Chapter 24 Community-Acquired Pneumonia
Pneumonia and influenza remain common causes of death in the United States (ranked 7th) and globally (ranked 6th). More than 60,000 deaths were attributed to pneumonia in 2005 in the United States. In Europe, the incidence of lower respiratory tract infections reached 25.8 million in 2002, yielding only to diarrheal illness as a most common disease. The mean length of hospital stay for pneumonia exceeds 5 days, and readmission rate within 30 days after hospital discharge approaches 20%. The overall economic health care system burden associated with community-acquired pneumonia (CAP) is approximately $40 billion annually in the United States and reaches 10 billion in Europe. According to British Thoracic Society guidelines, age-standardized rate of hospital admissions due to CAP rose by 34% from 1997 to 2004. CAP also is the most common cause of severe sepsis. Admission to the intensive care unit (ICU) is required in up to 20% of cases of CAP. Because the incidence of pneumonia is substantially higher among elderly persons, it is anticipated that in view of the aging population, the incidence and health care burden of pneumonia will only increase. In the United States, approximately 4.2 million outpatient clinic visits for pneumonia were recorded for 2006, and this number has been increasing ever since. At the same time, despite introduction of novel antimicrobials, imaging modalities, and biomarker testing, mortality attributable to CAP has not changed significantly since the introduction of penicillin.
The clinical presentation and diagnosis of CAP are complex. Presence of classic symptoms such as fever, generalized fatigue, cough, sputum production, dyspnea, pleuritic chest pain, and hemoptysis is highly variable, and ranges from nearly 90% for cough to less than 15% for hemoptysis. Many factors influence the clinical presentation of CAP, including the patient’s age, comorbid conditions, and lifestyle factors, as well as the causative microbe. Presence of certain symptoms, as discussed further on, may help identify the offending organism. However, the significant variability in the clinical presentation of CAP makes it virtually impossible to diagnose the disease, let alone the causative agent, from the clinical presentation alone, and further diagnostic tests are usually needed.
Probability of an atypical presentation, in which the classic symptoms are lacking, increases with patient age and number of comorbid conditions. In general, any compromise of the patient’s immune system can lead to silencing of clinical symptoms despite rapidly progressive underlying infection. Absence of fever and cough is common in the elderly population; rather, altered mental status, generalized malaise, tachypnea, and tachycardia are often the only manifestations of pneumonia in this population. Such atypical clinical presentations can delay the correct diagnosis and treatment by several days, which probably leads to increased mortality.
The major causes of pneumonia have been divided into the typical organisms, such as Streptococcus pneumoniae, Haemophilus influenzae, and Klebsiella pneumoniae, and the atypical pathogens, such as Mycoplasma pneumoniae, Chlamydophila spp., Coxiella burnetii, and viruses. Historical descriptions of differences in clinical presentation between these two groups of pathogens have been widely used and still are commonly regarded as important. CAP caused by the typical organisms has been characterized as of more acute onset, with manifestations including fever with intense chills, along with cough, usually productive of purulent or bloody sputum and occasionally associated with pleuritic chest pain. Findings suggestive of pulmonary consolidation (such as dullness to percussion, rales, bronchial breathing) also were thought to be part of the typical presentation, as well as leukocytosis with neutrophil predominance and occasionally presence of circulating immature leukocytes (bands).
By contrast, pneumonia caused by “atypical” pathogens has been described as being of more gradual onset, with lower body temperature, nonproductive cough, and white blood cell counts in the normal to high-normal range. Systemic manifestations such as generalized malaise and muscle aches can dominate the clinical picture.
Unfortunately, studies have failed to demonstrate the accuracy of such purported differences in clinical presentation of CAP in distinguishing between the typical and atypical pathogens. Accordingly, this distinction should not be relied on to make an etiologic diagnosis or decisions about antibiotic treatment.
Increased age favors infection with S. pneumoniae, group B streptococci, Moraxella catarrhalis, H. influenzae, gram-negative bacilli, and Chlamydophila pneumoniae. Aspiration pneumonia risk increases with age as well as risk for pneumonia due to multiple organisms. It seems that an apparent decrease in frequency of Legionella infection has been noted among persons older than 80 years. Every year over 65 increases the risk for pneumonia. The annual incidence of CAP in noninstitutionalized elderly people is estimated to be 25 to 44 per 1000, compared with 4.7 to 11.6 per 1000 in the general population. The risk of infection severe enough to necessitate hospital admission also increases markedly with age, ranging from 1.6 per 1000 adults 55 to 64 years of age to 11.6 per 1000 after age 75. Age is one of the main predictive factors for mortality associated with CAP. The death rate for pneumonia or influenza has been evaluated at 9 per 100,000 in the elderly population, rising to 217 per 100,000 among patients with one risk factor and to 979 per 100,000 among those with more than one.
