European Respiratory Society
Community-Acquired Pneumonia

Community-acquired pneumonia remains the leading cause of hospitalisation for infectious disease in Europe, and a major cause of morbidity and mortality. This issue of the European Respiratory Monograph brings together leading experts in pulmonology, infectious diseases and critical care from around the world to present the most recent advances in the management of community-acquired pneumonia. It provides a comprehensive overview of the disease, including chapters on microbiology, pathophysiology, antibiotic therapy and prevention, along with hot topics such as viral pneumonias and pneumonia associated with inhaled corticosteroids.

  • European Respiratory Monographs
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  2. Page vii
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  4. Page 1
    Correspondence: T. Welte, Dept of Pulmonary Medicine, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. E-mail,

    This article describes the epidemiology of community-acquired pneumonia (CAP) in Europe. Lower respiratory tract infections are the fifth leading cause of death worldwide with the bulk of the mortality attributable to CAP. Pneumonia disproportionately affects elderly populations and demographic changes within Europe are leading to an older, more comorbid population at high risk of pneumonia. Consequently, recent data suggests a progressive rise in hospitalisations for pneumonia throughout Europe over the past 10 years.

    CAP places a substantial burden on healthcare with costs largely attributable to inpatient care. Antibiotic resistance, particularly Streptococcus pneumoniae resistance to penicillin and macrolides, is rapidly increasing in Europe and poses a serious threat to future effective treatment. Prevention of pneumonia requires an understanding of the population risk factors, which will be discussed in this chapter.

  5. Page 13
    Correspondence: S. Ewig, Thoraxzentrum Ruhrgebiet, Kliniken für Pneumologie und Infektiologie, EVK Herne und Augusta-Kranken-Anstalt Bochum, Bergstrasse 26, 44791 Bochum, Germany. Email:

    The pneumonia triad includes community-acquired pneumonia (CAP), nosocomial pneumonia and pneumonia in the immunosuppressed host. The triad allows for clinical decisions regarding initial assessment of severity, selection of treatment setting, extent of diagnostic testing and empiric antimicrobial treatment.

    CAP in elderly patients and those in nursing homes, albeit with different clinical characteristics, could not be proven to be associated with different pathogen patterns to CAP. Recently, the concept of CAP has been challenged by healthcare-associated pneumonia (HCAP), including a set of predictors for the presence of multidrug-resistant (MDR) pathogens. However, HCAP criteria were poorly predictive for MDR pathogens. Attempts at defining individual predictors for such pathogens are ongoing. Hospitalisation and exposure to antimicrobial treatment within the last 3–6 months seem to be the most important predictive factors.

    Nosocomial pneumonia occurs in non-ventilated and ventilated patients. Early and late onset pneumonia should be determined, with careful reference to the correct starting point (hospitalisation not intubation), as well as comorbidity and antimicrobial exposure. Several risk factors have been defined for the presence of MDR pathogens.

    Pneumonia in the immunosuppressed host includes a variety of different immunosuppressive conditions which are associated with specific timetables and thresholds for different pathogen patterns.

  6. Page 25
    Correspondence: M. Lung, Dept of Microbiology, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 119, 08035, Barcelona, Spain. Email:

    In the setting of community-acquired pneumonia (CAP), the conventional microbiological workup is based on culture-based techniques and antigen testing, with a fundamental role in the identification, confirmation and contribution of antibiotic sensitivity of bacterial pathogens involved in its aetiology. However, this is the era of molecular testing and, certainly in past years, novel approaches based on nucleic acid amplification for detection, identification and quantification, as well as sequence-based techniques, have led to important improvements in the diagnosis or exclusion of certain diagnoses, and in the management and monitoring of lower respiratory tract infections. Such approaches attempt to provide accuracy, high sensitivity and specificity, and reduce the turnaround time. Phenotypic methods remain important in the diagnosis of bacterial CAP and molecular approaches, which are increasingly standardised and accessible, are being incorporated more frequently into the routine diagnostic workup.

