Synopsis

Top Synopsis Synopsis of main summary... 1 Introduction and methods 2 Incidence, mortality and... 3 Aetiology and epidemiology 4 Clinical features 5 Radiological, general and... 6 Severity assessment 7 General management 8 Antibiotic management 9 Complications and failure... 10 Prevention and vaccination... 11 Acknowledgements and... Appendix 1 Appendix 2 Appendix 3 Appendix 4 References

Scope of these guidelines (sections 1.1-1.7)

• These guidelines refer to the management of adults with community acquired pneumonia (CAP) of all ages in the community or in hospital. They have been developed to apply to the UK healthcare system and population, but they should equally be applicable to any other countries which operate similar healthcare services.
• They are not aimed at patients with known predisposing conditions such as cancer or immunosuppression admitted with pneumonia to specialist units such as oncology, haematology, palliative care, infectious diseases units, or AIDS units.
• They do NOT apply to the much larger group of adults with non-pneumonic lower respiratory tract infection, including illnesses labelled as acute bronchitis, acute exacerbations of chronic obstructive pulmonary disease (COPD), or "chest infections".
• Details of methods, the level of evidence, and grading of recommendations are given in the text (sections 1.8-1.15) and appendices and are summarised briefly for easy reference in table 1.

	Synopsis of main summary points

Top Synopsis Synopsis of main summary... 1 Introduction and methods 2 Incidence, mortality and... 3 Aetiology and epidemiology 4 Clinical features 5 Radiological, general and... 6 Severity assessment 7 General management 8 Antibiotic management 9 Complications and failure... 10 Prevention and vaccination... 11 Acknowledgements and... Appendix 1 Appendix 2 Appendix 3 Appendix 4 References

AETIOLOGY AND EPIDEMIOLOGY (SECTION 3)

• Only a small range of pathogens causes CAP, with Streptococcus pneumoniae being the most frequent (tables 2-6, fig 3) [Ib].
• The frequency of pathogens can vary in specific patient groups. Mycoplasma and legionella infections are less frequent in the elderly (box 1, fig 5) [Ib].
• The low frequency of legionella, staphylococcal, Chlamydia psittaci and Coxiella burnetii infection in patients with CAP, together with the likely high frequency of the relevant epidemiological risk factors in the general population (for example, recent travel or contact with someone with an influenza type disease) suggests that routine enquiry about such factors is likely to be misleading [IV].
• Only in those with severe illness, where the frequency of legionella and staphylococcal infection is higher, may enquiry about foreign travel and influenza symptoms be of predictive value [IV].
• Knowledge of increased mycoplasma activity in the community during an epidemic period may help guide the clinician to the increased likelihood of mycoplasma infection (fig 4) [IV].

CLINICAL AND RADIOLOGICAL FEATURES (SECTIONS 4, 5.1-5.3)

• The likely aetiological agent causing CAP cannot be accurately predicted from clinical or radiological features [II].
• The term "atypical" pneumonia should be abandoned as it incorrectly implies that there is a characteristic clinical presentation for patients with infection caused by "atypical" pathogens [II].
• Elderly patients with CAP more frequently present with non-specific symptoms and are less likely to have a fever than younger patients [II].
• Radiological resolution often lags behind clinical improvement from CAP, particularly following legionella and bacteraemic pneumococcal infection [III].
• Radiographic changes caused by atypical pathogens clear more quickly than those associated with pneumonia caused by bacterial infection [III].
• Radiological resolution is slower in the elderly and in cases where there is multilobe involvement [Ib].

MANAGEMENT

• Figure 1 provides an algorithm for the management of adult patients with CAP in the community, and fig 2 provides an algorithm for the management of adult patients with CAP in hospital (see over).

  
  

