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Rationale: Streptococcus pneumoniae is a common cause of community-acquired pneumonia. Currently, it is believed that many cases of pulmonary infection with negative results on pathogenic testing are caused by S. pneumoniae. There have been no reports of the detection of S. pneumoniae antigen in lung lavage fluid., Patient Concerns: An elderly male patient with suboptimal fasting blood glucose control and a history of liver abscess., Diagnosis: Chest computed tomography (CT) revealed inflammatory lesions in both lungs with consolidation in the middle lobe of the right lung., Interventions: After admission, we collected alveolar lavage fluid in a timely manner and performed pneumococcal antigen detection and etiological testing., Outcomes: Prompt testing for pneumococcal antigen in bronchoalveolar lavage fluid yielded a positive clinical outcome. Subsequent analysis via bacterial culture of sputum and next-generation sequencing (mNGS) of BALF definitively identified S. pneumoniae as the etiological agent. Following the analysis of drug sensitivity test results from the identified pathogens, adjustments were made to the antibiotic regimen, and appropriate pus puncture drainage was performed. Subsequently, the patient's condition improved, leading to discharge., Conclusion: The identification of S. pneumoniae antigen in bronchoalveolar lavage fluid may facilitate earlier and more precise diagnosis of pneumonia attributed to S. pneumoniae., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We report a clinical case of a child with an invasive pneumococcal disease caused by two different pneumococcal serotypes that belonged to different sequence types. She was a 15-month-old girl with pneumonia and pleural effusion in which S. pneumoniae colonies with different morphologies grew, one from the blood culture (characteristic greyish appearance) and the other from the pleural fluid (mucoid appearance). The isolate from blood was serotype 22 F (ST698/CC698/GPSC61), while the isolate from the pleural fluid was serotype 3 (ST180/CC180/GPSC12). The patient fully recovered after treatment with intravenous ampicillin followed by oral amoxicillin., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CH is Principal Investigator and AF is the Chief Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer https://www.bristol.ac.uk/translational-health-sciences/research/bcvc/research/avoncap-study/. RC, AC, GQ, GO, RK, and LD also receive research funding from Pfizer via the AvonCAP study. AF leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) pneumococcal subcommittee. Funding for the AvonCAP study was provided by Pfizer, however, the manuscript development and the analysis that is the subject of this manuscript were conducted independently of the AvonCAP study and Pfizer., (Copyright: © 2024 Challen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We report a case of a 62-year-old female presenting with shortness of breath, who was subsequently diagnosed with Austrian syndrome. The patient had a complicated clinical course, including invasive central nervous system pneumococcal disease, pneumococcal bacteremia, and mitral valve vegetation with possible leaflet perforation. Despite aggressive treatment, her condition continued to worsen. We will discuss the clinical features of this disease, approaches to diagnosis and treatment, and outcomes in light of this rare condition.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections., Competing Interests: Funded by a European Society for Paediatric Infectious Diseases Small Grant to M.J.C. With support from Wellcome (Clinical Research Training Fellowship to M.J.C., 104439/Z/14/Z) and the NIHR (Academic Clinical Lectureship). The wider study was supported by Gavi, the Vaccine Alliance through its support of the PneumoNepal Project (https://pneumonepal.org/). A.J.P. was chair of the UK Department of Health and Social Care’s Joint Committee on Vaccination and Immunisation (JCVI) during the study period and was a member for WHO’s Strategic Advisory Group of Experts on Immunization during this period. Detection of respiratory viruses was done by Micropathology Ltd, Warwick, UK and the authors are grateful for the support of Dr. Colin Fink and Dr. Marie Voice in particular. The views expressed in this report do not necessarily represent the views of the Joint Committee on Vaccination and Immunisation, NIHR, or WHO. This work received funding from the Wellcome Trust (now Wellcome). The other authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Pneumonia is a major cause of death among adults living with HIV in South Africa, but the etiology of many cases remains unknown. This study evaluated the utility of a nanofluidic qPCR assay to detect and serotype Streptococcus pneumoniae in urine samples from patients hospitalized with community-acquired pneumonia (CAP). The nanofluidic qPCR assay was optimized to target 13 pneumococcal serotypes and 4 reference genes. Archived urine samples collected from patients > 15 years of age hospitalized with pneumonia between April 2018 and August 2019 were retrospectively tested using the nanofluidic qPCR assay, BinaxNOW urine antigen test, and standard LytA qPCR. Blood culture was undertaken on a subset of the samples at the discretion of the attending physician. Cohens' Kappa statistics were used to determine the concordance between the methods. Of the 828 adults hospitalized for CAP, urine samples were available in 53% (n = 439). Of those, a random subset of 96 (22%) samples underwent testing. Of the participants included in the final analysis, the mean age was 45.8 years (SD 16.2), 49% (n = 47) were female, 98% (n = 94) were black, and 66% (n = 63) were living with HIV infection. The nanofluidic qPCR method was able to detect PCV13 vaccine strains spiked into urine samples; however, the method failed to detect any pneumococcus in clinical samples. In comparison, 19% of the pneumonia cases were attributed to S. pneumoniae using urine antigen testing. Nanofluidic qPCR is unable to detect and serotype Streptococcus pneumoniae in urine samples of South Africans hospitalized with CAP., (© 2023. The Author(s).)

