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1 Dept Respiratory Medicine, Manchester Royal Infirmary, Manchester, UK, 2 Istituto di Tisiologia e Malattie dell'Apparato Respiratorio, Università degli Studi di Milano, IRCCS Ospedale Maggiore di Milano, Milan, Italy. 3 Chefarzt der Klinik für Pneumologie, Beatmungsmedizin und Infektiologie, Bochum, and, 7 Lungenlinik Unterstedt, Daikonierkrankenhaue Rotenburg, Rotenburg, Germany. 4 Pneumologie et Reanimation, Paris, France. 5 Microbiology Lab, University Hospital Antwerp, Antwerp, Belgium. 6 Smittskyddsenheten, Norrbacka, Stockholm, Sweden. 8 Clinic de Pneumologia I Cirurgia Toràcica, Hospital Clinic I Provincial de Barcelona, Barcelona, Spain. 9 Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands.
CORRESPONDENCE: M. Woodhead, Dept of Respiratory Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. Fax: 44 1612764989. E-mail: mark.woodhead{at}cmmc.nhs.uk
Received: May 11, 2005
Accepted August 16, 2005
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ABSTRACT |
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 TOP ABSTRACT BACKGROUNDRECOMMENDATION SUMMARYMANAGEMENT OUTSIDE HOSPITALMANAGEMENT INSIDE HOSPITALPREVENTIONREFERENCES |
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BACKGROUND |
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TOPABSTRACTBACKGROUNDRECOMMENDATION SUMMARYMANAGEMENT OUTSIDE HOSPITALMANAGEMENT INSIDE HOSPITALPREVENTIONREFERENCES |
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A systematic literature search was performed to retrieve relevant publications from 1966 through to December 31, 2002, which critically appraised and rated the pertinent clinical evidence, summarised these ratings in levels of evidence, and translated the best available evidence into graded clinical recommendations (table 1).
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How were the antibiotic recommendations developed?
The formulation of the antibiotic recommendations merits specific comment. As with other recommendations, these were based on evidence of both benefit and harm with respect to particular antibiotics. However, robust evidence to support individual recommendations was found to be absent. This was partly because individual antibiotic studies do not capture all outcomes of importance in antibiotic management and also because there may be variation in factors, such as the prevalence of antibiotic resistance of leading pathogens like Streptococcus pneumoniae, that might determine antibiotic recommendation in different geographical locations which cannot be addressed by a single recommendation. Bacterial antibiotic resistance is common in some countries, but its clinical relevance is often unclear. Factors such as, lack of statistical power to assess an outcome, selective patient recruitment, lack of subject blinding, and lack of assessment of impact on the wider community (especially with regard to antimicrobial resistance), were common to most clinical studies of antibiotic effect. Use of such studies could, therefore, only be used to support a consensus view from the Guideline authors.
The antibiotic recommendations should be interpreted with the above in mind and it should be accepted that an individual recommendation may not be suitable in every clinical setting. When an antibiotic is stated as "preferred" this should be taken to mean that in the view of the authors, based on available evidence, in usual everyday management, this antibiotic would have advantages over others. This is not to say that other antibiotics might not be effective and in some, usually less common, situations might even be preferred.
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RECOMMENDATION SUMMARY |
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TOPABSTRACTBACKGROUNDRECOMMENDATION SUMMARYMANAGEMENT OUTSIDE HOSPITALMANAGEMENT INSIDE HOSPITALPREVENTIONREFERENCES |
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When should cardiac failure be considered?
In patients aged >65 yrs, with orthopnoea, displaced apex beat and/or a history of myocardial infarction (C3).
When should pulmonary embolism be considered?
In patients with one of the following characteristics: a history of deep vein thrombosis (DVT) or pulmonary embolism; immobilisation in past 4 weeks; or malignant disease (C3).
When should chronic airway disease be considered?
In patients with at least two of the following: wheezing; prolonged expiration; history of smoking; and symptoms of allergy. Lung-function tests should be considered to assess the presence of chronic lung disease (C3).
How to differentiate between pneumonia and other respiratory tract infections
A patient should be suspected of having pneumonia when acute cough and one of the following signs/symptoms are present: new focal chest signs; dyspnoea; tachypnoea; fever lasting >4 days.
If pneumonia is suspected, a chest radiograph should be performed to confirm the diagnosis (C1).
Should the primary care physician test for a possible microbiological aetiology of LRTI?
Microbiological investigations are not usually recommended in primary care (C1–C3).
Treatment
Should symptomatic acute cough be treated?
Both dextromethorphan and codeine can be prescribed in patients with a dry and bothersome cough (C1). Expectorant, mucolytics, antihistamines and bronchodilators should not be prescribed in acute LRTI in primary care (A1).
When should antibiotic treatment be considered in patients with LRTI?
Antibiotic treatment should be considered in patients with LRTI in the following situations: suspected or definite pneumonia (see How to differentiate between pneumonia and other respiratory tract infections); selected exacerbations of chronic obstructive pulmonary disease (COPD; see What are the indications for antibiotic treatment of exacerbations of COPD?); aged >75 yrs and fever; cardiac failure; insulin-dependent diabetes mellitus; and serious neurological disorder (stroke etc.; C2).
What are the indications for antibiotic treatment of exacerbations of COPD?
An antibiotic should be given during exacerbations of COPD in patients with all three of the following symptoms: increased dyspnoea; increased sputum volume; and increased sputum purulence. In addition, antibiotics should be considered for exacerbations in patients with severe COPD (C1).
Which antibiotics should be used in patients with LRTI?
Tetracycline and amoxicillin are first-choice antibiotics. In case of hypersensitivity, newer macrolides, such as azithromycin, roxithromycin or clarithromycin, are good alternatives in countries with low pneumococcal macrolide resistance. National/local resistance rates should be considered when choosing a particular antibiotic. When there are clinically relevant bacterial resistance rates against all first-choice agents, treatment with levofloxacin or moxifloxacin may be considered (C4; table 2).
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How should patients with LRTI be monitored?
A patient should be advised to return if symptoms take >3 weeks to disappear.
Clinical effects of the antibiotic treatment should be expected within 3 days and patients should be instructed to contact their doctor if this effect is not noticeable. Seriously ill patients, i.e. having at least two of the following symptoms/characteristics, should already be seen 2 days after the first visit: high fever; tachypnoea; dyspnoea; relevant comorbidity; aged >65 yrs.
All patients or persons within their environment should be advised to contact their doctor again if: fever exceeds 4 days; dyspnoea gets worse; patients stop drinking; or consciousness decreases (C3).
Management inside hospital
Community-acquired pneumonia
Who should be admitted to hospital?
