT-Plus in 3/2019. Post-transplant worsening of pulmonary nodules was noted in 12 (40%) patients and bronchoscopy was performed in six of them. Note that only 1 (3%) of the patients that had pre-existing pulmonary nodules developed a pulmonary infection (invasive pulmonary aspergillosis diagnosed 33 days after ITx). Our cohort survival at one year post-transplant was 79%. ConclusionPreexisting pulmonary nodules was common in our ITx cohort. However, only one case of pulmonary infection was noted among those who had preexisting pulmonary nodules. Clinical monitoring is essential. Disclosures All Authors: No reported disclosures

1303. A Rare Case of Legionella micdadei Lung Abscess in an Immunocompromised Patient

Abstract Background Legionella micdadei is the most common legionella species causing infection after L. pneumophila. It usually causes infection in immunocompromised hosts and leads to nodules with tendency to cavitate. It is difficult to culture which makes diagnosis challenging. We report a case or L. micdadei in an immunocompromised host with cavitary pneumonia. Methods Case Report. An 82 year-old female presented with upper abdominal pain for one day duration. She has history of hypertension, coronary artery disease, hyperlipidemia, heart failure, and hypothyroidism. She was diagnosed with hypersensitivity pneumonia 5 months prior, treated with prednisone (40 mg daily). The pain was not associated with nausea, vomiting or diarrhea. She was found with hypoxia despite she denied shortness of breath, cough, hemoptysis or chest pain. There was no fever, chills, headache, myalgia or upper respiratory symptoms. She was afebrile, tachycardic 134/min and hypoxic to 88% on room air. White cell count was 22x10(3) /mcL (90% neutrophils), hemoglobin was 10.4 g/dL, creatinine was 1.23 mg/dL and lactic acid was 3.6 mmol/L. Chest CT scan showed left lower lobe cavitary lesion with surrounding infiltrates (image 1). Quantiferon gold, serum galagtomannan, B-D-glucan, and vasculitis work-up were negative. Bronchoscopy showed a patent airway. Bronchial smears and cultures were negative for bacteria, fungi and mycobacteria. The patient was treated with ceftriaxone and metronidazole with de-escalation to amoxicillin/clavulanate. Bronchial culture was positive for legionella micdadei after discharge, azithromycin was added. Image 1. Cavitary lesion on thoracic CT Results Our patient was considered immunocompromised given steroid use, predisposing her for L. micdadei infection. L. micdadei is considered an opportunistic infection and was reported in hematologic malignancy population. It can cause an invasive lung disease with lung cavities. It needs special media for growth making it difficult to diagnose especially it is not detected by legionella urine antigen. Conclusion L. micdadei should be considered in the differential diagnosis for cavitary lung lesions in immunocompromised patients. Disclosures All Authors: No reported disclosures

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

BackgroundPneumococcal 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. MethodsActive 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. Results11129 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. ConclusionSeven 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)

301. Detection of Pneumococcal Pneumonia During SARS-CoV-2 Infection

Background Streptococcus pneumoniae (pneumococcus) is a common colonizer of the upper respiratory tract and can progress to cause invasive and mucosal disease. Additionally, infection with pneumococcus can complicate respiratory viral infections (influenza, respiratory syncytial virus, etc.) by exacerbating the initial disease. Limited data exist describing the potential relationship of SARS-CoV-2 infection with pneumococcus and the role of co-infection in influencing COVID-19 severity.MethodsInpatients and healthcare workers testing positive for SARS-CoV-2 during March-August 2020 were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and for inpatients only, serotype-specific urine antigen detection (UAD) assays (to identify pneumococcal pneumonia). A multinomial multivariate regression model was used to examine the relationship between pneumococcal detection and COVID-19 severity.ResultsAmong the 126 subjects who tested positive for SARS-CoV-2, the median age was 62 years; 54.9% of subjects were male; 88.89% were inpatients; 23.5% had an ICU stay; and 13.5% died. Pneumococcus was detected in 17 subjects (13.5%) by any method, including 5 subjects (4.0%) by RT-qPCR and 12 subjects (13.6%) by UAD. Little to no bacterial growth was observed on 21/235 culture plates. Detection by UAD was associated with both moderate and severe COVID-19 disease while RT-qPCR detection in saliva was not associated with severity. None of the 12 individuals who were UAD-positive died.ConclusionPneumococcal pneumonia (as determined by UAD) continues to occur during the ongoing pandemic and may be associated with more serious COVID-19 outcomes. Detection of pneumococcal carriage may be masked by high levels of antibiotic use. Future studies should better characterize the relationship between pneumococcus and SARS-CoV-2 across all disease severity levels.Disclosures Akiko Iwasaki, PhD, 4Bio (Consultant, Advisor or Review Panel member)Adaptive Biotechnologies (Consultant, Advisor or Review Panel member)Blavatnik (Grant/Research Support)HHMI (Grant/Research Support)Mathers (Grant/Research Support)NIH (Grant/Research Support)Spring Discovery (Grant/Research Support)Spring Discovery (Consultant, Advisor or Review Panel member)Vedanta InProTher (Consultant, Advisor or Review Panel member)Yale School of Medicine (Grant/Research Support) Nathan D. Grubaugh, PhD, Tempus Labs (Consultant) Ronika Alexander-Parrish, RN, MAEd, Pfizer (Employee, Shareholder) Adriano Arguedas, MD, Pfizer (Employee) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) Daniel Weinberger, PhD, Affinivax (Consultant)Merck (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support) Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support)

