Urinary Antigen Test Research Articles

SARS-CoV-2-Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020-2021).

Legionnaires’ Disease (LD) is a severe, sometimes fatal interstitial pneumonia due to Legionella pneumophila. Since the inception of the SARS-CoV-2 pandemic, some contradictory reports about the effects of lockdown measures on its epidemiology have been published, but no summary evidence has been collected to date. Therefore, we searched two different databases (PubMed and EMBASE) focusing on studies that reported the occurrence of LD among SARS-CoV-2 cases. Data were extracted using a standardized assessment form, and the results of such analyses were systematically reported, summarized, and compared. We identified a total of 38 articles, including 27 observational studies (either prospective or retrospective ones), 10 case reports, and 1 case series. Overall, data on 10,936 SARS-CoV-2 cases were included in the analyses. Of them, 5035 (46.0%) were tested for Legionella either through urinary antigen test or PCR, with 18 positive cases (0.4%). A pooled prevalence of 0.288% (95% Confidence Interval (95% CI) 0.129–0.641), was eventually calculated. Moreover, detailed data on 19 co-infections LD + SARS-CoV-2 were obtained (males: 84.2%; mean age: 61.9 years, range 35 to 83; 78.9% with 1 or more underlying comorbidities), including 16 (84.2%) admissions to the ICU, with a Case Fatality Ratio of 26.3%. In summary, our analyses suggest that the occurrence of SARS-CoV-2–Legionella infections may represent a relatively rare but not irrelevant event, and incident cases are characterized by a dismal prognosis.

P30 Bacterial coinfection and prescribing trends in SARS-CoV-2 infection in two UK hospitals

ObjectivesTo describe antibiotic prescribing and early bacterial and fungal coinfection in patients admitted to two London hospitals with COVID-19.MethodsA retrospective review of adults with PCR-confirmed SARS-CoV-2 infection admitted between 9 February and 10 May 2020. Demographics, critical care unit (CCU) admission, antibiotic prescribing and microbiology results within 10 days of COVID-19 diagnosis were analysed.ResultsIn total, 1155 patients were identified; 32.9% (380) died during admission and 12.4% (143) had positive microbiology. After excluding likely contaminants, 6.9% (80) had evidence of coinfection. The most common organisms isolated from blood cultures were Escherichia coli 9.5% (7), Klebsiella pneumoniae 4.0% (3), and MSSA 2.7% (2). Organisms isolated from lower respiratory tract samples included Candida albicans 44.4% (12), Staphylococcus aureus 22.2% (6), Klebsiella species 11.0% (3), Pseudomonas aeruginosa 11.0% (3) and Citrobacter species 11% (3). Legionella and pneumococcal urinary antigen tests were positive in 0/117 and 2/71 episodes, respectively. Patients admitted to CCU during their inpatient stay were more likely to have positive microbiology compared with patients managed outside CCU (26.2% versus 11.0%, P<0.001). Ninety-one percent (1051) of all patients received antibiotics. Clarithromycin (24.2% total antibiotic use) and amoxicillin (21%) were most frequently used, followed by piperacillin/tazobactam (12.6%), gentamicin (10.6%), co-amoxiclav (9.3%) and meropenem (3.2%). Patients given piperacillin/tazobactam or meropenem had a higher length of stay and mortality.ConclusionsBacterial coinfection in COVID-19 is uncommon, but more frequent in patients requiring CCU admission. Antibiotic use was widespread, despite lack of microbiological evidence of coinfection. When present, infection was more likely due to Gram-negative bacteria. Future local clinical and antimicrobial guidelines should reflect these findings.

Misdiagnosis Due to False-Positive Detection of Pneumococcal Urinary Antigen.