The decision to hospitalise remains a clinical decision. However, this decision should be validated against at least one objective tool of risk assessment. Both the pneumonia severity index (PSI) and the CURB index (mental confusion, urea, respiratory rate, blood pressure; see later sections) are valid tools in this regard. In patients with a PSI of IV and V, and/or a CURB of 
2, hospitalisation should be seriously considered (A3).
Additional requirements of patient management, as well as social factors not related to pneumonia severity, must be considered as well.
Who should be considered for intensive care unit admission?
Criteria of acute respiratory failure, severe sepsis or septic shock and radiographic extension of infiltrates should prompt consideration of the admission to the intensive care unit (ICU) or an intermediate care unit.
The presence of at least two of the following indicates severe community-acquired pneumonia (CAP) and can be used to guide ICU referral: systolic blood pressure <90 mmHg; severe respiratory failure (arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) <250); involvement of more than two lobes on a chest radiograph (multilobar involvement); requirement for either mechanical ventilation or requirement of vasopressors >4 h (septic shock; A3).
What laboratory studies should be performed?
The amount of laboratory and microbiological work-up should be determined by the severity of pneumonia (A3).
What is the value of blood cultures in the diagnosis of CAP?
Blood cultures should be performed in all patients with CAP who require hospitalisation (A3).
What other invasive techniques for normally sterile specimens can be useful in the laboratory diagnosis of pneumonia?
The following invasive techniques can be useful in laboratory diagnosis. 1) Diagnostic thoracentesis should be performed when a significant pleural effusion is present (A3). 2) Due to the inherent potential adverse effects, trans-thoracic needle aspiration can only be considered on an individual basis for some severely ill patients with a focal infiltrate, in whom less invasive measures have been nondiagnostic (A3). 3) Bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL). BAL may be the preferred technique in nonresolving pneumonia (A3). Bronchoscopic sampling of the lower respiratory tract can be considered in intubated patients and selected nonintubated patients where gas exchange status allows (A3).
What is the value of sputum examination?
Gram stain is recommended when a purulent sputum sample can be obtained from patients with CAP and is processed timely (A3).
A culture from a purulent sputum specimen of a bacterial species compatible with the morphotype observed in the Gram stain, which is processed correctly, is worthwhile for confirmation of the species identification and antibiotic susceptibility testing (B3).
What can antigen tests offer in the diagnosis of CAP?
Legionella pneumophila serogroup 1 antigen detection in urine is recommended for patients with severe CAP and in other patients where this infection is clinically or epidemiologically suspected (A3).
What can serological tests offer in the diagnosis of pneumonia?
Serological tests for the management of the individual patient with CAP are not recommended (A3).
Serology for infections caused by Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella is more useful in epidemiological studies rather than in the routine management of the individual patient (A3).
Are amplification tests useful for the diagnosis of CAP?
Application of molecular tests for the detection of influenza and respiratory syncytial virus (RSV) may be considered during the winter season, and for the detection of atypical pathogens provided the tests are validated and the results can be obtained sufficiently rapidly to be therapeutically relevant (A3).
What classification should be used for treatment?
Antimicrobial treatment has to be empiric and should follow an approach according to the individual risk of mortality. The assessment of severity according to mild, moderate and severe pneumonia implies a decision regarding the most appropriate treatment setting (ambulatory, hospital ward, ICU; A4). Antimicrobial treatment should be initiated as soon as possible (A3).
The guidance of empiric initial antimicrobial treatment should follow: 1) general patterns of expected pathogens according to pneumonia severity and additional risk factors; 2) regional and local patterns of microbial resistance; 3) considerations of tolerability and toxicity of antimicrobial agents in the individual patient.
What initial empiric treatments are recommended?
The treatment options for hospitalised patients with moderate and severe CAP are shown in tables 3 and 4, respectively.
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What should be the duration of treatment?
The appropriate duration of antimicrobial treatment has not been settled. In comparative studies, the usual duration of treatment is 
7–10 days. Intracellular pathogens, such as Legionella spp. should be treated for at least 14 days (C4).
When should i.v. be used and when should the switch to oral occur?
In mild pneumonia, treatment can be applied orally from the beginning (A3). In patients with moderate pneumonia, sequential treatment should be considered in all patients except the most severely ill. The optimal time to switch to oral treatment is also unknown; it seems reasonable to target this decision according to the resolution of the most prominent clinical features upon admission (A3).
Which additional therapies are recommended?
Low molecular heparin is indicated in patients with acute respiratory failure (A3). The use of noninvasive ventilation is not yet a standard of care, but may be considered particularly in patients with COPD (B3). The treatment of severe sepsis and septic shock is confined to supportive measures (A3). Steroids have no place in the treatment of pneumonia unless septic shock is present (A3).
How should response be assessed and when should chest radiographs be repeated?
Response to treatment should be monitored by simple, clinical criteria including body temperature, respiratory and haemodynamic parameters. The same parameters should be applied to judge the ability of hospital discharge (A3). Complete response, including radiographic resolution, requires longer time periods. Discharge decisions should be based on robust markers of clinical stabilisation (A3).
How should the nonresponding patient be assessed?
The two types of treatment failures, nonresponding pneumonia and slowly resolving pneumonia, should be differentiated (A3). The evaluation of nonresponding pneumonia depends on the clinical condition. In unstable patients, full reinvestigation followed by a second empiric antimicrobial treatment regimen is recommended. The latter may be withheld in stable patients. Slowly resolving pneumonia should be reinvestigated according to clinical needs in relation to the condition and individual risk factors of the patient (C3).
Exacerbations of COPD
Which hospitalised patients with COPD exacerbations should receive antibiotics?
The following hospitalised patients with COPD should receive antibiotics. 1) Patients with all three of the following symptoms: increased dyspnoea; sputum volume; and sputum purulence (a Type I Anthonisen exacerbation; A2). 2) Patients with only two out of the three symptoms above (a Type II Anthonisen exacerbation) when increased purulence of sputum is one of the two cardinal symptoms (A2). 3) Patients with a severe exacerbation that requires invasive or noninvasive mechanical ventilation (A2). 4) Antibiotics are generally not recommended in Anthonisen Type II without purulence and Type III patients (one or none of the above symptoms; A2).
What stratification of patients with COPD exacerbation is recommended to direct treatment?
The following groups of COPD patients are recommended to direct treatment. Group A: patients not requiring hospitalisation (mild COPD, see Management outside hospital; A3). Group B: admitted to hospital (moderate–severe COPD) without risk factors for Pseudomonas aeruginosa infection (A3). Group C: admitted to hospital (moderate–severe COPD) with risk factors for P. aeruginosa (A3).
What are the risk factors for P. aeruginosa?
