Community-acquired pneumonia (CAP) is a leading cause of adult morbidity and mortality worldwide despite decades of effective antibiotics and vaccination initiatives. There have been no recent significant improvements in outcomes, including 30-day mortality. The bacterium Streptococcus pneumoniae is the most prevalent causative pathogen in CAP, being found in up to half of cases. In September 2006 a childhood pneumococcal vaccine (PCV-7) was introduced, leading to reductions in vaccine-type (VT) pneumococcal disease in infants, with possible additional benefits reported in adults. However, the effect that infant PCV-7 vaccination has on adult disease has to date been inadequately described in a small fraction of patients with invasive CAP, almost exclusively in populations in the US. These issues are explored fully in the literature review, encompassing chapters 1, 2 and 3. New strategies for CAP are therefore required. The outcome of CAP can be improved by a) preventing the disease by vaccination and herd immunity, and b) ameliorating the course of the disease after it has been acquired. This thesis presents a collection of studies that aim to acquire observational data to investigate these two issues. The majority of the included studies are drawn from a two year prospective cohort study of consecutive adults with CAP admitted to a large UK teaching hospital trust between September 2008 and September 2010. After obtaining informed consent, the presence of pneumococcal disease in each participant was established by testing urine samples for pneumococcal capsular polysaccharide, a test which has a high sensitivity and specificity. The urine samples were subsequently tested for pneumococcal serotype. A full record of care processes, investigations, and clinical outcomes was made, and child contact in the month preceding admission was assessed. These methods are described more fully in chapter 4. Chapter 5 presents the data on the pneumococcal serotypes found in the cohort over a two year period, and links them to epidemiological characteristics in the study population. The most prevalent serotypes were 14, 1, 8, 3 and 19A, with VT serotypes less frequent in the second year of the study. Chapter 6 examines the association that infecting serotype has with disease manifestation and patient characteristics. Infection with a serotype not contained within PCV-7 (NVT) was associated with younger and fitter patients, a higher rate of complications such as para-pneumonic effusion, and hypotension at admission. The effect of child contact on pneumococcal disease is reported in chapter 7. Prior contact with a child aged ≤8 years was particularly associated with pneumococcal aetiology, and contact with a PCV-7 vaccinated child independently associated with NVT CAP. The findings from these three chapters are unique in that they relate individual pneumococcal serotype to specific clinical disease patterns, epidemiology and transmission in both invasive and non-invasive pneumococcal CAP for the first time. They show a change in serotype distribution in adults following the introduction of PCV-7 in infants, which is important to inform future vaccine development for both adults and children. Furthermore, different serotypes are associated with different clinical disease patterns, which may have a significant impact on the disease that clinicians see at the “front door” given that the serotype distribution of pneumococcal CAP may be changing. Finally, the link between child vaccination and adult disease provides more direct evidence for the transmission of pneumococci from children to adults as a mechanism for the development of CAP in adults. The second part of this thesis looks at current care processes, and how these might be improved. Chapters 8, 9 and 10 relate to efforts to better predict prognosis, and chapters 11 and 12 with how patents with CAP may be better managed at the “front door”. Symptoms are clearly important to patients, but the role of symptoms in management and outcome is unclear. Chapter 8 presents a study validating a symptom score that has not yet entered routine use, but which is shown to correlate with clinical outcomes, and may be useful in assessing outcome in low severity CAP. The influence that oxygenation status at admission has on outcome is poorly understood. Chapter 9 describes a study showing that whilst hypoxaemia does positively predict adverse outcome, it is not as predictive as existing severity scores. The presence of hypoxaemia may however identify a subset of patients who are classified as low severity by existing severity scoring, but are nevertheless at increased risk of adverse outcome. Severity scoring is the cornerstone of management in adult CAP, and is explored in chapter 10. Current severity scores adequately predict mortality in CAP, but often generate a group of “moderate severity” where appropriate management is often unclear. This study looked at the effect of pre-admission functional status on outcome in conjunction with existing severity scores in this difficult group, and validated a novel severity score for predicting need for escalation of care, SMART-COP. Incorporation of functional status does marginally improve the performance of existing severity scores, but may be of more use as a post-severity score test to identify sub-groups of patients with moderate severity CAP who are at increased risk of death. Chapter 11 looks at the influence that making a prompt diagnosis (rather than prompt treatment with antibiotics, as has previously been studied) has on outcome, using the time between admission and first chest radiograph as a surrogate measure. Whilst an early chest radiograph was not associated with an improvement in mortality, it was associated with a shorter length of hospital stay, and may therefore be regarded as a marker of good quality care. There is current debate as to the role of the speciality physician in the front-door early assessment of patients, and whether early review of patients with CAP may improve outcome compared with management by a non-specialty physician. Chapter 12 looks at the effect that early specialist senior respiratory review has on outcome for adults with CAP, showing a clear benefit on length of hospital stay to early consultant review. In conclusion, this thesis provides an up-to-date picture of the circulating pneumococcal serotypes in non-invasive adult CAP, and correlates infecting serotype to clinical and epidemiological parameters. It also identifies five areas of clinical care where management processes could be improved. By addressing of these aspects the outcome of CAP may be improved in the future.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:559568 |
| Date | January 2012 |
| Creators | Bewick, Thomas |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/12432/ |
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