IntroductionThe detection of pneumococcal antigens in urine is an alternative to gram staining, and their culture is central to the diagnosis of pneumococcal pneumonia. We present a case of the false-positive detection of urinary Streptococcus species pneumococcal antigen with a BinaxNOW test. This resulted in delayed diagnosis of a liver abscess.Case descriptionA 70-year-old woman presented to the emergency department with a 1-day history of chills and difficulty walking. She had a fever and her physical examination was normal. Non-contrast chest computed tomography (CT) revealed a slight ground-glass opacity in the left lower lobe. Laboratory tests revealed liver injury and elevated C-reactive protein levels. A urinary pneumococcal antigen test was positive, and she was diagnosed with acute bronchopneumonia caused by Streptococcus pneumoniae. She was treated with ceftriaxone. However, abdominal contrast-enhanced CT performed the next day revealed portal vein thrombus and a left lobe liver abscess. Streptococcus constellatus was detected in a puncture specimen of the liver abscess. It was concluded that the positive urinary pneumococcal antigen test was a false-positive owing to Streptococcus infection.DiscussionFalse-positive results might be explained by the presence of C-polysaccharide antigens in the cell wall of S. pneumoniae. The positive urinary antigen test together with the finding of slight ground-glass opacity in the left lung on chest CT initially led to misdiagnosis. False positives may result in misdiagnosis and unnecessary antimicrobial therapy.ConclusionThe overuse of the pneumococcal urinary antigen tests can lead to false positives and misdiagnosis.LEARNING POINTSFalse-positive pneumococcal urinary antigen results may lead to the misdiagnosis of pneumococcal pneumonia caused by Streptococcus pneumoniae and unnecessary antimicrobial therapy.False-positive results can occur in patients with infections caused by other Streptococcus species (e.g., liver abscess caused by Streptococcus constellatus).The optimal use of pneumococcal urinary antigen tests needs to be studied in clinical practice settings.

Q Fever Masquerading as Legionnaires Disease in an Endovascular Stent Infection

Abstract Background Legionellosis in the setting of preexisting endovascular prosthetic graft may represent a Coxiella burnetii infection as antibody cross-reactivity exists. Methods We present a 63-year-old man status-post endovascular aneurysm repair (EVAR) with a history of ankylosing spondylitis, chronic obstructive pulmonary disease asthma, coronary artery disease with myocardial infarction, hypertension, and hyperlipidemia who presented with clinical symptoms of legionellosis. This was confirmed with a positive urine antigen test. Results He completed a 21-day course of azithromycin for Legionella. His leukocytosis and liver function tests normalized, but he had continued lethargy and a persistently elevated erythrocyte sedimentation rate and C-reactive protein. Imaging showed a radiographically infected EVAR graft (placed 10 months prior). The EVAR was explanted and the operating room cultures grew C. burnetii. Prolonged hydroxychloroquine and doxycycline therapy were required for vascular manifestations of Coxiella as azithromycin provides inappropriate coverage. Conclusions Persistent constitutional symptoms in the setting of an EVAR require expanded investigation, especially in the setting of legionellosis.

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.

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.

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.

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.

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

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)

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.

Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients With Community-Acquired Pneumonia Admitted Within a Large Academic Health System.

BackgroundLimited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT.MethodsThis was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients’ outcomes.ResultsWe evaluated 910 patients, 121 (13.3%) of whom were PUAT positive. No difference in baseline characteristics, including severity of illness, was observed between groups. Initial de-escalation occurred in 82.9% and 81.2% of PUAT-positive and -negative patients, respectively (P = .749). Median time to de-escalation was shorter in the PUAT-positive group (1 [interquartile range {IQR}, 0–2] day vs 1 [IQR, 1–2] day, P = .01). Within 24 hours of PUAT, more patients in the PUAT-positive group had atypical coverage discontinued (61.3% vs 47.2%, P = .026) without difference in methicillin-resistant Staphylococcus aureus (MRSA) agent discontinuation (or antipseudomonal de-escalation). Among the PUAT-positive group, unadjusted analysis demonstrated shorter median length of stay in patients who were de-escalated compared to those who were not (6 [IQR, 4–10] vs 8 [IQR, 7–12] days, P = .0005), without difference in the incidence of Clostridioides difficile, in-hospital mortality, or 30-day infection-related readmission.ConclusionsWe observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.