At least two out of the following four are risk factors for P. aeruginosa: 1) recent hospitalisation (A3); 2) frequent (more than four courses per year) or recent administration of antibiotics (last 3 months; A3); 3) severe disease (forced expiratory volume in one second (FEV1) <30%; A3); 4) previous isolation of P. aeruginosa during an exacerbation or patient colonised by P. aeruginosa (A3).
Which microbiological investigations are recommended for hospitalised patients with COPD exacerbation?
In patients with severe exacerbations of COPD (Group C patients), difficult to treat microorganisms (P. aeruginosa) or potential resistances to antibiotics (prior antibiotic or oral steroid treatment, prolonged course of the disease, more than four exacerbations per year and FEV1 <30%), sputum cultures or endotracheal aspirates (in mechanically ventilated patients) are recommended (A3).
Which initial antimicrobial treatments are recommended for patients admitted to hospital with COPD exacerbation?
In patients without risk factors for P. aeruginosa, several options for antibiotic treatment are available. The selection of one or other antibiotic depends on the severity of the exacerbation, local pattern of resistances, tolerability, cost and potential compliance. Amoxicillin or tetracycline is recommended for mild exacerbations (which might usually be managed at home) and co-amoxiclav for those admitted to hospital with moderate–severe exacerbations (A2).
In patients with risk factors for P. aeruginosa, ciprofloxacin is the antibiotic of choice when the oral route is available. When parenteral treatment is needed, ciprofloxacin or a ß-lactam with anti-pseudomonal activity are available options. The addition of aminoglycosides is optional (A2).
The use of the oral or i.v. route depends on the stability of the clinical condition and the severity of exacerbation. Switch (i.v. to oral) is recommendable by day 3 of admission if the patient is clinically stable. (A3)
How should the nonresponding patient with COPD exacerbation be assessed?
After close re-evaluation of noninfectious causes of failure (i.e. inadequate medical treatment, embolisms, cardiac failure, other), a careful microbiological reassessment, as mentioned in the microbiological diagnosis section, is recommended (C3).
The recommendation for treatment in cases of failure includes an antibiotic change with good coverage against P. aeruginosa, S. pneumoniae resistant to antibiotics and nonfermenters and to subsequently adjust the new antibiotic treatment according to microbiological results (C3).
General recommendations for exacerbations of bronchiectasis
The general recommendations are as follows. 1) Periodical surveillance of colonisation is advisable (B3), frequency must be indicated. 2) The majority of patients with exacerbations will benefit from antibiotic treatment (B3). 3) Obtaining a sputum sample for culture before starting antibiotic treatment is recommended in most cases and particularly in those requiring hospitalisation (B3). 4) For empirical antibiotic treatment patients have to be stratified according to the potential risk of Pseudomonas spp. infection (B3). Recommended antibiotics are summarised in table 5. Empirical antibiotics have to be adjusted or modified according to sputum culture results (A3).
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What is the role of prophylactic antibiotic therapy in CB or COPD?
The prophylactic use of antibiotics in patients with CB or COPD as a matter of prevention is not recommended (A1).
According to the opinion of experts, it might be justified to use long-term antibiotic therapy in selected patients with bronchiectasis who suffer from frequent bacterial exacerbations, but no data from controlled studies are available for an evidence-based recommendation (C4).
The use of nebulised antibiotics for the prevention of LRTI in patients with bronchiectasis has not been studied systematically so far. Therefore, no evidence for its use could be found and the use of this approach is not recommended (C4).
Does antibiotic treatment of upper respiratory tract infections prevent LRTI?
Treatment of upper respiratory tract infections (URTI) with antibiotics will not prevent LRTI (A1).
Does treatment with inhaled steroids or long-acting ß2-agonists prevent LRTI?
The regular use of inhaled steroids (B1) or of long-acting ß2-agonists (C4) as preventive approaches for LRTI is not recommended. This does not mean that they might not prevent exacerbations of COPD, which is an issue beyond the scope of this document.
Does regular physiotherapy prevent LRTI?
Physiotherapy is not recommended as a preventive approach against LRTI (C4).
Do anti-viral substances prevent influenza virus infection?
Prevention of influenza by anti-viral substances is only recommended in unusual situations (for example, in outbreaks within closed communities; A1).
Are oral mucolytics useful for the prevention of LRTI?
The regular use of oral mucolytics in patients with CB and COPD as a matter of prevention against LRTI is not recommended (B1). The regular use of oral mucolytics in patients with bronchiectasis as a matter of prevention against LRTI is also not recommended (B1).
Is there evidence that homeopathic substances prevent LRTI?
The use of homeopathic substances is not recommended as a preventive approach against LRTI (C4).
Prevention by vaccination
Should the influenza vaccine be used to prevent LRTI?
For influenza vaccination, the following are recommended. 1) The influenza vaccine should be given yearly to those at increased risk for complications due to influenza (A1). The vaccination is recommended for immunocompetent adults belonging to one, or more, of the following categories: aged 65 yrs; institutionalisation; chronic cardiac diseases; chronic pulmonary diseases; diabetes mellitus; chronic renal diseases; haemoglobinopathies; and females who will be in the second or third trimester of pregnancy during the influenza season. 2) Repeated vaccinations are safe and do not lead to a decreased immune response (B1). 3) In adults an inactivated, rather than live attenuated, vaccine is recommended (A1). 4) In healthcare personnel yearly vaccination is recommended, especially in settings where elderly persons or other high-risk groups are treated (B2).
Should pneumococcal vaccine be used to prevent LRTI?
For pneumococcal vaccination the following are recommended. 1) The evidence for vaccination with the 23-valent polysaccharide pneumococcal vaccine is not as strong as that for the influenza vaccination, but it is recommend that the vaccine be given to all adult persons at risk from pneumococcal disease (B4). 2) Risk factors for pneumococcal disease are: age 65 yrs; institutionalisation; dementia; seizure disorders; congestive heart failure; cerebrovascular disease; COPD; history of a previous pneumonia; chronic liver disease; diabetes mellitus; functional or anatomic asplenia; and chronic cerebrospinal fluid leakage (B3). Although smoking seems to be a significant risk factor in otherwise healthy, younger adults, measures aimed at reducing smoking and exposure to environmental tobacco smoke should be preferred in this group. 3) Revaccination, once, can be considered in the elderly, 5–10 yrs after primary vaccination (B3).
What is the best way to implement influenza and pneumococcal vaccination policies?
Active interventions to enhance vaccination with either or both vaccines are effective and needed to achieve adequate vaccination coverage of the targeted population (B1).
