Community-acquired pneumonia (CAP) is a major respiratory disease with a high prevalence in the general population, clinical heterogeneity and variable severity. Both in the USA and in Europe, CAP is the most frequent cause of death due to infection and it has implications for healthcare systems worldwide. Pneumonia usually causes symptoms for 3–4 weeks, and daily activities may be impaired for a further 3 weeks on average. The reported incidence of pneumonia varies considerably from country to country and study to study, with a consistently higher incidence in very young children and elderly adults. In Europe, the mean age of the population is increasing sharply, and this is likely to lead to a significant increase in pneumonia hospital admissions and costs.
Pneumonia that occurs 48 h or more after hospital admission, and which was not incubating at the time of admission, is defined as hospital-acquired pneumonia (HAP), while pneumonia that arises more than 48–72 h after endotracheal intubation is defined as ventilator-associated pneumonia (VAP).
The overall incidence of CAP in general practice in Europe is reported to range 1.7–11.6 cases per 1000 people per year in adults (table 1). In the European Union (EU), about 3 370 000 cases are expected annually. Hospitalisation rates differ widely between European countries, ranging from 20–50%, meaning that there are about 1 million hospital admissions for CAP per year in the EU. Age-standardised hospital admission rates for pneumonia are shown in figure 3. It is important to note that while most patients are treated on an outpatient basis, most studies are based on hospitalised patients and the true extent of pneumonia is not known.
|Country||Study period||Age years||Cases per 1000 population|
|Finland||1981–1982||15–29||4.2 M; 4.6 W|
|30–44||5.6 M; 5.9 W|
|45–59||9.8 M; 7.0 W|
|60–74||25.0 M; 9.0 W|
|>75||65.2 M; 19.6 W|
|>60||33.0 M; 11.8 W|
|Spain||1993–1995||15–39||1.2 M; 1.0 W|
|40–64||1.8 M; 1.4 W|
|>64||5.2 M; 1.9 W|
|1999–2001||15–44||0.8 M; 0.6 W|
|45–64||1.4 M; 0.7 W|
|65–74||3.2 M; 1.6 W|
|>75||8.7 M; 3.0 W|
|All ages||1.6 M; 0.9 W|
|2002–2005||65–74||3.0 M; 2.2 W|
|75–84||5.3 M; 2.8 W|
|>85||10.0 M; 7.9 W|
|All ages||4.2 M; 2.9 W|
|All ages||1.7 M; 1.7 W|
Table 1 – Pneumonia incidence in Europe in the outpatient setting. M: men; W: women. Reproduced and modified from Welte et al., 2012, with permission from the publisher.
The incidence of HAP is ~0.5–2.0% among all hospitalised patients, and while it is the second-commonest nosocomial infection, it is first in terms of mortality (ranging from 30% to more than 70%). The incidence in different hospitals and different wards of the same hospital varies considerably.
Causes and pathogenesis
The main organisms causing CAP in Europe are shown in figure 4. Streptococcus pneumoniae is the most frequent causative agent of pneumonia in Europe.
Antibiotic resistance is one of the major threats undermining the treatment of respiratory infections, with potentially important clinical and economic implications. Data from the European Antimicrobial Resistance Surveillance Network (EARS-net) show that in Europe almost 10% of S. pneumoniae strains are resistant to penicillin and 15% to macrolide antibiotics (figure 5). Moreover, new difficult-to-treat bacteria are emerging in pneumonia, e.g. methicillin-resistant Staphylococcus aureus (MRSA) and several Gram-negative bacteria (e.g. multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa), particularly in elderly patients living in long-term care facilities. However, data from European studies generally suggest a low frequency of multidrug-resistant organisms (< 10%) in patients from the community with pneumonia. Viral and mixed viral–bacterial infections are reported in about 10–20% of CAP cases.
Gram-negative pathogens are the main cause of HAP. P. aeruginosa, Acinetobacter baumannii, microorganisms belonging to the family Enterobacteriaceae (Klebsiella spp., Enterobacter spp., Serratia spp., etc.) and, under certain conditions, microorganisms such as Haemophilus influenzae, are involved in HAP aetiology. Among Gram-positive pathogens, S. aureus, Streptococcus spp. and S. pneumoniae are the most common agents, accounting for 35–39% of all cases. Nonbacterial pathogens such as Aspergillus spp. and viruses (cytomegalovirus) have been described. There are significant geographical differences in the rates of antibiotic resistance between European areas and even within countries, from one hospital to another.