  Synopsis of main recommendations Investigations (section 5) GENERAL INVESTIGATIONS FOR PATIENTS MANAGED IN THE COMMUNITY (SECTION 5.5) General investigations, including a chest radiograph, are not necessary for the majority of patients with suspected community acquired pneumonia (CAP) who are managed in the community [C]. Out of hours and emergency general practitioner assessment centres should consider using pulse oximeters to allow for simple assessment of oxygenation [D]. MICROBIOLOGICAL INVESTIGATIONS FOR PATIENTS MANAGED IN THE COMMUNITY (SECTION 5.8) Microbiological investigations are not recommended routinely [D]. Examination of sputum should be considered for patients who do not respond to empirical antibiotic therapy [D]. Examination of sputum for Mycobacterium tuberculosis should be considered for patients with a persistent productive cough, especially if malaise, weight loss or night sweats, or risk factors for tuberculosis (e.g. ethnic origin, social deprivation, the elderly) are present [D]. Serological investigations may be considered during outbreaks (e.g. Legionnaires' disease) or epidemic mycoplasma years, or when there is a particular clinical or epidemiological reason [D]. GENERAL INVESTIGATIONS FOR PATIENTS ADMITTED TO HOSPITAL (SECTION 5.6) All patients should have the following investigations performed on admission: chest radiograph [C]; full blood count [B-]; urea, electrolytes and liver function tests [C]; C reactive protein (CRP) when locally available [B-]; oxygenation assessment [C]. MICROBIOLOGICAL INVESTIGATIONS FOR PATIENTS ADMITTED TO HOSPITAL (SECTIONS 5.7-5.9) It is not necessary or appropriate to perform a full range of microbiological investigations on every patient with CAP. The investigations performed should be guided by the severity of pneumonia, epidemiological risk factors, and the response to treatment (table 7) [D]. Blood culture is recommended for all patients, preferably before antibiotic treatment is commenced [D]. Sputum samples should be sent for culture and sensitivity tests from patients with non-severe CAP who are able to expectorate purulent samples and have not received prior antibiotic treatment. Specimens should be transported rapidly to the laboratory [D].  Sputum cultures should also be performed for patients with severe CAP or those who fail to improve [D]. Laboratories should offer a reliable Gram stain for patients with severe CAP or complications, as on occasions this can give immediate indication of likely pathogens. Routine performance or reporting of sputum Gram stain on all patients is unnecessary but can aid the laboratory interpretations of culture results [D]. Laboratories performing sputum Gram stains should adhere to strict and locally agreed criteria for interpretation and reporting of results [B+]. Paired serological tests should be performed for all patients with severe CAP, those who are unresponsive to -lactam antibiotics, and for selected patients with particular epidemiological risk factors or in whom a specific microbiological diagnosis is important for public health measures (fig 6) [D]. Serological tests should be extended to all patients admitted to hospital with CAP during outbreaks and when needed for the purposes of surveillance. The criteria for performing serological tests in these circumstances should be agreed locally between clinicians, laboratories, and public health officers [D]. Pneumococcal antigen tests should be used for patients with severe CAP, if available locally [D]. Investigations for legionella infection are recommended for all patients with severe CAP, for other patients with specific risk factors, and for all patients with CAP during outbreaks [D]. Rapid testing and reporting for legionella urine antigen should be available in at least one laboratory per region [D]. Legionella culture should be specifically requested by clinicians on laboratory request forms from patients with severe CAP, or where legionella infection is suspected on epidemiological grounds [D]. Legionella cultures should be routinely performed on invasive respiratory samples (e.g. obtained by bronchoscopy) from patients with CAP [D]. Serological assays with complement fixation tests (CFTs) are widely available and should remain the mainstay of diagnosis for atypical and common respiratory viral pathogens [C]. Chlamydial antigen detection tests should be available for invasive respiratory samples from patients with severe CAP or where there is a strong suspicion of psittacosis [D]. The CFT remains the most suitable and practical serological assay for routine diagnosis of respiratory mycoplasmal and chlamydial infections [B-]. There is no currently available serological test that can reliably detect infections due to Chlamydia pneumoniae. Severity assessment (section 6) GENERAL RECOMMENDATIONS Severity assessment is recommended as the key to planning appropriate management both in the community and in hospital [D]. Certain adverse prognostic features (detailed below) have been associated with an increased risk of death and should be assessed in all patients [A-]. None of the available predictive models or the algorithms provided in these guidelines allow the unequivocal categorisation of patients into definite risk groups and they should be regarded as an aid to clinical judgement, which is essential in assessing appropriate management [D] Regular reassessment of severity during the course of the illness is mandatory if management is to be adjusted appropriately [D]. ADVERSE PROGNOSTIC FEATURES "Pre-existing" adverse prognostic features Age 50 years and over [Ib]. Presence of coexisting disease [Ib]. "Core" clinical adverse prognostic features (CURB) Confusion: new mental confusion (defined as an Abbreviated Mental Test score of 8 or less, see box 2) [Ib]. Urea: raised >7 mmol/l (for patients being seen in hospital) [Ib]. Respiratory rate: raised 30/min [Ib]. Blood pressure: low blood pressure (systolic blood pressure <90 mm Hg and/or diastolic blood pressure 60 mm Hg) [Ib]. "Additional" clinical adverse prognostic features Hypoxaemia (SaO2 <92% or PaO2 <8 kPa) regardless of FiO2 [Ib]. Oxygen saturation measurements may be available to some general practitioners in the community who have oximeters. Bilateral or multilobe involvement on the chest radiograph [Ib]. IDENTIFYING THOSE PATIENTS WHO CAN USUALLY BE SAFELY TREATED AT HOME (FIG 7) Patients who display no adverse prognostic features are at low risk of death and do not normally require hospitalisation for clinical reasons [D]. Patients who display two or more "core" adverse prognostic features are at high risk of death and should be referred urgently to hospital [D]. For all other patients the decision to treat at home or refer to hospital is a matter of clinical judgement [D].  When deciding on home treatment, the patient's social circumstances and wishes must be taken into account in all instances [D]. IDENTIFYING THOSE WITH SEVERE CAP IN HOSPITAL (FIG 8) Patients who have two or more "core" adverse prognostic features are at high risk of death and should be managed as having severe pneumonia [A-]. Patients who display one "core" adverse prognostic feature are at increased risk of death. The decision to treat such patients as having severe or non-severe pneumonia is a matter of clinical judgement, preferably from an experienced clinician. This decision can be assisted by considering "pre-existing" and "additional" adverse prognostic features [D]. Patients who display no adverse prognostic features can be managed as having non-severe pneumonia and may be suitable for outpatient treatment or early hospital discharge [B+]. REVIEWING SEVERITY STATUS AFTER INITIAL ASSESSMENT (SECTION 6.7) Regular assessment of disease severity is recommended for all patients following hospital admission. The "post take" round by a senior doctor and the medical team provides one early opportunity for this review [D]. All patients who display one or more "core" adverse prognostic features on admission should be reviewed medically at least 12 hourly until shown to be improving [D]. General management of CAP (section 7) IN THE COMMUNITY (SECTIONS 7.1-7.2) The need for hospital referral should be assessed using the recommended severity criteria and clinical judgement [C]. Those with features of severe infection should be admitted urgently to hospital [C]. Patients with suspected CAP should be advised not to smoke, to rest, and to drink plenty of fluids [D]. Pleuritic pain should be relieved using simple analgesia such as paracetamol [D]. Nutritional supplements should be considered in prolonged illness [C]. Pulse oximetry, with appropriate training, should become increasingly available to general practitioners for assessment of severity and oxygen requirement for patients with CAP and other acute respiratory illnesses [D]. Review of patients in the community with CAP is recommended after 48 hours or earlier if clinically indicated. "Core" and "additional" adverse prognostic features should be assessed as part of the clinical review [D]. Those who fail to improve after 48 hours of treatment should be considered for hospital admission or chest radiography [D]. IN HOSPITAL (SECTION 7.3) All patients should receive appropriate oxygen therapy with monitoring of oxygen saturations and FiO2 with the