Community-acquired Pneumonia In Adults Research Articles

Effectiveness of S100 calcium-binding protein A12 combined with modified early warning score in the clinical diagnosis of adult community-acquired pneumonia.

Recent studies have found that S100 serum calcium-binding protein A12 (S100A12) has important significance in the expression of acute infectious diseases, and has high clinical application value in the differential diagnosis, prognosis and other aspects of acute infectious diseases. The accuracy of modified early warning score (MEWS) in evaluating the disease risk level of critically ill patients is comparable to Acute Physiology and Chronic Health Evaluation (APACHE II). Based on MEWS, 108 adult community-acquired pneumonia (CAP) patients were divided into the low-risk, intermediate-risk, and high-risk groups. The differences in invasive mechanical ventilation rate and mortality rate among each group were compared, and the differences of S100A12 in different levels of MEWS scores were compared through one-way analysis of variance. According to the prognosis after 30 days, the patients were divided into the death group and the survival group. Univariate and multivariate logistic regression analyses were used to study the influencing and independent factors of 30-day death in CAP patients. The sensitivity and specificity of S100A12, procalcitonin (PCT), and MEWS scores in predicting the 30-day death in CAP patients were evaluated using the receiver operating characteristic (ROC) curve, as well as the area under each indicator curve. The serum S100A12 concentration increased with the increase in the MEWS stratification, and the mechanical ventilation and mortality rates also increased significantly. Univariate and multivariate analyses were used to explore the factors influencing mortality in adult CAP patients after 30 days. The receiver-operating characteristics curve was used to analyze the sensitivity, specificity, and area under the curves of serum S100A12, PCT, and MEWS in predicting mortality in CAP patients after 30 days. The serum S100A12, PCT, and MEWS can effectively predict the mortality risk in adult CAP patients after 30 days. Serum S100A12 combined with MEWS has a high clinical application value in evaluating the severity and prognosis of adult CAP.

Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO)

BackgroundCommunity-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region.MethodsRESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis.DiscussionThe RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Рабдомиолиз — редкое внелегочное проявление внебольничной пневмонии, вызванной Mycoplasma pneumonia

Aim. To present a clinical case of a 19-year-old patient with community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae, which was complicated by a rare extrapulmonary manifestation in the form of rhabdomyolysis. Key points. The clinical case demonstrates a variant of mycoplasma CAP in an adult patient. M. pneumoniae infection was confirmed by a positive PCR test. Characteristic is contact with a patient with mycoplasma CAP in an infectious focus, a flu-like onset of the disease. Unlike most mild mycoplasma infections with a minimally expressed clinical picture and inflammatory response, the patient had a long period of febrile temperature and severe intoxication, significant laboratory changes and bilateral polysegmental lung damage. The development of signs of rhabdomyolysis (myalgia, increased creatine phosphokinase (CPK) to 2066 U/L, myoglobinuria) in the acute period of the disease is a rare extrapulmonary manifestation of mycoplasma CAP in adults, dangerous for the development of acute renal failure (ARF). Conclusion. The patient's young age, timely initiation of hydration, and antibacterial therapy aimed at M. pneumoniae made it possible to prevent the development of acute renal failure due to rhabdomyolysis. An increase in CPK, in the absence of other explanations for this phenomenon, should include mycoplasma CAP in the differential diagnosis of rhabdomyolysis. Keywords: community-acquired pneumonia, Mycoplasma pneumoniae, creatine phosphokinase, rhabdomyolysis.

Pneumococcal serotypes and risk factors in adult community acquired pneumonia 2018–20: a multicentre UK cohort study

BackgroundHigher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. MethodsWe conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. FindingsOf 1921 adults hospitalised with CAP, 781 (40·7%, 95% confidence intervals (CI) 38·5-42·9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31·0%, 95% CI 27·8-34·3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70·7%, 95% CI 64·5-76·0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2·8-5·6%), and PCV20-non13-serotypes in 192 (24·6%), with serotype 8 most prevalent (123/192, 64·1%, 95% CI 57·1-70·5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p<0·001) and less likely to be male (44% versus 61%, p=0·01). PPV23-non13-serotypes were found in 252 (32·3%, 95% CI 29·1-35·6%) pneumococcal CAP patients. InterpretationDespite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. FundingUnrestricted investigator-initiated research grant from Pfizer; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

Etiology of community-acquired pneumonia in children and adults based on 2015–2022 bacteriological and molecular genetic studies

The data on etiology of community-acquired pneumonia (CAP) remain contradictory, which is often assessed only according to bacteriological studies coming to a conclusion about the low frequency of major main pathogenStreptococcus pneumoniaеisolation. At the same time, there are very few observations of parallel examination of patients with CAP simultaneously by bacteriological and molecular genetic methods. There are no observations on the etiology of CAP in the long-term dynamics. The aim of the work is to analyze the etiology of CAP in children and adults based on 2015–2022 bacteriological and molecular genetic studies. The etiology of pneumonia was assessed using the data on posterior pharyngeal wall washes from 418 children and 483 adults hospitalized with a primary diagnosis of CAP at two large Perm medical organizations in 2015–2022. The samples were examined by the bacteriological method and polymerase chain reaction using commercial test systems with the amplifier “CFX96” (Bio-Rad, USA). The results showed thatS. pneumoniaе, despite implementing decreed vaccinations against pneumococcal infection, it remains the leading causative agent of CAP in both children and adults. The 2015–2022 frequency of pneumococcal discharge according to bacteriological studies was 9.7 per 100 examined, according to molecular genetic studies — 48.5 per 100 examined among children and adults in the study area. According to 2021–2022 vs 2015–2017 bacteriological studies, the frequency ofStaphylococcus aureusexcretion among children increased significantly, andS. pneumoniaеincreased among adults. According to the results of molecular genetic studies among children and adults, no significant changes in the etiology of CAP were found. In 2021–2022, SARS-CoV-2-positive vs SARS-CoV-2-negative patients with CAP infected had higher rate of isolatedS. aureus,KlebsiellapneumoniaеandHemophilus influenzae, i.e., those pathogens whose number increased in the long-term follow-up observations.

Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

Predictors of hospital mortality and multidrug-resistant pathogens in hospitalized pneumonia patients residing in the community

Background and objectiveThe 2019 ATS/ADSA guidelines for adult community-acquired pneumonia (CAP) eliminated healthcare-associated pneumonia (HCAP) and considered it to be a form of CAP. This concept, however, was based on studies with relatively small sample sizes. MethodsWe investigated the risk factors of 30-day mortality, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in patients with pneumonia coming from the community using the Diagnosis Procedure Combination database, a nationwide discharge database of acute care hospitals. Furthermore, we compared these factors between CAP and HCAP. ResultsA total of 272,337 patients aged ≥20 years with pneumonia were grouped into 145,082 CAP patients and 127,255 HCAP patients. The 30-day mortality rate (8.9 % vs.3.3 %), MRSA infection (2.4 % vs. 1.4 %), and Pseudomonas aeruginosa infection (1.6 % vs. 1.0 %) were significantly higher in HCAP than in CAP patients. Multivariable logistic regression analysis showed that 12 of 13 identified predictors of mortality (i.e., high age, male, underweight, non-ambulatory status, bedsore, dehydration, respiratory failure, consciousness disturbance, hypotension, admitted in critical care, comorbidity of heart failure, and chronic obstructive pulmonary disease) were identical in CAP and HCAP patients. Similarly, five of six distinct risk factors for MRSA infection, and three of three for Pseudomonas aeruginosa infection were identical between the patients. ConclusionThe risk factors for mortality and MRSA or Pseudomonas aeruginosa infection were almost identical in patients with CAP and HCAP. The assessment of individual risk factors for mortality and MRSA or Pseudomonas aeruginosa infection in CAP and abandoning categorization as HCAP can improve and simplify empiric therapy.

The distribution of myeloid-derived suppressor cells subsets and up-regulation of programmed death-1/PD-L1 axis in peripheral blood of adult CAP patients.

Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP). This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients.

Guideline on treating community-acquired pneumonia with Chinese patent medicines

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data

ObjectiveEpidemiological information is essential in providing appropriate empiric antimicrobial therapy for pneumonia. This study aimed to clarify the epidemiology of community-acquired pneumonia (CAP) by conducting a systematic review of published...

Readmission following hospital admission for community-acquired pneumonia in England

IntroductionReadmission rates following hospital admission with community-acquired pneumonia (CAP) have increased in the UK over the past decade. The aim of this work was to describe the cohort of patients...

The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

CHARACTERISTICS OF COMMUNITY ACQUIRED PNEUMONIA AT A SINGLE CENTER IN CENTRAL SRI LANKA DURING COVID-19 PANDEMIC: A DESCRIPTIVE CROSS-SECTIONAL STUDY.

Introduction and Objective:Community acquired pneumonia (CAP) is associated with increased mortality and morbidity. The disease severity is multifactorial, co-morbid conditions and advanced age are the most important risk factors. At present, there is a sparsity in published data on CAP in Sri Lankan adults and adolescents. Aim of study to identify complications and outcome of CAP.Methods:A single center descriptive prospective study was carried out in Respiratory Unit 11 in National Hospital-Kandy, Sri Lanka, among diagnosed CAP patients during six months from 1st of September 2020 to 28th of February 2021. Data were analyzed by SPSS (Statistical Package for Social Sciences) 21 package. Results:105 cases were analyzed; of which 35.2% had complications. Parapenumonic effusion was the commonest complication, whilst pyothorax was the rarest complication. Nine patients (24%) had multiple complications. Prevalence of complications significantly correlated with CURB 65 score (pearson correlation coefficient 0.57, p value 0.001). 93.3% of patients survived with treatment, however 6.6% of them demised with male predominance and all had at least 2 preexisting diseases. Five deaths (71.4%) occurred in the intensive care unit. During follow up, 3.8% were diagnosed with bronchial malignancy, 5.7% pulmonary tuberculosis, 2.8% other chronic infections (melioidosis) and 1.9% chronic organizing pneumonia, respectively.Conclusion:CAP is a major health concern in central Sri Lanka during COVID-19 pandemic. Most CAP patients recovered completely. Mortality 6.6% with male predominance. Parapneumonic effusion was the commonest complication. Number of Complications had significant correlation with CURB 65 score

Diagnostic and Prognostic Roles of Procalcitonin and Other Tools in Community-Acquired Pneumonia: A Narrative Review.

Community-acquired pneumonia (CAP) is among the most common causes of death and one of the leading healthcare concerns worldwide. It can evolve into sepsis and septic shock, which have a high mortality rate, especially in critical patients and comorbidities. The definitions of sepsis were revised in the last decade as "life-threatening organ dysfunction caused by a dysregulated host response to infection". Procalcitonin (PCT), C-reactive protein (CRP), and complete blood count, including white blood cells, are among the most commonly analyzed sepsis-specific biomarkers also used in pneumonia in a broad range of studies. It appears to be a reliable diagnostic tool to expedite care of these patients with severe infections in the acute setting. PCT was found to be superior to most other acute phase reactants and indicators, including CRP as a predictor of pneumonia, bacteremia, sepsis, and poor outcome, although conflicting results exist. In addition, PCT use is beneficial to judge timing for the cessation of antibiotic treatment in most severe infectious states. The clinicians should be aware of strengths and weaknesses of known and potential biomarkers in expedient recognition and management of severe infections. This manuscript is intended to present an overview of the definitions, complications, and outcomes of CAP and sepsis in adults, with special regard to PCT and other important markers.