LEGIONELLA INFECTION IN THE MIDST OF COVID-19 PANDEMIC

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: With the COVID-19 pandemic, when 90% of ICU has COVID-19 patients, it's common to overlook other rare causes of acute hypoxic respiratory failure. Our case highlights the importance of maintaining a broad differential for pneumonia and importance of early urine legionella antigen testing. CASE PRESENTATION: 55 year-old male with no significant medical history presented with 8 day history of fever, chills and dry cough. Exam was unremarkable except bilateral rales. Labs were significant for elevated inflammatory markers done as part of a COVID panel with C-reactive protein >190, troponin 0.063, d-dimer >20, ferritin 15k, lactate dehydrogenase 682, Creatinine kinase 553 and WBC 31.1, absolute lymphocyte 0.7, AST 179, ALT 91, ALP 164, Total Bilirubin 6.0, Sodium 123, BUN 130, Creatinine 12.4. Chest X-ray significant for bilateral ground glass opacity, He was admitted to ICU for acute hypoxic respiratory failure. Despite high suspicion, COVID-19 test was negative thrice, including lower respiratory sampling. However, his urine legionella antigen testing was positive. ICU course was complicated by septic shock, renal failure requiring renal replacement therapy, acute liver failure and acute respiratory failure requiring mechanical ventilation and later tracheostomy. He was treated with 14 day course of antibiotics and later weaned off the ventilator. DISCUSSION: Severe legionnaires' disease, though uncommon, has a very similar presentation as COVID-19 pneumonia. Fever, dry cough, shortness of breath, diarrhea being the most common clinical presentation, whereas laboratory findings significant for elevated inflammatory markers including CRP, CK and LDH are noted in both the diseases (1). Liver and renal failure are also equally involved in both the disease. However, severe hyponatremia and elevated WBC count should raise higher suspicion for Legionella than COVID-19. Our patient presented as a diagnostic challenge with many clinical features that resemble both diseases. The early detection of Legionella pneumonia was imperative to our patient's recovery with prompt treatment with empiric antibiotics. First-line diagnostic testing typically occurs by looking for urine antigens, which tests for the most virulent legionella species, L. pneumophila serogroup 1 (2). Although culture diagnosis remains the gold standard and the most specific diagnostic testing, urine antigen testing allows for early diagnosis and earlier tailoring of antibiotics (3). Thus, for all patients with increased suspicion for COVID-19, we recommend co-testing for urine legionella antigen to rule out Legionnaires' pneumonia. CONCLUSIONS: In conclusion, our case report suggests that we should not overlook typical presentations of known diseases even in the midst of a pandemic. It serves as a reminder to continue early testing for treatable diseases, like Legionella, so as to not miss an opportunity to save a life. REFERENCE #1: Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;(published online Jan 24). https://doi.org/10.1016/S0140-6736(20)30183-5 REFERENCE #2: Cunha BA, Burillo A, Bouza E. Legionnaires' disease. Lancet. 2016;387(10016):376-385. doi:10.1016/S0140-6736(15)60078-2 REFERENCE #3: Fields BS, Benson RF, Besser RE. Legionella and Legionnaires' disease: 25 years of investigation. Clin Microbiol Rev. 2002;15(3):506-526. doi:10.1128/cmr.15.3.506-526.2002 DISCLOSURES: No relevant relationships by trisha arno, source=Web Response No relevant relationships by Brian Cuneo, source=Web Response No relevant relationships by Kejal Gandhi, source=Web Response

