Pneumonia

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23

Pneumonia

By any of several criteria, pneumonia (infection of the pulmonary parenchyma) must be considered one of the most important categories of disease affecting the respiratory system. First, pneumonia is extraordinarily common, accounting for nearly 10% of admissions to many large general hospitals. Overall, it has been estimated that more than 5 million cases of pneumonia occur each year in the United States. Second, pneumonia is a significant cause of death. More than 80,000 Americans die of bacterial pneumonia each year, making it the sixth most common cause of death overall and the leading cause of death from infection in the nation. It is no wonder that Sir William Osler referred to pneumonia as “the captain of the men of death,” particularly as he spoke before the era of effective antibiotic therapy. For many types of pneumonia, medical therapy with antibiotics (along with supportive care) has great impact on the duration and outcome of the illness. Because of the effectiveness of treatment, the diseases discussed in this chapter are typically gratifying to treat for all involved medical personnel. Unfortunately, the emerging trend during the past 20 years has been acquisition of antibiotic resistance by some of the organisms causing pneumonia, and treatment of pneumonia has had to evolve to keep pace.

Although many of the specific agents causing pneumonia are considered here, this chapter is organized primarily as a general discussion of the clinical problem of pneumonia. As appropriate, the focus on individual etiologic agents highlights some characteristic features of each that are particularly useful to the physician. Also covered is a commonly used categorization of pneumonia based on the clinical setting: community-acquired versus nosocomial (hospital-acquired) pneumonia. In current clinical practice, the approach to evaluation and management of these two types of pneumonia is often quite different.

The chapter concludes with a brief discussion of several infections that were uncommon or primarily of historical interest until September 11, 2001. After the terrorist attacks on the World Trade Center and the Pentagon, the threat of bioterrorism became a reality when spores of Bacillus anthracis sent through the mail resulted in cases of cutaneous and inhalational anthrax. In addition to reviewing inhalational anthrax, the chapter briefly describes two other organisms considered to be of concern as potential weapons of bioterrorism: Yersinia pestis (the cause of plague) and Francisella tularensis (the cause of tularemia).

Etiology and Pathogenesis

The host defenses of the lung are constantly challenged by a variety of organisms, including both viruses and bacteria (see Chapter 22). Viruses in particular are likely to avoid or overwhelm some of the upper respiratory tract defenses, causing a transient, relatively mild clinical illness with symptoms limited to the upper respiratory tract. When host defense mechanisms of the upper and lower respiratory tracts are overwhelmed, microorganisms may establish residence, proliferate, and cause a frank infectious process within the pulmonary parenchyma. With particularly virulent organisms, no major impairment of host defense mechanisms is needed; pneumonia may occur even in normal and otherwise healthy individuals. At the other extreme, if host defense mechanisms are quite impaired, microorganisms that are not particularly virulent and unlikely to cause disease in a healthy host may produce a life-threatening pneumonia.

In practice, several factors frequently cause enough impairment of host defenses to contribute to the development of pneumonia, even though individuals with such impairment are not considered “immunosuppressed.” Viral upper respiratory tract infections, ethanol abuse, cigarette smoking, heart failure, and preexisting chronic obstructive pulmonary disease (COPD) are a few of the contributing factors. More severe impairment of host defenses is caused by diseases associated with immunosuppression (e.g., advanced AIDS), various underlying malignancies (particularly leukemia and lymphoma), and use of corticosteroids and other immunosuppressive or cytotoxic drugs. In these cases associated with impairment of host defenses, individuals are susceptible to both bacterial and more unusual nonbacterial infections (see Chapters 24 to 26).

Common contributing factors for pneumonia in the immunocompetent host are:

Microorganisms, especially bacteria, find their way to the lower respiratory tract in two major ways. The first is by inhalation, whereby organisms are usually carried in small droplet particles inhaled into the tracheobronchial tree. The second is by aspiration, whereby secretions from the oropharynx pass through the larynx and into the tracheobronchial tree. Aspiration is usually thought of as a process occurring in individuals unable to protect their airways from secretions by glottic closure and coughing. Although clinically significant aspiration is more likely to occur in such individuals, everyone is subject to aspirating small amounts of oropharyngeal secretions, particularly during sleep. Defense mechanisms seem able to cope with this nightly onslaught of bacteria, and frequent bouts of aspiration pneumonia are not experienced.

Less commonly, bacteria reach the pulmonary parenchyma through the bloodstream rather than by the airways. This route is important for the spread of certain organisms, particularly Staphylococcus. When pneumonia results in this way from bacteremia, the implication is that a distant primary source of bacterial infection is present or that bacteria were introduced directly into the bloodstream (e.g., with intravenous drug abuse).