Purpose: To evaluate the impact of an optimal and reproducible cutoff value set according to a predefined lymphopenia scale as an early predictor of in-hospital mortality and other outcomes in patients hospitalized with pneumococcal pneumonia and positive urinary antigen at admission to the emergency department., Methods: An observational cohort study was conducted based on analysis of a prospective registry of consecutive immunocompetent adults hospitalized for pneumococcal pneumonia in two tertiary hospitals. Generalized additive models were constructed to assess the smooth relationship between in-hospital mortality and lymphopenia., Results: We included 1173 patients. Lymphopenia on admission was documented in 686 (58.4%). No significant differences were observed between groups regarding the presence of comorbidities. Overall, 299 (25.5%) patients were admitted to intensive care and 90 (7.6%) required invasive mechanical ventilation. Fifty-nine (5%) patients died, among them 23 (38.9%) in the first 72 h after admission. A lymphocyte count < 500/μL, documented in 282 (24%) patients, was the predefined cutoff point that best predicted in-hospital mortality. After adjustment, these patients had higher rates of intensive care admission (OR 2.9; 95% CI 1.9-4.3), invasive mechanical ventilation (OR 2.2; 95% CI 1.2-3.9), septic shock (OR 1.8; 95% CI 1.1-2.9), treatment failure (OR 2.1; 95% CI 1.2-3.5), and in-hospital mortality (OR 2.2; 95% 1.1-4.9). Severe lymphopenia outperformed PSI score in predicting early and 30-day mortality in patients classified in the higher-risk classes., Conclusion: Lymphocyte count < 500/μL could be used as a reproducible predictor of complicated clinical course in patients with an early diagnosis of pneumococcal pneumonia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background/aims: The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea., Methods: We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status., Results: The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased., Conclusion: Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.

Objectives: To analyze the differences in short- and long-term prognosis and the predictors of survival between patients with community-acquired Legionella and Streptococcus pneumoniae pneumonia, diagnosed early by urinary antigen testing (UAT)., Methods: Prospective multicenter study conducted in immunocompetent patients hospitalized with community-acquired Legionella or pneumococcal pneumonia (L-CAP or P-CAP) between 2002-2020. All cases were diagnosed based on positive UAT., Results: We included 1452 patients, 260 with community-acquired Legionella pneumonia (L-CAP) and 1192 with community-acquired pneumococcal pneumonia (P-CAP). The 30-day mortality was higher for L-CAP (6.2%) than for P-CAP (5%). After discharge and during the median follow-up durations of 11.4 and 8.43 years, 32.4% and 47.9% of patients with L-CAP and P-CAP died, and 82.3% and 97.4% died earlier than expected, respectively. The independent risk factors for shorter long-term survival were age >65 years, chronic obstructive pulmonary disease, cardiac arrhythmia, and congestive heart failure in L-CAP and the same first three factors plus nursing home residence, cancer, diabetes mellitus, cerebrovascular disease, altered mental status, blood urea nitrogen ≥30 mg/dl, and congestive heart failure as a cardiac complication during hospitalization in P-CAP., Conclusion: In patients diagnosed early by UAT, the long-term survival after L-CAP or P-CAP was shorter (particularly after P-CAP) than expected, and this shorter survival was mainly associated with age and comorbidities., Competing Interests: Declarations of competing interests The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Community-acquired pneumonia is a common diagnosis in children. Among the many children whose symptoms and/or chest X-ray is consistent with community-acquired pneumonia, it can be difficult to distinguish the rare cases of differential diagnoses that require specific management. The aim of this educational article is to provide clinicians with a series of questions to ask themselves in order to detect a possible differential diagnosis of pneumonia in children. The value of this approach is illustrated by 13 real clinical cases in which a child was misdiagnosed as having lobar pneumonia. What is Known: • When a lobar pneumonia is diagnosed, an appropriate antibiotic treatment leads to the resolution of the clinical signs in most cases. • However, several diseases can be look-alikes for pneumonia and mislead the practitioner. What is New: • This article provides a new approach to identify differential diagnoses of pneumonia in children. • It is illustrated by 13 real-life situations of children misdiagnosed as having pneumonia., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We compared the performance of STANDARD F S. pneumoniae Ag FIA with that of BinaxNOW S. pneumoniae Antigen Card using 206 urine samples. The performance of STANDARD F was highly comparable to that of BinaxNOW. STANDARD F assay could be a valuable tool for diagnosis of invasive pneumococcal disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Necrotizing pneumonia rarely occurs in children, but when it does it can be complicated by bronchopleural fistula, empyema, pneumothorax, sepsis, and acute respiratory distress syndrome (ARDS). Antimicrobial therapy is the cornerstone of its management; however, surgery is necessary in some cases. Ideally, surgical interventions are kept to a minimum, but this is not always possible if there is a mass effect from air and fluid in the pleural space, pulmonary necrosis leading to massive hemoptysis, uncontrolled sepsis, or difficulties with assisted ventilation. Case Presentation: Herein we present a patient with refractory pyopneumothorax and ARDS due to pneumococcal necrotizing pneumonia complicated by a bronchopleural fistula. The patient's clinical condition deteriorated despite antibiotics, surgical drainage, and assisted ventilation. Owing to pneumothorax with a high percentage of air leakage, bilateral diffuse collapse of the lungs, and insufficient oxygenation, surgical treatment was considered, but because of the patient's lack of tolerance for surgery due to hemodynamic reasons and the complications associated with surgery, medical treatment was determined to be more appropriate. Surfactant treatment was administered to the patient, resulting in significant clinical improvement. Conclusion: To the best of our knowledge, this is the first report of the use of surfactant to treat ARDS due to necrotizing pneumonia. Based on the presented case, we think surfactant can be considered as a salvage treatment for such patients.