aim to maintain PaO2 8 kPa and SaO2 92%. High concentrations of oxygen can safely be given in uncomplicated pneumonia [D]. Oxygen therapy in patients with pre-existing chronic obstructive pulmonary disease complicated by ventilatory failure should be guided by repeated arterial blood gas measurements [C]. Patients should be assessed for volume depletion and may require intravenous fluids [C]. Nutritional support should be given in prolonged illness [C]. Temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration should be monitored and recorded initially at least twice daily and more frequently in those with severe pneumonia or requiring regular oxygen therapy [C]. The CRP level should be remeasured [B-] and the chest radiograph repeated [C] in patients who are not progressing satisfactorily. ON THE INTENSIVE CARE UNIT (SECTION 7.4) Detailed recommendations are outside the scope of these guidelines. Patients with CAP admitted to an intensive care unit (ICU) should be managed by specialists with appropriate training in intensive care and respiratory medicine [D]. Bronchoscopy can be valuable to remove retained secretions, obtain samples for culture for other microbiological investigations, and to exclude endobronchial abnormality [C]. FOLLOW UP PLANNING: WHEN TO REPEAT THE CHEST RADIOGRAPH AND WHAT ACTION TO TAKE IF THE RADIOGRAPH HAS NOT RETURNED TO NORMAL (SECTIONS 5.2, 5.3, 7.5) The chest radiograph need not be repeated prior to hospital discharge in those who have made a satisfactory clinical recovery [D]. At discharge or at follow up, patients should be offered access to information about CAP such as a patient information leaflet [D]. Clinical review should be arranged for all patients at around 6 weeks, either with their general practitioner or in a hospital clinic [D]. It is the responsibility of the hospital team to arrange the follow up plan with the patient and the general practitioner [D]. A chest radiograph should be arranged at that time for those patients who have persistent symptoms or physical signs or who are at higher risk of underlying malignancy (especially smokers and those over 50 years) [C].  In a patient who is improving clinically and for whom there are no concerning clinical features, it will usually not be necessary to perform further investigations just because radiological improvement lags behind clinical recovery [B+]. Further investigations which may include bronchoscopy should be considered in patients with persisting signs, symptoms, and radiological abnormalities about 6 weeks after completing treatment [C]. Antibiotic management (section 8) EMPIRICAL ANTIBIOTIC CHOICE IN THE COMMUNITY (TABLE 8) Amoxicillin remains the preferred agent but at a higher dose than previously recommended [D]. A macrolide (erythromycin or clarithromycin) is offered as an alternative choice and for those patients who are hypersensitive to penicillins [D]. For those patients referred to hospital with suspected CAP, general practitioners may consider administering antibiotics immediately where the illness is considered to be life threatening or where there are likely to be delays (over 2 hours) in admission [D]. EMPIRICAL ANTIBIOTIC CHOICE FOR ADULTS HOSPITALISED WITH NON-SEVERE CAP (TABLE 9) Most patients can be adequately treated with oral antibiotics [C]. Combined oral therapy with amoxicillin and a macrolide (erythromycin or clarithromycin) is preferred for patients who require hospital admission for clinical reasons [D]. Oral monotherapy should be considered in the following circumstances: Amoxicillin monotherapy: (i) those previously untreated in the community or (ii) those admitted to hospital for non-clinical reasons who would otherwise be treated in the community (e.g. the elderly or socially isolated) [D]. Monotherapy with a macrolide may be suitable for patients who have failed to respond to an adequate course of amoxicillin prior to admission. Deciding on the adequacy of prior therapy is difficult and is a matter of individual clinical judgement. It is therefore recommended that combination antibiotic therapy is the preferred choice in this situation and that the decision to adopt monotherapy is reviewed on the "post take" round within the first 24 hours of admission [D]. When oral treatment is contraindicated, recommended parenteral choices include intravenous ampicillin or benzylpenicillin, together with erythromycin or clarithromycin [D]. New fluoroquinolones are not recommended as first line agents or for community use for pneumonia, but may provide a useful alternative in selected hospitalised patients with CAP [C]. A fluoroquinolone active against S pneumoniae is an alternative regimen for those intolerant of penicillins or macrolides or where there are local concerns over Clostridium difficile associated diarrhoea. However, experience with such newer fluoroquinolones in the treatment of CAP and their interaction and side effect profile is at present limited and further reported experience is required [B-]. Levofloxacin is the only recommended agent currently licensed in the UK. EMPIRICAL ANTIBIOTIC CHOICE FOR ADULTS HOSPITALISED WITH SEVERE CAP (TABLE 9) Patients with severe pneumonia should be treated immediately after diagnosis with parenteral antibiotics [B-]. An intravenous combination of a broad spectrum -lactamase stable antibiotic such as co-amoxiclav or a second generation (e.g. cefuroxime) or third generation (e.g. cefotaxime or ceftriaxone) cephalosporin together with a macrolide (e.g. clarithromycin or erythromycin) is preferred [C]. For those who are intolerant of -lactam or macrolide therapy or where there are local concerns over C difficile associated diarrhoea, a fluoroquinolone with enhanced activity against S pneumoniae together with intravenous benzylpenicillin is offered as an alternative [D]. Levofloxacin is currently the only such fluoroquinolone licensed in the UK. ROUTE OF ANTIBIOTIC ADMINISTRATION (BOXES 4 AND 5) The oral route is recommended in those with non-severe pneumonia admitted to hospital provided there are no contraindications to oral therapy [B+]. Patients treated initially with parenteral antibiotics should be transferred to an oral regimen as soon as clinical improvement occurs and the temperature has been normal for 24 hours, providing there is no contraindication to the oral route [B+]. The choice of route of administration should be reviewed initially on the "post take" round and then daily [D]. Ward pharmacists could play an important role in facilitating this review by highlighting prescription charts where parenteral antibiotic treatment continues [D]. DURATION OF ANTIBIOTIC ADMINISTRATION (TABLE 10) For patients managed in the community and most of those admitted to hospital with non-severe and uncomplicated pneumonia, treatment with appropriate antibiotics for 7 days is recommended [C].  For patients with severe microbiologically undefined pneumonia, 10 days of treatment is proposed. This should be extended to 14-21 days where legionella, staphylococcal, or Gram negative enteric bacilli pneumonia are suspected or confirmed [C]. FAILURE TO IMPROVE (TABLE 12, BOX 6) For patients who fail to improve as expected, there should be a careful review by an experienced clinician of the clinical history, examination, prescription chart, and results of all available investigation results [D]. Further investigations, including a repeat chest radiograph, CRP and white cell count, and further specimens for microbiological testing should be considered in the light of any new information after the clinical review [D]. When a change in empirical antibiotic treatment is considered necessary, a macrolide could be substituted for or added to the treatment for those with non-severe pneumonia treated with amoxicillin monotherapy in the community or in hospital [C]. For those with non-severe pneumonia in hospital on combination therapy, changing to a fluoroquinolone with effective pneumococcal cover is an option [C]. The addition of rifampicin may be considered for those with severe pneumonia not responding to combination antibiotic treatment [C]. ANTIBIOTIC THERAPY WHEN A SPECIFIC PATHOGEN HAS BEEN IDENTIFIED (TABLE 11) If a specific pathogen has been identified, the guidelines recommend specific antibiotic options [C]. Prevention: vaccination strategies (section 10) INFLUENZA VACCINATION (SECTION 10.2) Influenza vaccination is recommended for those at "high risk" of mortality from influenza or complicating pneumonia [C]. These "high risk" groups include those with chronic lung, heart, renal and liver disease, diabetes mellitus, immunosuppression due to disease or treatment, and those aged over 65 years [C]. Influenza vaccine is contraindicated for those with hypersensitivity to hens' eggs [C]. PNEUMOCOCCAL VACCINATION (SECTION 10.3) Pneumococcal vaccination is recommended by the Departments of Health for all those aged 2 years or older in whom pneumococcal infection is likely to be more common or serious, although there is no evidence that it is effective in preventing CAP in such "at risk" groups [A+]. Pneumococcal vaccine should not be given during acute infection and is not recommended during pregnancy. Re-immunisation within 3 years is contraindicated [C]. Pneumococcal and influenza vaccines can be given together at different sites [A-].

