The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly: Exploratory analysis of the CAPiTA trial.

OBJECTIVES: Our objective was to evaluate whether vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) prevents the incidence of community-acquired pneumonia (CAP) caused by influenza (influenza-associated CAP, IA-CAP) or other respiratory viruses in the elderly. METHODS: This analysis was part of the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double blind, randomized, placebo-controlled trial in 84 496 immunocompetent individuals aged ≥65 years. CAP was defined by clinical and radiological criteria, and oropharyngeal swabs were collected from all individuals referred to a sentinel centre with a clinical suspicion of pneumonia. Presence of influenza A and B, parainfluenza 1, 2, 3 and 4, human adeno-, boca-, corona-, metapneumo-, rhino- and respiratory syncytial viruses was determined by real-time PCR. RESULTS: Of 3209 episodes of suspected pneumonia, viral aetiology was tested in 2917 and proportions with influenza virus, human metapneumovirus and respiratory syncytial virus were 4.6%, 2.5% and 3.1%, respectively. There were 1653 oropharyngeal swabs for PCR testing available from 1814 episodes that fulfilled criteria for CAP, yielding 23 first episodes of IA-CAP in the PCV13 and 35 in the in placebo group-vaccine efficacy for IA-CAP of 34.4% (95% CI -11.1% to 61.2%; p 0.117). Annual influenza vaccination was received by 672 (87.2%) in the PCV13 group and 719 (87.7%) in the placebo group of the confirmed CAP cases. CONCLUSION: In a randomized study of 84 496 elderly individuals with a high uptake of influenza vaccination, PCV13 was not associated with a statistically significant reduction of influenza or virus-associated CAP. Overall incidence of non-influenza viral pneumonia was low.

Predicting pneumococcal community-acquired pneumonia in the emergency department: evaluation of clinical parameters.

The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission.

Guideline adherence for empirical treatment of pneumonia and patient outcome. Treating pneumonia in the Netherlands.

INTRODUCTION: According to the Dutch guidelines, severity of community acquired pneumonia (CAP) (mild, moderate-severe, severe) should be based on either PSI, CURB65 or a 'pragmatic' classification. In the last mentioned, the type of ward of admission, as decided by the treating physician, is used as classifier: no hospital admission is mild, admission to a general ward is moderate-severe and admission to an intensive care unit (ICU) is severe CAP. Empiric antibiotic recommendations for each severity class are uniform. We investigated, in 23 hospitals, which of the three classification systems empirical treatment of CAP best adhered to, and whether a too narrow spectrum coverage (according to each of the systems) was associated with a poor patient outcome (in-hospital mortality or need for ICU admission). PATIENTS AND METHODS: Prospective observational study in 23 hospitals. RESULTS: 271 (26%) of 1047 patients with CAP confirmed by X-ray were categorised in the same severity class with all three classification methods. Proportions of patients receiving guideline-adherent antibiotics were 62.9% (95% CI 60.0-65.8%) for the pragmatic, 43.1% (95% CI 40.1-46.1%) for PSI and 30.5% (95% CI 27.8-33.3%) for CURB65 classification. 'Under-treatment' based on the pragmatic classification was associated with a trend towards poor clinical outcome, but no such trend was apparent for the other two scoring systems. CONCLUSIONS: Concordance between three CAP severity classification systems was low, implying large heterogeneity in antibiotic treatment for CAP patients. Empirical treatment appeared most adherent to the pragmatic classification. Non-adherence to treatment recommendations based on the PSI and CURB65 was not associated with a poor clinical outcome.

New trends in the prevention and management of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality worldwide. This review summarises current trends and knowledge gaps in CAP management and prevention. Although Streptococcus pneumoniae is the most frequent cause of CAP, identification of the microbial cause of infection remains unsuccessful in most episodes, and little is known about the aetiology of CAP in immunocompromised patients. Urinary antigen testing has become standard care for diagnosing Legionella infection, and pneumococcal urinary antigen testing is now recommended in the Dutch guidelines to streamline antibiotic therapy in patients hospitalised with CAP. In primary care C-reactive protein determination is recommended to improve antibiotic prescription for lower respiratory tract infections. In patients hospitalised with CAP, three strategies are considered equally effective for choosing empirical antibiotic treatment. Yet, more (and better designed) studies are needed to determine the best strategy, as well as to determine optimal (which usually means the minimum) duration of antibiotic therapy and the role of adjuvant treatment with corticosteroids. The effectiveness of the 23-valent pneumococcal polysaccharide vaccine in preventing invasive pneumococcal disease and pneumococcal CAP remains debated, and whether the newer conjugate vaccines are more effective remains to be determined. Many of these questions are currently being addressed in large-scaled trials in the Netherlands, and their results may allow evidence-based decisions in CAP management and prevention.

Rationale and design of CAPITA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults.

The burden of community-acquired pneumonia (CAP) among the elderly is high and has increased over the last decades. Streptococcus pneumoniae is the most common cause of CAP and in 10% the infection may be fatal. Although the 23-valent polysaccharide pneumococcal vaccine (23vPS) is considered effective in the prevention of invasive pneumococcal disease in the elderly population, the evidence is mainly from nonrandomised observational studies and effects on the occurrence of pneumonia have not been demonstrated. Conjugated pneumococcal vaccines which also stimulate T-cell dependent immune responses induced antibody responses in elderly persons which are similar to those induced by a primary series of 7-valent conjugated pneumococcal vaccine (7vPnC) in infants, and the response appeared similar or superior for all vaccine serotypes to that induced by 23vPS. The primary objective of the planned trial entitled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults) is to establish the efficacy of a 13-valent PnC vaccine in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adult persons aged 65 years and older. This is a parallel group, randomised, placebo-controlled trial, with a 1:1 random allocation to vaccine or placebo vaccine. The occurrence of the primary outcome of vaccine-serotype specific (VT)-CAP will be established in hospitals on the basis of three sets of criteria: (1) a clinical definition of CAP; (2) independent interpretation of chest radiograph consistent with pneumonia: and (3) determination of S. pneumonia serotype. the trial will be critical to determine the position of conjugate pneumococcal vaccines in the prevention of pneumococcal disease.