Pneumococcal Antigen Research Articles

New testing guidelines for community-acquired pneumonia.

The purpose of this article is to review diagnostic testing recommendations outlined in the current American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) community-acquired pneumonia (CAP) guideline and the 2021 ATS guideline for noninfluenza respiratory viruses. Diagnostic testing in CAP with gram stain, lower respiratory and blood cultures, Streptococcal and Legionella urinary antigens are not routinely recommended unless identified as severe CAP or with risk factors for Methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa infection. Influenza virus testing remains a strong recommendation during periods of community viral spread.An additional 2021 ATS clinical practice guideline reviewed the use of molecular testing for noninfluenza viral pathogens in adults with suspected CAP and recommended testing in those hospitalized with severe CAP and/or various immunocompromising conditions. Diagnostic testing remains an important component of confirming and treating CAP. The CAP guideline includes recommendations surrounding diagnostic testing with lower respiratory gram stain and culture, blood cultures, Legionella and Pneumococcal urinary antigen, influenza viral testing and serum procalcitonin.There is a strong recommendation to obtain influenza virus testing during periods of community spread. However, the use of other diagnostics such as gram stain, lower respiratory and blood culture, and urinary antigen testing are dependent on severity of illness and whether a patient has been identified as having strong risk factors for MRSA or P. aeruginosa infection. The 2021 ATS clinical practice document did not routinely recommend testing noninfluenza respiratory viruses unless identified as having severe CAP and/or various immunocompromising conditions.

Bacterial co-infection at hospital admission in patients with COVID-19

ObjectivesWe described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19.MethodsObservational cohort study was performed at the Hospital Clinic of Barcelona (February 2020–February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included.ResultsA total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57–3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69–4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11–2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19.ConclusionsBacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%.

Diagnostic significance of the determination of streptococcus pneumoniae antigen in the urine of children with community acquired pneumonia

Community-acquired pneumonia remains an urgent problem in modern pediatrics. Taking into account the variety of pathogens of community-acquired pneumonia, an important task is to identify the etiology of this disease rapidly. Early diagnostics is able to increase the effectiveness of treatment and exclude the irrational prescription of antibacterial drugs or the formation of resistable microflora. Traditional methods of etiotropic diagnostics do not always meet such criteria as timeliness, minimal invasiveness, and simplicity of reproduction. Meeting these requirements is especially important in pediatric practice due to the difficulty of venous access, collection of spontaneous or induced sputum and negative childhood denial reaction to invasive manipulation. Recently, active efforts have been made to identify the early markers con-firming the etiology of pulmonary inflammation, while the criteria for timeliness and non-invasiveness are met by methods for determining pathogen antigens in accessible media such as saliva and urine.Considering the fact that Streptococcus pneumoniae remains one of the main causative agents of pneumonia, its testing is of great practical importance. This article presents an overview of modern methods of etiotropic diagnosis of community-acquired pneumonia and the results of our own study of the effectiveness of detecting pneumococcal antigens in urine using express tests. Attention is focused on the use of minimally invasive methods for identifying the pathogen in practical pulmonology. Evaluation of the effectiveness of rapid testing was carried out in comparison with the results of bacterial sputum culture for pneumococcus. The analysis of the obtained results showed the high sensitivity and specificity of the Alere Binax Now test when checking the etiology of community-acquired pneumonia in children.

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.

Susceptibility to infections and adaptive immunity in adults with heart failure.