Alcohol consumption may potentially lead to impaired level of consciousness, predisposing the drinker to aspiration pneumonia by impairing the cough reflexes, with alterations in the mechanisms of swallowing and mucociliary clearance. Owing to the immunosuppressive effects and impairment of innate lung defenses attributable to high alcohol intake, heavy drinking increases the risk of infection with gram-negative organisms. Alcohol impairs the function of lymphocytes, neutrophils, monocytes, and alveolar macrophages. Each of these factors contributes to the reduced bacterial clearance from the airways in these patients. Whether alcoholism predisposes to increased pneumonia severity in general is controversial; however, S. pneumoniae infections tend to be more severe in alcoholic patients. Also, infections caused by gram-negative bacilli and L. pneumophila occur more frequently in heavy drinkers.
Airway colonization is common in patients with chronic obstructive pulmonary disease (COPD), as is impairment of innate lung defense mechanisms. Patients with COPD appear to be at increased risk for CAP, and pathogens such as H. influenzae and M. catarrhalis become more prevalent. Very pronounced decrease in forced expiratory volume in 1 second (FEV1), along with bronchiectasis, predisposes affected patients to infection with Pseudomonas aeruginosa. Invasive aspergillosis has been described as an often fatal complication of high-dose corticosteroid treatment of exacerbations of COPD in patients with severely compromised lung function. Conditions leading to altered level of consciousness (narcotic use, alcohol consumption, cerebrovascular disease, dementia), poor dental hygiene, history of head and neck surgery affecting swallowing mechanisms, and upper gastrointestinal tract disease all are predisposing factors for development of aspiration pneumonia. Usual culprit organisms include anaerobes and members of the oral and enteric flora.
Patients with a compromised immune system are at increased risk for development of CAP. The list of possible pathogens is long and only increases with worsening degree of immunodeficiency. Immunosuppression achieved with medications predisposes to infections with otherwise rare pathogens such as Pneumocystis jiroveci, Mycobacterium avium complex, Histoplasma spp., Coccidioides spp., Cryptococcus neoformans, Mucoraceae spp., and Toxoplasma, to name a few. Some examples of comorbid conditions leading to an immunocompromised state are chronic liver disease, heart failure, cancer, diabetes, lymphoproliferative disease, human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), and immunoglobulin deficiencies. Malnutrition, which frequently accompanies such conditions, also leads to alterations in cellular immunity and decreased levels of secretory immunoglobulin A (IgA), increasing the chance of airway colonization and/or infection with gram-negative bacilli.
Geographic location and professional history also seem to play a role in susceptibility to CAP. Occupations associated with exposure to dusts, fumes, and various chemicals (such as construction work, painting, and mining, to name a few) increase the risk of acquiring CAP in general, with S. pneumoniae being the most likely pathogen. Exposure to contaminated water supply and cooling towers of air-conditioning units increases the chance of acquiring Legionnaire’s disease. Legionella organisms thrive in warm water, and could then be spread in water mist. Contact with animals may lead to pneumonia due to Yersinia pestis (plague, for which rodents constitute a natural reservoir), Francisella tularensis (tularemia, with rabbits, voles, and muskrats as carriers), C. burnetii (Q fever, transmitted by sheep, dogs, and cats), Rhodococcus (present in horses) or Chlamydophila psittaci (psittacosis, transmitted by birds).
Both the frequency and the severity of pneumonia increase in institutionalized patients. Oropharyngeal colonization by gram-negative bacilli or S. aureus plays a major role here. Epidemics of viral infections also are frequent in this patient population. The main microorganisms isolated in cases of pneumonia diagnosed in institutional environments are, in order of decreasing frequency, S. pneumoniae, S. aureus, gram-negative bacilli, and H. influenzae.
Susceptibility to infection is increased by a number of malnutrition-related phenomena, such as a decreased level of secretory IgA, a failure of macrophage recruitment, and alterations in cellular immunity. As a result, the frequency of respiratory tract colonization by gram-negative bacilli is increased in patients with malnutrition and the incidence and severity of respiratory infections are increased. Malnutrition acts in association with other comorbid conditions frequently found in patients with pneumonia, such as alcohol consumption, COPD, chronic respiratory failure, and neurologic disease.
Smoking alters mucociliary transport, humoral and cellular defenses, and epithelial cell function and increases adhesion of S. pneumoniae and H. influenzae to the oropharyngeal epithelium. Also, smoking predisposes to infection by influenza viruses, L. pneumophila, and S. pneumoniae. Smoking itself, however, is not a risk factor for pneumonia severity.
Clinical presentation of CAP can be rather nonspecific, especially in elderly and debilitated persons. Risk factors for specific causative agents, such as history of recent travel into endemic areas, is an important part of the clinical history in a patient with suspected CAP. Because of the inaccuracy of a purely clinical diagnosis, additional investigations are required to confirm the diagnosis, identify the causative pathogen, and initiate appropriate treatment. These are discussed in Chapter 23. Table 24-1 summarizes the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) recommendations of tests proven to be useful in different settings for investigating and treating CAP.