LEGIONNAIRES' DISEASE: A FATAL FORM OF COMMUNITY-ACQUIRED PNEUMONIA

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Legionella pneumophila is gram-negative bacilli known to cause community-acquired pneumonia (CAP), also termed Legionnaires' disease. While pneumonia is the most common manifestation, extrapulmonary infections include renal injury and rhabdomyolysis. Age, immunosuppression and multi-system infection increase mortality, even with early initiation of therapy. CASE PRESENTATION: A 30-year-old male with history of bipolar disease, alcohol and tobacco abuse presented with diarrhea, fever and confusion for three days. He was found to be febrile, tachycardic, encephalopathic and hypoxic requiring high-flow nasal cannula. Initial evaluation revealed leukocytosis, acute liver injury, acute renal injury, respiratory alkalosis, lactic acidosis, and elevated troponin and creatine kinase levels. Chest x-ray (CXR) showed a dense left upper lobe consolidation. Sepsis was worked up and he was given intravenous fluids and antibiotics (Vancomycin, Cefepime, Metronidazole, Azithromycin). Over several hours, he became oliguric, tachypnic and hypotensive requiring vasopressors, continuous renal replacement therapy (CRRT) and mechanical ventilation. Urinary legionella antigen returned positive so Levofloxacin was added. Despite antibiotics and CRRT, his shock worsened and he ultimately had pulseless electrical activity arrest with demise. DISCUSSION: The presence of acute renal injury in Legionnaires' disease increases mortality up to 51% so early diagnosis is crucial to guide management. The urinary antigen test for L. pneumophila only identifies serogroup 1, which is the most common type. When prevalence is high, specificity of this test is >99%. Severe cases of CAP should be tested for Legionella as half of patients with Legionnaires' disease will require intensive care. Rhabdomyolysis occurs due to direct toxin invasion and renal injury occurs subsequently or due to sepsis. Levofloxacin or Azithromycin are the antibiotics of choice as they are bactericidal and reach high intracellular concentrations. There are twenty-two known cases of Legionnaires' disease with rhabdomyolysis and acute renal injury. Nearly all patients with this triad survived and of those who did, all received antibiotics and about half required hemodialysis (HD). To our knowledge, there is only one other case where the outcome was death despite several days of HD. In comparison, presentation to death occurred in less than twenty-four hours in our case. Cause of death was refractory hyperkalemia due to rhabdomyolysis-induced renal injury despite CRRT. CONCLUSIONS: Even with timely diagnosis and treatment of Legionnaires' disease, renal involvement portends a high mortality rate. At the earliest evidence of renal injury in Legionnaires' disease complicated by rhabdomyolysis, immediate placement of central venous catheters and early initiation of CRRT is mandatory and may be life saving. REFERENCE #1: Soni AJ, Peter A. Established association of legionella with rhabdomyolysis and renal failure: A review of the literature. Respir Med Case Rep. 2019 Oct 28;28:100962. REFERENCE #2: Mercante, J. W., & Winchell, J. M. (2015). Current and emerging Legionella diagnostics for laboratory and outbreak investigations. Clinical microbiology reviews, 28(1), 95–133. REFERENCE #3: Straus W.L., Plouffe J.F., File T.M. Risk factors for domestic acquisition of Legionnaires' disease. Ohio Legionnaires Disease group. Arch. Intern. Med. 1996;156(15):1685–1692. DISCLOSURES: No relevant relationships by Allen Roberts, source=Web Response No relevant relationships by Jigna Solanki, source=Web Response