AimsHeart failure (HF) is a systemic inflammatory disorder with infections being an important cause of morbidity and mortality. We asked if HF patients have a higher susceptibility to infections compared with the general population and if a subtle secondary immunodeficiency facilitates infectious complications.Methods and resultsIn a cohort of 92 patients with HF with reduced ejection fraction, we analysed recirculating lymphocyte subpopulations, serum immunoglobulin levels, and specific antibody titres against pneumococcal antigens. We quantified susceptibility to infections of the respiratory tract with a validated questionnaire and compared it to the general population. Susceptibility to infections of the respiratory tract was comparable in HF patients and the general population. Hypogammaglobulinaemia was present in 16% of HF patients, but anti‐pneumococcal titres showed no evidence of specific secondary antibody deficiency. Relative lymphopaenia in our HF cohort was due to B lymphocytopenia with a relative reduction in naive B‐cells and expansion of memory B‐cells while CD4+ and CD8+ T‐lymphocytes as well as NK‐cell counts were comparable between HF and healthy donors. The intake of the angiotensin receptor neprilysin (CD10) inhibitor (ARNI) sacubitril/valsartan was associated with increased B‐lymphocyte counts, possibly by an increased output of CD10+ transitional B lymphocytes from the bone marrow.ConclusionDespite a reduction of B lymphocytes in HF and mild hypogammaglobulinaemia, patients showed no evidence of secondary immunodeficiency or increased susceptibility to infections. The relevance of B‐cell lymphopenia in HF patients and modulation of B‐cell counts under ARNI treatment remains to be investigated.

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.

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.

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)

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

Immunohistochemistry in Historical Perspective: Knowing the Past to Understand the Present.

Immunohistochemistry is an extraordinary and extensively used technique whereby antibodies are used to detect antigens in cells within a tissue section. It has numerous applications in medicine, particularly in cancer diagnosis. It was Albert Hewett Coons, Hugh J Creech, Norman Jones, and Ernst Berliner who conceptualized and first implemented the procedure of immunofluorescence in 1941. They used fluorescein isothiocyanate (FITC)-labelled antibodies to localize pneumococcal antigens in infected tissues. Since then, with improvement and development of protein conjugation, enzyme labels have been introduced, such as peroxidase and alkaline phosphatase. The history of immunohistochemistry (IHC) combines physiology, immunology, biochemistry, and the work of various Nobel Prize laureates. From von Behring who was awarded de first Nobel Prize in 1901 for his work on serum therapy to the 1984 Nobel Prize for the discovery of monoclonal antibodies by Milstein, Kohler, and Jerne, IHC is a story of cooperation and collaboration which led to the development of this magnificent technique that is used daily in anatomical pathology laboratories worldwide.

Protective activity of mixtures of pneumococcal antigens in infection caused by &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; serotype 3

Introduction. Pneumococcal diseases remain relevant for the whole world. On the one hand, this is due to the high prevalence of pneumococcus and the other hand, the growth of antibiotic-resistant strains and the constant change of clinically significant serotypes of the pathogen.The aim of the research was to study of the protective activity of a mixture of pneumococcal antigens.Material and methods. we used preparations of a capsular polysaccharide (CPS) obtained from Streptococcus pneumoniae serotype 3; protein-containing fraction (PCF) obtained from an aqueous extract of cells of S. pneumoniae serotype 6B; recombinant pneumolysin (rPly). Mice were immunized intraperitoneally twice with an interval of 14 days with mixtures of bacterial antigens: CPS + PCF; CPS + rPly; PCF + rPly. To assess the protective activity of the studied drugs after double immunization animals were infected intraperitoneally with S. pneumoniae serotype 3. To study the effect of mixtures of bacterial preparations on the infectious process in the lungs immunized mice were infected with S. pneumoniae serotype 3. The humoral immune response was studied with IgG using the method of ELISA.Results. The CPS + rPly mixture protected mice from intraperitoneal infection with S. pneumoniae serotype 3 regardless of the infecting dose. Immunization with CPS + PCF or CPS + rPly mixtures influenced a significant decrease the number of seeded bacterial cells from lungs during the entire observation period (72 h) compared to the control. Administration of mixtures of bacterial antigens of CPS + PCF, CPS + rPly or PCF + rPly to animals led to a significant increase of the level of antibodies to all antigens, however, the highest levels of IgG were determined to PCF and rPly.Conclusion. The results obtained suggest that different antigenic drugs in mixtures affect different mechanisms of immunity activation.