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

BackgroundFew studies have measured the burden of community-acquired pneumonia (CAP) and pneumococcal vaccine-type CAP in Japan after the introduction of the 23-valent pneumococcal polysaccharide vaccine into the adult national immunization program (NIP) for individuals ≥ 65 years of age in 2014. In this study, we estimated the incidences of CAP and Streptococcus pneumoniae CAP among Japanese adults between 2015 and 2020.Research QuestionWhat are the incidences of CAP and S pneumoniae CAP among Japanese adults? What are the common pneumococcal serotypes detected in patients with S pneumoniae CAP?Study Design and MethodsThis prospective, population-based, multicenter, active surveillance study enrolled adults ≥ 18 years of age with clinically and radiologically confirmed CAP in Goto City, Japan. S pneumoniae was detected using standard-of-care blood and sputum cultures, BinaxNOW, and serotype-specific urinary antigen detection assays.ResultsA total of 2,103 patients with CAP were enrolled; 84% were ≥ 65 years of age and 6.7% died during the study. The annual CAP, S pneumoniae CAP, 13-valent pneumococcal conjugate vaccine (PCV13) serotype CAP, and 20-valent pneumococcal conjugate vaccine (PCV20) serotype CAP incidences per 100,000 population were 1,280, 227, 63, and 110, respectively. S pneumoniae was detected in 17.8% of all patients with CAP by any detection method, with 4.9%, 5.5%, and 8.6% of cases of CAP resulting from PCV13, 15-valent pneumococcal conjugate vaccine, and PCV20 serotypes, respectively. Applying Goto’s incidence and case fatality rate to the Japanese population, assuming PCV20 has the same vaccine efficacy and duration of protection as PCV13 and if licensed in Japan for the prevention of CAP, the inclusion of PCV20 in the NIP for adults ≥ 65 years of age could prevent 29,036 cases of CAP and 2,275 CAP-related deaths per year.InterpretationGiven the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Few studies have measured the burden of community-acquired pneumonia (CAP) and pneumococcal vaccine-type CAP in Japan after the introduction of the 23-valent pneumococcal polysaccharide vaccine into the adult national immunization program (NIP) for individuals ≥ 65 years of age in 2014. In this study, we estimated the incidences of CAP and Streptococcus pneumoniae CAP among Japanese adults between 2015 and 2020. What are the incidences of CAP and S pneumoniae CAP among Japanese adults? What are the common pneumococcal serotypes detected in patients with S pneumoniae CAP? This prospective, population-based, multicenter, active surveillance study enrolled adults ≥ 18 years of age with clinically and radiologically confirmed CAP in Goto City, Japan. S pneumoniae was detected using standard-of-care blood and sputum cultures, BinaxNOW, and serotype-specific urinary antigen detection assays. A total of 2,103 patients with CAP were enrolled; 84% were ≥ 65 years of age and 6.7% died during the study. The annual CAP, S pneumoniae CAP, 13-valent pneumococcal conjugate vaccine (PCV13) serotype CAP, and 20-valent pneumococcal conjugate vaccine (PCV20) serotype CAP incidences per 100,000 population were 1,280, 227, 63, and 110, respectively. S pneumoniae was detected in 17.8% of all patients with CAP by any detection method, with 4.9%, 5.5%, and 8.6% of cases of CAP resulting from PCV13, 15-valent pneumococcal conjugate vaccine, and PCV20 serotypes, respectively. Applying Goto’s incidence and case fatality rate to the Japanese population, assuming PCV20 has the same vaccine efficacy and duration of protection as PCV13 and if licensed in Japan for the prevention of CAP, the inclusion of PCV20 in the NIP for adults ≥ 65 years of age could prevent 29,036 cases of CAP and 2,275 CAP-related deaths per year. Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Take-home PointsStudy Question: What are the incidences of community-acquired pneumonia (CAP) and Streptococcus pneumoniae CAP among Japanese adults?Results: The annual incidences of CAP and S pneumoniae CAP were high in Goto City (1,280 and 227 cases per 100,000 population, respectively) and increased with age.Interpretation: Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Study Question: What are the incidences of community-acquired pneumonia (CAP) and Streptococcus pneumoniae CAP among Japanese adults? Results: The annual incidences of CAP and S pneumoniae CAP were high in Goto City (1,280 and 227 cases per 100,000 population, respectively) and increased with age. Interpretation: Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality. Age of 65 years of older and certain medical conditions are risk factors for CAP,1Torres A. Peetermans W.E. Viegi G. Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review.Thorax. 2013; 68: 1057-1065Crossref PubMed Scopus (406) Google Scholar and the incidence and mortality of CAP are highest among the elderly.2Ramirez J.A. Wiemken T.L. Peyrani P. et al.Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality.Clin Infect Dis. 2017; 65: 1806-1812Crossref PubMed Scopus (280) Google Scholar,3Theilacker C. Sprenger R. Leverkus F. et al.Population-based incidence and mortality of community-acquired pneumonia in Germany.PLoS One. 2021; 16e0253118Crossref Scopus (15) Google Scholar With 28.7% of the Japanese population being 65 years of age or older, pneumonia was ranked the fifth leading cause of death in 2019 (77.2 deaths per 100,000 population).4Dunne E.M. Cilloniz C. von Mollendorf C. et al.Pneumococcal vaccination in adults: what can we learn from observational studies that evaluated PCV13 and PPV23 effectiveness in the same population?.Archivos de Bronconeumología. 2023; Crossref Scopus (0) Google Scholar Because Japan has become the first super-aged society in the world,5D’Ambrogio E. Japan’s aging society. European Parliament website.https://www.europarl.europa.eu/RegData/etudes/BRIE/2020/659419/EPRS_BRI(2020)659419_EN.pdfDate accessed: September 16, 2022Google Scholar the burden of pneumonia is expected only to increase. Streptococcus pneumoniae is a leading cause of bacterial CAP. However, the use of pneumococcal conjugate vaccine (PCV) has reduced the proportion of disease attributed to S pneumoniae in children and adults.6Moore M.R. Link-Gelles R. Schaffner W. et al.Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance.Lancet Infect Dis. 2015; 15: 301-309Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar,7Sherwin R.L. Gray S. Alexander R. et al.Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae serotypes in US adults aged ≥50 years with community-acquired pneumonia.J Infect Dis. 2013; 208: 1813-1820Crossref PubMed Scopus (0) Google Scholar In June 2010, a 7-valent PCV was introduced into the national immunization program (NIP) for children in Japan, replaced by a 13-valent PCV (PCV13) in 2013.8Yanagihara K. Kosai K. Mikamo H. et al.Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan.Int J Infect Dis. 2021; 102: 260-268Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar PCV13 coverage in Japanese children is high (> 95%), and a substantial decline (45%) in the CAP hospitalization rate has been observed among children younger than 5 years.9Takeuchi N. Naito S. Ohkusu M. et al.Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan.Epidemiol Infect. 2020; 148: e91Crossref PubMed Scopus (16) Google Scholar Currently, two pneumococcal vaccines are available in Japan for adults. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) was introduced into the adult NIP in October 2014 for adults ≥ 65 years of age and for adults 60 to 64 years of age with certain medical conditions.8Yanagihara K. Kosai K. Mikamo H. et al.Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan.Int J Infect Dis. 2021; 102: 260-268Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar The cumulative vaccination rate of PPSV23 among adults ≥ 65 years of age was 74% at the end of 2018.10Naito T. Suzuki M. Fujibayashi K. et al.The estimated impact of the 5-year national vaccination program on the trend of 23-valent pneumococcal polysaccharide vaccine vaccination rates in the elderly in Japan, 2009-2018.J Infect Chemother. 2020; 26: 407-410Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar In 2014, PCV13 was approved in adults ≥ 65 years of age in Japan, and in 2020, this approval was extended to include individuals 6 to 64 years of age with underlying medical conditions. However, PCV13 is not included in the adult NIP in Japan.11Fukusumi M. Chang B. Tanabe Y. et al.Invasive pneumococcal disease among adults in Japan, April 2013 to March 2015: disease characteristics and serotype distribution.BMC Infect Dis. 2017; 17: 2Crossref PubMed Scopus (37) Google Scholar Recently, higher-valent PCVs—15-valent PCV (including PCV13 serotypes plus serotypes 22F and 33F; Merck & Co., Inc.) and 20-valent PCV (PCV20; including PCV13 serotypes and seven additional serotypes: 8, 10A, 11A, 12F, 15B, 22F, and 33F; Pfizer, Inc.)—have been licensed by the US Food and Drug Administration and European Medicines Agency for use in adults ≥ 18 years of age12Committee for Medicinal Products for Human Use, European Medicines AgencySummary of opinion (initial authorisation): Apexxnar. European Medicines Agency website.https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-apexxnar_en.pdfDate accessed: September 16, 2022Google Scholar, 13Committee for Medicinal Products for Human Use, European Medicines AgencySummary of opinion (initial authorisation): Vaxneuvance. European Medicines Agency website.https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-vaxneuvance_en.pdfDate accessed: September 16, 2022Google Scholar, 14Kobayashi M. Farrar J.L. Gierke R. et al.Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. adults: updated recommendations of the Advisory Committee on Immunization Practices - United States, 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 109-117Crossref PubMed Scopus (87) Google Scholar and are undergoing clinical evaluations in Japan. In an aging society like Japan, it is important to understand the burden of CAP in adults and the degree to which CAP may be prevented with the current and next-generation pneumococcal vaccines. However, while studies have been conducted measuring the burden of CAP and vaccine-type (VT) CAP in Japan, the most comprehensive data were obtained between 2011 and 2013,15Morimoto K. Suzuki M. Ishifuji T. et al.The burden and etiology of community-onset pneumonia in the aging Japanese population: a multicenter prospective study.PLoS One. 2015; 10e0122247Crossref Scopus (128) Google Scholar which was before PPSV23 introduction into the NIP for older adults in 2014. Herein, we present the results from a population-based CAP incidence study among adults in Goto City, Japan, between 2015 and 2020. Although the population aging rate (≥ 65 years) in Goto City (36.8% in 2015) was higher than that in Japan as a whole (29.1% in 2021),16Statistics Bureau of JapanPopulation estimates. Statistics Bureau of Japan website.https://www.stat.go.jp/english/index.htmlDate accessed: January 18, 2023Google Scholar Goto City is epidemiologically similar to Japan as whole. Therefore, the findings in this study are generalizable to Japan. This was a prospective, multicenter, active-surveillance, population-based incidence study. Residents ≥ 18 years of age in Goto City, Japan, with suspected CAP were screened at all hospitals and outpatient clinics. Goto City is located in the southwest part of Japan, encompassing 11 inhabited islands. Of the 39,808 inhabitants, 85% are ≥ 18 years of age.17Glick H.A. Miyazaki T. Hirano K. et al.One-year quality of life post-pneumonia diagnosis in Japanese adults.Clin Infect Dis. 2021; 73: 283-290Crossref Scopus (11) Google Scholar Study participants were recruited between December 2015 and November 2020. All health-care facilities in Goto City, including four hospitals and 25 outpatient clinics, were include in the study. The study was approved by the ethics review committees and was registered in the University Hospital Medical Information Network (registration ID: [removed]). Patients signed the written informed consent before enrollment. All patients who sought treatment at the participating health-care facilities and demonstrated signs, symptoms, and radiographic evidence of pneumonia were screened for inclusion. To be included, patients: (1) had to be ≥ 18 years of age; (2) had to be a resident of Goto City; (3) had to have a diagnosis of pneumonia based on the presence of two or more of the signs and symptoms of cough; purulent sputum; fever (axillary temperature ≥ 37° C); dyspnea, tachypnea, or both; WBC count of > 10,000/mm3 or > 15% bands or WBC count of < 4,500/mm3; elevated C-reactive protein (CRP) level; hypoxemia; or abnormal auscultatory findings suggestive of pneumonia; (4) had to show a pneumonia pattern (eg, alveolar infiltrative shadow associated with air bronchogram) on chest radiography or chest CT scan imaging; and (5) had to be willing and able to provide a urine sample. Patients were excluded if: (1) they were transferred to a participating health-care facility after having been hospitalized for ≥ 48 h at another hospital. (2) they had hospital-acquired pneumonia (ie, pneumonia developed ≥ 48 h after hospitalization), (3) they had received PPSV23 or PCV13 within the past 30 days (because vaccine receipt may cause false-positive urinary antigen detection [UAD] results), or (4) they had been enrolled previously in the study within the past 30 days. For patients who were eligible for the study, demographics, medical history, pneumococcal vaccination history within the last 5 years, pneumonia severity on admission, and clinical outcomes were collected. Patients were followed for up to 30 days after enrollment. The pneumococcal vaccination history was confined to 5 years because PPSV23 was introduced into the adult NIP in 2014 and the study participants were recruited between 2015 and 2020. Further, only a small proportion of participants had received PCV13. Therefore, confining pneumococcal vaccination history