Many individual infectious agents are associated with development of pneumonia. The frequency with which each agent is involved is difficult to assess and depends to a large extent on the specific population studied. The largest single category of agents is probably bacteria. The other two major categories are viruses and Mycoplasma. Of the bacteria, the organism most frequently associated with pneumonia is Streptococcus pneumoniae, in common parlance often called pneumococcus. It has been estimated that in adults, approximately one-half of all pneumonias serious enough to require hospitalization are pneumococcal in origin.

Streptococcus pneumoniae (pneumococcus) is the most common cause of bacterial pneumonia. The polysaccharide capsule is an important factor in its virulence.

Bacteria

S. pneumoniae, a normal inhabitant of the oropharynx in a large proportion of adults, is a gram-positive coccus seen in pairs or diplococci. Pneumococcal pneumonia is commonly acquired in the community (i.e., in nonhospitalized patients) and frequently occurs following a viral upper respiratory tract infection. The organism has a polysaccharide capsule that interferes with phagocytosis and therefore is an important factor in its virulence. There are many antigenic types of capsular polysaccharide, and for host defense cells to phagocytize the organism, antibody against the particular capsular type must be present. Antibodies contributing in this way to the phagocytic process are called opsonins (see Chapter 22).

Staphylococcus aureus is another gram-positive coccus but usually appears in clusters when examined microscopically. Three major settings in which this organism is seen as a cause of pneumonia are (1) as a secondary complication of respiratory tract infection with the influenza virus; (2) in the hospitalized patient, who often has some impairment of host defense mechanisms and whose oropharynx has been colonized by Staphylococcus; and (3) as a complication of widespread dissemination of staphylococcal organisms through the bloodstream.

A variety of gram-negative organisms are potential causes of pneumonia, but only a few of the most important examples from this group of organisms are mentioned here. Haemophilus influenzae, a small coccobacillary gram-negative organism, is often found in the nasopharynx of normal individuals and in the lower airways of patients with COPD. It can cause pneumonia in children and adults, the latter often with underlying COPD as a predisposing factor. Klebsiella pneumoniae, a relatively large gram-negative rod normally found in the gastrointestinal tract, has been best described as a cause of pneumonia in the setting of underlying alcoholism. Pseudomonas aeruginosa, found in a variety of environmental sources (especially in the hospital environment), is seen primarily in patients who are debilitated, hospitalized, and often previously treated with antibiotics.

Factors predisposing to oropharyngeal colonization and pneumonia with gram-negative organisms are:

The bacterial flora normally present in the mouth are potential etiologic agents in the development of pneumonia. A multitude of organisms (both gram-positive and gram-negative) that favor or require anaerobic conditions for growth are the major organisms comprising mouth flora. The most common predisposing factor for anaerobic pneumonia is aspiration of secretions from the oropharynx into the tracheobronchial tree. Patients with impaired consciousness (e.g., as a result of coma, alcohol or drug ingestion, or seizures) and those with difficulty swallowing (e.g., as a result of stroke or diseases causing muscle weakness) are prone to aspirate and are at risk for pneumonia caused by anaerobic or mixed mouth organisms. In addition, patients with poor dentition or gum disease are more likely to develop aspiration pneumonia because of the larger burden of organisms in their oral cavity.

Anaerobes normally found in the oropharynx are the usual cause of aspiration pneumonia.

In some settings such as prolonged hospitalization or recent use of antibiotics, the type of bacteria residing in the oropharynx may change. Specifically, aerobic gram-negative bacilli and S. aureus are more likely to colonize the oropharynx, and any subsequent pneumonia resulting from aspiration of oropharyngeal contents may include these aerobic organisms as part of the process.

The two final types of bacteria mentioned here are more recent additions to the list of etiologic agents. The first of these organisms, Legionella pneumophila, was identified as the cause of a mysterious outbreak of pneumonia in 1976 affecting American Legion members at a convention in Philadelphia. Since then it has been recognized as an important cause of pneumonia occurring in epidemics as well as in isolated sporadic cases and seems to affect both previously healthy individuals and those with prior impairment of respiratory defense mechanisms. Retrospectively, several prior outbreaks of unexplained pneumonia have been shown to be due to this organism. Although the organism is a gram-negative bacillus, it stains very poorly and is generally not seen by conventional staining methods.

The other organism, Chlamydophila pneumoniae, has been recognized in epidemiologic studies as the cause of approximately 5% to 10% of cases of pneumonia. It is an obligate intracellular parasite that appears more related to gram-negative bacteria than to viruses, the category in which it previously had been placed. Diagnosis is rarely made clinically because of the lack of distinguishing clinical and radiographic features, and the organism is not readily cultured. As a result, serologic studies serve as the primary means of diagnosis, although they are infrequently obtained.

Many other types of bacteria can cause pneumonia. Because all of them cannot be covered in this chapter, the interested reader should consult some of the more detailed publications listed in the references at the end of this chapter.