Intranasal vaccination with protein bodies elicit strong protection against Streptococcus pneumoniae colonization

Protein bodies (PBs) are particles consisting of insoluble, aggregated proteins with potential as a vaccine formulation. PBs can contain high concentrations of antigen, are stable and relatively resistant to proteases, release antigen slowly and are cost-effective to manufacture. Yet, the capacity of PBs to provoke immune responses and protection in the upper respiratory tract, a major entry route of respiratory pathogens, is largely unknown.In this study, we vaccinated mice intranasally with PBs comprising antigens from Streptococcus pneumoniae and evaluated the level of protection against nasopharyngeal colonization. PBs composed of the α-helical domain of pneumococcal surface protein A (PspAα) provided superior protection against colonization with S. pneumoniae compared to soluble PspAα. Immunization with soluble protein or PBs induced differences in antibody binding to pneumococci as well as a highly distinct antigen-specific nasal cytokine profile upon in vivo stimulation with inactivated S. pneumoniae. Moreover, immunization with PBs composed of conserved putative pneumococcal antigens reduced colonization by S. pneumoniae in mice, both as a single- and as a multi-antigen formulation.In conclusion, PBs represent a vaccine formulation that elicits strong mucosal immune responses and protection. The versatility of this platform offers opportunities for development of next-generation vaccine formulations.

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.

Time Trend of the Sensitivity of the Pneumococcal Urinary Antigen Test for Diagnosing Pneumococcal Community-Acquired Pneumonia: An Analysis of 15-Year, Prospective Cohort Data.

IntroductionWhether the sensitivity of the BinaxNOW Streptococcus pneumoniae urinary antigen test kit (BinaxNOW), adjusted by some variables including vital signs, laboratory examinations and pneumonia severity, has been decreasing is unknown. The aim of the present study was to investigate whether BinaxNOW sensitivity has decreased recently and to identify the predictors of the BinaxNOW result, including the time trend.MethodsThis prospective cohort study enrolled consecutive patients with pneumococcal community-acquired pneumonia who were hospitalised at Kurashiki Central Hospital from January 2001 to December 2015. Pneumococcal community-acquired pneumonia was defined as positive blood or pleural effusion or sputum culture results. To evaluate the effect of the time trend for the sensitivity of BinaxNOW, time series regression analysis was performed. In addition, predictors of the BinaxNOW result were examined by multivariable analysis using variables such as sex, vital signs, blood tests such as C-reactive protein, albumin, blood urea nitrogen, creatinine, white blood cell count, haematocrit and platelets, antibiotic pre-treatment, bacteraemia, and pneumonia severity, in addition to time trend and seasonality.ResultsA total of 446 patients were included. BinaxNOW sensitivity showed a significant, gradual decrease from 2001 (81.3%) to 2015 (48.7%). On multivariable analysis [odds ratio (95% confidence interval)], bacteraemia [2.516 (1.387–4.561), P = 0.002] was a predictor of a positive BinaxNOW result, whereas male sex [0.467 (0.296–0.736), P = 0.001], white blood cell count [0.959 (0.930–0.989), P = 0.008] and the time trend per year [0.900 (0.859–0.943), P < 0.001] were predictors of a negative BinaxNOW result.ConclusionsThe sensitivity of BinaxNOW decreased over a 15-year period. We should be careful when interpreting BinaxNOW results in daily clinical practice, and the development of a new kit with good sensitivity is anticipated.Trial registration numberUMIN000004353.

Impact of Pneumococcal Urinary Antigen Testing in COVID-19 Patients: Outcomes from the San Matteo COVID-19 Registry (SMACORE).