  
  

View larger version (29K): [in this window] [in a new window]   Figure 1   Synopsis of the management of adult patients seen in the community with suspected CAP.

View larger version (34K): [in this window] [in a new window]   Figure 2   Synopsis of the management of adult patients seen in hospital with suspected CAP.

	1  Introduction and methods

Top Synopsis Synopsis of main summary... 1 Introduction and methods 2 Incidence, mortality and... 3 Aetiology and epidemiology 4 Clinical features 5 Radiological, general and... 6 Severity assessment 7 General management 8 Antibiotic management 9 Complications and failure... 10 Prevention and vaccination... 11 Acknowledgements and... Appendix 1 Appendix 2 Appendix 3 Appendix 4 References

1.1 Introduction

Community acquired pneumonia (CAP) is common. It is associated with significant morbidity, mortality and utilisation of health service resources (see section 2). Changes over the last decade suggest that it is appropriate to review the UK guidelines for the management of CAP published in 1993.

1.2 Available management guidelines for CAP

Recognising the clinical importance of CAP, numerous countries have developed national guidelines in the last decade, including the UK,¹ USA,^2 3 Canada,⁴ France,⁵ and Italy,⁶ among others. Those from the British Thoracic Society (BTS)¹ and the American Thoracic Society³ received much publicity and differed with regard to likely aetiology and antibiotic management.

More recently the Infectious Disease Society of America² and the Canadian Infectious Diseases Society working with the Canadian Thoracic Society⁴ have updated their recommendations for North America, and the Centers for Disease Control and Prevention of the USA have also published their own recommendations, specifically regarding the treatment and control of drug resistant Streptococcus pneumoniae.⁷ The European Respiratory Society⁸ has also provided a review of the management of lower respiratory tract infections, including pneumonia, to cover Europe. (Since finalising the contents of these guidelines, the American Thoracic Society has also published its own revised guidelines for North America.⁹)

However, it may be unwise to extrapolate national guidelines from other countries to the UK for a number of reasons:

(1) They should depend on the results of good CAP studies performed within that country. There are substantial differences in study results from different parts of the world (see section 3).^6 10

(2) Diagnosis and management of CAP will be influenced by the organisation of the health system. In common with some other countries, the UK has a network of National Health Service general practitioners who are the first port of call for most people with an acute illness and without cost to the patient. They will often diagnose and manage a patient without any investigations or secondary care advice. General practitioners usually only refer patients to hospital either just for a chest radiograph or because of clinical concern and the likely need for admission.

(3) By contrast, other health services such as in the USA depend on primary care physicians or specialists, some operating on a fee for service basis and usually operating from well equipped clinics or emergency rooms with easy and immediate access to radiology and other investigations. In such circumstances most patients with suspected pneumonia will be diagnosed by chest radiography and investigated before deciding on optimum management either as an outpatient or by admission to hospital.

(4) There is a difference in antimicrobial agents licensed and available in different countries. For instance, levofloxacin is the only fluoroquinolone with some enhanced pneumococcal activity licensed and available in the UK at the time of preparing these guidelines, whereas other countries also have available newer agents such as moxifloxacin.

1.3 What problems have become apparent with the 1993 BTS CAP guidelines?

Firstly, these were consensus guidelines¹ which relied on UK CAP studies performed in the early 1980s,^11-15 all of which had design limitations which question the application of their results to current UK practice.

Secondly, they have also been criticised for not clearly differentiating between CAP and non-pneumonic lower respiratory tract infections such as acute exacerbations of chronic obstructive pulmonary disease and thus encouraging overtreatment of some patients, particularly the elderly. The severity criteria proposed by the 1993 BTS guidelines resulted in many patients both with and without pneumonia being identified as severely ill. These factors have been blamed for the dramatic increase in the use of intravenous broad spectrum antibiotics, combination antibiotic therapy, antibiotic costs, and side effects, particularly Clostridium difficile associated diarrhoea.^16-18

New guidelines must try to address these areas of misunderstanding. Unfortunately, there have been no comprehensive, prospective hospital studies of CAP published in the UK since the early 1980s, although there have been a number of focused hospital and community studies to address specific areas.^13 19-23 While providing useful information about particular facets of CAP, such studies do not allow a balanced overview of its current aetiology in the UK.

By contrast, CAP continued to be actively studied in other countries during the 1990s.^24-29 These data suggest that the importance of S pneumoniae infection is waning as the frequency of newer pathogens such as Chlamydia pneumoniae and "non-penicillin responsive" pathogens such as the aerobic Gram negative enteric bacilli increase, including the Enterobacteriaceae and Pseudomonas aeruginosa.

1.4 What changes have happened in the area of CAP in the last two decades?

Over the last decade there is perceived to have been a change in the pattern of adult CAP in the UK. This has resulted in a pressure to alter the empirical management of CAP to new broader spectrum antibiotics and also combination antibiotic therapy.

These perceived changes include:

(1) Increasing emphasis on new pathogens, particularly C pneumoniae and Legionella species and on older pathogens such as Moraxella catarrhalis and Gram negative enteric bacilli, but the clinical relevance to UK practice needs to be clarified (see section 3).

(2) The increasing age of the population, many with co-morbid illness, and the marked increase in the use of residential and nursing homes over the last few years is perceived to provide an expanding "at risk" population for respiratory pathogens such as Gram negative enteric bacilli³⁰ who therefore require broad spectrum antibiotic therapy (see section 3).

(3) The admission of patients for non-medical reasons (such as inadequate social support for the elderly) and the common use of antibiotics for minor respiratory illness in the community³¹ may encourage the hospital doctor to use broad spectrum antibiotics because of the perceived problem of either failed community therapy or antibiotic resistant bacteria in hospitalised patients who have not responded to initial antibiotics.

(4) A change in delivery of acute medical services in most hospitals, with integration of adult and geriatric medicine and the use of assessment and admissions wards and loss of continuity of care throughout the admission, has encouraged the use of a "belt and braces" management strategy for all types of patients with CAP in order to cover all pathogens and "be safe", with an emphasis on parenteral and combination antibiotic therapy. This occurs especially in the elderly who are perceived to be at increased risk of complicated bacterial infections, but also at risk of antibiotic related morbidity including C difficile associated diarrhoea (see sections 3, 6 and 8).

(5) Patients with CAP will usually be assessed and admitted by relatively inexperienced medical trainees which may contribute to overtreatment "to be safe".³² It is now recommended that the "consultant post take" round within 24 hours of admission is a part of good medical practice³³ [IVb] and this valuable resource needs to be integrated into guideline practice for the management of patients hospitalised with pneumonia (section 7).

(6) Reports of increasing antibiotic resistance of common respiratory pathogens have produced recent worries about antibiotic resistance in the UK from Government expert committees.^34 35 Such concerns have already influenced antibiotic prescribing in several European countries and in North America.³⁶ The issue of penicillin resistant pneumococci is particularly relevant. It is important to review whether such changes in antibiotic resistance are now clinically important in UK practice³⁷ and in countries with similar characteristics (see section 8).