to the previous 5 years should have provided a reasonable coverage estimate. The risk status of participants (high risk, at risk, and low risk) was determined based on the presence of certain medical conditions (based on Shea et al18Shea K.M. Edelsberg J. Weycker D. Farkouh R.A. Strutton D.R. Pelton S.I. Rates of pneumococcal disease in adults with chronic medical conditions.Open Forum Infect Dis. 2014; 1: ofu024Crossref PubMed Google Scholar and on the US Advisory Committee on Immunization Practices guidelines) (e-Table 1). Sputum and specimens from normally sterile sites were collected as part of standard-of-care practice and underwent culture at Goto Central Hospital Laboratory. S pneumoniae isolates then were sent to the German National Reference Center for Streptococci for confirmatory testing and serotyping using the Quellung reaction. Urine samples were collected as a study-related procedure for BinaxNOW S pneumoniae antigen card, and UAD assays were performed at Pfizer’s Vaccines Research and Development Laboratory. The UAD assays are multiplex immunoassays based on the Luminex technology. By capturing serotype-specific S pneumoniae polysaccharides secreted in human urine, the UAD assays simultaneously can detect multiple S pneumoniae serotypes.19Kalina W.V. Souza V. Wu K. et al.Qualification and clinical validation of an immunodiagnostic assay for detecting 11 additional Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Infect Dis. 2020; 71: e430-e438Google Scholar,20Pride M.W. Huijts S.M. Wu K. et al.Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Vaccine Immunol. 2012; 19: 1131-1141Crossref PubMed Scopus (87) Google Scholar The UAD 1 assay detects all 13 serotypes contained in PCV13 (1, 3, 4, 5, 6A/C, 6B, 7F/A, 9V/A, 14, 18C/A/B/F, 19A, 19F, and 23F), and the UAD 2 assay detects 11 additional serotypes (2, 8, 9N, 10A/39, 11A/D/F, 12F, 15B/C, 17F/A, 20A/B, 22F/A, and 33F/A). The UAD 1 and 2 assays and corresponding positivity cutoff values were validated clinically, demonstrating high sensitivity and specificity against urine specimens obtained from patients with radiography-confirmed bacteremic CAP.19Kalina W.V. Souza V. Wu K. et al.Qualification and clinical validation of an immunodiagnostic assay for detecting 11 additional Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Infect Dis. 2020; 71: e430-e438Google Scholar,20Pride M.W. Huijts S.M. Wu K. et al.Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Vaccine Immunol. 2012; 19: 1131-1141Crossref PubMed Scopus (87) Google Scholar However, the sensitivity and specificity for nonbacteremic CAP have not been determined because of a lack of a reference standard for this outcome. A patient was defined as having CAP if the patient met all the eligibility criteria described previously, was defined as having pneumococcal CAP if the patient had CAP and showed positive culture results for S pneumoniae (including sputum) or BinaxNOW or UAD assay test positive results and was defined as having PCV13 VT CAP or PCV20 VT CAP if the patient had pneumococcal CAP with one of the PCV13 serotypes or PCV20 serotypes detected by culture (including sputum) or the UAD assays. Descriptive statistical analysis was performed. Continuous variables were summarized as mean ± SD, medians, and minimum and maximum values, and a difference in two means and its CI were evaluated by the two-sample t test. Categorical variables were described as frequencies and percentages, and a difference in two proportions and its CI were evaluated by z test based on the binomial theory. Incidences of CAP, pneumococcal CAP, PCV13 VT CAP, and PCV20 VT CAP were calculated with the numerators based on the number of cases and denominators using age-specific population data of Goto City.21McLaughlin J.M. Jiang Q. Gessner B.D. et al.Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: a systematic review and pooled analysis.Vaccine. 2019; 37: 6310-6316Crossref Scopus (31) Google Scholar Incidence per 100,000 population was shown by age group (18-64 years, 65-79 years, and ≥ 80 years) and by study year (2015 through 2020). For estimating the effect of introducing PCV20 into the adult NIP in Japan, we assumed PCV20 vaccine efficacy (VE) to be the same as that of PCV13 VE, which is 45.56% for the prevention of first episodes of vaccine-type CAP in adults ≥ 65 years of age, as demonstrated in the CAPiTA study.22Bonten M.J. Huijts S.M. Bolkenbaas M. et al.Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.N Engl J Med. 2015; 372: 1114-1125Crossref PubMed Scopus (836) Google Scholar This assumption was made because PCV20 is built on the manufacturing platform successfully established by PCV13 and the immune responses to PCV20 in adults have been noninferior to PCV13.23Essink B. Sabharwal C. Cannon K. et al.Pivotal phase 3 randomized clinical trial of the safety, tolerability, and immunogenicity of 20-valent pneumococcal conjugate vaccine in adults aged ≥18 years.Clin Infect Dis. 2022; 75: 390-398Crossref PubMed Scopus (0) Google Scholar To calculate CAP cases preventable by PCV20, the PCV20 VT CAP annual incidence rate from Goto City was multiplied by Japan’s population to obtain annual PCV20 VT CAP cases among adults ≥ 65 years of age. Then the annual PCV20 VT CAP cases were multiplied by PCV20 VE of 45.56% to arrive at the number of cases per year preventable by PCV20. To calculate CAP-related deaths preventable by PCV20, the annual all-cause CAP death rate from Goto City was multiplied by Japan’s population to obtain annual all-cause CAP deaths among adults ≥ 65 years of age. Then, the annual all-cause CAP deaths were multiplied by the proportion of CAP cases caused by PCV20 serotypes and PCV20 VE of 45.56% to arrive at CAP-related deaths per year preventable by PCV20. In Japan, the use of PCV13 in adults ≥ 65 years of age is extremely low, and recent evidence supports limited protection against nonbacteremic pneumonia (which makes up by far most cases of pneumococcal pneumonia) in adults vaccinated with PPSV23.4Dunne E.M. Cilloniz C. von Mollendorf C. et al.Pneumococcal vaccination in adults: what can we learn from observational studies that evaluated PCV13 and PPV23 effectiveness in the same population?.Archivos de Bronconeumología. 2023; Crossref Scopus (0) Google Scholar,10Naito T. Suzuki M. Fujibayashi K. et al.The estimated impact of the 5-year national vaccination program on the trend of 23-valent pneumococcal polysaccharide vaccine vaccination rates in the elderly in Japan, 2009-2018.J Infect Chemother. 