We previously reported that despite the use of pneumococcal conjugate vaccines (PCVs), vaccine serotypes remained important causes of pneumonia with pleural effusion and empyema (pediatric complicated pneumococcal pneumonia [PCPP]). We cultured and performed PCR on 174 pleural fluid samples recovered from pediatric patients in Portugal from 2016 to 2019 to identify and serotype Streptococcus pneumoniae. Most PCPP cases ( n  = 87/98) were identified by PCR only. Serotypes 3 (67%), 14, and 8 (5% each) were the most frequent. Vaccine breakthrough cases were seen among age-appropriately, 13-valent, PCV vaccinated children (median: 3 years, range: 17 months to 7 years), mostly with serotype 3 ( n  = 27) but also with serotypes 14 and 19A ( n  = 2 each). One breakthrough was seen with serotype 14 in an age-appropriately, 10-valent, PCV-vaccinated child and another with serotype 3 in a child to whom the 23-valent polysaccharide vaccine was administered. While the relative risk of serotype 1 PCPP decreased almost 10-fold from the period of 2010 to 2015 to the period of 2016 to 2019 (relative risk [RR] = 0.106), that of serotype 3 PCPP almost doubled (RR = 1.835). Our data highlight the importance of molecular diagnostics in identifying PCPP and document the continued importance of serotype 3 PCPP, even when PCV13 use with almost universal coverage could be expected to reduce exposure to this serotype. IMPORTANCE The use of conjugate vaccines against Streptococcus pneumoniae in children has led to substantial reductions in pneumococcal invasive disease. However, the reductions seen in each of the 13 serotypes currently included in the highest-valency vaccine approved for use in children (PCV13), were not the same. It is becoming clear that most vaccine breakthroughs worldwide involve serotype 3 and are frequently associated with complicated pneumonia cases, often with empyema or pleural effusion. Here, we show that despite almost universal PCV13 use, which would be expected to reduce vaccine serotype circulation and further reinforce vaccine direct protection, pneumococci and serotype 3 remain the major causes of pediatric complicated pneumonia. Molecular methods are essential to identify and serotype pneumococci in these cases, which frequently reflect vaccine breakthroughs. A broader use of molecular diagnostics will be essential to determine the role of this important serotype in the context of PCV13 use in different geographic regions.

Background/objectives: Urinary antigen tests have been used for the rapid identification of Streptococcus pneumoniae infection in patients with pneumonia, thereby leading to earlier targeted therapy than when using conventional diagnostic culture methods. This study aimed to update the knowledge on the diagnostic accuracy of urinary antigen tests for S. pneumoniae among patients with acute respiratory failure suspected of pneumonia based on a systematic review and meta-analysis., Methods: A systematic search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials for studies published up to 3 June 2020. Prospective and retrospective cohort studies (in English) that reported on the diagnostic performance of urinary antigen tests versus culture or smear diagnostic methods in adult patients with clinically diagnosed pneumonia were selected and analysed. The QUADAS-2 tool was used to assess the risk of bias, and a bivariate random effects model was applied to perform a meta-analysis of the selected studies., Results: A total of 2179 studies were screened, of which 30 met the eligibility criteria for quality assessment and meta-analysis. Overall, data from 12 366 patients, including 1548 patients (12.5%) with the target condition and suspected pneumococcal pneumonia, were included in the analysis. The overall quality of the included studies was determined to be serious. The calculated pooled sensitivity and specificity were of 0.66 (95% CI 0.62 to 0.69) and 0.90 (95% CI 0.85 to 0.93), respectively., Conclusions: The urinary antigen test is useful for achieving a definitive diagnosis of S. pneumoniae infection in patients with pneumonia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the effect of pneumococcal urinary antigen test (UAT) usage on broad-spectrum antibiotic treatment in community-acquired pneumonia (CAP)., Methods: Patients admitted to 32 Swedish hospitals between 2011 and 2014 were retrospectively included from the Swedish National Quality Register of CAP. Using propensity score matched data, stratified by CRB-65 score, we studied the effect of performing UAT and of positive test results on treatment with broad-spectrum β-lactam monotherapy (BSBM) and antibiotics with coverage for atypical bacteria compared to narrow-spectrum β-lactam monotherapy (NSBM)., Results: UAT was performed for 4,995/14,590 (34.2%) patients, 603/4,995 (12.1%) of whom had positive test results. At day three, performing UAT was not associated with decreased use of BSBM (OR 1.07, 95% CI 0.94-1.23) but was associated with increased atypical coverage among patients with CRB-65 score 2 (OR 1.47, 95% CI 1.06-2.02). A positive UAT was associated with decreased BSBM use (OR 0.39, 95% CI 0.25-0.60) and decreased atypical coverage (OR 0.25, 95% CI 0.16-0.37), predominantly in non-severe CAP. At day one, performing UAT was associated with atypical coverage among patients with CRB-65 scores 2 (OR 2.60, 95% CI 1.69-3.98) and 3-4 (OR 3.69, 95% CI 1.55-8.79), and a positive test reduced the odds of BSBM treatment among CRB-65 score 3-4 patients (OR 3.49, 95% CI 1.02-12.0)., Conclusions: Performing UAT had no overall effect on decreasing the use of BSBM treatment by day three of hospitalization, yet non-severely ill patients with positive UAT results were less likely to be treated with BSBM and antibiotics with atypical coverage., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022. Published by Elsevier Ltd.)

Objective(s): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017., Methods: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]., Results: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP., Conclusion(s): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: We investigated the pathogenesis of pneumococcal pneumonia using clinical specimens collected for pneumonia surveillance in The Gambia., Methods: Lung aspirates and nasopharyngeal swabs from 31 patients were examined by culture, quantitative polymerase chain reaction (qPCR), whole genome sequencing, serotyping, and reverse-transcription qPCR., Results: Five lung aspirates cultured pneumococci, with a matching strain identified in the nasopharynx. Three virulence genes including ply (pneumolysin) were upregulated >20-fold in the lung compared with the nasopharynx. Nasopharyngeal pneumococcal density was higher in pediatric pneumonia patients compared with controls (P < .0001)., Conclusions: Findings suggest that changes in pneumococcal gene expression occurring in the lung environment may be important in pathogenesis., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

A 61-year-old woman was transferred with a complaint of a fever and productive cough. She had tested positive for Mycobacterium avium and Nocardia cyriacigeorgica at least twice, and Streptococcus pneumonia (PISP) was isolated (3+) from her purulent sputum. As radiological findings, a lower lung field-dominant infiltration shadow and nodular shadow with cavity were recognized in the bilateral lung fields. We diagnosed her with pneumococcal pneumonia co-infection with M. avium and N. cyriacigeorgica. She was treated with MEPM for pneumococcal pneumonia, a standard regimen containing clarithromycin for pulmonary M. avium complex (MAC) disease, and sulfamethoxazole/trimethoprim for pulmonary nocardiosis. She improved with appropriate treatment.