1313. Disease Burden and Real-world Clinical Practice for the Treatment of Hospital-Acquired Bacterial Pneumonia Using a Japanese Large-scale Claims Database: A Retrospective Cohort Study

BackgroundWith an aging population and increasing healthcare utilization, the frequency of hospital-acquired pneumonia (HAP) is expected to increase. Since HAP is life threatening, appropriate diagnosis and treatment are required; however, large-scale Japanese data focusing on patient profiles and treatment patterns is lacking.MethodsThe demographics and treatment patterns of HAP were examined using a large-scale Japanese claims database from Jan. 2016 to Apr. 2018. The HAP population included patients who received injection antibiotics ≧3 consecutive days after admission, but not within 2 days after admission, and those whose reason for hospitalization was not pneumonia but had a diagnosis of pneumonia after hospitalization (based on ICD-10 codes).Results2,968 HAP patients (mean age 77 years, 64.9% male) contributing 2,979 total HAP episodes were included. The 12-month pre-index mean Charlson Comorbidity Index (CCI) score was 4.0±3.1 (mean±SD), CCI scores ≧4 comprised 44.0%. Most HAP episodes (77.6%) occurred ≧5 days after hospitalization. During the 12month pre-index period including outpatients, 84.9% of patients had some type of pneumonia record, 9.1% had VAP (ventilator associated pneumonia) records, and 7.4% had anti-MRSA prescription records. For post-index HAP treatment, ampicillin/sulbactam (36.4%, 8.2±3.8 days) and piperacillin/tazobactam (22.0%, 8.8±4.4 days) were frequently prescribed as the first antibiotic prescription. Ceftriaxone (19.4%) and meropenem (9.8%) were also frequently prescribed. Examinations prescribed during HAP: 30.5% blood culture tests, 28.2% sputum examinations and 29.2% urine antigen tests. The overall mortality rate of HAP in overall hospitalization post-index was 22.0%, in which 14.4% of deaths occurred within 30 days. The mean (±SD) length of overall hospital stay was 49.9 (±34.2) days (11.3 days for HAP period), with 12.4% ICU use and 17.6% ventilator use. The median total cost during hospitalization was ¥1,924,848.18 (&19,248).ConclusionThe data revealed patient characteristics, treatment patterns, mortality rates and healthcare costs in Japanese HAP patients. This database approach should prove useful for discussing antibiotics usage trends in highly aging Japan.Disclosures Masahiro Kimata, PhD, MSD K.K., Tokyo, Japan (Employee) Yosuke Aoki, MD, PhD, MSD K.K., Tokyo, Japan (Other Financial or Material Support, Honorarium for Lecturing)SHIONOGI & Co., Ltd (Grant/Research Support, Other Financial or Material Support, Honorarium for Lecturing) Adachi Noriaki, n/a, MSD K.K., Tokyo, Japan (Employee) Takeshi Akiyama, MSc, MSD K.K., Tokyo, Japan (Independent Contractor) Akiko Harada, n/a, MSD K.K., Tokyo, Japan (Employee)

Evaluation of OIDx Histoplasma Urinary Antigen EIA.

A sandwich enzyme immunoassay (EIA) for the detection of Histoplasma antigens (Ag) in urine, developed by Optimum Imaging Diagnostics (OIDx) was evaluated. A verification using a standardized reference panel of urine samples found sensitivity of 92%, specificity of 32% and accuracy of 51%. In this study, the OIDx Histoplasma urinary Ag EIA displayed high sensitivity, however, in non-histoplasmosis cases this EIA displayed false-positive results in 68% of specimens tested.

Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin

Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP. In LEAP 1, adults (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR). Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections. Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.