2020; 26: 407-410Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Therefore, we expect prior vaccination with either PCV13 or PPSV23 to have little or no effect on the calculations of the potential benefit of PCV20 against pneumonia. Of 2,105 patients screened, 2,103 patients were eligible and included in the analysis population (Table 1). Two screened patients were not included in the analysis because the radiographic findings were not compatible with CAP. The mean age at consent was 77.6 years, 1,765 patients (83.9%) were ≥ 65 years of age, and 53.9% were female. The mean pneumonia severity index (PSI) score on admission was 108.9, with 39.0% and 28.6% of patients having class IV or V PSI scores, respectively. The mean CURB-65 score was 1.7 and 20.7% of patients had a CURB-65 score of 3 to 5. Pneumococcal vaccination within the previous 5 years was reported for 414 of 2,103 patients (19.7%), with 6.8% in adults 18 to 64 years of age and 22.2% in adults ≥ 65 years of age. In total, 70.7% of all patients were hospitalized; the mean hospital stay duration was 14.1 days. Mortality during the study was 6.7% (141/2,103), and in-hospital mortality was 6.2% (130/2,103). Among patients who died, 94.3% (133/141) were ≥ 65 years of age and 5.7% (8/141) were 18 to 64 years of age. Among patients ≥ 18 years of age, 18 to 64 years of age, and ≥ 65 years of age, 69.5%, 64.5%, and 70.4% were at risk or high risk, respectively (Table 2).Table 1Demographics and Clinical Characteristics of Patients With CAPVariableAge Group, y18-64 (n = 338)≥ 65 (n = 1,765)≥ 18 (n = 2,103)Age at consent, y No.3381,7652,103 Mean ± SD51.1 ± 12.182.6 ± 8.677.6 ± 14.8 Median56.084.082.0 Interquartile range19-6465-10319-103Sex Female186 (55.0)948 (53.7)1,134 (53.9) Male152 (45.0)817 (46.3)969 (46.1)Pneumonia severity index No.3381,7642,102 Mean ± SD64.6 ± 32.3117.4 ± 34.0108.9 ± 38.9 Median57.0115.0109.0 Interquartile range13-19455-27513-275 GradeI139 (41.1)102 (5.8)241 (11.5)II82 (24.3)46 (2.6)128 (6.1)III43 (12.7)267 (15.1)310 (14.7)IV59 (17.5)762 (43.2)821 (39.0)V14 (4.1)587 (33.3)601 (28.6)Missing1 (0.3)1 (0.1)2 (0.1)CURB-65 score No.3381,7652,103 Mean ± SD0.3 ± 0.61.9 ± 0.91.7 ± 1.0 Median0.02.02.0 Interquartile range0-41-50-5 0254 (75.1)0 (0.0)254 (12.1) 160 (17.8)708 (40.1)768 (36.5) 222 (6.5)624 (35.4)646 (30.7) 31 (0.3)328 (18.6)329 (15.6) 41 (0.3)102 (5.8)103 (4.9) 50 (0.0)3 (0.2)3 (0.1)Prior vaccine Pneumococcal vaccine within 5 y23 (6.8)391 (22.2)414 (19.7) Prior PPSV23 use9 (2.7)376 (21.3)385 (18.3) Prior PCV13 use15 (4.4)14 (0.8)29 (1.4)Hospitalized Yes145 (42.9)1,342 (76.0)1,487 (70.7) No193 (57.1)423 (24.0)616 (29.3)Hospitalization durationaOnly participants with hospital admission date and discharge date were included in the analysis. No.1239871,110 Mean ± SD13.2 ± 7.714.2 ± 6.914.1 ± 7.0 Median12.013.013.0 Interquartile range1-401-351-40Hospitalization duration ≥ 30 dbPatients with ongoing hospitalization status and with study end date 30 d after hospital admission date were included, in addition to patients with actual stays of ≥ 30 d.27 (8.0)373 (21.1)400 (19.0)Death8 (2.4)133 (7.5)141 (6.7) Death caused by pneumonia5 (1.5)100 (5.7)105 (5.0)Time from hospitalization to death No.8130138 Mean ± SD12.5 ± 9.012.4 ± 8.612.4 ± 8.6 Median11.010.510.5 Interquartile range3-281-311-31Death in hospital7 (2.1)123 (7.0)130 (6.2)Death after hospital discharge1 (0.3)7 (0.4)8 (0.4)Data are presented as No. (%), unless otherwise indicated. CAP = community-acquired pneumonia; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.a Only participants with hospital admission date and discharge date were included in the analysis.b Patients with ongoing hospitalization status and with study end date 30 d after hospital admission date were included, in addition to patients with actual stays of ≥ 30 d. Open table in a new tab Table 2Baseline Medical Characteristics of Patients With CAPVariableAge Group, y18-64 (n = 338)≥ 65 (n = 1,765)≥ 18 (n = 2,103)Risk level High86 (25.4)593 (33.6)679 (32.3) At risk132 (39.1)650 (36.8)782 (37.2) Low120 (35.5)522 (29.6)642 (30.5)High risk Chronic renal failure19 (5.6)189 (10.7)208 (9.9) Immunosuppressive therapy41 (12.1)205 (11.6)246 (11.7) Immunodeficiency0 (0.0)0 (0.0)0 (0.0) AIDS0 (0.0)0 (0.0)0 (0.0) HIV infection0 (0.0)0 (0.0)0 (0.0) Hematologic cancer3 (0.9)41 (2.3)44 (2.1) Cancer (solid tumor)43 (12.7)276 (15.6)319 (15.2) Organ transplantation1 (0.3)0 (0.0)1 (0.0) Biologic agent2 (0.6)8 (0.5)10 (0.5) Splenectomy2 (0.6)9 (0.5)11 (0.5) No. of high-risk conditions162 (18.3)473 (26.8)535 (25.4)223 (6.8)106 (6.0)129 (6.1)31 (0.3)13 (0.7)14 (0.7)≥ 40 (0.0)1 (0.1)1 (0.0)1 with ≥ 1 at-risk condition38 (11.2)313 (17.7)351 (16.7)≥ 2 with ≥ 1 at-risk condition10 (3.0)84 (4.8)94 (4.5)At risk COPD20 (5.9)331 (18.8)351 (16.7) Asthma44 (13.0)167 (9.5)211 (10.0) Congestive heart failure10 (3.0)339 (19.2)349 (16.6) Diabetes mellitus38 (11.2)404 (22.9)442 (21.0) Liver disease38 (11.2)220 (12.5)258 (12.3) Smoke100 (29.6)93 (5.3)193 (9.2) No. of at-risk conditions197 (28.7)435 (24.6)532 (25.3)228 (8.3)173 (9.8)201 (9.6)36 (1.8)34 (1.9)40 (1.9)≥ 41 (0.3)8 (0.5)9 (0.4)Other risk factors Used antibiotics in the past 90 d72 (21.3)545 (30.9)617 (29.3) Living with children88 (26.0)19 (1.1)107 (5.1)Data are presented as No. (%). CAP = community-acquired pneumonia. Open table in a new tab Data are presented as No. (%), unless otherwise indicated. CAP = community-acquired pneumonia; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine. Data are presented as No. (%). CAP = community-acquired pneumonia. Among all patients, the annual incidence of CAP was 1,280 cases per 100,000 population. CAP incidence increased with age, and the incidence among adults ≥ 80 years of age was 11.8 times the incidence among adults 18 to 64 years of age (4,288 per 100,000 population vs 362 per 100,000 population) and 3.2 times the incidence among those 65 to 79 years of age (4,288 per 100,000 population vs 1,352 per 100,000 population) (Fig 1). A similar relationship between incidence and age was observed for pneumococcal CAP, PCV13 VT CAP, and PCV20 VT CAP. In all adults 18 to 64 years of age, those 65 to 79 years of age, and those ≥ 80 years of age, annual incidences per 100,000 population were 227, 89, 260, and 645, respectively, for pneumococcal CAP; 63, 23, 80, and 171, respectively, for PCV13 VT CAP; and 110, 47, 159, and 244, respectively, for PCV20 VT CAP. Extrapolating the CAP incidence and the case fatality rate to Japan’s population and assuming PCV20 has the same VE and duration of protection as PCV13,22Bonten M.J. Huijts S.M. Bolkenbaas M. et al.Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.N Engl J Med. 2015; 372: 1114-1125Crossref PubMed Scopus (836) Google Scholar if licensed, PCV20 immunization in Japanese adults ≥ 65 years of age could prevent 29,036 CAP cases and 2,275 CAP-related deaths per year. Between 2015 and 2020, CAP incidence and pneumococcal CAP incidence generally remained stable, except for year 5 (December 2019-November 2020) during which the incidences were lower compared with other study years (Fig 2). Urine samples were not collected in 68 of 2,103 patients (3.2%); however, S pneumoniae was detected by culture in 5 of 68 patients (7.3%) from whom a urine sample was not collected. Among 2,099 patients who had diagnostic results available, S pneumoniae was detected in 373 patients (17.8%) by UAD assays, BinaxNOW, or culture (Table 3). S pneumoniae was detected by UAD alone in 78 of 2,099 patients (3.7%; 78/373 patients [20.9%] with pneumococcal CAP), by BinaxNOW alone in 125 of 2,099 patien