S. pneumoniae is the most common bacterium isolated from patients with CAP. It is a saprophyte of the respiratory tract, which can easily proliferate as soon as natural defenses decline (as with increasing age, alcoholism, diabetes, smoking, or immunosuppression). In the classic presentation, the onset of pneumococcal pneumonia is abrupt, characterized by intense and prolonged chills and considerable pleuritic chest pain. Symptoms and signs are rapidly progressive, with high fever (core body temperature close to 40° C [104° F]), tachycardia, and tachypnea; cough is common, as are oliguria and cyanosis. At this stage, a nasolabial herpes simplex lesion may develop, crackles are heard, and chest radiographs show homogeneous lobar or segmental consolidation. Without antibiotic treatment, cough persists, with eventual production of rust-colored sputum. Leukocytosis is frequent, and blood cultures are positive in 10% to 20% of patients if specimens are obtained before antibiotic therapy. Arterial blood gas analysis reveals decreases in PaO2 and PaCO2. Recrudescence of symptoms may occur after a few days; then the fever resolves and an abundant diuresis ensues. Radiologic and physical signs characteristically regress rapidly and considerably. The rapid rate of multiplication of S. pneumoniae, together with the high risk for secondary complications (e.g., empyema, meningitis, septicemia), makes any case of S. pneumoniae pneumonia a medical emergency.
Streptococcal species other than S. pneumoniae rarely cause pneumonia, but among these, S. pyogenes most often is involved, more in the young than in the elderly. Pneumonia caused by S. pyogenes occurs after viral infections such as measles, varicella, or rubella in infants and after influenza, measles, or varicella in adults. The clinical presentation is that of typical pneumonia. Pleural effusion and empyema frequently develop, and other complications include pneumothorax, pericarditis, mediastinitis, and bronchopleural fistula.
The severity of Staphylococcus infection is due to the prevalence of its resistance to multiple antibiotics and to lung tissue lysis as part of the infection, leading to formation of bullae and their subsequent rupture into the pleura (pneumothorax, pneumopyothorax), with consequent serious ventilatory defects and septicemia. Staphylococcal infection is acquired by inhalation or aspiration through the airways or occurs by hematogenous spread. Airborne contamination may follow a viral infection such as influenza or measles, or it may be linked to comorbidity (COPD, carcinoma, laryngectomy, seizure); hematogenous spread is the result of bacteremia (endocarditis, infective foci with discharge into the bloodstream). Direct bloodstream infection caused by intravenous drug abuse is the most common cause in many inner-city hospital emergency departments. The clinical presentation may be unusual compared with typical pneumonia when the infection develops through vascular dissemination (e.g., dyspnea, cough, and purulent sputum might be masked by symptoms of endocarditis or the primary infective focus) or when the infection is causing a pleural effusion, empyema, or lung abscess. The chest radiograph may show two possible features: central or segmental consolidation secondary to aspiration or multiple infiltrates that are generally nodular early on and can subsequently progress to parenchymal consolidation with or without cavitation after vascular spread of the infection. Abscess, pleural effusion, and empyema are frequent, as well as septicemia. Overall outcome depends on associated diseases, spread of infection, and resistance of Staphylococcus to antibiotics.
Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent infectious agent associated with skin and soft tissue infections in the community setting. Community-acquired MRSA also can cause severe pulmonary infections, including necrotizing pneumonia and empyema. It is more virulent than health care–associated MRSA isolates. Community-acquired MRSA usually contains the gene encoding Panton-Valentine leukocidin and the SCCmec type IV element and belongs to the USA300 pulsed-field gel electrophoretic pattern. Panton-Valentine leukocidin is a toxin that creates lytic pores in the cell membranes of neutrophils and induces the release of neutrophil factors that promote inflammation and tissue destruction. Community-acquired MRSA typically is more susceptible to a wider class of antibiotics than those with activity against health care–associated MRSA. The optimal antibiotic treatment for Panton-Valentine leukocidin-positive community-acquired MRSA infection is unknown; however, antibiotics with activity against MRSA and the ability to inhibit toxin production may be optimal (linezolid or clindamycin for susceptible isolates).
Most invasive infections due to H. influenzae result from encapsulated, typable strains rather than from nonencapsulated, nontypable strains. An exception is in patients with COPD, in whom the nontypable strains often are the etiologic agents of pneumonia and occasionally even cause an associated bacteremia. A history of upper respiratory tract infection is common. Small pleural effusions can occur, but empyema and cavitation are rare.