Objectives: To determine the causes of lobar pneumonia in rural Gambia., Design and Setting: Population-based pneumonia surveillance at seven peripheral health facilities and two regional hospitals in rural Gambia. 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in August 2009 and replaced by PCV13 from May 2011., Methods: Prospective pneumonia surveillance was undertaken among all ages with referral of suspected pneumonia cases to the regional hospitals. Blood culture and chest radiographs were performed routinely while lung or pleural aspirates were collected from selected, clinically stable patients with pleural effusion on radiograph and/or large, dense, peripheral consolidation. We used conventional microbiology, and from 8 April 2011 to 17 July 2012, used a multiplex PCR assay on lung and pleural aspirates. We calculated proportions with pathogens, associations between coinfecting pathogens and PCV effectiveness., Participants: 2550 patients were admitted with clinical pneumonia; 741 with lobar pneumonia or pleural effusion. We performed 181 lung or pleural aspirates and multiplex PCR on 156 lung and 4 pleural aspirates., Results: Pathogens were detected in 116/160 specimens, the most common being Streptococcus pneumoniae (n=68) , Staphylococcus aureus (n=26) and Haemophilus influenzae type b (n=11). Bacteria (n=97) were more common than viruses (n=49). Common viruses were bocavirus (n=11) and influenza (n=11). Coinfections were frequent (n=55). Moraxella catarrhalis was detected in eight patients and in every case there was coinfection with S. pneumoniae . The odds ratio of vaccine-type pneumococcal pneumonia in patients with two or three compared with zero doses of PCV was 0.17 (95% CI 0.06 to 0.51)., Conclusions: Lobar pneumonia in rural Gambia was caused primarily by bacteria, particularly S. pneumoniae and S. aureus . Coinfection was common and M. catarrhalis always coinfected with S. pneumoniae . PCV was highly efficacious against vaccine-type pneumococcal pneumonia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Invasive pneumococcal disease (IPD) is often fatal, requiring prompt diagnosis and treatment. To evaluate the factors associated with IPD in adults, we retrospectively investigated its characteristics compared to pneumococcal pneumonia without confirmation of invasion (PP)., Methods: Patients >18 years with PP (n = 79) and IPD (n = 53) from whom Streptococcus pneumoniae was isolated were enrolled from two hospitals between 2011 and 2017. Clinical backgrounds, blood test results at admission, initial antimicrobials administered, isolate serotypes, and outcomes were compared between the PP and IPD groups., Results: Patients with IPD exhibited higher mortality (28.3%) than those with PP (2.5%) (p<0.001), regardless of the type of antimicrobials first administered. The majority (80.0%) of fatal cases of IPD were due to vaccine serotypes. Almost all patients with PP (97.4%) and IPD (88.7%) had underlying disease. C-reactive protein (CRP) ≥17.0 mg/dL (odds ratio [OR], 7.1; 95% CI, 2.7-19.0; p<0.001), white blood cell counts <11.0 × 10 3 /μL (OR, 3.2; 95% CI, 1.3-8.4; p = 0.016), and platelet (PLT) counts <16.2 × 10 4 /μL (OR, 2.8; 95% CI, 1.1-7.4; p = 0.036) were significantly more common in IPD. Moreover, 89.5% of cases with both CRP ≥23.8 mg/dL and PLT <18.5 × 10 4 /μL were diagnosed with IPD., Conclusion: Laboratory blood test findings at admission, particularly high CRP and low PLT values, are useful early indicators of IPD in adults. These results could be used to initiate rapid and intensive treatment and improve prognosis., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of the study was to assess the performance of real-time PCR targeting the lytA gene (rtPCR-lytA) in plasma, urine and nasopharyngeal (NP) samples for the diagnosis of pneumococcal community-acquired pneumonia (P-CAP)., Methods: Prospective observational study including all consecutive adults with CAP from November 2015 to May 2017. P-CAP was defined if pneumococcus was identified using conventional methods (CM) and/or a positive rtPCR-lytA was detected in blood, urine or NP samples (NP cut-off ≥8000 copies/mL). Diagnostic performance of each test was calculated., Results: A total of 133 individuals with CAP were included. Of these, P-CAP was diagnosed in 62 (46.6%). The proportion of P-CAP diagnosed by rtPCR-lytA methods was significantly higher than that diagnosed by CM (87.1% versus 59.7%, p 0.005). The rtPCR-lytA identified Streptococcus pneumoniae in 25 patients (40.3% of all individuals with P-CAP) whose diagnosis would have been missed by CM. NP-rtPCR-lytA allowed diagnosis of 62.3% of P-CAP. A nasopharyngeal colonization density ≥2351 copies/mL predicted P-CAP diagnosis (area under the curve = 0.82, sensitivity 83.3%, specificity 80.9%). There was a positive correlation between increasing bacterial load in blood and CURB-65 score (Spearman correlation coefficient r = 0.4, p 0.001), pneumonia severity index (r = 0.3, p 0.02) and time to clinical stability (r = 0.33, p 0.01). Median bacterial load in blood was higher in P-CAP patients with bacteraemia (0.65 × 10 3 versus 0 × 10 3 copies/mL, p 0.002), intensive care unit admission (0.68 × 10 3 versus 0 × 10 3 copies/mL, p 0.04) or mechanical ventilation (7.45 × 10 3 versus 0 × 10 3 copies/mL, p 0.04)., Conclusions: The use of rtPCR-lytA methods significantly increased the diagnosis of P-CAP compared with CM. Nasopharyngeal swabs rtPCR-lytA detection, with an accurate cut-off value, was the most promising among molecular methods for the diagnosis of P-CAP., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens., Methods: The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis., Results: Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5-6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%., Conclusions: Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments., (© 2021. The Author(s).)

