Key messages

• In severe community-acquired pneumonia, we recommend the association of a second- or third-generation cephalosporin in addition to erythromycin and rifampin (rifampicin).

• After effective therapy, an improvement in the clinical features of pneumonia should be seen in 48 to 72 h.

• When a patient is not responding or is deteriorating during empirical therapy, several complications and factors associated with the antibiotic, the organism, and the host should be considered.

• Duration of therapy should be individualized depending upon the severity of illness, the rapidity of clinical response, and the infecting agent. Community-acquired pneumonia

Epidemiology and definition of severe community-acquired pneumonia

Community-acquired pneumonia remains an important cause of mortality in developed nations and accounts for 2.8 per cent of all hospital admissions. In the United States 50 000 deaths per year are attributed to it. It has been estimated that, annually, about 0.4 to 4 per 1000 individuals require hospitalization because of pneumonia. During the last 25 years, mortality has ranged from 4 to 24 per cent in adult patients admitted to hospital with community-acquired pneumonia. Severe community-acquired pneumonia is defined as a life-threatening pneumonia acquired in the community in non-immunocompromized patients requiring admission to an intensive care unit (ICU). There is little information about its frequency relative to the total number of pneumonias within and outside hospitals. However, epidemiological studies suggest that 3 to 5 per cent of cases of community-acquired pneumonia will be severe enough to require ICU admission. Most patients with severe community-acquired pneumonia have chronic underlying diseases such as chronic obstructive pulmonary disease or other forms of chronic respiratory failure. Other frequent underlying chronic conditions are alcoholism and diabetes mellitus. Over 30 per cent of cases involve previously healthy patients.


Several studies report the etiology of severe community-acquired pneumonia. In most of them, Streptococcus pneumoniae and Legionella pneumophila are the two most frequent micro-organisms. However, L pneumophila is much less frequent than Strep. pneumoniae in the overall population of community-acquired pneumonia, indicating that the former micro-organism produces more severe forms. Hemophilus influenza, other Gram-negative bacilli, and Mycoplasma pneumoniae are also frequently involved. Staphylococcus species, although infrequent in most series, were the second most frequent type of micro-organism involved in a recent large series of 299 cases of severe community-acquired pneumonia. Table 1 shows the different etiologies of severe community-acquired pneumonia in order of frequency.

Table 1 Micro-organisms most commonly causing severe community-acquired pneumonia in order of frequency


In view of the epidemiological data on severe community-acquired pneumonia we suggest the following empirical antibiotic regimens.

1. In healthy patients aged below 60 years, we recommend the association of a second-generation (cefuroxime) or third-generation (cefotaxime or ceftriaxone) cephalosporin in addition to erythromycin and rifampin (rifampicin) to cover L pneumophila. In those countries with a high prevalence of penicillin-resistant Strep. pneumoniae, cefotaxime (2 g every 8 h) must be administered.

2. In patients older than 60 years or with an underlying chronic condition, we suggest adding an aminoglycoside (at least during the first 3 days of treatment) since the presence of Gram-negative bacilli, other than H. influenzae, is more likely and the combination of an aminoglycoside with a b-lactam can be of help in the case of bacteremia.

3. In patients with chronic bronchiectasis presenting with severe community-acquired pneumonia we have to consider the possibility of Pseudomonas aeruginosa so that the administration of antipseudomonal combinations (ceftazidime plus amikacin, imipenem, ciprofloxacin, etc.) is mandatory.

Obviously initial antibiotic regimens have to be modified in relation to microbiological findings in both rapid initial tests and cultures. The role of the new macrolides and new quinolones for severe community-acquired pneumonia has still to be assessed.

Duration of treatment

The duration of treatment has not yet been well established, but it seems reasonable to maintain antibiotic treatments for a period of 10 to 14 days. In confirmed cases of severe L. pneumophila it is advisable to administer antibiotics for 2 to 3 weeks. In the case of Ps. aeruginosa pneumonia the duration of treatment should be at least 2 weeks.

If empirical therapy is used, evaluation of clinical response is essential so that non-responding patients can be identified and appropriately evaluated. After effective therapy, an improvement in the clinical features of pneumonia should be seen in 48 to 72 h. Therefore therapy should not be changed in the first 72 h unless there is a marked clinical deterioration. Fever can persist for 2 to 4 days, and leukocytosis usually resolves by the fourth day. Radiographic evidence of deterioration is common during therapy and may have prognostic significance in the setting of severe pneumonia, when it is a predictor of a poor outcome.

Causes of non-response to initial antibiotic therapy

When a patient is not responding or is deteriorating during empirical therapy, several complications and factors associated with the antibiotic, the organism, and the host should be considered.

1. Empyema is a relatively frequent complication of pneumonia which explains the lack of response to initial antibiotic therapy in some cases. Particularly because of concern about empyema, any patient with an inadequate clinical response to therapy should have repeat chest radiography, and any pleural fluid should be sampled, cultured, and analyzed for cell count and chemistry. Other complications such as septic metastases can occur in as many as 10 per cent of patients with bacteremic pneumonia (arthritis, meningitis, pericarditis, etc.).

2. The etiological agent may be resistant to the drugs used in the initial empirical regimen. This is the case in penicillin-resistant Strep. pneumoniae, particularly in areas with reported high rates of resistance. Pneumococcal resistance to erythromycin and cephalosporins should also be considered.

3. The infecting pathogen may not be covered by the initial antibiotic selection. This is the case with Staphylococcus aureus or Ps. aeruginosa which are not optimally covered by the therapies outlined above.

4. Alternatively, the infection could be caused by an agent that is not responsive to antibiotics (e.g. a virus). Additional unusual pathogens could be involved in the etiology of community-acquired pneumonia. Such infections should be considered when clinical and radiographic findings persist, and the differential diagnosis includes tuberculosis, endemic fungal pneumonia, and Pneumocystis carinii pneumonia.

5. It is also possible that the patient does not have pneumonia, as some non-infectious processes can present with clinical features that mimic pneumonia. These include pulmonary embolism, congestive heart failure, obstructing bronchogenic carcinoma, and certain inflammatory lung diseases (e.g. bronchiolitis obliterans and organizing pneumonia, Wegener's granulomatosis, eosinophilic pneumonia).

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