HEREDITARY MULTIPLE EXOSTOSES PRESENTING WITH CHEST PAIN IN ADOLESCENT MALE

TOPIC: Pediatrics TYPE: Fellow Case Reports INTRODUCTION: Hereditary multiple exostoses (HME) is a syndrome characterized by presence of two or more osteochondromas (exostoses) in the appendicular or axial skeleton. Here, we present a case of an adolescent patient presenting with chest pain as the only symptom of an intrathoracic exostosis leading to the diagnosis of HME. CASE PRESENTATION: A previously healthy 15-year-old male presented to the pediatric pulmonary clinic for months-long history of recurrent left-sided chest pain, without any associated symptoms. Chest x-ray showed an ill-defined nodular opacity in the left upper lobe, with central calcification identified. Additional work-up with spirometry, complete blood count, fungal antibody panel, and Histoplasma urine antigen testing was normal. Family history was positive for pulmonary embolism and "blood clotting issues" with no specific syndromes identified. A chest computed tomography angiography (CTA) with contrast was ordered for further evaluation.Chest CTA revealed a large bony exostosis arising from the anterior aspect of the left third rib, with two areas of surrounding nodular soft tissue measuring 3 cm x 1.3 cm x 2.6 cm. There was extension into the lung abutting the pleura and lateral aspect of the mediastinum. Additional bony protuberances were noted along the left fifth rib, right second rib, and bilateral scapulae. A diagnosis of HME was made because of the presence of multiple exostoses. Due to continued chest pain he was referred to cardiothoracic surgery. The decision was made to monitor symptoms and obtain repeat imaging in six months to monitor growth or worsening lung impingement. DISCUSSION: HME is characterized by the presence of two or more exostoses in the appendicular or axial skeleton. The most common location of exostoses is in the appendicular skeleton. Though rare, involvement of the ribs can occur [1]. Previous case reports have identified presence of multiple costal exostoses in patients with known HME [1,2]. The patient presented here represents a case with chest pain as the only presenting complaint prior to diagnosis of HME being made. The presence of a costal exostosis should be considered in adolescents presenting with chest pain if other more common causes are ruled out. The presence of multiple exostoses supports the diagnosis of HME. Cases of HME with costal exostoses can be associated with intrathoracic complications, including hemothorax, pneumothorax, and pericardial effusion [3]. Supportive care and observation is the usual plan of care. However, if complications develop, surgical resection may be necessary and cardiothoracic surgery consultation is recommended. CONCLUSIONS: Chest pain may be the only presenting symptom in pediatric patients with HME. REFERENCE #1: Mazza D, Fabbri M, Calderaro C, Iorio C, Labianca L, Poggi C, Turturro F, Montanaro A, Ferretti A. Chest pain caused by multiple exostoses of the ribs: A case report and a review of literature. World J Orthop. 2017 May 18;8(5):436-440 REFERENCE #2: Khosla A, Parry RL. Costal osteochondroma causing pneumothorax in an adolescent: a case report and review of the literature. J Pediatr Surg. 2010 Nov;45(11):2250-3. REFERENCE #3: Yan G, Littlewood A, Latimer MD. Unusual cause of pleuritic chest pain in a child. BMJ Case Rep. 2016 Nov 28;2016:bcr2016217307. DISCLOSURES: No relevant relationships by Brooke Gustafson, source=Web Response No relevant relationships by Lisa Ulrich, source=Web Response

Diagnostic Challenges of Binax Urinary EIA for Detection of Legionella pneumophila

A middle-aged African American male with a history of stage 2 chronic kidney disease status post double kidney transplant was admitted after developing symptoms of respiratory infection during the peak of COVID-19. The patient rapidly developed acute hypoxemic respiratory failure. Differentials for the patient included COVID-19, opportunistic infection such as mycoplasma, and legionella. During the admission, the patient had numerous infectious disease screening tests run including a COVID-19 test and Binax urine antigen test for legionella that all came back negative.

Atypical bacterial co-infections among patients with COVID-19: A study from India.

Emerging evidence shows co‐infection with atypical bacteria in coronavirus disease 2019 (COVID‐19) patients. Respiratory illness caused by atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila may show overlapping manifestations and imaging features with COVID‐19 causing clinical and laboratory diagnostic issues. We conducted a prospective study to identify co‐infections with SARS‐CoV‐2 and atypical bacteria in an Indian tertiary hospital. From June 2020 to January 2021, a total of 194 patients with laboratory‐confirmed COVID‐19 were also tested for atypical bacterial pathogens. For diagnosing M. pneumoniae, a real‐time polymerase chain reaction (PCR) assay and serology (IgM ELISA) were performed. C. pneumoniae diagnosis was made based on IgM serology. L. pneumophila diagnosis was based on PCR or urinary antigen testing. Clinical and epidemiological features of SARS‐CoV‐2 and atypical bacteria‐positive and ‐negative patient groups were compared. Of the 194 patients admitted with COVID‐19, 17 (8.8%) were also diagnosed with M. pneumoniae (n = 10) or C. pneumoniae infection (n = 7). Confusion, headache, and bilateral infiltrate were found more frequently in the SARS CoV‐2 and atypical bacteria co‐infection group. Patients in the M. pneumoniae or C. pneumoniae co‐infection group were more likely to develop ARDS, required ventilatory support, had a longer hospital length of stay, and higher fatality rate compared to patients with only SARS‐CoV‐2. Our report highlights co‐infection with bacteria causing atypical pneumonia should be considered in patients with SARS‐CoV‐2 depending on the clinical context. Timely identification of co‐existing pathogens can provide pathogen‐targeted treatment and prevent fatal outcomes of patients infected with SARS‐CoV‐2 during the current pandemic.