Pneumonia最新文献

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality across the lifespan, with the highest burden seen in infants and older adults. Recently approved immunizing agents, including long-acting neutralizing monoclonal antibodies and a maternal vaccine for passive immunization of newborns, and three vaccines for adults aged 60 years and older who are vulnerable to RSV disease, have the potential to prevent severe RSV-associated disease if implemented successfully. The use of these agents will be implemented in some Italian regions over the next few months, although no consistent timelines or decisions for adoption at the national level are expected. A multidisciplinary group of experts in neonatology, obstetrics and gynecology, respiratory medicine, geriatric medicine, hygiene, and public health reviewed the evidence on RSV prevention and present here their considerations on implementing an RSV prevention strategy in Italy. Given the associated disease burden, it is essential to move quickly to deploy these agents in vulnerable populations, enhance surveillance to accurately detect/predict seasonal trends in RSV activity and measure the impact of prevention strategies. Continuing research combined with widespread use of more sensitive testing is needed to identify vulnerable populations and risk factors. Policies are needed to support these preventive measures in the Italian healthcare system, and access must be accompanied by educational initiatives and advocacy to promote acceptance by HCPs and the target population.

Background: Streptococcus pneumoniae (the pneumococcus) is a leading cause of community-acquired pneumonia. Pneumococci are categorised into serotypes, based on the type of capsular polysaccharide produced, which has important implications for virulence, vaccine impact and global surveillance. Recently, we identified a novel serotype, which we named 33G, that is comprised of an O-acetylated hexasaccharide repeat unit. In this study, we report and describe variants of 33G, designated 33G-like, which we isolated from the nasopharynx of two adults hospitalised with pneumonia in Mongolia.

Methods: Serological comparison of 33G and 33G-like pneumococci were conducted by Quellung serotyping. Genetic analysis of the capsular polysaccharide loci was performed using whole genome sequencing. Polysaccharide composition was determined using ¹H nuclear magnetic resonance.

Results: By Quellung serotyping, 33G pneumococci type as both 10B and 33B whereas 33G-like pneumococci type as both 10B and 33F. Genomic analysis of the capsular polysaccharide locus revealed 33G-like loci are identical to 33G, except for frameshift mutations in the wciG gene which encodes an acetyltransferase responsible for the O-acetylation of beta-galactofuranose (β-Galf) in the capsular polysaccharide repeat unit. We constructed an artificial 33G-like by deleting wciG in a 33G strain and confirmed this gene was responsible for the serological differences between 33G and 33G-like pneumococci. Lastly, ¹H nuclear magnetic resonance confirmed the O-acetylation present in the 33G polysaccharide is absent in the 33G-like polysaccharide.

Conclusions: Here, we have provided serological, genetic and biochemical evidence that the 33G-like capsule differs to 33G and all other pneumococcal serotypes, meeting the requirements to be designated as a new serotype, which we have named 33H.

Background: An increase in hospitalizations for respiratory illnesses due to Mycoplasma pneumoniae was reported in France in late October 2023. Data in primary care are scarce and microbiological or radiological investigations are not routinely recommended for community-acquired pneumonia.

Methods: We computed weekly incidence rates of pneumonia and bronchiolitis cases from the electronic records of French general practitioners from January 2016 to August 2024. These weekly incidences were described in the light of the Covid-19 pandemic, overall and by age group. For better interpretation, the weekly incidences of pneumonia and bronchiolitis were compared with virological surveillance data of acute respiratory infections observed in general practice.

Results: During the 2016-2024 period, 108,539 cases of pneumonia and 46,411 cases of bronchiolitis were identified from 51,351,414 consultations. The incidence of pneumonia consultations in general practice during the 2022-2023 and 2023-2024 seasons is similar to that observed before the Covid-19 pandemic, after two seasons of low incidence (2020-2021 and 2021-2022). However, the 2023-2024 pneumonia epidemic is the strongest ever observed in children (0-14 years, and especially among the 5-14 years) in general practice since 2016, with an earlier onset. Regarding the incidence of bronchiolitis in children, the 2023-2024 season was in line with the 2021-2022, 2022-2023 and pre-pandemic seasons. No abnormal circulation of classical seasonal viruses was observed during the 2023-2024 season.

Conclusions: The sharp increase in pneumonia cases observed this season among children in primary care settings requires the implementation of studies to understand the cause and to confirm or refute the possible association with M. pneumoniae as observed in hospitals. Given the impact of the Covid-19 pandemic on the circulation of pathogens, it would be useful to extend, even on a temporary basis, the traditional microbiological surveillance in primary care to include common bacterial pathogens affecting the upper and lower respiratory tract, such as M. pneumoniae, S. pneumoniae or Streptococcus A.

Background: Pneumococcal pneumonia continues to be a significant global health burden, affecting both children and adults. Traditional diagnostic methods for sputum analysis remain challenging. The objective of this study was twofold: to develop a rapid and easy-to-perform assay for the identification of Streptococcus pneumoniae (Spn) directly in sputum specimens using fluorescence microscopy, and to characterize with high-resolution confocal microscopy the ultrastructure of pneumococci residing in human sputum.