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MANAGEMENT OUTSIDE HOSPITAL |
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TOPABSTRACTBACKGROUNDRECOMMENDATION SUMMARYMANAGEMENT OUTSIDE HOSPITALMANAGEMENT INSIDE HOSPITALPREVENTIONREFERENCES |
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There are three important diagnostic issues concerning LRTI in daily primary care practice. First, it is important to assess whether the symptoms of the patient are actually caused by an infection or by another noninfectious disorder, such as asthma, COPD, heart failure or lung infarction. Secondly, if it is likely that the patient has a respiratory tract infection, what part of the respiratory tract is affected? Does the patient have an acute bronchitis or is it pneumonia? Thirdly, the GP would ideally like information regarding the nature of the microbiological pathogen(s) involved. Does the patient have a viral or bacterial infection, or both, and which viruses and bacteria are involved? The word "ideally" is used here because testing for the presence of pathogens involved is often not useful.
When should aspiration pneumonia be considered?
Aspiration should be excluded, especially in patients who have difficulties with swallowing, for instance, after cerebral vascular events and in certain psychiatric diseases. There are, however, no studies to support this expert opinion.
Recommendation
Aspiration pneumonia should be considered in patients who have difficulties with swallowing and who show signs of an acute LRTI. In these patients a chest radiograph should be performed (C3).
When should cardiac failure be considered?
Cardiac failure might be very difficult to detect. There are few studies available on its diagnosis in primary care. A history of myocardial infarction and a finding of a displaced apex beat were the best predictors of left ventricular dysfunction in a study of 259 patients with suspected cardiac failure 2. Another study showed older age, male sex, orthopnoea, a history of myocardial infarction and absence of COPD to be predictors of cardiac failure 3.
Recommendation
Cardiac failure should be considered in patients aged >65 yrs with either orthopnoea, displaced apex beat and/or a history of myocardial infarction (C3).
When should pulmonary embolism be considered?
Pulmonary embolism (PE) can present with a simple acute cough and be difficult to discern from an LRTI. The absence of signs of DVT, immobilisation in the past 4 weeks, a history of DVT or PE, haemoptysis, pulse >100 and malignant disease, shows that PE is highly unlikely 4.
Recommendation
PE should be considered in patients with one of the following characteristics: a history of DVT or pulmonary embolism; immobilisation in past 4 weeks; or malignant disease (C3).
When should chronic airways disease be considered?
Chronic lung disorders, such as asthma and COPD, can also present exacerbations with symptoms, such as coughing, sputum and dyspnoea. The few available studies show that a considerable portion of patients with an acute cough or a diagnosis of acute bronchitis do in fact have asthma or COPD (up to 45% in patients with an acute cough >2 weeks) 5–7. Wheezing, prolonged expiration, number of pack-yrs, a history of allergy and female sex appear to have predictive values for the presence of asthma/COPD 5. This is relevant because lung medication, e.g. ß-agonists and steroids, have been shown to be beneficial in these exacerbations.
Recommendation
Lung function tests should be considered to assess the presence of chronic lung disease in patients with at least two of the following signs: wheezing; prolonged expiration; history of smoking; and symptoms of allergy (C3).
There is, however, still considerable discussion as to whether exacerbations of asthma and COPD are in fact viral or bacterial LRTIs in such patients. Viral respiratory tract infections can trigger exacerbations, but there is controversy as to whether a microbiological infection is a clinically relevant phenomenon during exacerbation. The implications of this uncertainty for daily practice will be discussed in the Treatment section.
How to differentiate between pneumonia and other respiratory tract infections
Respiratory symptoms, such as cough and dyspnoea, can be caused by inflammation of the trachea, bronchi, bronchioli and the lung parenchyma. There are also cough receptors in the upper respiratory tract and, thus, cough can also be caused by URTIs. However, whether URTIs are a frequent cause of acute cough is uncertain. Studies into the relationship between sinusitis and cough, for instance, are only carried out in patients with chronic cough and suffer from methodological flaws. Hence, there is no evidence supporting the widely accepted concept of post-nasal drip being an important cause of acute cough 8–10. This does not mean that patients with a URTI cannot have an LRTI at the same time.
Differentiating between tracheitis and acute bronchitis is impossible in daily practice and not relevant. Usually these two entities are taken together and often acute tracheobronchitis is only referred to as acute bronchitis. Differentiating between acute bronchitis and pneumonia is, on the other hand, important. Pneumonia is a more severe infection than acute bronchitis with a higher risk for complications and prolonged course of symptoms.
The gold standard for the diagnosis of pneumonia is a chest radiograph. However, LRTI symptoms reported to the GP are extremely common (100 per 1,000 persons·yr–1), and only 5–10% of these patients have pneumonia. This means that it is neither feasible nor cost-effective to perform radiological tests in all patients with lower respiratory tract symptoms.
There are several studies on the diagnostic value of signs and symptoms for the presence of an infiltrate on the chest radiograph. However, interpretation of the results of these studies is difficult because of the low numbers of patients with pneumonia who are included, thus, encountering the problem that signs, like a dull percussion note or a pleural rub, are only present in a minority of patients with pneumonia; if present, a pneumonia is very likely, but absence of these signs will not make the GP any wiser. Focal chest signs perhaps are more helpful. One study found that in patients with focal auscultatory abnormalities, 39% did have pneumonia as opposed to 5–10% in all patients with an acute cough. In patients without focal signs the probability of 5–10% was reduced to 2% 11. Only a few studies also looked at the diagnostic value of combinations of signs and symptoms as physicians always do in daily practice. Fever, absence of URTI symptoms, dyspnoea/tachypnoea and abnormal chest signs were usually present in these models 12. None of these algorithms have been properly validated in other populations.
There is also discussion on the value of additional tests, such as C-reactive protein (CRP). Some studies have shown that an elevated level of CRP in the patient's serum (>50 mg·mL–1) could increase the chance that the patient involved does have pneumonia 13, 14. Sufficient data on the additional diagnostic value of CRP, next to history and physical examination, are not yet available.
Based on the discussion in the literature and the expertise of the members of the ERS Task Force the following diagnostic strategy is advocated.
Recommendation
A patient should be suspected of having pneumonia when the following signs and symptoms are present.
An acute cough and one of the following: new focal chest signs; dyspnoea; tachypnoea; or fever >4 days. If pneumonia is suspected, a chest radiograph should be performed to confirm the diagnosis (C1).
Should the primary care physician test for a possible microbiological aetiology of LRTI?
The main reason for detecting a microbiological cause of symptoms would be to select patients who could benefit from antibiotic treatment and enable therapy with narrow-spectrum antibiotics to contain bacterial resistance, side-effects and costs. In addition, public health is sometimes served by detection of particular pathogens, such as tuberculosis and legionella. Other important infections, e.g. influenza, are usually monitored by public health authorities. Conversely, one should note that a large proportion of patients with LRTI do not benefit from antimicrobial treatment, irrespective of the aetiology of their disease. Only in certain sub-groups of patients, such as very young children, very old patients and patients with serious chronic comorbidity, e.g. COPD, cardiac failure or diabetes, could assessment of the microbiological aetiology be useful.