Generation of Human Embryonic Stem Cell-Derived Lung Organoids for Modeling Infection and Replication Differences between Human Adenovirus Types 3 and 55 and Evaluating Potential Antiviral Drugs.

Human adenoviruses type 3 (HAdV-3) and type 55 (HAdV-55) are frequently encountered, highly contagious respiratory pathogens with high morbidity rate. In contrast to HAdV-3, one of the most predominant types in children, HAdV-55 is a reemergent pathogen associated with more severe community-acquired pneumonia (CAP) in adults, especially in military camps. However, the infectivity and pathogenicity differences between these viruses remain unknown as in vivo models are not available. Here, we report a novel system utilizing human embryonic stem cells-derived 3-dimensional airway organoids (hAWOs) and alveolar organoids (hALOs) to investigate these two viruses. Firstly, HAdV-55 replicated more robustly than HAdV-3. Secondly, cell tropism analysis in hAWOs and hALOs by immunofluorescence staining revealed that HAdV-55 infected more airway and alveolar stem cells (basal and AT2 cells) than HAdV-3, which may lead to impairment of self-renewal functions post-injury and the loss of cell differentiation in lungs. Additionally, the viral life cycles of HAdV-3 and -55 in organoids were also observed using Transmission Electron Microscopy. This study presents a useful pair of lung organoids for modeling infection and replication differences between respiratory pathogens, illustrating that HAdV-55 has relatively higher replication efficiency and more specific cell tropism in human lung organoids than HAdV-3, which may result in relatively higher pathogenicity and virulence of HAdV-55 in human lungs. The model system is also suitable for evaluating potential antiviral drugs, as demonstrated with cidofovir. IMPORTANCE Human adenovirus (HAdV) infections are a major threat worldwide. HAdV-3 is one of the most predominant respiratory pathogen types found in children. Many clinical studies have reported that HAdV-3 causes less severe disease. In contrast, HAdV-55, a reemergent acute respiratory disease pathogen, is associated with severe community-acquired pneumonia in adults. Currently, no ideal in vivo models are available for studying HAdVs. Therefore, the mechanism of infectivity and pathogenicity differences between human adenoviruses remain unknown. In this study, a useful pair of 3-dimensional (3D) airway organoids (hAWOs) and alveolar organoids (hALOs) were developed to serve as a model. The life cycles of HAdV-3 and HAdV-55 in these human lung organoids were documented for the first time. These 3D organoids harbor different cell types, which are similar to the ones found in humans. This allows for the study of the natural target cells for infection. The finding of differences in replication efficiency and cell tropism between HAdV-55 and -3 may provide insights into the mechanism of clinical pathogenicity differences between these two important HAdV types. Additionally, this study provides a viable and effective in vitro tool for evaluating potential anti-adenoviral treatments.