Methods: We fluorescently labeled antibodies against the pneumococcal capsule (Spn-FLUO). The specificity and sensitivity of Spn-FLUO for detecting Spn was evaluated in vitro and in vivo using mouse models of carriage and disease, human nasopharyngeal specimens, and sputum from patients with pneumococcal pneumonia. Spn was confirmed in the specimens using culture and a species-specific qPCR assay. Spn strains were serotyped by Quellung. Confocal microscopy and Imaris software analysis were utilized to resolve the ultrastructure of pneumococci in human sputum.

Results: Compared with cultures and qPCR, Spn-FLUO demonstrated high sensitivity (78-96%) in nasopharyngeal samples from mice and humans. The limit of detection (LOD) in nasopharyngeal samples was ≥ 1.6 × 10⁴ GenEq/ml. The specificity in human nasopharyngeal specimens was 100%. In lung specimens from mice infected with pneumococci, Spn-FLUO reached 100% sensitivity with a LOD of ≥ 1.39 × 10⁴ GenEq/ml. In human sputum, the sensitivity for detecting Spn was 92.7% with a LOD of 3.6 × 10³ GenEq/ml. Ultrastructural studies revealed that pneumococci are expectorated as large aggregates with a median size of 1336 μm².

Conclusions: Spn-FLUO is a rapid and sensitive assay for detecting Spn in human sputum within 30 min, encompassing a range of both vaccine and non-vaccine serotypes associated with pneumococcal pneumonia. The study highlights that most pneumococci form aggregates in human sputum.

Background: Pneumococcal pneumonia is a common disease with a significant impact on morbidity and mortality among the elderly population. The main purpose of this meta-analysis was to estimate the prevalence of community-acquired pneumonia (CAP) in elderly individuals caused by Streptococcus pneumoniae (S. pneumoniae).

Methods: A systematic search of the PubMed, Web of Science, and Scopus databases was conducted for relevant studies published between January 2013 and December 2023. Subgroup analysis and meta-regression were used to identify the sources of heterogeneity affecting the 87,430 patient studies obtained from 47 papers that met the inclusion and exclusion criteria.

Results: The combined prevalence rate for S. pneumoniae among all CAP patients included in the study was 14.8% (95% confidence interval [CI]: 12.3-17.8%). The 5-year pooled prevalence decreased from 16.5% (95% CI: 15.0-18.2%) in 1996-2000 to 8.4% (95% CI: 6.3-11.0%) in 2016-2020 for bacterial culture alone and from 17.4% (95% CI: 16.3-18.7%) to 13.5% (95% CI: 10.7-16.8%) for bacterial culture and urinary antigen testing (UAT) combined (P < 0.001). The most prevalent serotype was serotype 3, followed by serotypes 8, 19 A, 22 F, 11 A, 5, 9 N, 12 F, 6 A, and 10 A. The vaccine-serotype coverage was 53.5% for PCV 13, 60.5% for PCV 15, 85.2% for PCV 20 and 88.6% for PPSV 23.

Conclusion: These findings indicate a decrease in the overall burden of pneumococcal CAP among elderly individuals over the decade, which lends support to the proposition that the delivery of immunization should be expanded across the life course.

Purpose: Studies on COVID-19 mortality during the Omicron-predominant wave have focused primarily on the inpatient/emergency room setting, and real-world data including both inpatients and outpatients are lacking.

Methods: Patients diagnosed with COVID-19 (n = 27,440,148) or influenza (n = 8,179,641) from January 2020 to April 2023 were identified using nationwide claims data in Japan. Patients with COVID-19 in the Omicron-predominant wave were compared with their counterparts in earlier waves, and a subset of the former group (May 2022-April 2023) was compared with patients with influenza as controls.

Results: The mortality rates (average number of deaths/cases per week) of COVID-19 decreased over time, being 2.7% (169/6312), 2.1% (397/18,754), 0.7% (195/28,273), and 0.4% (1613/378,848) in the wild-type-, Alpha-, Delta-, and Omicron-predominant waves, respectively. However, the number of deaths increased substantially in the Omicron-predominant wave, especially among the elderly (e.g., in the Delta- and Omicron-predominant waves, the average numbers of deaths/cases per week were < 1/5527 (< 0.01%) and 4/105,763 (< 0.01%) respectively, in patients aged 0-19, versus 101/925 (10.9%) and 1212/20,771 (5.8%), respectively, in patients aged ≥ 80). The mortality rate was lower for patients with COVID-19 than in those with influenza among those aged ≤ 39 years but higher among those aged ≥ 40 years.

Conclusions: In the Omicron-predominant wave, the mortality rate of COVID-19 decreased, but the number of patients increased, leading to a substantial increase in the number of deaths, especially among the elderly. The mortality rate of COVID-19 was higher than that of influenza in the elderly but not in the young, highlighting the need for age-specific interventions.

Background: A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population.