  7. Page 42
    Correspondence: S.B. Gordon, Dept of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Email:

    Pneumococcal pneumonia is the explosive pulmonary and systemic inflammatory consequence of a disrupted host–pathogen relationship normally compartmentalised and optimally balanced as nasopharyngeal carriage. Pathogen, host and environmental factors combine to allow proliferation of pneumococci in the alveolar space. The local threat and the related threat of bacterial invasion resulting in sepsis are met with brisk responses from the epithelium and alveolar macrophages resulting in massive neutrophil ingress and loss of alveolar integrity. This immune response comes at the temporary cost of severely impaired respiratory function but, in most cases, is characterised by regulated resolution resulting in restoration of normal pulmonary architecture and function, as well as protection against future infection. The pathophysiology of pneumococcal pneumonia is informative in both treatment strategy and vaccine design. This chapter summarises recent discoveries in both host defence and pathogen virulence relating these subjects to future vaccination and treatment.

  8. Page 64
    Correspondence: F. Blasi, Dipartimento di Fisiopatologia Medico Chirurgica e dei Trapianti, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, Italy. Email:

    The term “atypical pneumonia” currently identifies pneumonia cases due to Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila, but this definition is not universally recognised. These infections, together with Streptococcus pneumoniae, are the leading cause of pneumonia in outpatients and they are also responsible for hospitalised pneumonia. Due to the fact that these bacteria are naturally resistant to β-lactams, they should be promptly identified, although single clinical or instrumental signs with a sufficient differential diagnostic accuracy have not been described. The use of scoring systems in order to make a weighted evaluation of individual signs and symptoms has been attempted, but results are as yet inconclusive. The use of specific testing (culture, serology and molecular biology) might be useful in identifying a greater number of atypical pneumonia, although each test has important limitations regarding accuracy and feasibility. An approach based on the evaluation of clinical risk associated with the combination of specific tests could be useful for a personalised antibiotic therapy.

  9. Page 74
    Correspondence: G.G.U. Rohde, Dept of Respiratory Medicine, Maastricht University Medical Center, P. Debyelaan 25, 6202AZ Maastricht, the Netherlands. Email:

    Viral community-acquired pneumonia (CAP) constitutes approximately 40% of CAP episodes in children and 25% in adults. Respiratory syncytial virus is the most prevalent virus in childhood CAP, whereas in adults influenza plays the most important role. Clinically, viral CAP frequently presents as a disease of gradual onset associated with upper respiratory tract symptoms. Chest pain and leukocytosis are frequently absent compared to bacterial CAP. Co-infection with different respiratory viruses or with bacteria is frequent. In particular, Streptococcus pneumoniae as a bacterial pathogen appears to be involved in co-infections. The severity of viral CAP compared to bacterial CAP or mixed CAP is difficult to appraise. However, it seems that in children bacterial CAP appears to be associated with higher mortality, whereas in adults viral CAP is associated with higher mortality. Clearly more research is needed and the increasing availability of molecular diagnostic methods, as well as emerging therapeutic interventions, will contribute to a better understanding of viral CAP.

  10. Page 88
    Correspondence: J.D. Chalmers, Tayside Respiratory Research Group, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. Email:

    Community-acquired pneumonia (CAP) remains a leading cause of death worldwide and a major burden on healthcare resources. CAP may vary in severity, from a mild disease managed in the community to a very severe illness requiring hospital or intensive care unit (ICU) admission. Illness severity is not always obvious at presentation and therefore a range of severity assessment tools have been developed to aid clinical decision making. Severity assessment tools have been proven to aid the site of care decision, increasing the proportion of low-risk patients managed at home. Most severity tools were initially developed to predict mortality risk, and recent validation studies have demonstrated that risk of death is not always a good indicator for ICU care. Other severity scores have been developed recently with the aim to predict ICU admission or other clinical decisions. The introduction of biomarkers as prognostic indicators of severe CAP, whether used alone or in conjunction with other clinical severity of illness scores, is a promising area for future research. There remains no consensus on which is the best severity assessment tool in CAP. The most recent and relevant data regarding clinical prediction tools and biomarkers to predict severity in CAP are reviewed in this chapter.