Two separate issues should be addressed here: 1) detecting whether the patient has an LRTI of bacterial origin; and 2) testing which species of bacteria are involved and assessing the antibiotic resistance of these possible pathogens.
The colour of expectorated sputum is often said to be related to bacterial LRTI. One study of patients with an exacerbation of COPD showed a clear relationship between purulence and quantity of bacteria in sputum 15. Whether these findings can be confirmed by others, and if this also applies for patients without chronic lung disease, is still unknown. Serum levels of CRP are also used to assess the presence of a bacterial aetiology. However, the results of studies in this field are equivocal 16–18. Studies on the diagnostic value of Gram stain in primary care patients with LRTI are lacking. However, hospital-based studies on the use of Gram stain in CAP show low sensitivity for detecting possible pathogens 19. Bacterial colonisation (as opposed to infection) was not taken into account in these studies. It is unlikely that this test performs better in primary care, where, on average patients, have milder disease forms.
The reasons for not advocating Gram stain also apply to culturing sputum samples and measuring pneumococcal antigen in sputum and urine. Possible bacterial pathogens are only detected in 20–50% of patients and a distinction between colonisation and a new bacterial infection is difficult.
Recommendation
Microbiological investigations are not usually recommended in primary care. Differentiating between viral and bacterial infections is difficult in primary care patients. Indications for treatment should, therefore, be based on assessment of severity of the clinical syndrome (see Treatment section). Also, the physician should be aware of local bacterial resistance rates (C1–3).
Treatment
Most episodes of LRTI are self-limiting and will last between 1–3 weeks. However, some sub-groups of patients need symptomatic or causal treatment. In addition, all patients who contact their primary-care physician with an LRTI should be informed about the severity of their disease and its prognosis.
Should symptomatic acute cough be treated?
In general, cough should be regarded as a physiological phenomenon, which is triggered by inflammation of the mucosa and helps to clear mucus from the bronchial tree. Suppression of cough is, therefore, not logical when the patient coughs up relevant quantities of sputum. However, cough can be very bothersome and tiring, especially at night. Hence, when the patient has a dry and frequent cough and nights are disturbed, suppression of cough can be useful. Dextromethorphan showed some effect in patients with acute cough, whereas studies on codeine in the same patients failed to show beneficial effects 20, 21. However, in patients with chronic cough both agents did diminish coughing 22.
Recommendation
Both dextromethorphan and codeine can be prescribed in patients with a dry and bothersome cough (C1).
Besides cough suppressants, there are many over-the-counter medicines available for coughing complaints. Expectorants, mucolytics and antihistamines are sold in great quantities, but consistent evidence for beneficial effects is lacking 21. The same applies for inhaled bronchodilators in uncomplicated acute cough. To date, studies have not shown relevant beneficial effects 23.
Recommendation
Expectorant, mucolytics, antihistamines and bronchodilators should not be prescribed in acute LRTI in primary care (A1).
An important notion is that serious chronic disease, such as asthma, COPD, cardiac failure or diabetes, tends to flare up when the patient experiences an LRTI. Thus, their primary physician should consider temporarily altering the dosage of the patient's chronic medication.
When should antibiotic treatment be considered in patients with LRTI?
In the average patient with an uncomplicated LRTI in primary care, not suspected of pneumonia, antibiotic treatment has shown no benefit compared with placebo. A Cochrane review concluded that antibiotic treatment in patients with acute bronchitis had a modest beneficial effect not outweighing the side-effects of treatment. The review was hampered by the use of various outcome measures in the included randomised controlled trials (RCTs) 24, 25. Some guidelines conclude that in LRTI where there is no suspicion of pneumonia and the diagnosis acute bronchitis should be applied, antibiotics are, therefore, not indicated. This point of view does not take into account that in subsets of patients with acute bronchitis at risk for complications, effects of antibiotics were never evaluated. There are some indications that in the elderly, antibiotic treatment has more clinical effects than in young adults 26. Patients with pneumonia also have an elevated risk of complications. Placebo-controlled RCTs in patients suspected of having pneumonia outside hospital are absent. However, since a large proportion of these suspected pneumonias are related to bacterial pathogens and 10–20 % of these patients have a complicated disease course, it is advised to also treat these patients with an antibiotic.
Recommendation
Based on the risk for complications in certain subgroups of patients with an LRTI, antibiotic treatment is advocated in patients with an LRTI and: suspected or definite pneumonia (see How to differentiate between pneumonia and other respiratory tract infections); selected exacerbations of COPD (see What are the indications for antibiotic treatment of exacerbations of COPD?); aged >75 yrs and fever; cardiac failure; insulin-dependent diabetes mellitus; a serious neurological disorder (stroke etc.; C2).
What are the indications for antibiotic treatment of exacerbations of COPD?
There is considerable discussion on whether exacerbations of COPD are in fact LRTIs in patients with COPD. However, in daily practice the majority of exacerbations are treated with antibiotics. Studies on antibiotic treatment, including outpatients, show conflicting results. A meta-analysis showed a small effect on lung function 27. The authors concluded that antibiotics might have a beneficial effect, especially in patients with a low FEV1. This conclusion was underlined by a re-evaluation of these data, in which patients were stratified according to baseline lung function 28. Another more recent meta-analysis had the same conclusions 29. This conclusion and the fact that papers in these meta-analyses included both in- and outpatients, makes it uncertain as to whether antibiotic treatment in exacerbations in all primary care patients is useful. The two studies carried out in primary care failed to show relevant effects 30, 31. However, data on patients with severe exacerbations and exacerbations of mild and severe COPD in primary care were lacking. A key clinical trial in patients with an exacerbation of COPD showed modest beneficial effects in patients with two or more of the following three symptoms: increased sputum volume, increased sputum purulence and increased dyspnoea 32. In conclusion, there is some evidence on beneficial effects of antibiotics in patients with severe COPD and in patients with exacerbations characterised by the above three symptoms. However, it should be noted that these criteria are subjective and based on only one study. More research in this field is needed.
Recommendation
An antibiotic should be given in exacerbations of COPD in patients with at least the following symptoms: increased dyspnoea, increased sputum volume and increased sputum purulence. In addition, antibiotics should be considered for exacerbations in patients with severe COPD (C1).
Which antibiotics should be used in patients with LRTI?
Scientifically robust, randomised, controlled, clinical trials are not available to guide this decision. S. pneumoniae, and to a lesser extent H. influenzae, are the most common bacterial pathogens in LRTI (Appendix 1). Empiric antibiotic treatment should be directed at these pathogens, even though M. pneumoniae does occur periodically. At the same time, local bacterial resistance rates should be taken into account. It is important to note that most national data on bacterial resistance rates are from microbiological laboratories where only a very small proportion of the cultures originate from primary care. Thus, these data are likely to give an overestimation of bacterial resistance outside hospital. However, it has been shown that in some European countries bacterial resistance is a relevant problem in outpatients.