Mycoplasma pneumoniae pneumonias usually occur in small epidemics, particularly in closed populations. The clinical presentation commonly is that of an atypical pneumonia, as described earlier. M. pneumoniae infections mimic, to some extent, the presentation of viral respiratory infections, but the incubation period is longer (10 to 20 days) than for viruses, and the fever generally is of mild to moderate severity, with core body temperature below 39° C (102.2° F). Within a few days, most symptoms subside, although the low-grade fever and cough frequently persist. A history of a preceding upper respiratory tract infection may be found in up to 50% of patients. A variety of extrapulmonary manifestations may be encountered, including arthralgia, cervical lymphadenopathy, bullous myringitis, diarrhea, immune hemolytic anemia, meningitis, meningoencephalitis, myalgia, myocarditis, hepatitis, nausea, pericarditis, skin eruptions, and vomiting. Diffuse crackles occasionally are heard. Infiltrates usually are localized in the lower lobes and regress very slowly over 4 to 6 weeks. Pleural effusions and mediastinal lymphadenopathy are rare.
Psittacosis is a pneumonia caused by an intracellular bacterium, Chlamydia psittaci, which is responsible for ornithosis in domestic fowl. C. psittaci can be transmitted to humans by inhalation from infected birds, including canaries, parakeets, parrots, pigeons, and turkeys. The clinical presentation is that of an atypical pneumonia. After a 7- to 14-day incubation period, the onset may be abrupt. Fever with temperatures of 38° to 40° C (100.4° to 104.0° F), possibly with chills, is associated with arthralgia, headache, myalgia, dyspnea, and thoracic pain. Cough may be severe, and sputum, if any, usually is mucoid. Splenomegaly and a macular rash are evocative of psittacosis. The radiographic appearance is variable but typically includes lower lobe infiltration. Hepatitis, phlebitis, encephalitis, myocarditis, renal failure, and intravascular coagulation are unusual complications. Despite the efficiency of antibiotics such as tetracycline and erythromycin, psittacosis is associated with a mortality rate of approximately 1%. Relapse is prevented by continuing treatment for 2 weeks after return to a normal temperature.
Previously known as the TWAR (Taiwan acute respiratory) agent, Chlamydia pneumoniae has been recognized as a pathogen responsible for pneumonia since 1985. The incidence of pneumonia caused by C. pneumoniae is uncertain because of the lack of reliable diagnostic tests. However, it does appear to be an important cause of pneumonia in all age groups. The clinical presentation is that of an atypical pneumonia in young adults; in elderly persons, the course may be severe, particularly if comorbid conditions are present. Sore throat may precede the onset of fever (with temperatures in the range of 37.7° to 39° C [100° to 102.2° F]) and a nonproductive cough. The chest radiograph shows subsegmental infiltrates, which usually clear over 2 to 4 weeks.
Legionella organisms are aerobic gram-negative intracellular bacilli; approximately 30 species have been identified, the most common being L. pneumophila. Water- and air-conditioning systems are their natural reservoirs; spread of the bacilli occurs by air, but no transmission between human beings has been reported. L. pneumophila infection may cause an asymptomatic seroconversion, a single episode of pyrexia, and mild to severe pneumonia. The nonpneumonic illness is known as Pontiac fever and is associated with fever, chills, headache, and upper respiratory tract symptoms. Pneumonia occurs either sporadically or in small epidemics and is more likely to occur in immunocompromised persons. After 2 to 8 days of incubation, headache, myalgia, high fever, and chills precede pneumonia by a few days. Initially, there is a nonproductive cough that may become productive of watery or even purulent sputum. Dyspnea, hemoptysis, and chest pain are frequent manifestations. Extrapulmonary symptoms and signs are numerous and include abdominal pain, agitation, watery diarrhea, arthralgia, confusion, skin rash, headache, hematuria, hyponatremia, hypophosphatemia, myalgia, nausea, oliguria, proteinuria, renal failure, seizures, splenomegaly, and vomiting. Leukocytosis, neutropenia, lymphopenia, and hepatic inflammation may be observed. The chest radiograph shows consolidation, often unilateral and dense, initially localized and then spreading gradually. Pleural effusion frequently is present; cavitation is rare. The outcome depends on the early clinical recognition and treatment and on comorbid conditions. Mortality is increased in immunosuppressed patients and in those who have complications of the infection.
Gram-negative bacilli include various members of the families Enterobacteriaceae and Pseudomonadaceae, in particular K. pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. Gram-negative bacilli are more often responsible for nosocomial pneumonia than for CAP. CAP attributable to these agents may result from their colonization of the oropharynx, followed by inhalation or microaspiration of the organisms; however, most of these patients meet criteria for health care–associated pneumonia, such as residence in long-term care facilities. Comorbidity is usual in patients who acquire these pneumonias. The clinical presentation is that of a typical pneumonia. The prognosis is poor, particularly in cases featuring immunodepression, alcoholism, neutropenia, and old age.