Background: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine., Methods: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20)., Results: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes., Conclusions: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: To explore the negative predictive value (NPV) of C-reactive protein (CRP) at admission to exclude complicated disease manifestations of pneumococcal disease., Methods: A Dutch multicentre retrospective cohort study was conducted between 01-01-2012 and 30-06-2020. Adults with positive blood cultures for Streptococcus pneumoniae, whose CRP was measured at admission and whose infection focus was known, were included. Electronic medical and microbiological records were reviewed., Results: Of the 832 bacteraemic patients enrolled, 30% had complicated manifestations of pneumococcal disease; most frequent were pleural effusion (8.9%), pleural empyema (5.4%) and meningitis (7.5%). Compared to solitary pneumonia, patients with pleural effusion and empyema presented with higher CRP levels. Although low CRP levels did not exclude complicated disease in general, a CRP level < 114 mg/L at admission could reliably exclude empyema among adult pneumonia patients with an NPV of 93% and a specificity of 26%. However, in cases where pleural fluid was present, CRP levels were mostly > 114 mg/L, such that suspicion of empyema could only be ruled out in a minority of cases (10%)., Conclusions: Complicated manifestations are prevalent in adult pneumococcal bacteraemia. Low blood CRP levels can reliably exclude the development of pulmonary empyema. Practical value may be largest in settings without thoracic imaging at hand., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Spain introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood National Immunization Program in 2015-2016 with coverage of 3 doses of 94.8% in 2018. We assessed the evolution of all pneumococcal, PCV13 vaccine type (VT), and experimental PCV20-VT (PCV13 + serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F) hospitalized community-acquired pneumonia (CAP) in adults in Spain from 2011-2018., Methods: A prospective observational study of immunocompetent adults (≥18 years) admitted to 4 Spanish hospitals with chest X-ray-confirmed CAP between November 2011 and November 2018. Microbiological confirmation was obtained using the Pfizer serotype-specific urinary antigen detection tests (UAD1/UAD2), BinaxNow test for urine, and conventional cultures of blood, pleural fluid, and high-quality sputum., Results: Of 3107 adults hospitalized with CAP, 1943 were ≥65 years. Underlying conditions were present in 87% (n = 2704) of the participants. Among all patients, 895 (28.8%) had pneumococcal CAP and 439 (14.1%) had PCV13-VT CAP, decreasing from 17.9% (n = 77) to 13.2% (n = 68) from 2011-2012 to 2017-2018 (P = .049). PCV20-VT CAP occurred in 243 (23.8%) of those included in 2016-2018. The most identified serotypes were 3 and 8. Serotype 3 accounted for 6.9% (n = 215) of CAP cases, remaining stable during the study period, and was associated with disease severity., Conclusions: PCV13-VT caused a substantial proportion of CAP in Spanish immunocompetent adults 8 years after introduction of childhood PCV13 immunization. Improving direct PCV13 coverage of targeted adult populations could further reduce PCV13-VT burden, a benefit that could be increased further if PCV20 is licensed and implemented., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

The aim of the present study was to investigate the predictors of targeted therapy (TT) for pneumococcal community-acquired pneumonia (PCAP) with a positive urinary antigen test (UAT) and compare the outcomes with those of nontargeted therapy. This prospective cohort study enrolled consecutive PCAP patients with a positive UAT who were hospitalized at Kurashiki Central Hospital from October 2010 to November 2019. A total of 286 patients were included. Of them, 56 patients (19.6%) were included in the TT group. On multivariate analysis, identification of Gram-positive diplococci by Gram stain (OR [95% CI]: 2.46 [1.32-4.63]) was a positive predictor, whereas aspiration pneumonia (0.17 [0.03-0.59]) and CURB-65 score (0.59 [0.42-0.81]) were negative predictors of TT. Initial treatment failure and 30-day mortality were not significantly different. The UAT is not used enough for TT, and TT for PCAP did not have worse outcomes., Competing Interests: Declaration of competing interest The authors report no conflicts of interest relevant to this article., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Serotype-specific diagnosis of pneumococcal community-acquired pneumonia in children under age 5 years would mark a major advancement for understanding pneumococcal epidemiology and supporting vaccine decision-making., Methods: A Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and subsequently validated in adults, but its applicability to children is unknown. This study aimed to set appropriate cutoffs for use of the UAD in a healthy pediatric population and apply these cutoffs in children with pneumonia in sub-Saharan Africa. The cutoffs were determined by assessing 379 urines obtained from healthy children under age 5 years from the Bobo-Dioulasso area for serotypes included in 13-valent pneumococcal conjugate vaccine (UAD-1) and the 11 other serotypes unique to 23-valent pneumococcal polysaccharide vaccine (UAD-2)., Results: Based on the assigned cutoff values, among 108 children who met the World Health Organization consolidation endpoint criteria, UAD-1 and UAD-2 were positive in 23.3% and 8.3%, respectively; among 364 children with clinically suspected pneumonia who did not meet the World Health Organization criteria, UAD-1 and UAD-2 were positive for 6.6% and 3.6%, respectively. Pneumococcal carriage prevalence was similar among pneumonia cases (30%) versus controls (35%) as was semiquantitative carriage density., Conclusions: UAD-1 and UAD-2 were able to distinguish community controls from children with pneumonia, particularly pneumonia with consolidation. Future studies are needed to confirm these results and more fully assess the contribution of pneumococcal carriage and concurrent viral infection., Competing Interests: J.M. and B.D.G. were employees of Agence de Medicine Preventive during the implementation of the study and currently work for Pfizer Inc. M.W.P. and Q.J. currently work for Pfizer Inc. E.B. worked for Pfizer Inc. during the previous 3 years but is not currently an employee. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The urinary antigen test (UAT) is a rapid diagnostic method for pneumococcal pneumonia, but the high false-negative rate of 30% may affect its reliability. To maximize the utility of UAT, it is necessary to investigate the patient factors affecting UAT results. However, there is no report elucidating the association between its utility and pre-existing lung abnormalities. We retrospectively reviewed 388 patients with pneumococcal pneumonia confirmed by blood and/or sputum culture tests. Finally, 94 of 388 patients who had the results of UAT and computed tomography scans were enrolled to evaluate the association between the utility of UAT and patient factors including pulmonary emphysema and fibrosis. The overall positive rate of UAT was 69.1%. The positive rates of UAT in the patients with emphysema were significantly lower than those in individuals without emphysema (33.3% and 77.6%, p < 0.001). Univariate logistic regression analysis showed that the presence of emphysema was associated with a low positive rate (odds ratio 6.944, 95% confidence interval 2.268-21.231). Multivariate logistic analysis showed that the presence of emphysema and lower levels of serum blood urea nitrogen (BUN) were significantly and independently associated with a low positive rate. The combination of emphysema and BUN can potentially stratify the positive rate of UAT in patients with pneumococcal pneumonia. Patients with pneumococcal pneumonia and emphysema have a lower positive rate of UAT. Additionally, the combination of emphysema and serum BUN value may be useful to evaluate the reliability of the negative results of pneumococcal UAT.