Despite low rates of bacterial co-infections, most COVID-19 patients receive antibiotic therapy. We hypothesized that patients with positive pneumococcal urinary antigens (PUAs) would benefit from antibiotic therapy in terms of clinical outcomes (death, ICU admission, and length of stay). The San Matteo COVID-19 Registry (SMACORE) prospectively enrolls patients admitted for COVID-19 pneumonia at IRCCS Policlinico San Matteo, Pavia. We retrospectively extracted the data of patients tested for PUA from October to December 2020. Demographic, clinical, and laboratory data were recorded. Of 469 patients, 42 tested positive for PUA (8.95%), while 427 (91.05%) tested negative. A positive PUA result had no significant impact on death (HR 0.53 CI [0.22–1.28] p-value 0.16) or ICU admission (HR 0.8; CI [0.25–2.54] p-value 0.70) in the Cox regression model, nor on length of stay in linear regression (estimate 1.71; SE 2.37; p-value 0.47). After adjusting for age, we found no significant correlation between urinary antigen positivity and variations in the WHO ordinal scale and laboratory markers at admission and after 14 days. We found that a positive PUA result was not frequent and had no impact on clinical outcomes or clinical improvement. Our results did not support the routine use of PUA tests to select COVID-19 patients who will benefit from antibiotic therapy.

Early Bacterial Identification among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Clinical Trial.

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15–0.30; adjusted odds ratio, 0.23; 95% CI, 0.16–0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57; 95% CI, 1.01–2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT 04359693).

Protective role of PhtD and its amino and carboxyl fragments against pneumococcal sepsis

The implementation of polysaccharide-based vaccines has massively reduced the incidence of invasive pneumococcal diseases. However, there is great concern regarding serotype replacement and the increase in antibiotic resistant strains expressing non-vaccine capsular types. In addition, conjugate vaccines have high production costs, a limiting factor for their implementation in mass immunization programs in developing countries. These limitations have prompted the development of novel vaccine strategies for prevention of Streptococcus pneumoniae infections. The use of conserved pneumococcal antigens such as recombinant proteins or protein fragments presents an interesting serotype-independent alternative. Pht is a family of surface-exposed proteins which have been evaluated as potential vaccine candidates with encouraging results. The present work investigated the immune responses elicited by subcutaneous immunization of mice with the polyhistidine triad protein D (PhtD) and its amino and carboxyl terminal fragments. The proteins were immunogenic and protective against pneumococcal sepsis in mice. Antibodies raised against PhtD increased complement C3b deposition on the pneumococcal surface, mainly mediated by the alternative pathway. Sera from mice immunized with PhtD and PhtD_Cter promoted an increase in bacterial uptake by mouse phagocytes. The interaction of PhtD with the complement system regulator factor H was investigated in silico and in vitro by ELISA and western blot, confirming PhtD as a factor-H binding protein. Our results support the inclusion of PhtD and more specifically, its C-terminal fragment in a multicomponent serotype independent vaccine and suggests a role for the complement system in PhtD-mediated protection.

Coinfections among hospitalized patients with covid-19 in the first pandemic wave

BackgroundCOVID19 is the novel respiratory illness caused by SARS-CoV-2. The presence of other potentially pathogenic microorganisms could worsen the prognosis of these patients. Aim: The study aims to describe coinfections in COVID-19 patients and contrast it between standard ward and critical care patients at Hospital Central de la Defensa Gómez Ulla (HCDGU). MethodsA retrospective study was carried out of patients with COVID-19 confirmed with RTPCR admitted to the HCDGU from March 5, 2020 to May 7 of 2020. FindingsOf a total of 703 patients with COVID-19, 75(10.7%) had other microbiologically confirmed infections: 9% (58/648) in standard ward patients and 31.5%(17/54) in critical care patients. In total 86 samples of the 75 patients presented some microorganism; clinically relevant bacteraemias, 50%, respiratory cultures, 32.6% and pneumococcal positive antigens, 17.4%. ConclusionsWe found a low frequency of microorganism coinfection in COVID-19 patients, however in critical care these coinfections increased considerably.

Characterization of the Anti-Inflammatory Capacity of IL-10-Producing Neutrophils in Response to Streptococcus pneumoniae Infection.

Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10-/-) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.