In neutropenic patients, Gram-negative bacteria are the main pathogens, being responsible for about 70% of cases; fungal and mixed infections are involved in about 10% and 10–15% of cases, respectively.
HIV infection impairs humoral immunity by causing quantitative and functional defects in CD4+ lymphocytes, leading to an increased risk of bacterial infections, with S. pneumoniae and H. influenzae being the most frequent pathogens. The incidence of fungal infections, mainly caused by Pneumocystis jiroveci, increases when the patient’s CD4+ count is below 200 cells·mL-1.
In the past decade, outbreaks of new infectious agents have been reported. One of these outbreaks was caused by the severe acute respiratory syndrome (SARS)-coronavirus (CoV), a pathogenic coronavirus that emerged from a zoonotic reservoir and was associated with severe respiratory syndromes with a high mortality rate. The prompt global response to this outbreak, which stopped the spread of the disease, demonstrated the importance of intensive international collaborative efforts as well as timely and thorough investigations.
Clinical manifestations and consequences
Pneumonia is defined as an acute illness with cough and at least one of the following: new focal chest signs; fever of more than 4 days’ duration or dyspnoea/tachypnoea, without other obvious cause; and radiographic evidence of lung shadowing that is likely to be new. Sepsis and cardiovascular complications are the main cause of early treatment failure, i.e. in the first 3 days after admission. Early and appropriate antibiotic treatment is associated with a better outcome.
Antibiotics are the treatment of choice for pneumonia, both in the outpatient and hospital setting. The ERS/ESCMID guidelines indicate different antibiotic approaches according to setting, risk factors and severity. The appropriate use of antibiotics is a vitally important intervention in the effort to reduce antibiotic resistance rates.
Age-standardised mortality rates for pneumonia are shown in figure 6. The risk of death from pneumonia increases with age. A Finnish study showed a six-fold increase in incidence between the ages of 30–44 years and 75 years or older. In Portugal, case fatality rates were 4.5% for patients aged 18–50 years, 19.4% for those aged more than 50 years and 24.8% for those aged more than 75 years. A UK study reported case-fatality rates of 5.6% in those aged less than 65 years and 47.2% for those aged more than 85 years. The study also found a 12-fold greater likelihood of death within 30 days of hospital admission for adults aged more than 85 years compared with those aged less than 65 years.
Variables associated with pneumonia mortality
- Over 65 years of age
- Female sex
- Use of oral corticosteroids
- Pneumonia due to more than one organism
- Pleural effusion
- Intensive care unit admission
- Atypical pneumonia
- Hospital-acquired pneumonia
- Recent hospitalisation
- Serious underlying disease
- Acute renal failure
- Bacteraemic pneumonia
- Ineffective initial therapy
- Multilobar involvement
- Impaired alertness
- Septic shock
Over the past century, human life expectancy has increased dramatically in developed countries. In 2004, the EU had approximately 455 million inhabitants, of whom one-sixth were over 65 years of age (Eurostat 2004). If current trends in fertility, mortality and migration rates continue, the population is expected to peak in 2023, at which time one-third of the population will be over 65 years old. Clearly, the burden of pneumonia will be even more important in the years to come.
The risk of pneumonia-related mortality increases three-fold if pneumonia is due to S. pneumoniae, with a mortality rate ranging from 6.4% to more than 40% in the different settings of out-, in- and intensive care unit patients. Mortality does not seem to be related to antibiotic resistance. Pneumococcal pneumonia is accompanied by bacteraemia (bacteria detectable in the blood) in 10–30% of cases.
Patients with pneumonia who survive hospitalisation may still experience adverse outcomes after discharge, including readmission and death due to a relapse of pneumonia or other causes. Early readmission rates range 8–46%, with readmission particularly occurring in patients who show signs of instability at discharge and contributing considerably to medical resource use and costs. In patients with pneumonia, the mortality rate within 90 days after discharge can be as high as 14%; even at 1 year, mortality is still considerably higher after hospitalisation with pneumonia than in the general population or in those hospitalised for other reasons. CAP is also associated with a significant increase in the risk of cardiovascular events and death from cardiac causes.
Intensive care unit admission criteria for pneumonia patients are highly variable between European countries, and the admission rate ranges 3–5% in Italy to more than 10% in Belgium.