  11. Page 105
    Correspondence: B. Klapdor, Thoraxzentrum Ruhrgebiet, Kliniken für Pneumologie und Infektiologie, EVK Herne und Augusta-Kranken-Anstalt Bochum, Bergstrasse 26, 44791 Bochum, Germany. Email:

    During recent decades, specific phenotypes of patients with community-acquired pneumonia (CAP) have been described, exerting distinctive clinical features, severity, aetiology and outcome. Today, CAP in the elderly (≥65 years) clearly forms the core group within the concept of CAP. Clinical presentation may be oligosymptomatic, and comorbid conditions are present in a high proportion of patients. In contrast, CAP in younger patients (<65 years) has a more typical clinical presentation. Mortality is low and Mycoplasma pneumoniae is the second most common pathogen. The main feature of nursing home-acquired pneumonia is a very high mortality, which is mainly driven by poor functional status. Clinical presentation of patients with CAP and chronic obstructive pulmonary disease (COPD) is typically more severe, despite a similar mortality compared to patients without COPD. In addition, Pseudomonas aeruginosa has to be taken into account in patients with severe COPD. Aspiration as a cause of pneumonia is underdiagnosed. Patients suffering from dysphagia, for example, are at risk of recurrent pneumonia.

  12. Page 117
    Correspondence: M.P. Wise, Adult Critical Care, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK. Email:

    Diagnosing community-acquired pneumonia within time-pressured consultations in primary care is challenging. The traditional tools of history and examination poorly predict the presence of radiographic pneumonia. Point-of-care testing with biomarkers, such as C-reactive protein, is feasible and cost-effective, and may help clinicians to better target antibiotic prescription to those who will receive meaningful benefit, thus limiting overuse in those who are unlikely to benefit. Widespread use of antibiotics in primary care for respiratory tract infections is driving antimicrobial resistance and strategies, e.g. the use of enhanced communication skills by clinicians has proved effective in safely reducing antibiotic prescribing. Most patients with community-acquired pneumonia can be successfully managed in the community, with antibiotics prescribed according to national guidelines. Assessment of patients who require referral to secondary care can be aided by using severity of illness tools, such as CRB65 (confusion, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years), which measure perturbations in simple physiological measures and antibiotic treatment targeted accordingly.

  13. Page 130
    Correspondence: S. Esposito, Paediatric High Intensity Care Unit, Dept of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Via Commenda 9, 20122 Milan, Italy. Email:

    Community-acquired pneumonia (CAP) is one of the most common infections of infants and children in developing and industrialised countries. Given the clinical, social and economic importance of CAP for the paediatric age group, there is general agreement that a prompt and adequate therapeutic approach is essential in order to reduce the impact of the disease. However, there are various issues that make it difficult to establish a rational approach to the treatment of paediatric CAP, including difficulty in identifying the aetiology of the disease, the emergence of resistance of the most frequent bacterial pathogens to commonly used antibiotics, and the lack of certain information about the possible preventive role of the recently marketed pneumococcal vaccine. More research is required in many areas, including the aetiological agents associated with CAP complications, the absence of a paediatric CAP severity score, a better definition of second-line antibiotic therapies, how to follow-up on patients with CAP, and the cost-effectiveness of vaccines against respiratory pathogens.

  14. Page 140
    Correspondence: M. Woodhead, Dept of Respiratory Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. Email:

    In adults who present with community-acquired pneumonia, it has become standard practice to commence empirical antibiotic therapy without waiting for the results of tests to identify the microbial cause. The reasons for this include the morbidity and mortality of the condition and the lack of sensitivity of microbial tests. In addition to reviewing the evidence behind these statements, this chapter describes the available antibiotics, and the international guideline recommendations for empirical antibiotic therapy and the reasons for the recommendations.

  15. Page 155
    Correspondence: R. Menendez, Service of Pneumology, Hospital Universitario y Politecnico La Fe, Bulevar Sur s/n, 46026 Valencia, Spain. Email:

    Antibiotics are the cornerstone of treatment in community-acquired pneumonia (CAP), and scientific societies deliver updated recommendations regarding choice and duration. Initial severity, patient’s characteristics and site of care are key for initial decisions, whereas stability influences switching of route and duration of treatment. Clinical objective criteria for switching therapy have been proved safe for patient outcome, beneficial for reducing antibiotic pressure, and cost saving. Strategies for early switch therapy are included in guidelines although a better implementation through predefined criteria and/or clinical pathways is warranted. Earlier switching is related to shorter duration of treatment and length of hospital stay. Recent meta-analyses have demonstrated no negative outcomes with shorter courses (≤7 days) in mild-to-moderate episodes while fewer studies are available in severe CAP. Biomarkers appear to be useful for customising the total duration of antibiotic treatment. Most recent recommendations have reduced the duration of treatment to 5–7 days.