A 44-year-old previously well woman presented with features of respiratory sepsis including a productive cough and fevers, with a recent preceding influenza-like illness. She was diagnosed with community-acquired pneumonia on chest radiograph, influenza infection via nasopharyngeal swab and Streptococcus pneumoniae bloodstream infection with associated purulent pericarditis. She was managed with pericardial drainage and concurrent treatment with antibiotics and made an excellent recovery. This case highlights the complications of both influenza and S. pneumoniae infections, and the importance of prevention via vaccination., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the proportion of patients meeting the 2010 SPILF-AFSSAPS guiding criteria for Streptococcuspneumoniae in patients consulting at the emergency departments of four French university hospitals for acute community-acquired pneumonia (CAP) suspicion., Patients and Methods: The PACSCAN study prospectively included 319 patients. Medical history, clinical, biological, and radiological presentations were collected. An adjudication committee retrospectively classified the diagnostic certainty based on the initial chest CT scan data and the follow-up data up to Day 28. S. pneumoniae was looked for according to the clinician's choice of blood culture, pneumococcal urinary antigen test, nasopharyngeal PCR, and/or sputum microbiological examination., Results: All patients (100%) met at least one criterion for S. pneumoniae CAP and six (2%) met all criteria. The distribution of criteria ranged from 32% (chest pain criterion) to 86% (age≥40years criterion). These figures were respectively 100%, 3%, 38%, and 82% when the study population was restricted to the 139 patients with definite or probable CAP, according to the adjudication committee. Taking into account the microbiological results, the criteria taken one by one or combined did not make it possible to differentiate the 19 S. pneumoniae CAP from the other CAPs., Conclusion: The 2010 SPILF-AFSSAPS guiding criteria for S. pneumoniae CAP are found in very variable proportions and do not, in their current form, make it possible to accurately guide towards a pneumococcal etiology in patients included in the PACSCAN study., (Copyright © 2020. Published by Elsevier Masson SAS.)

Introduction : When evaluating the public health value of adult pneumococcal conjugate vaccine (PCV) for pneumonia, regulatory agencies and vaccine technical committees (VTCs) emphasize vaccine serotype (VT), radiologically confirmed community-acquired pneumonia (CAP) to the exclusion of clinically defined pneumonia and thus may underestimate PCV's public health value. Areas covered : We review the critiques that have been raised to using clinically defined pneumonia as a complement to VT-CAP in evaluating the public health value of adult PCVs. Expert opinion : PCV13 efficacies for preventing hospitalized CAP ranged from 6% to 11% and for a combination of primary and secondary care from 4% to 12%, with relatively high associated rate reductions. These efficacy values are larger than estimated from multiplying PCV13 efficacy against vaccine-type CAP by the proportion of CAP identified as vaccine-type through tests, such as a serotype-specific urinary antigen detection assay. Current understanding of pneumococcal epidemiology and limitations of diagnostic tests suggest the efficacy values for clinically defined outcomes are plausible and potentially generalizable. Regulatory agencies and VTCs have accepted clinically defined outcomes for assessing pediatric vaccines and - while additional studies assessing adult clinical CAP VE are needed - they might consider existing data when evaluating adult PCV use.

Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae ( Spn )-a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H 2 O 2 ) as a virulence strategy. Apart from H 2 O 2 , Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.

Reports of invasive disease due to Streptococcus pneumoniae have declined since the introduction of pneumococcal conjugate vaccines (PCV7 and PCV13). The incidence of invasive diseases due to S. pneumoniae that are not addressed by the vaccines, however, has increased in children and adults, creating a global public health problem. Previously, we established the loop-mediated isothermal amplification (LAMP) method for a PCV13 serotype-specific assay. In the current study, we developed a rapid, simple, and cost-effective assay to detect serotypes in the 23-valent pneumococcal polysaccharide vaccine (PPSV23) using the LAMP method. In this study, LAMP primer sets for serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F of S. pneumoniae were developed. The reactivity, specificity, and sensitivity of LAMP assays were determined and compared to those of conventional PCR. The feasibility of LAMP assays in clinical application in patients with invasive pneumococcal diseases was validated by defining the detection limit of the LAMP assay with bacterial genomic DNA-spiked blood specimens. The specificity of each LAMP assay was determined using 44 serotypes of pneumococcal strains. Their sensitivity was 100 copies per reaction versus 103 to 106 copies per reaction for PCR assays. Using DNA-spiked blood specimens, excluding the LAMP assay that targeted serotype 22F (103 copies per reaction), the limit of detection of the LAMP assay was similar to that with purified DNA as the template (102 copies per reaction), compared with 103 to >106 copies per reaction for PCR assays. In conclusion, a rapid and simple LAMP-based PPSV23-targeted serotype detection assay was developed for use in many countries. This study is the first report of a LAMP-based assay for identification of PPSV23 serotypes. Further evaluation of this assay is needed through surveillance and vaccine efficacy studies., Competing Interests: The authors have declared that no competing interests exist.