(7) The marketing of newer antibiotics (particularly macrolides and fluoroquinolones) is exposing doctors to increasing pressure to use them "to cover all likely pathogens" because of concerns about changes in pathogens, antibiotic resistance, and the "at risk" population. Some of these compounds may appear to have attractive properties for the management of CAP, but guidance is needed on the strength of the available comparative data of these newer antibiotics (see section 8). In these guidelines we only consider antibiotics licensed and available in the UK at the time of preparation of the document.

(8) Newer serological, molecular biological, and antigen detection techniques are now available for the diagnosis of viral, atypical, and bacterial pathogensfor example, urine antigen detection which has improved diagnosis of legionella infectionsand guidance is needed on when to request such tests (see section 5).

(9) There has been a dramatic increase in the use of both influenza vaccine (1.3 million doses in 1980/81 and 7 million in 1997/8) and pneumococcal vaccine (5000 doses in 1989 and 750 000 in 1997) in the community which may have influenced the aetiology of community acquired pneumonia (data provided by Dr Jane Leese, Department of Health). Advice is needed on the value of preventative strategies (see section 9 on guidelines on vaccination).

Summary

• Up to date guidelines are needed to review the current data and to assess the impact, if any, of these changes on new management guidelines of CAP in the UK.

1.5 What is the target end user audience?

We want these guidelines to be of value to:

• hospital based medical and other staff involved with managing adult patients with community acquired pneumonia;
• general practitioners;
• those teaching the subject at both undergraduate and postgraduate level.

The guidelines have been developed to apply to the UK healthcare system and population, but they should also be of value to other countries which operate similar healthcare services with appropriate modification to take into account differences in licensing and availability of antimicrobial agents.³⁸

1.6 What patient populations are included and excluded?

Our guidelines address the management of unselected adults with CAP who are managed by their general practitioner or admitted to hospital as an emergency.

They are not aimed at the much larger group of adults with non-pneumonic lower respiratory tract infection, including illnesses labelled as acute bronchitis, acute exacerbations of chronic obstructive pulmonary disease (COPD), or "chest infections".

Although there are similarities in the principles of management between pneumonic lower respiratory tract infection (CAP) and non-pneumonic lower respiratory tract infection, there are differences in the aetiology, severity assessment, management, and outcome. Recommendations for the antibiotic management of acute exacerbations of COPD are included in the published BTS guidelines on the management of chronic obstructive pulmonary disease.³⁹

We do not consider the management of pneumonia in:

(1) Patients where the pneumonia is an expected terminal event or who are known to have lung cancer, pulmonary tuberculosis, cystic fibrosis, primary immune deficiency or secondary immune deficiency related to HIV infection, or drug or systemic disease induced immunosuppression. We do include patients receiving oral corticosteroid therapy as this is a not uncommon situation for patients admitted on medical "take".

(2) Patients who have been in hospital within the previous 10 days and may have hospital acquired pneumonia. Patients admitted from healthcare facilities such as nursing homes and residential homes will be commented on separately.

(3) Children with CAP. Such guidelines are being published by the BTS guidelines committee on pneumonia in children.

Summary

• The guidelines are aimed to aid the management of unselected adults with CAP seen by a general practitioner or admitted to hospital as an emergency, on general medical "take", in the UK or in other countries with similar care systems.
• They are not aimed at patients with known predisposing conditions admitted with pneumonia to specialist units such as oncology, haematology, palliative care, infectious diseases or AIDS units.

1.7 Definitions

DEFINITION OF CAP

The diagnosis in hospital will be made with the benefit of a chest radiograph. In the community the recognition and definition of CAP by general practitioners in the UK, without the benefit of investigations or radiology, poses greater problems and the diagnosis will be invariably based only on clinical features.

DEFINITION OF CAP IN A COMMUNITY SETTING

The clinical definition of CAP that has been used in community studies has varied widely but has generally included a complex of symptoms and signs both from the respiratory tract and regarding the general health of the patients. Features such as fever (>38°C), pleural pain, dyspnoea, and tachypnoea and signs on physical examination of the chest (particularly when new and localising) seem most useful when compared with the gold standard of radiological diagnosis of CAP³⁸ [II].

Woodhead et al⁴⁰ found that 39% of adults treated with antibiotics for an acute lower respiratory tract infection associated with new focal signs on chest examination had evidence of CAP on chest radiograph compared with 2% of patients who did not have new focal chest signs [II]. By contrast, Melbye et al⁴¹ found that respiratory symptoms and signs were of only minor value in differentiating patients with radiographic pneumonia in a study of 71 patients suspected by their general practitioners of having CAP [II]. The clinical findings reported by the general practitioners to be most suggestive to them of CAP (typical history of cough, fever, dyspnoea, chest pains, and lung crackles on examination) had low predictive values; only a short duration of symptoms (less than 24 hours) was of significant predictive value.

Various prediction rules have been published for the diagnosis of CAP [II] but have generally shown the need for confirmatory radiographic evidence. Statistical modelling was used by Diehr et al⁴² to predict the presence of CAP in 1819 adults presenting as hospital outpatients with acute cough, 2.6% of whom had CAP on chest radiographic examination [II]. The presence of fever (>37.8°C), raised respiratory rate (>25 breaths/min), sputum production throughout the day, myalgia and night sweats, and absence of sore throat and rhinorrhoea were the only clinical features that predicted CAP when included in a diagnostic rule which had a sensitivity of 91% and a specificity of 40%.

For the purposes of these guidelines CAP in the community has been defined as:

• symptoms of an acute lower respiratory tract illness (cough and at least one other lower respiratory tract symptom);
• new focal chest signs on examination;
• at least one systemic feature (either a symptom complex of sweating, fevers, shivers, aches and pains and/or temperature of 38°C or more);
• no other explanation for the illness, which is treated as CAP with antibiotics.

DEFINITION OF CAP IN PATIENTS ADMITTED TO HOSPITAL (WHEN CHEST RADIOGRAPHY IS AVAILABLE)

Studies of CAP from different countries have used very different definitions and inclusion criteria^10 38 43; most have required a combination of symptoms, signs, and radiological features. The BTS study of CAP used a definition which included an acute illness with radiographic shadowing which was at least segmental or present in more than one lobe and was not known to be previously present or due to other causes.¹⁴ Like most studies, cases were excluded if pneumonia occurred distal to a known carcinoma or foreign body.

For the purposes of these guidelines CAP in hospital has been defined as:

• symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic shadowing for which there is no other explanation (e.g. not pulmonary oedema or infarction);
• the illness is the primary reason for hospital admission and is managed as pneumonia.

DEFINITION OF THE TERMS "ATYPICAL PNEUMONIA" AND "ATYPICAL PATHOGENS"

Another issue relevant to the aetiology, diagnosis, management, and prognosis of CAP is the use of the descriptive term "atypical" when describing pneumonia or groups of pathogens. The term "atypical pneumonia" has outgrown its historical usefulness and we do not recommend its continued use as it implies, incorrectly, a distinctive clinical pattern (see section 4.2).