Methods: We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010. Patients were assigned to one of three exposure categories according to their prescribing history in the 12 months prior to IPF diagnosis as follows: "regular" users (≥ 4 prescriptions), "irregular" users (1-3 prescriptions) and "non-users" (no prescriptions). We explored the association between PPI/ICS prescription and pneumonia hospitalisation and all-cause mortality using multinomial Cox regression models.

Results: A total of 17,105 people met our study inclusion criteria; 62.6% were male and 15.9% were current smokers. Median age at IPF diagnosis was 76.7 years (IQR: 69.6-82.7). 19.9% were regularly prescribed PPIs, and 16.0% ICS, prior to IPF diagnosis. Regular prescribing of PPIs and ICS was positively associated with hospitalisation for pneumonia; the adjusted HR for pneumonia hospitalisation comparing regular PPI users with non-users was 1.14 (95%CI: 1.04-1.24); for regular ICS users the corresponding HR was 1.40 (95%CI: 1.25-1.55). We also observed a small increased risk for all-cause mortality in the "regular ICS user" group compared with the "non-user" control group (HR_adj = 1.19, 1.06-1.33). We found no evidence of an association between PPI prescribing and all-cause mortality.

Conclusion: Prolonged prescription of medications used to treat common comorbidities in IPF may be associated with increased risks for severe respiratory infections. These findings point to a need to adopt an adequate risk-benefit balance approach to the prescribing of ICS-containing inhalers and PPIs in people with IPF without evidence of comorbidities, especially older patients and/or those with more advanced disease in whom respiratory infections are more likely to result in poorer outcomes.

Background: Current guidelines recommend empiric antibiotic therapy for patients who require hospitalization for community-acquired pneumonia (CAP). We sought to determine whether clinical, imaging or laboratory features in patients hospitalized for CAP in whom PCR is positive for a respiratory virus enable exclusion of bacterial coinfection so that antibiotics can be withheld.

Methods: For this prospective study, we selected patients in whom an etiologic diagnosis was likely to be reached, namely those who provided a high-quality sputum sample at or shortly after admission, and in whom PCR was done to test for a respiratory virus. We performed quantitative bacteriologic studies on sputum to determine the presence of bacterial infection or coinfection and reviewed all clinical, imaging and laboratory studies.

Results: Of 122 CAP patients studied, 77 (63.1%) had bacterial infection, 16 (13.1%) viral infection, and 29 (23.8%) bacterial/viral coinfection. Underlying pulmonary disease and a history of smoking were more common in bacterial pneumonia. Upper respiratory symptoms were more common, and mean white blood cell (WBC) counts were lower viral pneumonia. Nevertheless, no clinical, laboratory or imaging findings allowed exclusion of bacterial coinfection in patients who tested positive for a respiratory virus. In fact, patients with bacterial/viral coinfection were sicker than those with bacterial or viral pneumonia; 30% were admitted required transfer to the ICU during their hospital course, compared to 17% and 19% of patients with bacterial or viral infection, respectively (p < .05). In this study, 64.4% of patients who tested positive for a respiratory virus had a bacterial coinfection.

Conclusions: If a test for a respiratory virus test is positive in a patient hospitalized for CAP, no sufficiently differentiating features exclude bacterial coinfection, thereby supporting the recommendation that empiric antibiotics be administered to all patients who are sufficiently ill to require hospitalization for CAP.

Background: Pneumococcal disease, caused by Streptococcus pneumoniae, imposes a significant global health burden, particularly affecting vulnerable groups such as the elderly and immunocompromised. The 23-valent pneumococcal polysaccharide vaccine (PPV23) is designed to protect against 23 serotypes of Streptococcus pneumoniae. However, there is ongoing debate about its effectiveness in reducing all-cause mortality. This systematic review and meta-analysis aimed to evaluate the efficacy of PPV23 in reducing all-cause and pneumonia-related mortality among adults.

Methods: A systematic search was conducted across PubMed, Embase, and Web of Science, focusing on studies that evaluated the mortality outcomes of adults vaccinated with PPV23 compared to non-vaccinated adults. Both randomized controlled trials (RCTs) and observational studies were included, while case reports, case series, and non-human studies were excluded. Data extraction and quality assessment were facilitated by Nested Knowledge software, using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for RCTs.

Results: The search yielded 826 records, with 19 studies meeting the inclusion criteria. The pooled analysis of four RCTs showed no significant reduction in all-cause mortality (RR = 1.030; 95% CI: 0.945, 1.122). However, analysis of pneumonia-related mortality across various studies indicated a significant reduction (HR = 0.504; 95% CI: 0.316, 0.693). Moderate to high heterogeneity was noted in mortality studies, and a potential publication bias was identified.

Conclusion: The findings suggest that while PPV23 may not significantly reduce all-cause mortality, it is effective in reducing pneumonia-related mortality among adults, particularly in those at higher risk. These results support the continued use of PPV23 in targeted adult populations, emphasizing the need for more primary studies to explore its effectiveness across diverse groups.