Chamira Rodrigo

Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia

Infant 13-valent pneumococcal conjugate vaccination (PCV13) was introduced to the UK in 2010. Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known. Beginning in 2008, a 5-year prospective cohort study of adults admitted to hospital with community-acquired pneumonia (CAP) was conducted. Pneumococcal serotype was established using a validated multiplex immunoassay (Bio-Plex; Bio-Rad, Hercules, CA, USA). The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 (95% CI 76.6–83.3) and 23.4 (95% CI 21.6–25.3) per 100 000 population, respectively. A decline in CAP (incidence rate ratio (IRR) per year 0.96, 95% CI 0.94–0.99; p=0.016) and pneumococcal CAP (IRR per year 0.84, 95% CI 0.80–0.89; p<0.001) was observed over the 5-year period of the study. Between the pre- and post-PCV13 periods of the study, the incidence of CAP due to serotypes included in the PCV7 declined by 88% (IRR 0.12, 95% CI 0.08–0.20; p<0.001), and CAP due to the additional 6 serotypes in PCV13 declined by 30% (IRR 0.70, 95% CI 0.51–0.96; p=0.024). Incidence of adult pneumococcal pneumonia declined over the last 5 years, with serotypes included in PCV13 declining post-PCV13 introduction, indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease. These effects may accrue over the coming years with implications for national pneumococcal vaccination policies in adults. This is the first study to indicate herd protection from infant PCV13 on adult non-bacteraemic pneumococcal pneumonia http://ow.ly/HHP75

Single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia

The benefits of β-lactam/macrolide combination therapy over β-lactam therapy alone for the treatment of hospitalised community-acquired pneumonia (CAP) in relation to pneumonia severity are uncertain. We studied 5240 adults hospitalised with CAP from 72 secondary care trusts across England and Wales. The overall 30-day inpatient (IP) death rate was 24.4%. Combination therapy was prescribed in 3239 (61.8%) patients. In a multivariable model, combination therapy was significantly associated with lower 30-day IP death rate in patients with moderate-severity CAP (adjusted OR 0.54, 95% CI 0.41 to 0.72) and high-severity CAP (adjusted OR 0.76, 95% CI 0.60 to 0.96) but not low-severity CAP.

Pneumococcal serotypes in adult non-invasive and invasive pneumonia in relation to child contact and child vaccination status

Background On a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few individual level studies have been performed describing the pneumococcal serotypes associated with adult community acquired pneumonia (CAP) and quantifying associations with child contact and child vaccination status. Methods Pneumococcal serotypes were determined using a validated multiplex immunoassay (Bio-Plex) in a large prospective cohort of adults hospitalised with CAP. Child (<16 years old) contact history and child pneumococcal vaccination status were obtained from patients and public health records, respectively. Results Of 1130 participants, 329 (29.1%) reported child contact, and pneumococcal infection was identified in 410 (36.3%). Pneumococcal CAP was commoner in adults with child contact (148/329 (45.0%) vs 262/801 (32.7%); adjusted OR 1.63, CI 1.25 to 2.14; p<0.001). A serotype was determined in 263 of 410 (64.1%) adults with pneumococcal CAP; 112 (42.6%) reported child contact, 38 (33.9%) with a vaccinated child. Adults in contact with a vaccinated child were significantly less likely to have vaccine-type CAP compared with adults in contact with an unvaccinated child (6 of 38 (15.8%) vs 25 of 74 (33.8%), respectively; OR 0.37, 95% CI 0.14 to 0.99; p=0.044). Conclusions Pneumococcal aetiology in adult CAP is independently associated with child contact and implicated serotypes are influenced by child vaccination status. This is the first study to demonstrate these associations at an individual rather than population level; it affirms that ‘herd protection’ from childhood vaccination extends beyond adult invasive disease to pneumococcal CAP.

Effect of Corticosteroid Therapy on Influenza-Related Mortality: A Systematic Review and Meta-analysis

BACKGROUND Most studies have reported that corticosteroid therapy adversely influences influenza-related outcomes. METHODS Electronic databases were searched from inception to March 2013 for experimental and observational studies investigating systemic corticosteroid therapy for presumed influenza-associated complications. Meta-analysis of Observational Studies in Epidemiology guidelines were adopted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models, and heterogeneity was assessed using the I(2) statistic. Quality of evidence was assessed using the Grading Assessment, Development, and Evaluation system. RESULTS We identified 16 eligible studies (3039 individuals), all of which were observational; 10 (1497 individuals) were included in the meta-analysis of mortality, of which 9 studied patients with 2009 pandemic influenza A virus subtype H1N1. Risk of bias was greatest in the comparability domain of the Newcastle-Ottawa scale, consistent with potential confounding by indication, and data specific to mortality were of low quality. Meta-analysis found an increased odds of mortality (OR, 2.12; 95% CI, 1.36-3.29) associated with corticosteroid therapy. Subgroup analysis of adjusted estimates from 4 studies with very low statistical heterogeneity found a similar association (OR, 2.58; 95% CI, 1.39-4.79). CONCLUSIONS No completed clinical trials were identified. Evidence from observational studies, with important limitations, suggests that corticosteroid therapy for presumed influenza-associated complications is associated with increased mortality.