  16. Page 168
    Correspondence: M. Ferrer, UVIIR, Servei de Pneumología, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Email:

    Patients with severe community-acquired pneumonia (CAP) often present acute respiratory failure (ARF). In less severe cases, oxygen therapy titrated to achieve acceptable arterial oxygenation is indicated.

    Noninvasive ventilation (NIV) is often indicated in patients with CAP and severe ARF. The populations of patients with CAP with better response to NIV are those with previous cardiac or respiratory disease. Thus, the use of NIV in patients with CAP without these pre-existing diseases should be very cautious and under strict monitoring conditions due to high rates of treatment failure. Unnecessary delay in intubation of patients who fail treatment with NIV seems to be associated with mortality.

    Continuous positive airway pressure (CPAP) has been used to treat ARF in several conditions characterised by alveolar collapse. However, the efficacy in pneumonia seems to be limited to immunosuppressed patients with pulmonary complications. The helmet is a promising new interface for the use of NIV or CPAP, particularly in hypoxaemic nonhypercapnic patients.

    Invasive mechanical ventilation is indicated in patients with life-threatening ARF or in those who have failed NIV treatment.

  17. Page 184
    Correspondence: A.K. Jaehne, Dept of Emergency Medicine, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202, USA. Email:

    Community-acquired pneumonia is one of the most common causes of severe sepsis and septic shock, accounting for up to 45% of cases admitted to hospitals. Early identification and illness severity stratification followed by early intervention using a bundled treatment approach have been shown to improve outcomes. This includes blood cultures before antibiotics, fluid resuscitation with 30 mL·kg−1 body weight to target a mean arterial blood pressure of at least 65 mmHg, central venous pressure between 8 and 12 mmHg, and a central venous oxygen saturation of 70% within 6 h of diagnosis. In addition, early and appropriate introduction of ventilator assistance not only improves gas exchange, it further reduces the imbalance between oxygen delivery and utilisation. The mortality reduction is also accompanied by a decrease in duration of mechanical ventilation, vasopressor use, and intensive care unit and hospital length of stay.

  18. Page 205
    Correspondence: S. Aliberti, Dept of Health Science, University of Milan Bicocca, Clinica Pneumologica, AO San Gerardo, Via Pergolesi 33, Monza, Italy. Email:

    Clinical stability is the first step of clinical improvement in patients with pneumonia. Clinical stability has been proven to be useful in guiding the switch of antibiotic therapy from intravenous to oral formulations. Given its importance in patient management, several sets of criteria have been created to standardise its definition. However, a single set of criteria cannot fit everybody; therefore, a personalised approach based on the resolution of the patient’s most prominent clinical features should be considered. Moreover, it is important to choose the set of criteria that best fits the standard of care at each site of practice. Clinical failure is considered a predictive factor of adverse clinical outcomes. The identification of the aetiology of clinical failure is important to determine the subsequent patient management. The term “nonresolving pneumonia” is used to indicate a failure to improve without clinical deterioration. Few epidemiological data have been published on this condition. Therefore, future studies should specifically address this topic.

  19. Page 219
    Correspondence: M.I. Restrepo, South Texas Veterans Health Care System ALMD, 7400 Merton Minter Boulevard, San Antonio, TX, 78229, USA. Email:

    Several novel non-antibiotic therapies have been used in patients with pneumonia. Among many alternatives, anti-inflammatory and immunomodulatory agents such as corticosteroids, statins, nonsteroid anti-inflammatory medications, immunoglobulins and anticoagulants have been tested. Other agents, such as angiotensin-converting enzyme inhibitors and mucolytics, showed a potential beneficial effect on airways protection mechanisms and secretion clearance. The therapeutic effect of nonpharmacological strategies (i.e. chest physiotherapy) has also been considered. However, other than use of corticosteroids in certain populations, there is still a need for further research before these medications are recommended for clinical use. This chapter discusses the evidence regarding novel non-antibiotic therapies and the association with clinical outcomes in patients with pneumonia.