Outcomes of community-acquired pneumonia using the Pneumonia Severity Index versus the CURB-65 in routine practice of emergency departments.

The Pneumonia Severity Index (PSI) and the CURB-65 score assess disease severity in patients with community-acquired pneumonia (CAP). We compared the clinical performance of both prognostic scores according to clinical outcomes and admission rates. A nationwide retrospective cohort study was conducted using claims data from adult CAP patients presenting to the emergency department (ED) in 2018 and 2019. Dutch hospitals were divided into three categories: "CURB-65 hospitals" (n=25), "PSI hospitals" (n=19) and hospitals using both ("no-consensus hospitals", n=15). Main outcomes were hospital admission rates, intensive care unit admissions, length of hospital stay, delayed admissions, readmissions and all-cause 30-day mortality. Multilevel logistic and Poisson regression analysis were used to adjust for potential confounders. Of 50 984 included CAP patients, 21 157 were treated in CURB-65 hospitals, 17 279 in PSI hospitals and 12 548 in no-consensus hospitals. The 30-day mortality was significantly lower in CURB-65 hospitals versus PSI hospitals (8.6% and 9.7%, adjusted odds ratio (aOR) 0.89, 95% CI: 0.83-0.96, p=0.003). Other clinical outcomes were similar between CURB-65 hospitals and PSI hospitals. No-consensus hospitals had higher admission rates compared to the CURB-65 and PSI hospitals combined (78.4% and 81.5%, aOR 0.78, 95% CI: 0.62-0.99). In this study, using the CURB-65 in CAP patients at the ED is associated with similar and possibly even better clinical outcomes compared to using the PSI. After confirmation in prospective studies, the CURB-65 may be recommended over the use of the PSI since it is associated with lower 30-day mortality and is more user-friendly.

Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis

ObjectivesTo find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults.DesignSystematic review and duration-effect meta-analysis.Data sourcesMEDLINE, Embase and CENTRAL through 25 August 2021.Eligibility criteriaAll randomised controlled trials...

The Role of Biomarkers in Influenza and COVID-19 Community-Acquired Pneumonia in Adults.

Pneumonia is a growing problem worldwide and remains an important cause of morbidity, hospitalizations, intensive care unit admission and mortality. Viruses are the causative agents in almost a fourth of cases of community-acquired pneumonia (CAP) in adults, with an important representation of influenza virus and SARS-CoV-2 pneumonia. Moreover, mixed viral and bacterial pneumonia is common and a risk factor for severity of disease. It is critical for clinicians the early identification of the pathogen causing infection to avoid inappropriate antibiotics, as well as to predict clinical outcomes. It has been extensively reported that biomarkers could be useful for these purposes. This review describe current evidence and provide recommendations about the use of biomarkers in influenza and SARS-CoV-2 pneumonia, focusing mainly on procalcitonin (PCT) and C-reactive protein (CRP). Evidence was based on a qualitative analysis of the available scientific literature (meta-analyses, randomized controlled trials, observational studies and clinical guidelines). Both PCT and CRP levels provide valuable information about the prognosis of influenza and SARS-CoV-2 pneumonia. Additionally, PCT levels, considered along with other clinical, radiological and laboratory data, are useful for early diagnosis of mixed viral and bacterial CAP, allowing the proper management of the disease and adequate antibiotics prescription. The authors propose a practical PCT algorithm for clinical decision-making to guide antibiotic initiation in cases of influenza and SARS-CoV-2 pneumonia. Further well-design studies are needed to validate PCT algorithm among these patients and to confirm whether other biomarkers are indeed useful as diagnostic or prognostic tools in viral pneumonia.