Due to proven efficacy, vast experience with their use and low costs, tetracycline and amoxicillin are first-choice antibiotics, provided that locally there is no clinically relevant bacterial resistance (see Appendix 1) against both agents. Macrolides are not recommended for acute exacerbations of COPD (AECOPD) because of reduced activity against H. influenzae, and very high rates of pneumococcal resistance to macrolides in many European countries, but could be used for other LRTI when local bacterial resistance rates impair the effectiveness of first choice agents and in case of intolerance to these agents. Quinolones are not recommended because of concerns regarding the potential for resistance development in the community, but can be second-choice treatment in case of clinically relevant pneumococcal resistance against amoxicillin and tetracyclines, or major intolerance, such as immunoglobulin (Ig)E-mediated allergy to ß-lactams. The new ketolides have little added value over macrolides and are usually more expensive. Cephalosporins also do not have a clear added value.
Recommendation
Tetracycline and amoxicillin are first-choice antibiotics. Tetracycline has the advantage that it also covers M. pneumoniae.
In case of hypersensitivity, a newer macrolide, such as azithromycin, roxithromycin or clarithromycin, is a good alternative in countries with low pneumococcal macrolide resistance. National/local resistance rates should be considered when choosing a particular antibiotic. When there are clinically relevant bacterial resistance rates against all first-choice agents, treatment with levofloxacin or moxifloxacin may be considered (C4).
Is anti-influenza treatment useful in patients with LRTI?
Influenza is an important pathogen causing LRTI and is the only viral pathogen susceptible for treatment in primary care. Amantadine and rimantadine have been available for several decades. A recent meta-analysis indicated that both agents reduce the duration of symptoms on average by one day 33. However, these drugs have been shown to induce resistance, do not work against influenza B and have frequent side-effects, mainly neurological and gastro-intestinal 34. Since 1995, new anti-viral compounds, oseltamivir and zanamivir, have been introduced. A recent meta-analysis concluded that both agents reduced symptom duration by, on average, 0.7–1.5 days in healthy adults with a clinical flu syndrome, provided that treatment was started within 48 h of the onset of the clinical syndrome 35. However, data on patients at risk for complications were very scarce. Monto et al. 36 noticed a relative reduction of complications of influenza of 29%, and a beneficial effect of treatment in patients aged >50 yrs (3 days difference). The same effect reached statistical significance in high-risk patients when patients from all available trials were pooled. However, the number of high-risk patients was limited and studies did not examine mortality as an end-point. In addition, one should realise that in the vast majority of cases, patients consult their GP far too late to benefit from anti-viral treatment.
Recommendation
The empirical use of anti-viral treatment in patients suspected of having influenza is usually not recommended (B1). Only in high-risk patients who have typical influenza symptoms (fever, muscle ache, general malaise and respiratory tract infection), for <2 days, and during a known influenza epidemic, can anti-viral treatment be considered (C1).
How should patients with LRTI be monitored?
There are no studies assessing what would be the best follow-up procedures in primary care patients with LRTI. The natural course of an uncomplicated LRTI will take 1–3 weeks.
Recommendation
A patient should be advised to return if the symptoms take >3 weeks to disappear.
Clinical effects of antibiotic treatment should be expected within 3 days and patients should be instructed to contact their doctor if this effect is not noticeable. Seriously ill patients, i.e. having at least two of the following symptoms/characteristics, should already be seen 2 days after the first visit: high fever; tachypnoea; dyspnoea; relevant comorbidity; aged >65 yrs.
All patients or persons within their environment should be advised to contact their doctor again if fever exceeds 4 days, dyspnoea gets worse, patients stop drinking or consciousness decreases (C3).
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MANAGEMENT INSIDE HOSPITAL |
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TOPABSTRACTBACKGROUNDRECOMMENDATION SUMMARYMANAGEMENT OUTSIDE HOSPITALMANAGEMENT INSIDE HOSPITALPREVENTIONREFERENCES |
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Two tools have been developed to guide this decision, the PSI 37 and the CURB index 38, 39.
PSI
The PSI has primarily been developed to detect those patients who can safely be treated as outpatients. According to this score, the main determinants of pneumonia severity are increasing age, comorbidity and vital sign abnormalities. However, the calculation of the PSI score requires additional laboratory, blood gas and chest radiograph data (table 6) 37.
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The PSI has been used to validate clinical pathways. It has been found to be helpful in reducing avoidable hospital admissions, length of hospital stay and, therefore, overall costs. An impact on mortality has not been shown 42.
The PSI has three disadvantages. First, the classification of risk is a classification of the risk of mortality. This is the most important, but not the only consideration on which the decision to hospitalise should be based. The needs for supplemental oxygen or drainage of pleural effusions have been detected as main reasons to hospitalise low-risk patients 41. Secondly, increasing age is a leading determinant within the scoring system. This may lead to an underestimation of pneumonia severity in younger patients. The third disadvantage, is the complexity of the score with the need to compute a score from 20 variables.
CURB index
The CURB index is composed of four variables (three clinical and one laboratory), which have been shown to bear important prognostic potential as part of predictive rules for pneumonia mortality in hospitalised patients (table 7) 38, 44. These variables reflect age, acute respiratory failure and symptoms of severe sepsis or septic shock. Patients who do not meet any of the four variables are at minor risk (mortality 1%), whereas those who meet one/two or three/four are at a risk of 8 and 30%, respectively.
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The CURB index bears two advantages as compared with the PSI. First, it is based on acute pneumonia severity and not on age and comorbidity, thereby avoiding the underestimation of pneumonia severity in younger patients or potential biases resulting from comorbidities not known or apparent at first evaluation. Secondly, it is much easier to calculate.
These objective tools should not replace subjective clinical judgment, but serve as an aid to improve the validity of clinical decision making. Moreover, nonclinical factors may justify hospitalisation in selected cases 47.
When a decision to treat as an outpatient has been made, a clinical reassessment 24–48 h after the first evaluation should be planned since deterioration is most likely to occur within this time 48. Hospitalisation of patients initially treated as outpatients is not frequent and has been observed within 10 days in only about 7.5% of cases. These patients are at higher risk of death and require a longer median time to return to usual activities 49. In case of doubt, hospitalisation should be the preferred choice. Predictors of complicated courses in seemingly low-risk patients have been identified, but not validated in independent cohorts 50.
Recommendation
The decision to hospitalise remains a clinical decision. However, this decision should be validated against at least one objective tool of risk assessment. Both the PSI and the CURB index are valid tools in this regard. In patients meeting a PSI of IV and V and/or a CURB of 2, hospitalisation is recommended. Additional requirements of patient management as well as social factors not related to pneumonia severity must be considered as well (A3).
