Community-acquired pneumonia: An update on therapy

Community-acquired pneumonia: An update on therapy

Pneumonia, an acute inflammation of the lung parenchyma, is a common and potentially serious disease. In the United States, the estimated annual incidence of pneumonia is 12 cases per 1000 population, and the estimated costs exceed $20 billion.1 Case rates for community- acquired pneumonia (CAP) have been estimated to be 258 per 100,000 population. This rate rises significantly, however, to 962 per 100,000 population among those aged 65 and older.2

From 1974 to 1994, the rate of pneumonia and influenza increased by 59%, partly a reflection of an aging population more susceptible to these diseases and more likely to die of them.3 Increased incidences of CAP have been observed among patients who have coexisting illnesses, such as chronic obstructive pulmonary disease (COPD), diabetes mellitus, renal insufficiency, congestive heart failure (CHF), and chronic liver disease.

The epidemiology and treatment of CAP have evolved. Developments include an increased number of newly identified or previously unrecognized pathogens, such as Chlamydia pneumoniae and Hantavirus; the increasing incidence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections; the increased risk of "global" pathogens, such as severe acute respiratory syndrome-associated coronavirus and the avian influenza virus strain H5N1; and the risk of exposure to pathogens such as anthrax that result from bioterrorism. The development of new methods of microbial detection, such as polymerase chain reaction, and the development of a number of new antimicrobials, such as ß-lactams, macrolides, fluoroquinolones, oxazolidinones, and streptogramins, are rapidly evolving as well.

Concurrent with these advances, however, has been the evolution of bacterial resistance mechanisms. In addition to MRSA, increased resistance is being identified among Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and a number of Gram-negative organisms.

In this article, we will review current practices in the management of CAP and examine ways to increase the effectiveness of diagnosis and therapy.


The microbiology of CAP varies with age and severity of disease. In addition, comorbidities and risk factors contribute to the variation among the potential pathogens.

A number of studies have found S pneumoniae to be the most frequently isolated organism in cases of CAP in which the offending pathogen was identified.4-9H influenzae and respiratory viruses are also common. Cases of CAP caused by atypical pathogens, such as Legionella species, Mycoplasma pneumoniae, and C pneumoniae, are frequent but varied. This variation may reflect differences in the population, location, and laboratory techniques used.

Table 1 lists 6 studies that examined causes of CAP in hospitalized patients.4-9 Five of these studies found the pathogens for outpatients and inpatients to be similar.4-7,9 In one ambulatory treatment series, in which serology alone was used to determine the cause among a relatively younger population without comorbidities, atypical pathogens accounted for nearly 50% of cases.10 In addition, various studies have estimated that the proportion of patients hospitalized for CAP who were infected with more than 1 pathogen ranged from 3% to almost 40%.6,11

The microbiology of severe CAP in patients admitted to the ICU is similar to that of non-ICU patients. S pneumoniae is the most frequently isolated pathogen, and it is increasingly common with advancing age. Two thirds of all cases of bacteremic pneumonia are caused by pneumococci, with an estimated mortality rate of 6% to 20%.

H influenzae and Gram-negative pathogens are also frequently isolated in cases of CAP.12 In patients with underlying diseases, such as COPD, Gram-negative infections tend to occur. Pseudomonas aeruginosa is rarely found in immunocompetent patients who do not have structural lung disease. Between 30% and 60% of cases do not yield an identifiable pathogen.13

Atypical pathogens, such as C pneumoniae and M pneumoniae, occur frequently among younger patients. Legionella species is most prevalent among 35- to 49-year-olds who have epidemiologic risk factors, including exposure to spas, recent travel and an overnight stay outside the home, renal or hepat- ic failure, diabetes, and systemic malignancy.14-16


The American Thoracic Society (ATS) published guidelines in 1993 and 2001 to assist the clinician in treating outpatients and inpatients with CAP and to provide criteria for stratifying patients according to severity of disease.17 The guidelines also list underlying risk factors for specific pathogens (Table 2) and contain treatment recommendations for all patient strata and indications for hospitalization.

The ATS guidelines emphasize the value of proper diagnostic assessment. However, because of the difficulty in identifying specific pathogens, the ATS recommends an initial empiric approach to therapy. Starting appropriate treatment should not be delayed, and the results of the initial workup should guide further management.

In 2000, the Infectious Diseases Society of America (IDSA) proposed guidelines that may lead to more efficient care of patients with CAP.18 The IDSA guidelines recommend an initial chest radiograph for all patients in whom CAP is suspected. The chest radiograph is particularly important in the assessment of hospitalized patients.