Viruses

Although viruses are extremely common causes of upper respiratory tract infections, they are diagnosed relatively infrequently as a cause of frank pneumonia, except in children. In adults, influenza virus is the most commonly diagnosed agent. The 2010 H1N1 influenza pandemic fortunately caused fewer deaths than originally anticipated and raised the profile of best practices for prevention, diagnosis, and treatment of this virus.

Outbreaks of pneumonia caused by adenovirus also are well described, particularly among military recruits. A relatively rare cause of a fulminant and often lethal pneumonia was described in the southwest United States, but cases in other locations have also been recognized. Hantavirus, the virus responsible for this pneumonia, is found in rodents and was previously described as a cause of fever, hemorrhage, and acute renal failure in other parts of the world.

An outbreak of a novel, highly contagious, and highly lethal pneumonia was reported in 2003 in East Asia and Canada. The outbreak, termed severe acute respiratory syndrome (SARS), was attributed to a novel coronavirus that may have evolved from a type normally found in the civet (a weasel-like mammal found in Chinese markets).

Mycoplasma

Mycoplasma appears to be a class of organisms intermediate between viruses and bacteria. Unlike bacteria, they have no rigid cell wall. Unlike viruses, they do not require the intracellular machinery of a host cell to replicate and are capable of free-living growth. Similar in size to large viruses, mycoplasmas are the smallest free-living organisms that have yet been identified. These organisms are now recognized as a common cause of pneumonia, perhaps responsible for a minimum of 10% to 20% of all cases. Mycoplasmal pneumonia occurs most frequently in young adults but is not limited to this age group. The pneumonia is generally acquired in the community—that is, by previously healthy, nonhospitalized individuals—and may occur in either isolated cases or localized outbreaks.

Mycoplasma, the smallest known free-living organism, is a frequent cause of pneumonia in young adults.

Pathology

The pathologic process common to all pneumonias is infection and inflammation of the distal pulmonary parenchyma. An influx of polymorphonuclear leukocytes (PMNs), edema fluid, erythrocytes, mononuclear cells, and fibrin is seen to a variable extent in all cases. Bacterial pneumonias in particular are characterized by an exuberant outpouring of PMNs into alveolar spaces as they attempt to limit proliferation of the invading bacteria.

Individual types of pneumonia may differ in exact location and mode of spread of the infection. In the past, a distinction was often made between pneumonias that follow a “lobar” distribution, those that behave more like a “bronchopneumonia,” and those with the pattern of an “interstitial pneumonia.” However, these distinctions are often difficult to make because individual cases of pneumonia frequently do not adhere to any one particular pattern but have mixtures of the three patterns in varying proportions. Given this limitation, a brief mention of the three major types follows.

Lobar Pneumonia.Lobar pneumonia has classically been described as a process not limited to segmental boundaries but rather tending to spread throughout an entire lobe of the lung. Spread of the infection is believed to occur from alveolus to alveolus and from acinus to acinus through interalveolar pores known as the pores of Kohn. The classic example of a lobar pneumonia is that due to S. pneumoniae, although many cases of pneumonia documented as being due to pneumococcus do not necessarily follow this typical pattern.

Bronchopneumonia.In bronchopneumonia, distal airway inflammation is prominent along with alveolar disease, and spread of the infection and the inflammatory process tends to occur through airways rather than through adjacent alveoli and acini. Whereas lobar pneumonias appear as dense consolidations involving part or all of a lobe, bronchopneumonias are more patchy in distribution, depending on where spread by airways has occurred. Many bacteria, such as staphylococci and a variety of gram-negative bacilli, may produce this patchy pattern.

Interstitial Pneumonia.In some cases of pneumonia, the organisms are not highly destructive to lung tissue even though an exuberant inflammatory process may be seen. Pneumococcal pneumonia classically (although not always) behaves in this way, and the healing process is associated with restoration of relatively normal parenchymal architecture. In other cases, when the organisms are more destructive, tissue necrosis may occur, with resulting cavity formation or scarring of the parenchyma. Many cases of staphylococcal and anaerobic pneumonias follow this more destructive course.

Interstitial pneumonias are characterized by an inflammatory process within the interstitial walls rather than alveolar spaces. Although viral pneumonias classically start as interstitial pneumonias, severe cases generally show extension of the inflammatory process to alveolar spaces as well.

Pathophysiology

Infections of the pulmonary parenchyma produce their clinical sequelae not only by altering the normal functioning of the lung parenchyma but also by inducing a more generalized systemic response to invading microorganisms. The major pathophysiologic consequence of inflammation and infection involving the distal air spaces is decreased ventilation to affected areas. If perfusion is relatively maintained, as it often is because of the vasodilatory effects of inflammatory mediators, ventilation-perfusion mismatch results, with low ventilation-perfusion ratios in diseased regions. When alveoli are totally filled with inflammatory exudate, there may be no ventilation to these regions, and extreme ventilation-perfusion inequality (i.e., shunt) results.

Pneumonia commonly results in ventilation-perfusion mismatch (with or without shunting) and hypoxemia.

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