We do, however, use the term "atypical pathogens" which, for the purposes of these guidelines, are defined as infections caused by Mycoplasma pneumoniae, C pneumoniae, C psittaci, and Coxiella burnetii. These pathogens are characterised by being difficult to diagnose early in the illness and are sensitive to antibiotics other than beta-lactams such as macrolides, tetracyclines, or fluoroquinolones. They are concentrated intracellularly which is the usual site of replication of these pathogens. We conclude that the term "atypical pathogens" is still useful to clinicians in guiding discussion about aetiology and management of CAP.

Legionella species, although sharing some of these characteristics, are not considered to be an "atypical pathogen" for the purpose of this document as there are different species and these can be acquired both in the community and hospital environment.

DEFINITION OF THE TERM "ELDERLY"

There is no agreed age cut off to define the term "elderly" and published guidelines have used very different definitions.^2 3 5-7 When referring to published research, wherever possible we define the age limits that are used in studies of CAP in older patients. When making recommendations we arbitrarily use the term "elderly" to include those adults aged 75 years and over.

1.8 Guidelines committee membership

As recommended by guideline developers,^44 45 a representative group of clinical specialists, a methodologist, and an information specialist were selected to join the committee. These included:

• four practising general physicians with a special interest in respiratory medicine and active research interest in respiratory infection (DH, GD, JTM, MAW)
• two general practitioners (PS, WFH)
• one clinical microbiologist (TB)
• two physicians with an interest in infectious diseases (DN, RGF)
• a specialist registrar trainee in general and respiratory medicine (WSL)
• a clinical epidemiologist/health services researcher (JW)
• a medical librarian/information scientist (RM)

1.9 Involvement with other groups

PS and WFH also acted as mandated representatives for the Royal College of General Practitioners, RGF for the British Infection Society, DN for the British Society for Antimicrobial Chemotherapy, and GD and JTM for the Standards of Care Committee of the British Thoracic Society.

Designated representatives of the following professional groups later provided formal review, comments on, and endorsement of the draft guidelines synopsis: Royal College of Physicians of London (including the Clinical Effectiveness and Evaluation Unit and the Advisory Committees on General Internal Medicine, Respiratory Medicine and Geriatrics), the Public Health Laboratory Service (including the Committee on Respiratory and Systemic Infections and the Primary Care Coordinating Committee), the British Geriatrics Society (including the BGS Executive Committee, the Policy Committee and the Special Interest Group in Respiratory Medicine), and the British Lung Foundation. The Lower Respiratory Tract Infection Guidelines Committee of the Scottish Intercollegiate Guidelines Network (SIGN) provided formal review and comments on the draft as part of the peer review process.

As CAP is usually an acute self-limiting disease we did not feel that patient involvement on the committee was appropriate. However, we did involve a group of 200 patients who had recently recovered from CAP in validating and revising a British Lung Foundation patient information leaflet on pneumonia⁴⁶ [III]. The leaflet, revised during 2001, is available on request from the British Lung Foundation headquarters (78 Hatton Gardens, London EC1N 8LD, UK) and regional offices.

1.10 Scope of the task and question setting

The broad remit of the group was determined by the BTS Standards of Care Committee and included producing updated and evidence based guidelines for the management of CAP in adults over 16 years for the UK. The group refined this remit by considering documented problems in the current management of CAP both in primary care and in hospital practice and issues arising from previously published guidelines for CAP, such as the 1993 BTS guidelines.¹

A postal questionnaire was sent to one consultant respiratory physician at each of the 263 UK hospitals listed in the BTS Directory of Respiratory Services enquiring about local written guidelines for the empirical management of CAP and their views about the 1993 BTS CAP guidelines. There were 215 responses (82%) which were reviewed and discussed by the committee when assessing question setting and guideline development.⁴⁷ From these sources the nine broad clinical areas listed below were identified. Each issue was expanded into specific clinical questions which were structured to facilitate easy literature searches.⁴⁸

1.11 Literature search, assessment strategy, and critical appraisal

LITERATURE SEARCH

Search strings developed by North Thames Regional Library service and published on the website (www.nthames-health.tpmde.ac.uk/evidence_strategies.htm) were adapted to our purpose by combining them with free text and key word terms for CAP to produce 16 search strategies. These were applied to locate all English language studies relevant to the aetiology, diagnosis, severity staging, investigation, prognosis, complications, or treatment of CAP in adults over 16 years. Initial searches were conducted on Medline (1966 onwards), Embase (1980 onwards), and the Cochrane Library in February 1998. These searches were repeated in May 1999 and again in January and September 2000 (on the latter occasions supplemented by a search of the National Library of Medicine PreMedline database featuring articles not yet fully indexed). A low yield of relevant references in sections on antibiotic management, non-antibiotic management, and complications led to a series of additional searches being conducted for these sections.

ASSESSMENT OF RELEVANCE

One individual (WSL) read the title and abstract of each article retrieved by the literature searches and decided whether the paper was definitely relevant, possibly relevant, or not relevant to the project. For each paper in the first and second categories the full paper was ordered and allocated to the relevant section(s). During the 2 year period of the project a total of 578 papers were judged to be relevant and circulated for critical appraisal.

CRITICAL APPRAISAL

At least two clinical experts were identified for each of the main clinical topic areas:

• Incidence and mortality (JTM, WSL)
• Aetiology and epidemiology (MAW, GD)
• Clinical and radiological features (DH, TB)
• General and microbiological investigations (DH, TB)
• Severity assessment (WSL, JTM)
• General management in hospital (GD, WSL, MAW)
• Antibiotic therapy (RGF, DH, DN)
• Complications and failure to improve (GD, WSL)
• Prevention including vaccination (GD, WFH)

Each expert independently judged the clinical relevance and scientific rigour of each paper assigned to them using generic study appraisal checklists (see appendices 1 and 2) adapted from published checklists.^45 49-51 With the wide range of study designs relevant to the questions,⁵² no single set of pass/fail criteria could be applied across all topic areas. Subject area experts determined the relevance of studies to CAP in the UK by examining the patient groups studied, the healthcare setting (primary care, etc), and the healthcare system where this might influence patient case mix at presentation.

Experts sorted studies into those relevant to their own topic area, those relevant to other areas (which were copied on to experts in other relevant sections), or those not relevant. The approximate agreement rates between assessors for this process was between 70% and 90% for different sections. They also added relevant studies from their own knowledge and personal research reference lists.

Experts individually assessed the literature selected and wrote a short document describing study findings and answering specific pre-identified questions. These documents were discussed by the whole committee to identify areas of overlap and gaps. Given the heterogeneous nature of the patient groups, outcomes, interventions, and tests studied, no formal meta-analysis was carried out.