Who should be considered for ICU admission?
Severe pneumonia remains very difficult to define. Several severity criteria have been tested for their potential to predict ICU admission. However, this approach depends on pre-clinical determinants, such as the structure of local healthcare facilities. It may be impossible to derive a universally applicable prediction rule for ICU admission.
Nevertheless, the severity criteria defined so far remain useful. These criteria describe patients at increased risk of death who should receive increased attention, and ICU admission should always be considered. Criteria of increased attention may also be made in alternative settings, such as intermediate care units or even a specialised regular ward.
The potential benefits of ICU treatment should be recognised. Patients with severe pneumonia are frequently admitted to the ICU exclusively for the initiation of mechanical ventilation and/or the management of septic shock. However, due to the potential benefit of noninvasive mechanical ventilation and the documented benefit of early treatment of severe sepsis, it is not adequate to restrict ICU resources to terminal events within the ongoing inflammatory cascades in severe sepsis. Instead, careful observation of unstable patients within the ICU or intermediate care units should be applied in order to allow early and precisely targeted interventions.
Criteria for severe pneumonia include: 1) factors reflecting acute respiratory failure (e.g. respiratory rate >30·min–1, Pa,O2/FI,O2 ratio <250); 2) factors reflecting severe sepsis or septic shock (e.g. hypotension (arterial systolic blood pressure <90 mmHg, arterial diastolic blood pressure <60 mmHg, renal failure, confusion); 3) factors reflecting amount and spread of infiltration on chest radiographs (infiltrates involving two or more lobes or bilateral infiltrates) 48, 51.
Although both the PSI and the CURB index provide valid estimations about the risk of the need for ICU admission, these indices have not been used to predict severe pneumonia in individual patients. Therefore, they may be only of limited value in guiding this decision. There is one predictive rule based on criteria originally proposed by the American Thoracic Society (ATS) CAP Guidelines 51 (table 8), which has been derived and validated for the prediction of ICU admission 48. This rule is composed of three minor criteria to be assessed at admission and two major criteria which may be met at admission as well as during follow-up. It is very easy to calculate and has been shown to have a moderate positive (75%) and excellent negative predictive value (95%) in a Spanish setting 48. However, probably for the reasons outlined above, it has been shown to perform less favourably in an American setting 52. Experience with this tool is limited. The implementation of an "admission decision support" in combination with specific recommendations for outpatient treatment has been successfully used and is encouraged 51, 53, 54.
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The use of these facilities should not be restricted to terminal events of the course of pneumonia, but extended to all patients who are unstable in terms of the criteria mentioned (A3).
What laboratory studies should be performed?
The differentiation of mild, moderate and severe pneumonia can direct different behaviours at diagnostic work-up by laboratory and microbiological studies. All patients hospitalised with suspected CAP should receive a chest radiograph. Laboratory studies in hospitalised patients on admission should include arterial blood gas or pulse oximetry determinations 55 and basic blood chemistry (red and white blood cell count, differential cell count, creatinine and urea nitrogen, aminotransferases, sodium, potassium). CRP cannot differentiate bacterial from nonbacterial pneumonia, and is only weakly associated with severity. However, the clinical course is closely reflected by the CRP course. CRP, interleukin 6 and procalcitonin have all been shown to bear independent prognostic potential 56, 57. However, due to the high cost and unproven cost-effectiveness, only CRP is recommended.
Mild pneumonia does not usually require any further microbiological studies 58. The usefulness of leukocyte counts and CRP is not proven in this group. A laboratory assessment including leukocytes and CRP, as well as a determination of blood gases, should be made in all hospitalised patients.
Recommendation
The amount of laboratory and microbiological work-up should be determined by the severity of pneumonia (A3). Microbiological work-up is primarily meant as an epidemiological investigation in order to guide future empiric antimicrobial policies. Occasionally, it might be helpful in guiding an individual treatment (A3).
Microbiological investigation
No study has shown that initial microbiological studies affect outcome 59. Nevertheless, many clinicians feel that microbial investigation may be of help in guiding treatment, particularly in the more severely ill patients.
Even if a particular pathogen is detected (e.g. by bedside antigen testing), narrowing of antimicrobial spectrum cannot be generally recommended until concerns regarding the prognostic role of mixed infections have been appropriately addressed. Mixed infections have been reported to be present in 5–38% of cases 38, 60 and were associated with severe pneumonia in one study 61. Moreover, several observational studies in hospitalised patients, comparing penicillin monotherapy and combination therapy of penicillin and macrolides, have raised substantial concerns into monotherapy due to adverse outcomes 62. Thus, the role of microbiological testing is not primarily to narrow treatment options in the individual patient, but to provide more confidence about the treatment option selected in individual cases (tables 9 and 10).
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60% of positive blood cultures 68, 69 and H. influenzae in various percentages from 2–13%. Other organisms are recovered in diminishing order of frequency from 14% to 2% and 1% in gram negative aerobes, streptococci (Streptococcus pyogenes and other), Staphylococcus aureus and mixtures of organisms, respectively 68. For most of the latter organisms it is difficult to decide whether they were present in the bloodstream or are skin contaminants.
Recommendation
Blood cultures should be performed in all patients with CAP who require hospitalisation (A3).
What other invasive techniques for normally sterile specimens can be useful in the laboratory diagnosis of pneumonia?
Thoracentesis
In 40% of CAP there may be an accompanying pleural effusion. Although specificity of pleural exudate culture is very high, the sensitivity is low because of the low incidence of invasion of the pleura 70. Therefore, Gram stain or cultures yielding bacterial pathogens from pleural fluid are likely to be an accurate reflection of the microbial cause of the pneumonia (table 11).
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Trans-thoracic needle aspiration
In recent years there has been a resurgence in the interest in, and growing experience with, trans-thoracic needle aspiration (TNA) for microbial diagnosis of CAP, especially in patients with severe CAP 71–75.
TNA allows a specimen to be obtained from the infected focus without interference of commensal flora, except for possible skin contaminants. In a review of studies of patients with CAP 70, TNA has yielded a positive culture in 33–80% of cases. From 13 studies in which the results of blood cultures were also known 74, the sensitivity of lung aspiration was estimated at 74% and that of blood cultures at 37%. Ruiz-Gonzalez et al. 72 obtained through TNA a microbiological diagnosis in 36 out of 55 (65%) patients with pneumonia of unknown aetiology by conventional methods.
The superiority of direct access to a lung lesion through TNA is also illustrated by a study that identified aetiology of infection in 12 out of 18 (67%) infiltrates with a corresponding nondiagnostic BAL 76.