The main distinction between the ATS and IDSA guidelines is that the IDSA puts greater emphasis on establishing the cause of CAP. According to the IDSA, identifying the specific cause not only helps guide treatment but also provides data for following CAP patterns in a given community.

The IDSA guidelines call for diagnostic studies, including sputum Gram stain, which makes the approach more pathogen-directed. When the pathogen is unknown, empiric therapy should be based on 6 factors:

• Patient age.

• Severity of disease.

• Comorbidities.

• Clinical features.

• Previous antibiotic therapy.

• Epidemiology.

Patient stratification

The ATS guidelines describe the spectrum of etiologic agents and the initial approach to therapy using patient stratification.17 This approach separates patients into categories that are based on place of therapy (outpatient setting, hospital ward, or ICU), coexisting cardiopulmonary disease (COPD, CHF), and modifying factors (risk factors for drug-resistant S pneumoniae [DRSP] and P aeruginosa and other Gram-negative organisms). It is important to note that patients at risk for HIV infection are excluded from these patient categories.

This approach to the choice of empiric therapy takes into account the severity of illness (reflected in the location of therapy) and the presence of risk factors that may predispose the patients to specific pathogens.

• Outpatients with no cardiopulmonary disease and no modifying factors: The most common pathogens include S pneumoniae, M pneumoniae, C pneumoniae, and respiratory viruses. Other pathogens include Legionella species, Mycobacterium tuberculosis, and endemic fungi.

• Outpatients with cardiopulmonary disease and/or one or more modifying factors: The presence of comorbidities and risk factors changes the likely pathogens. Although pneumococcus remains the most common pathogen, the probability of DRSP and other pathogens is increased and should be considered when choosing antibiotics.

Pneumococcal resistance has increased to a point that is clinically significant in the following classes of antibiotics: ß-lactams (penicillins, cephalosporins, and carbapenems); macrolides (erythromycin, azithromycin, and clarithromycin); lincosamines (clindamycin); tetracyclines and folate inhibitors (trimethoprim-sulfamethoxazole); and fluoroquinolones. Current information about the effectiveness of treatment of patients with DRSP infection is mixed. Several studies suggest that systemic, nonmeningeal infections with DRSP strains respond well to usual doses of ß-lactam antibiotics.19,20 However, other studies have found that the use of ß-lactam antibiotics for such infections is associated with an increased likelihood of mortality, especially among the elderly and patients with underlying diseases.21,22

If the patient is from a nursing home and has bronchiectasis, the possibility of infection with a Gram-negative organism (such as Escherichia coli, Klebsiella species, or P aeruginosa)should be considered. If the patient has poor dentition, impaired consciousness, or a swallowing disorder, aspiration of anaerobes should be considered. Less common pathogens include M catarrhalis, Legionella species, Mycobacterium species, and endemic fungi.

• Inpatients not in the ICU: Hospitalized patients usually have risk factors for DRSP or enteric Gram-negative organisms, and they may have underlying cardiopulmonary disease; these factors influence the likely pathogens. These patients are at risk for infection with pneumococci (including DRSP), H influenzae, atypical pathogens, enteric Gram-negative organisms (such as Enterobacteriaceae), and polymicrobial bacterial flora (including anaerobes if risk of aspiration is present). The incidence of Gram-negative infection is generally not high for hospitalized patients with CAP, but it rises among patients admitted to the ICU.

The possibility of tuberculosis should be considered in patients who are from countries in which this disease is endemic, in alcoholic patients, and in nursing home residents.Endemic fungal infections are also possible in specific epidemiologic settings, such as coccidioidomycosis in the southwestern United States and histoplasmosis in the eastern United States.

In a hospitalized patient without cardiopulmonary disease or modifying risk factors, the most likely pathogens are S pneumoniae, H influenzae, M pneumoniae, C pneumoniae, respiratory viruses, and Legionella species. Up to 40% of hospitalized patients may have a polymicrobial infection (bacterial and atypical pathogens).

• ICU patients: The pathogens most frequently identified in patients with severe pneumonia are S pneumoniae (including DRSP), Legionella species, H influenzae, enteric Gram-negative bacilli, S aureus, M pneumoniae, respiratory viruses, and certain miscellaneous pathogens (such as C pneumoniae, M tuberculosis, and endemic fungi). P aeruginosa should be considered only when specific risk factors are present (Table 2). Risk factors for S aureus infection include diabetes, renal failure, and recent influenza virus infection.


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