The reliability of the evidence in each study was graded from Ia to IVb using a new generic list of evidence levels (see appendix 3) developed from existing insights and checklists.^44 53 Disagreements were resolved by discussion. Where relevant, individual references used in this document are followed by an indication of the evidence level in square brackets.

1.12 Grading of recommendations and drafting of guidelines

GRADING OF RECOMMENDATIONS

Recommendations were graded from A+ to D as indicated by the strength of the evidence as listed in the table in appendix 4.

DRAFTING OF GUIDELINES

Once the outline guideline sections were complete and summarised, they were circulated to representatives of the professional bodies given above for comments.

A detailed guideline synopsis was circulated to the membership of the BTS prior to its winter 1999 conference. The guidelines were discussed in a plenary session at the conference and, in addition, 213 structured feedback forms from BTS members were analysed.

Revisions were made, which also included an updated literature search performed in February and September 2000, and the document content was finalised by the end of 2000. Thus, antibiotics which were not licensed for use in the UK by the end of 2000 could not be included in our recommendations. Similarly relevant products that are not licensed in the UK but are available in other countries are not reviewed. Updates to include any new relevant information or products are planned for the future.

1.13 Plans for updating these guidelines

Following the BTS protocol for guidelines revisions, the committee will meet on an annual basis and review new published evidence obtained from a structured literature search, comment on any newly licensed and relevant antibiotics, and issue guideline updates or revisions as necessary. Important changes will be posted on the BTS website (www.brit-thoracic.org.uk). The membership of the guideline committee will change over time on a rolling programme, dictated by the BTS Standards of Care Committee policy for guideline committee membership.

1.14 Auditing management of CAP

The management of CAP is a sufficiently common and important issue to warrant the development of audit measures of the process of care and outcome to evaluate the quality of care for CAP using guidelines as a standard of management. There is evidence from Hiriani and Macfarlane²² [III], Gleason et al⁵⁴ [II], and Gilbert et al⁵⁵ [II] that guidelines do guide and standardise management, but with less measurable effect on outcome.

The issue of choosing quality indicators and audit tools for CAP has recently been extensively reviewed⁵⁶[III]. With guidance from this review, an audit tool has been developed by the committee, refined by the BTS Audit Committee, and tested in pilot hospitals. This will be made available through the BTS website (www.brit-thoracic.org.uk).

1.15 Implementation of the guidelines

We expect that these guidelines will act as a framework for local development or modification of protocols after discussion with local clinicians and management. The subsequent dissemination, implementation, and evaluation of these guidelines should be undertaken by the hospital Quality and Clinical Effectiveness group in conjunction with relevant committees such as those responsible for therapeutics, antibiotic prescribing, or protocol development. Countries with similar health service systems will also find the framework of value, adapting the guidelines to take into account any relevant national differences in disease presentation and the availability of investigations and antimicrobial agents.

For maximal long term impact, the guidelines should be the subject of continuing education and quality improvement activities. Production of summary statements, algorithms, pocket sized reminders, wall charts, and material specific to primary care will be helpful for both individual doctors and departments working with patients with CAP.

	2  Incidence, mortality and economic consequences

Top Synopsis Synopsis of main summary... 1 Introduction and methods 2 Incidence, mortality and... 3 Aetiology and epidemiology 4 Clinical features 5 Radiological, general and... 6 Severity assessment 7 General management 8 Antibiotic management 9 Complications and failure... 10 Prevention and vaccination... 11 Acknowledgements and... Appendix 1 Appendix 2 Appendix 3 Appendix 4 References

2.1 How common is adult CAP in the community and in hospital?

Prospective population studies from the UK⁴⁰ [II], Finland ⁵⁷ [Ib], and North America⁵⁸ [Ib] have reported an annual incidence of CAP diagnosed in the community of between 5 and 11 per 1000 adult population. Pneumonia, diagnosed clinically by general practitioners, accounts for only 5%⁴⁰ [Ib] to 12%⁵⁹ [Ib] of all cases of adult lower respiratory tract infection treated with antibiotics by general practitioners in the community in the UK.

The incidence varies markedly with age, being much higher in the very young and the elderly. In the Finnish study the annual incidence in the 16-59 age group was 6 per 1000 population, 20 for those aged 60 years and over, and 34 per 1000 population for those aged 75 and over⁵⁷ [Ib]. A similar pattern was reported from Seattle, USA⁵⁸ [Ib].

Population based studies of the incidence of CAP requiring hospitalisation have reported overall incidences of 1.1 per 1000 adult population per annum in Canada⁶⁰ [Ib], 2.6 per 1000 in Spain²⁵ [II], 2.7 per 1000 population in Ohio, USA⁶¹ [Ib], and 4 per 1000 population in Pennsylvanian hospitals, USA⁶² [III].

The proportion of adults with CAP who require hospital admission in the UK has been reported as being between 22%⁴⁰ [Ib] and 42%⁶³ [III]. This figure varies in other countries, probably depending on the structure of the primary and secondary healthcare systems. In a Finnish prospective longitudinal population study 42% were admitted to hospital⁵⁷ [Ib]. A 50% admission rate was reported in one study from Spain but this only included patients referred by their general practitioner to the hospital emergency service for confirmation of the diagnosis of CAP²⁵ [II].

In Seattle, USA 15% were hospitalised⁶⁴ [Ib]. In the Pneumonia Patient Outcomes research multicentre, prospective cohort study of CAP in America, 41% of adults studied were managed initially as outpatients and the remainder were admitted to hospital. Of those initially treated as outpatients, only 7.5% were subsequently admitted, 56% because of the CAP and the rest because of worsening of a comorbid illness⁶⁵ [Ib].

The proportion of adults admitted to hospital with CAP who require management on an ICU varies from 5% in the BTS multicentre study⁶⁶ [II] to 10% in a Spanish study [II].⁶⁷ Between 8%²⁵ [II] and 10%²¹ [III] of medical admissions to an ICU are for severe CAP.

Summary

• The annual incidence in the community is 5-11 per 1000 adult population [Ib].
• CAP accounts for 5-12% of all cases of adult lower respiratory tract infection managed by general practitioners in the community [Ib].
• The incidence varies markedly with age, being much higher in the very young and the elderly [Ib].
• The incidence of CAP requiring admission to hospital varies between 1.1 and 4 per 1000 population [Ib].
• Between 22% and 42% of adults with CAP are admitted to hospital [Ib].
• Between 5% and 10% of adults admitted to hospital with CAP are managed on an ICU [II].

2.2 What is the mortality of CAP?

The reported mortality of adults with CAP managed in the community is low at less than 1%²⁵ [II], ⁴⁰ [Ib], ⁶⁵ [Ib]. Deaths in the community due to CAP are rare in the UK. In one study only seven cases were identified by coroners' post mortem examinations over 1 year in Nottingham, a large urban city of three quarters of a million, giving an incidence of 1 per 100 000 ⁶⁸ [III].