Background: Community-acquired pneumonia (CAP), especially pneumococcal CAP (P-CAP), is associated with a heavy burden of illness as evidenced by high rates of intensive care unit (ICU) admission, mortality, and costs. Although well-defined acutely, determinants influencing long-term burden are less known. This study assessed determinants of 28-day and 1-year mortality and costs among P-CAP patients admitted in ICUs., Methods: Data regarding all hospital and ICU stays in France in 2014 were extracted from the French healthcare administrative database. All patients admitted in the ICU with a pneumonia diagnosis were included, except those hospitalized for pneumonia within the previous 3 months. The pneumococcal etiology and comorbidities were captured. All hospital stays were included in the cost analysis. Comorbidities and other factors effect on the 28-day and 1-year mortality were assessed using a Cox regression model. Factors associated with increased costs were identified using log-linear regression models., Results: Among 182,858 patients hospitalized for CAP in France for 1 year, 10,587 (5.8%) had a P-CAP, among whom 1665 (15.7%) required ICU admission. The in-hospital mortality reached 22.8% at day 28 and 32.3% at 1 year. The mortality risk increased with age > 54 years, malignancies (hazard ratio (HR) 1.54, 95% CI [1.23-1.94], p = 0.0002), liver diseases (HR 2.08, 95% CI [1.61-2.69], p < 0.0001), and the illness severity at ICU admission. Compared with non-ICU-admitted patients, ICU survivors remained at higher risk of 1-year mortality. Within the following year, 38.2% (516/1350) of the 28-day survivors required at least another hospital stay, mostly for respiratory diseases. The mean cost of the initial stay was €19,008 for all patients and €11,637 for subsequent hospital stays within 1 year. One-year costs were influenced by age (lower in patients > 75 years old, p = 0.008), chronic cardiac (+ 11% [0.02-0.19], p = 0.019), and respiratory diseases (+ 11% [0.03-0.18], p = 0.006)., Conclusions: P-CAP in ICU-admitted patients was associated with a heavy burden of mortality and costs at one year. Older age was associated with both early and 1-year increased mortality. Malignant and chronic liver diseases were associated with increased mortality, whereas chronic cardiac failure and chronic respiratory disease with increased costs., Trial Registration: N/A (study on existing database).

BACKGROUND Increased susceptibility to bacterial infections is a hallmark of multiple myeloma (MM). Invasive infections with Streptococcus pneumoniae may be the first manifestation of underlying MM. Clinicians treating patients with invasive S. pneumoniae infections may consider searching for underlying MM in the presence of certain diagnostic findings. CASE REPORT A previously healthy 60-year-old man was referred from his general physician because of fever, cough, and chills despite treatment with clarithromycin. The patient had experienced night sweats, weight loss, and recurrent episodes of fever and cough during the last 3 months. Examination was significant for left-sided pulmonary rales. A chest X-ray showed a retrocardiac consolidation of the left lower lobe. The patient was started on empirical antimicrobial therapy for community-acquired pneumonia. Subsequently, blood and sputum cultures were positive for S. pneumoniae. Given the history of night sweats and weight loss, the discrepancy between elevated total protein and low albumin levels, and the diagnosis of pneumococcal bacteremia, multiple myeloma (MM) was suspected and confirmed by immunofixation and bone marrow biopsy. CONCLUSIONS This case showed that clinicians should be vigilant for features of MM, which are encountered during history (e.g., weight loss, bone pain) or routine laboratory workup (e.g., unexplained anemia, renal failure, hypercalcemia, or a discrepancy between elevated total protein and low albumin levels) in elderly patients presenting with invasive pneumococcal disease.

The performance of an immunofluorescence-based Streptococcus pneumoniae antigen detection test in pleural fluid (IF-PF) was evaluated. For proven and possible pneumococcal pneumonias global sensitivity and specificity were 92.6 (95 CI 76.6-97.9) and 80 (95 CI 62.7-90.5), respectively, with no significant differences between children and adults. Global diagnostic accuracy of IF-PF was 86% (74.2-93.7), and a substantial k index of concordance with culture/RT-PCR of 0.716 (0.535-0.896). IF-PF might be useful as a rapid complementary test for the etiologic diagnosis of pneumococcal pneumonia., (Copyright © 2020 Elsevier Inc. All rights reserved.)

BACKGROUND A lethal synergism between the influenza virus and Streptococcus pneumoniae has been identified. However, bacterial coinfection is considered relatively infrequent in hospitalized patients with COVID-19, and the co-prevalence of Streptococcus pneumoniae is low. MATERIAL AND METHODS We retrospectively analyzed the clinical characteristics and outcomes of patients subsequently admitted to AMITA Health Saint Francis Hospital between March 1 and June 30, 2020, with documented SARS-CoV-2 and S. pneumoniae coinfection. RESULTS We identified 11 patients with S. pneumoniae coinfection. The median age was 77 years (interquartile range [IQR], 74-82 years), 45.5% (5/11) were males, 54.5% (6/11) were white, and 90.9% (10/11) were long-term care facility (LTCF) residents. The median length of stay was 7 days (IQR, 6-8 days). Among 11 patients, 4 were discharged in stable condition and 7 had died, resulting in an inpatient mortality rate of 64%. CONCLUSIONS At our center, 11 patients with COVID-19 pneumonia who had confirmed infection with SARS-CoV-2 were diagnosed with Streptococcus pneumoniae infection while in hospital. All patients had pneumonia confirmed on imaging and a nonspecific increase in markers of inflammation. The in-hospital mortality rate of 64% (7 patients) was higher in this group than in previous reports. This study highlights the importance of monitoring bacterial coinfection in patients with viral lung infection due to SARS-CoV-2.