  20. Page 234
    Correspondence: P.M.A. Calverley, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Room 356, 4th Floor, UCD Building, Daulby Street, Liverpool, L69 3GA, UK. Email:

    Patients suffering from chronic obstructive pulmonary disease (COPD) are more likely to report community-acquired pneumonia than others of a similar age, with approximately 3% of patients per year being affected. COPD patients using inhaled corticosteroids are almost twice as likely to have pneumonia. These pneumonias do not appear to be more severe or confer a higher mortality than similar episodes in non-corticosteroid users. Drugs containing the fluticasone moiety show the strongest association with pneumonia irrespective of the dose used, while data for an association of pneumonia with budesonide is weaker. Pneumonic episodes may represent a failure of prior COPD exacerbations to fully resolve and may be related to a greater microbial load in the lower respiratory tract. To date, no association has been established between pneumonia and inhaled corticosteroid use in asthmatics nor is the oral anti-inflammatory drug roflumilast associated with an excess of pneumonia. More data are needed to allow a proper estimate of the risk/benefit balance of inhaled corticosteroids in COPD.

  21. Page 243
    Correspondence: S. Schembri, Tayside Respiratory Research Group, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. Email:

    Macrolides are frequently used antibacterials in the treatment of community acquired pneumonia (CAP). Observational data have suggested that macrolide use in CAP is associated with lower mortality and morbidity. Studies in other chronic respiratory conditions have demonstrated that macrolide antibiotics have anti-inflammatory effects, which extend beyond their antibacterial properties with immunomodulatory effects at multiple stages of the inflammatory cascade, affecting cytokine secretion, inflammatory and structural cells. These may account for some of the benefits seen in observational studies. However the use of macrolides is not without drawbacks; there is growing concern regarding increasing bacterial resistance, tolerability as well as cardiac and aural toxicities. New generation macrolides are being designed to try and overcome these pitfalls by retaining the excellent pharmacokinetics yet providing better safety and tolerability profiles. This review will discuss the rationale behind the use of macrolides in CAP, their anti-inflammatory effects and potential pitfalls.

  22. Page 256
    Correspondence: S. Krüger, Klinik für Pneumologie, Allergologie, Schlaf- und Beatmungsmedizin, Florence Nightingale Krankenhaus, Kreuzbergstr. 79, D-40489 Düsseldorf, Germany. Email:

    Cardiovascular complications and comorbidities in community-acquired pneumonia (CAP) are very frequent. Therefore, clinicians need to see CAP not as a simple accidental infection; rather, they should look at CAP patients as high-risk cardiovascular patients and thus diagnose and treat them in an appropriate way. Cardiac complications in the acute phase of CAP are most often seen in the first days of disease. Therefore, better monitoring, diagnostics and risk stratification in CAP with respect to cardiovascular diseases should be established. There is a higher long-term risk for cardiovascular events and mortality in CAP patients that has not been adequately recognised. Cardiovascular morbidity and mortality, especially in patients with known cardiovascular disease, might be reduced by influenza and pneumococcal vaccination.

  23. Page 266
    Correspondence: M.W. Pletz, Zentrum für Infektionsmedizin und Krankenhaushygiene, Universitätsklinikum Jena, Erlanger Allee 101, 07740 Jena, Germany. Email:

    Pneumococci are the most frequent pathogen in community-acquired pneumonia (CAP). Influenza is the most important virus for more severe upper and lower respiratory tract infection, including CAP. Animal and epidemiological studies have revealed synergistic effects between these two pathogens. Complimentary cohort studies have confirmed synergistic protective effects of both the influenza and pneumococcal vaccines.

    Currently, two types of pneumococcal vaccines are in clinical use, the pneumococcal polysaccharide vaccine (PPSV) and the pneumococcal conjugate vaccine (PCV). Data regarding efficacy against nonbacteraemic pneumonia in adults are conflicting (PPSV) or pending (PCV). Data from different countries demonstrate that PCV serotypes can be reduced in the whole population by vaccination of children, who are the main reservoir of pneumococci (herd protection).

    Beside the classical trivalent influenza split vaccine, several novel influenza vaccine types have been released during the last decade, such as a live attenuated vaccine for children, a cell culture-derived vaccine for patients with egg protein allergy and a tetravalent vaccine covering the two major influenza B lines.

    This chapter discusses the advantages and disadvantages of different vaccine types available for pneumococcus and influenza.