The reported mortality of adults admitted to hospital with CAP has varied widely. The BTS multicentre study reported a mortality of 5.7%¹⁴ [II] but did not study patients over the age of 74 years. Other UK studies have reported mortalities of 8%¹² [II], 12%¹¹ [Ib], and 14%⁶⁹ [Ib]. Countries with similar healthcare systems have reported hospital mortality rates of 4%⁵⁷ [Ib], 7%⁷⁰ [II], 8%⁷¹ [Ib], and 10%⁷² [Ib]. Mortality figures from North American hospital studies have tended to be higher, probably because more patients with CAP are provided with ambulatory care as outpatients and only those with more severe pneumonia or co-morbid disease are admitted to hospital.

The mortality of patients with severe CAP requiring admission to an intensive care unit (ICU) is high. This is likely to be particularly evident in health services such as the National Health Service where ICU beds are at a premium such that only critically ill patients in need of assisted ventilation can be admitted. ICU based studies in the UK report mortality rates of over 50%²¹ [III], ²² [III], ⁶⁶ [III], ⁷³ [III]. Nearly all of the patients required assisted ventilation. By contrast, the mortality rate in a large multicentre study of severe CAP in four French ICUs reported a mortality rate of 35% with a ventilation rate of only 52%⁷⁴ [Ib]. Similar figures were reported from another ICU based study in France⁷⁵ [II]. In a specialist ICU in Spain a mortality rate of 22% was reported, rising to 36% in the 61% of patients who required assisted ventilation⁶⁷ [II].

Summary

• The reported mortality rate of adults with CAP managed in the community in the UK is very low at less than 1% [Ib].
• The reported mortality rate of adults admitted to hospital with CAP in the UK has varied between 5.7% and 12% [Ib].
• The mortality rate of patients with severe CAP requiring admission to an ICU in the UK is high at over 50% [III].

2.3 What are the economic consequences of CAP?

A prevalence based burden of illness study estimated that CAP in the UK incurred a direct healthcare cost of £441 million annually at 1992-3 prices. The average cost for managing pneumonia in the community was estimated at £100 per episode compared with £1700-5100 for hospitalised patients. Hospitalisation accounted for 87% of the total annual cost⁶³ [III].

A similar exercise for the USA calculated that annual CAP costs amounted to $8.4 billion, 52% of the costs being for the inpatient care of 1.1 million patients and the remaining costs for the 4.4 million outpatient consultations. The average length of stay in hospital varied between 5.8 days for those under 65 years of age and 7.8 days for older patients⁷⁶ [III]. A prospective study of costs and outcome of CAP from five hospitals in North America concluded that the costs of antibiotic treatment varied widely but had no effect on outcome or mortality. Patients treated in hospitals with the lowest costs did not demonstrate worse medical outcomes⁵⁵ [Ib].

Summary

• The direct costs associated with CAP are high and mostly associated with inpatient care costs [III].
• Substantial cost savings could probably be made by strategies to prevent CAP, reduce the requirement for hospital admission, and shorten the length of hospital stay for patients with non-severe CAP [III].

2.4 What comments can be made about cost effectiveness of different treatments?

We are not able to provide any structured guidance on this subject. Modern guidelines should attempt to provide information not only on clinical management, but also on the assessment of robust published data on the cost effectiveness of therapies. However, it was noted that there is a clear deficiency of good quality comparative clinical data which would allow meaningful comparisons of management and antibiotic strategies for CAP, whether assessing for clinical or cost effectiveness outcomes.

Summary

• We have not attempted a systematic appraisal of current pharmacoeconomic evidence for CAP and do not give a structured view on cost effectiveness.
• Cost effectiveness data pertinent to UK practice do not exist at the time of writing and are an area for further research.

	3  Aetiology and epidemiology

Top Synopsis Synopsis of main summary... 1 Introduction and methods 2 Incidence, mortality and... 3 Aetiology and epidemiology 4 Clinical features 5 Radiological, general and... 6 Severity assessment 7 General management 8 Antibiotic management 9 Complications and failure... 10 Prevention and vaccination... 11 Acknowledgements and... Appendix 1 Appendix 2 Appendix 3 Appendix 4 References

3.1 Introduction

No two studies of the aetiology of CAP are the same. Apparent differences in the observed frequency of pathogens, while possibly real, may also be due to a number of other factors including health care delivery (distribution of management between primary and secondary care; hospital and ICU admission practices); population factors such as age mix, the frequency of alcoholism, comorbid diseases, immunosuppression, and malignancy; and study factors such as the type and number of samples collected, investigations performed, and interpretation of results. Frequently such details are not explicitly stated in the study methodology and, although we have not included studies which do not comply with certain standards, apparently similar studies may hide very different methodologies. With the exception of the elderly, few adequately powered studies using the same methodology have been used to compare different population groups. Conclusions about observed differences in the following data must therefore be treated with caution.

Many of the statements in the following text arise from a comparison of studies rather than data from individual studies. For this reason evidence grades follow statements to justify the conclusions, as well as individual references.

3.2 What are the causes of adult CAP in the UK?

These are set out in table 2, together with details of the relevant references (and grading of evidence from those individual references), grouped together according to whether patients have been managed in the community, in hospital, or on an ICU. For all these groups a common range of pathogens is regularly identified as causing CAP [Ib]. Although a single pathogen is identified in 85% of patients where an aetiology is found, the true frequency of polymicrobial CAP is not known and observed figures are dependent on the intensity of the investigation. S pneumoniae is the most frequently identified pathogen [Ib]. The relative frequency of pathogens in patients managed in the community and in hospital is probably similar, but the absence of more than one study in the community makes further conclusions uncertain. Legionella species and S aureus are identified more frequently in patients managed on the ICU [Ib]. The apparent difference in the frequency of M pneumoniae may depend on whether or not a study is performed in an epidemic year [II]. Gram negative enteric bacilli, C psittaci, and C burnetii are uncommon causes of CAP [Ib].

3.3 What are the causes of adult CAP in similar populations elswhere in the world?

The results and references of relevant studies from the remainder of Europe, Australia and New Zealand, and North America are compared in tables 3, 4, and 5. For patients managed in the community and in hospital, the frequency of pathogens is broadly similar to that in the UK [II]. This suggests that aspects of these guidelines will be applicable to other countries as well as the UK. The absence of studies using sensitive methods for pneumococcal polysaccharide capsular antigen detection for the identification of S pneumoniae may be the explanation for the lower frequency outside the UK (fig 3). The apparent differences in M pneumoniae may relate to the presence or absence of epidemics at the time of the study (fig 4). C pneumoniae is identified regularly in Europe and North America as well as in a recent UK study [II].