Recommendation
Due to the inherent potential adverse effects, TNA can only be considered on an individual basis for some severely ill patients, with a focal infiltrate in whom less invasive measures have been nondiagnostic (A3).
PSB and BAL
The specificity of bronchoscopy for the diagnosis of bacterial pathogens in CAP is not high because of contamination with the upper airway flora. The patient may be put at unnecessary additional risk because of already-compromised gas exchange.
Several techniques have been proposed to achieve accurate discrimination between colonisation and infection. Diagnostic accuracy is improved by the use of PSB, a technique introduced by Wimberley et al. 77, and BAL, at first using a bronchoscope but later not bronchoscopically taken (NB-BAL). The latter procedure is much more rapid and provides similar microbiological data in the diagnosis of ventilator-associated pneumonia 78, 79.
Quantitative bacterial culture is important for the assessment of these techniques. The cut-off point for diagnosing pneumonia has usually been set at 103 colony forming units (CFU)/mL by most investigators 70. A major criticism directed at the PSB technique is the relatively small amount of distal bronchial secretions examined, particularly in comparison with the technique of BAL where threshold values of 103 CFU·mL–1 to 104 CFU·mL–1 are used 70, 80–83.
Using 103 CFU·mL–1 as the threshold value for a positive culture, Cantral et al. 84 determined the sensitivity and the specificity as 90% and 97%, respectively. With a threshold value for a positive culture of 104 CFU·mL–1, the specificity of lavage cultures for potential pathogenic bacteria in relation to actual LRTI was 100% 83. Therefore, quantitative bacterial culture of potential pathogenic bacteria in BAL fluid is very specific, but is positive in only about one third of unselected immunocompetent adult patients with an LRTI 83.
The sensitivity of bronchoscopic BAL has been evaluated at 82–91% 85 and at 42–93% 86. NB-BAL introduced in an emergency department allowed early identification of pathogens in severe CAP, leading to changes in antibiotic therapy 87.
Recommendation
BAL may be the preferred technique in nonresolving pneumonia (A3). Bronchoscopic sampling of the lower respiratory tract can be considered in intubated patients and selected nonintubated patients, where gas exchange status allows (A3).
What is the value of sputum examination?
Gram strain
The most frequently submitted specimen in cases of pneumonia is sputum. To be of value for microbial diagnosis in CAP and early guide to therapy, Gram-stained sputum specimens must be representative of lower respiratory secretions and must be interpreted according to strict criteria by an experienced observer 70.
Sputum should be screened by microscopic examination for the relative number of polymorphonuclear cells and squamous epithelial cells in a low power (100x) field. Invalid specimens (10 squamous epithelial cells and 
25 polymorphonuclear cells/field) should not be examined further. The cytological interobserver variability of sputum quality is satisfactory 88, 89.
There are great controversies regarding the value of the Gram stain. A meta-analysis of 12 studies found wide variability in sensitivity (15–100%) and specificity (11–100%). However, most studies showing good sensitivity and specificity used routine sputum culture in the comparison 90. Gram-stained sputum smears can only be validated by comparing the results with those of a reference, e.g. specimens devoid of commensal flora, blood, pleural fluid cultures or TNA. There are relatively few studies in which this was carried out. Early studies 67, 91 concerned a limited number of patients, later studies involved larger numbers of patients. In a prospective study of bacteremic CAP 69, a predominant morphotype was observed in 79% of the acceptable specimens and a compatible organism was present in the blood of 85% of these patients. In another study, the conclusion was that in good-quality sputum, through the detection of a single or preponderant morphotype (±90%), the sensitivity and specificity for the detection of S. pneumoniae were 35.4 and 96.7%, respectively, and for H. influenzae 42.8 and 99.4%, respectively 92. When a purulent sample was available the Gram stain gave a presumptive diagnosis in 175 out of 210 cases (80%).
The main limitation is the difficulty to obtain good-quality, purulent sputum. Many pneumonia patients do not produce sputum, particularly older patients. In recent studies, satisfactory sputum specimens were obtained in: 47 out of 174 patients (32%) 69; 210 out of 533 patients (39%) 92; 23 out of 42 patients (55%) 93; 156 out of 205 adults (76%) 67; and 90% of young military recruits 94.
A low concordance of Gram-stained specimens examined by different technicians has been found 88, 89, whereas others found the results to be reproducible 95. There is a need for laboratory quality control.
With the many limitations concerning the sputum Gram stain, is there any role for this test in the management of CAP? The answer is yes, especially if a possible pathogen is present as a predominant organism.
Recommendation
Gram stain is recommended when a purulent sputum sample can be obtained from patients with CAP and is processed timely (A3).
Culture
Sensitivity and specificity of sputum cultures are reduced by contamination with flora colonising the upper respiratory tract. The value of sputum cultures in establishing a bacterial cause of LRTI depends on how the specimens are collected and processed.
The yield of sputum cultures has varied widely, from <20% for outpatients 58 to >90% for hospitalised patients 91. Good concordance has been found between the results of cultures of sputum and transtracheal aspirates 94, 96, particularly when good-quality sputum specimens are washed and cultures are quantified 97.
Drew 91 detected S. pneumoniae in up to 94% (29 out of 31) of specimens from patients whose blood culture was positive. Others conclude that in cases of bacteremic pneumococcal pneumonia, S. pneumoniae may be isolated in sputum culture in only 40–50% of cases when standard microbiological techniques are used. Purulent sputa can also be obtained from patients without pulmonary pathology 98. In some studies, the predictive value of sputum culture is low 99, even as low as 5% in cases of nonsevere CAP 58. In one study 68 in which 19 out of 48 (39.5%) of the bacteremic patients had sputum cultured, there was concordance of blood and sputum results for nine (47%) of the pairs and in another study 99 in 25 out of 51 (49.0%) of the pairs. Several approaches have been suggested to improve the sensitivity and specificity of sputum culture in CAP.
The sputum Gram stain is valuable in guiding the processing and interpretation of sputum cultures. Sputum culture results are most convincing when the organism(s) isolated in culture are compatible with the morphology of organisms present in >90% of leukocytes in the Gram stain 70. In the absence of an informative Gram stain, sputum cultures can only give a probable aetiological agent.
Recommendation
A culture from a purulent sputum specimen of a bacterial species compatible with the morphotype observed in the Gram stain, which is processed correctly, is worthwhile for confirmation of the species identification and antibiotic susceptibility testing (B3).
What can antigen tests offer in the diagnosis of CAP?
Rapid tests for the detection of S. pneumoniae in sputum, exudates, serum and urine have been applied over the years, most successfully counter immunoelectrophoresis, latex agglutination and enzyme immunoassays (EIA). Compared with cultures, many of these tests lack sensitivity and/or specificity or are not rapid. The latest addition is immunochromatography to be performe