The Relevance of Pneumococcal Serotypes

Pneumococcal disease leads to considerable mortality, morbidity and healthcare cost worldwide, and disease rates are predicted to increase due to an aging population. There are over 90 different pneumococcal serotypes identified to date, each with unique capsular characteristics capable of eliciting serotype-specific immunity in its host. Several recent studies have demonstrated important differences in invasiveness, disease severity, complications from disease and antibiotic resistance patterns that are specific to individual serotypes. This knowledge is particularly pertinent given the ongoing seroepidemiological changes worldwide, partly due to the introduction of pneumococcal conjugate vaccination to childhood immunization schedules. Further characterization of pneumococcal serotype-specific clinical features, and continued surveillance of serotypes in nasopharyngeal carriage and disease, will help guide treatment and prevention strategies in pneumococcal disease.

A care-bundles approach to improving standard of care in AECOPD admissions: results of a national project

This report describes a care bundles implementation project for COPD undertaken during 2013 in England and Wales. High-level data were collected on outcomes of care for 11 748 patients admitted with an acute exacerbation of COPD (AECOPD). Patient-level data on processes and outcomes of care were collected on 3272 COPD admissions, among which 1174 bundles were delivered. Analysis demonstrated a statistically significant reduction in mortality and length of hospital stay from some bundle elements. Outcomes, including bundle completion rates, were better when specialist respiratory review occurred. The results support wider use of care bundles for AECOPD.

British Thoracic Society community-acquired pneumonia care bundle: results of a national implementation project

In 2013, 16 UK hospital trusts participated in a quality improvement programme involving implementation of a community-acquired pneumonia (CAP) care bundle. High-level data were collected on 14 962 patients admitted with CAP; bundle implementation increased from 1% in October 2012 to 20% by September 2013. Analysis of patient-level data on 2118 adults (median age 75.3 years) found that in the bundle-implementation group, significantly more patients received antibiotics within 4 h of admission (adjusted OR 1.52, 95% CI 1.08 to 2.14, p=0.016) and 30-day inpatient mortality was lower (8.8% vs 13.6%; adjusted OR 0.59, 95% CI 0.37 to 0.95, p=0.03).

Time to first antibiotic and mortality in adults hospitalised with community-acquired pneumonia: a matched-propensity analysis.

A matched-propensity analysis of national data from the British Thoracic Society community-acquired pneumonia audit was conducted (n=13 725). Overall, time to first antibiotic (TFA) was ≤4 h in 63%. Adjusted 30-day inpatient (IP) mortality was lower for adults with TFA ≤4 h compared with TFA >4 h (adjusted OR 0.84, 95% CI 0.74 to 0.94; p=0.003). Increasing TFA was associated with greater OR of 30-day IP mortality (p value for trend=0.001), but no TFA threshold was evident. Although we found an association between TFA and mortality, we cannot say whether this is causal or whether TFA might just be a quality measure for overall or other processes of care.

Admission via the emergency department in relation to mortality of adults hospitalised with community-acquired pneumonia: an analysis of the British Thoracic Society national community-acquired pneumonia audit

Objective To determine the association between 30-day inpatient mortality and route of admission to hospital, for adults with community acquired pneumonia (CAP). Methods We studied 16 313 adults included in the British Thoracic Society (BTS) national CAP audit dataset. Comparisons were made between adults admitted via emergency departments (ED) with non-ED routes of admission, with regard to 30-day inpatient mortality. Secondary outcome measures were adherence to national CAP guidelines (time to first chest X-ray ≤4 h from admission; time to first antibiotic dose ≤4 h from admission; antibiotic choice; and antibiotic route of administration) by route of admission. Results Of adults hospitalised with CAP, 75.6% were admitted via ED; these adults had a greater prevalence of comorbid illness and higher disease severity in comparison with non-ED admissions. Adjusted 30-day inpatient mortality was similar for ED versus non-ED route of admission (OR 1.10, 95% CI 0.96 to 1.25). Admissions via ED were associated with faster processes of care (time to chest X-ray ≤4 h, adjusted OR 3.39, 95% CI 2.79 to 4.12; time to first antibiotic ≤4 h, adjusted OR 1.62, 95% CI 1.42 to 1.84) and greater use of intravenous antibiotics regardless of disease severity (adjusted OR 1.58, 95% CI 1.43 to 1.74). Conclusions Adults with CAP admitted via EDs have more comorbid illness and greater disease severity compared to those admitted via non-ED routes. Following adjustment for these differences, 30-day inpatient mortality was not associated with route of admission.

Authors’ response: single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia

We thank van der Eerden et al 1 for their interest in our work2. We agree that pathogen-directed therapy (PDT) is desirable in adults with community-acquired pneumonia (CAP) admitted to hospital. In their report, the authors claim that microbiological investigations including sputum and pleural fluid …