Background and Objectives: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients., Materials and Methods: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis., Results: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively ( p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71)., Conclusions: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.

Background: The Infectious Diseases Society of America recommends pneumococcal urinary antigen testing (UAT) when identifying pneumococcal infection would allow for antibiotic de-escalation. However, the frequencies of UAT and subsequent antibiotic de-escalation are unknown., Methods: We conducted a retrospective cohort study of adult patients admitted with community-acquired or healthcare-associated pneumonia to 170 US hospitals in the Premier database from 2010 to 2015, to describe variation in UAT use, associations of UAT results with antibiotic de-escalation, and associations of de-escalation with outcomes., Results: Among 159 894 eligible admissions, 24 757 (15.5%) included UAT performed (18.4% of intensive care unit [ICU] and 15.3% of non-ICU patients). Among hospitals with ≥100 eligible patients, UAT proportions ranged from 0% to 69%. Compared to patients with negative UAT, 7.2% with positive UAT more often had a positive Streptococcus pneumoniae culture (25.4% vs 1.9%, P < .001) and less often had resistant bacteria (5.2% vs 6.8%, P < .05). Of patients initially treated with broad-spectrum antibiotics, most were still receiving broad-spectrum therapy 3 days later, but UAT-positive patients more often had coverage narrowed (38.4% vs 17.0% UAT-negative and 14.6% untested patients, P < .001). Hospital rate of UAT was strongly correlated with de-escalation following a positive test. Only 3 patients de-escalated after a positive UAT result were subsequently admitted to ICU., Conclusions: UAT is not ordered routinely in pneumonia, even in ICU. A positive UAT result was associated with less frequent resistant organisms, but usually did not lead to antibiotic de-escalation. Increasing UAT and narrowing therapy after a positive UAT result are opportunities for improved antimicrobial stewardship., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: Nowadays, most cases of pneumococcal community-acquired pneumonia (PCAP) are diagnosed by positive urinary antigen. Our aims were to analyse process of care in patients hospitalised with non-bacteremic PCAP (NB-PCAP) and identify factors associated with poor outcome (PO) in this population. Methods: We conducted a prospective study, including patients hospitalised for NB-PCAP (positive urinary antigen and negative blood culture) over a 15 year period. We performed multivariate analysis of predisposing factors for PO, defined as need for mechanical ventilation and/or shock and/or in-hospital death. Results: Of the 638 patients included, 4.1% died in hospital and 12.8% had PO. Host-related factors were similar in patients with and without PO, but patients with PO had higher illness severity on admission. Adjusted analysis revealed the following independent factors associated with PO: being a nursing home resident (OR: 6.156; 95% CI: 1.827-20.750; p  = .003), respiratory rate ≥30 breaths/min (OR: 3.030; 95% CI: 1.554-5.910; p  = .001), systolic blood pressure <90 mmHg (OR: 4.789; 95% CI: 1.967-11.660; p  = .001), diastolic blood pressure <60 mmHg (OR: 2.820; 95% CI: 1.329-5.986; p  = .007), pulse rate ≥125 beats/min (OR: 3.476; 95% CI: 1.607-7.518; p  = .002), pH <7.35 (OR: 9.323; 95% CI: 3.680-23.622; p  < .001), leukocytes <4000/µL (OR: 10.007; 95% CI: 2.960-33.835; p  < .001), and severe inflammation (OR: 2.364; 95% CI 1.234-4.526; p  = .009). The area under the curve for predicting PO was 0.890 (95% CI: 0.851-0.929). Conclusions: Since patients with PO seem different and had worse in-hospital course, we identified eight independent risk factors for PO measurable on admission.

The non-encapsulated Streptococcus pneumoniae (NESp) has emerged and increased in the clinical setting. The majority of NESp strains have been isolated from the nasopharynxes of healthy carriers and from respiratory specimens of patients with otitis media. NESp strains were shown to be more effective than encapsulated counterparts at forming biofilms. Therefore, NESp should become one of the leading causes of emerging refractory respiratory disease after the introduction of pneumococcal conjugate vaccines. We report the first case of multidrug-resistant - including fluoroquinolone-resistant - NESp isolated from the intrabronchial aspirate of a patient with pneumonia. Drug-resistant NESp infections can possibly emerge as a clinical problem and thus the continuous monitoring of NESp infections is of utmost importance., Competing Interests: Declaration of Competing Interest All authors report no potential conflicts of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Although pneumococcal urinary antigen tests (PUATs) have universally been used for the diagnosis of pneumococcal pneumonia, data on the efficacy of these exams are limited. The objective of our study was to investigate the clinical impact of the PUAT in patients with community-onset pneumonia (CO-pneumonia)., Methods: We conducted a retrospective cohort study of patients diagnosed with CO-pneumonia. Patients were classified according to their PUAT results and were matched using the propensity score-matching method. The primary outcome was 30-day mortality., Results: A total of 1,257 patients were identified and 163 (13.0%) demonstrated positive PUAT results. The sensitivity and specificity values of PUAT for overall pneumococcal pneumonia were 56.5% and 91.4%, respectively. In the full cohort, there were no significant differences in 30-day mortality between the two groups (6.1% in the positive PUAT group vs. 8.2% in the negative PUAT group, p = 0.357). However, in the propensity-matched cohort, the 30-day mortality rates were lower in the positive PUAT group (5.6% vs. 17.4%, p = 0.001). With respect to secondary outcomes, the proportion of patients with potentially drug-resistant pathogens, changes in antibiotics, and failure rates of initial antibiotic therapy were significantly lower in the positive PUAT group than in the negative PUAT group of the propensity-matched cohort., Conclusion: We found that the sensitivity of the index test was low and specificity was high in this clinical setting. And our findings suggest that positive PUAT results may be associated with favorable clinical outcomes in patients with CO-pneumonia.