Clinical Presentation

Patients with CAP typically present with cough (90%), dyspnea (66%), sputum production (66%), and pleuritic chest pain (50%). Nonrespiratory symptoms such as malaise, headache, nausea, myalgias, arthralgias, abdominal pain, and mental confusion are seen in 10% to 30% of patients. Elderly patients often have fewer or less severe symptoms than younger patients do. Presenting signs on physical examination include fever (80%), tachypnea, tachycardia, and a generalized toxic state. Crackles on auscultation are common (80%), with indications of consolidation in up to 30% of patients.¹³

Evaluation with chest radiography should be undertaken in all patients who present with symptoms and signs suggestive of pneumonia.¹⁴ Standard posterior-anterior and lateral films classically reveal a segmental (Fig. 12-1) or lobar infiltrate, often with evidence of a parapneumonic effusion. Chest films also will help distinguish pneumonia from other disorders that may present with similar symptoms and can help assess the severity (e.g., multilobar involvement) of the illness. Contributing or causative factors, such as bronchial obstruction, lung abscess, and tuberculosis, can also be seen. The addition of computed tomography may occasionally be helpful in difficult cases, but there are few data to support its routine use in the initial evaluation of patients with CAP.

Figure 12–1 Posteroanterior (A) and lateral (B) chest radiographs demonstrating segmental pneumonia involving the superior segment of the left lower lobe.

Routine laboratory studies in ambulatory patients are rarely necessary but may occasionally steer the clinician toward hospital admission in equivocal cases. Laboratory studies in hospitalized patients should include complete blood count, electrolyte values and glucose concentration, renal and liver function tests, and assessment of oxygen saturation. Patients aged 15 to 54 years should undergo testing for human immunodeficiency virus (HIV) infection with informed consent.¹⁴ Tests used to identify an etiologic agent (including blood cultures and sputum Gram stain and culture) should be performed for all patients admitted with pneumonia, although some have questioned the utility of blood cultures in low-risk patients.¹⁵ Viral cultures have not been shown to be useful in the initial evaluation of patients with CAP and should not be routinely performed,¹⁶ although some improvement in the diagnostic yield has been demonstrated with real-time polymerase chain reaction analysis.¹⁷ Every attempt should be made to obtain these culture specimens before initiation of therapy, but not at the expense of unnecessary delays in treatment. Culture data should be correlated with the Gram stain result before narrowing antibiotic therapy. Significant pleural effusions should be tapped and sent for laboratory and culture studies. Routine serologic and cold agglutinin testing is generally not recommended in the initial evaluation of patients with CAP,³ but it may prove useful in select cases. This recommendation is based on the low failure rate seen with empiric therapy for patients treated in the outpatient setting. A pneumococcal urinary antigen assay recently approved by the Food and Drug Administration may be used to augment the standard diagnostic methods,^18–20 with the advantage of rapid results similar to the Gram stain. Sensitivity and specificity rates of 80% to 90% have been reported. Use of similar technology to detect pneumococcal antigen in sputum has also been reported.²¹

Patients with pneumonia due to Mycoplasma species often present with signs and symptoms reminiscent of a mild viral illness, with a more gradual onset and less intense nature. These infections, like other “atypical” infections, occur more frequently in younger patients. Headache, malaise, sore throat, low-grade fever, and rhinorrhea are common. Cough, when it is present, is frequently nonproductive and spasmodic in character. Extrapulmonary manifestations may predominate, with rash, arthralgias, and neurologic abnormalities present. The physical examination of the chest may yield minimal findings, although a wheeze and crackles can sometimes be appreciated. Radiologic findings include nodular or peribronchial infiltrates, an interstitial pattern of disease (Fig. 12-2), and occasional consolidation. Pleural effusions occur frequently. Although the white cell count is often normal, hemolytic anemia can be associated with a positive Coombs test result. Serologic diagnosis may be obtained through measurement of IgM or IgG titer by a complement fixation test.

Figure 12–2 Posteroanterior chest radiograph demonstrating a fine interstitial pattern due to Mycoplasma pneumonia.

Pneumonia due to Legionella (Legionella pneumophila) remains problematic since the initial recognized outbreak of the disease at an American Legion convention in Philadelphia in 1976. The organism is identified in 1% to 5% of patients hospitalized with pneumonia, with considerable variations in detection because of geographic patterns and difficulties in accurate diagnosis. Culture may still be the best way of identifying Legionella, along with a urinary antigen assay.²² However, the urinary antigen assay can remain positive months after the acute infection. Symptoms suggestive of pneumonia predominate (high fever, chills, dyspnea, cough), but extrapulmonary manifestations (gastrointestinal complaints, malaise, myalgias) are not uncommon. Radiographs usually reveal either patchy or diffuse interstitial infiltrates and occasionally consolidation (Fig. 12-3).

Figure 12–3 Posteroanterior (A) and lateral (B) chest radiographs demonstrating diffuse infiltrates with cavitation due to Legionella infection.

Pulmonary infection with Chlamydia organisms such as C. pneumoniae presents in similar fashion to other atypical pneumonias. Infection with this organism has also been associated with chronic diseases such as atherosclerotic coronary disease. Diagnostic tests used to identify this organism include direct tissue culture (sputum smear and culture are not helpful) and display of a fourfold increase in IgG titer or an IgM titer of 1:16 or higher by a microimmunofluorescence test.

Determination of Severity

One of the key decisions made in the initial evaluation of CAP, beyond establishing a presumptive diagnosis, pertains to the need for inpatient therapy. Many of the patients afflicted with CAP are elderly with significant comorbidities, for whom the progressive pulmonary infection is clearly life-threatening. On the other hand, improper admission for CAP therapy taxes the health-care system billions of dollars annually, as noted before. In the United States, less than 20% of patients with CAP are admitted for inpatient therapy but account for more than 90% of the costs related to the disease treatment.⁵ As a result, various guidelines have been developed to assist clinicians in the assessment of severity of illness at presentation. One such system, the Pneumonia Severity Index (PSI), was validated with data from almost 2300 patients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study.²³ On the basis of clinical parameters obtained at initial presentation, a risk score or class is determined (Fig. 12-4). Patients with a risk class of I to III had a low mortality rate (<1%) and were thought to be at low risk, thus amenable to outpatient management. Patients with a risk class of IV or V had higher mortality rates (9.3 and 27.0, respectfully) and were thought to be appropriate candidates for hospitalization. The value of the PSI has since been confirmed in multiple studies,^24–29 and it is endorsed within the guidelines set forth by the American Thoracic Society/Infectious Diseases Society of America.³ These guidelines emphasize a multistep process in determining the initial site of treatment based on (1) assessment of factors that compromise the safety of home care, (2) PSI score, and (3) clinical judgment. The PSI has been criticized, though, because of the relative complexity of the assessment required.

Figure 12–4 The Pneumonia Severity Index.

(Modified from Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia.)

In contrast, the British Thoracic Society has adopted an alternative prediction rule for risk stratification in the setting of CAP, termed CURB-65.³⁰ The CURB-65 uses five prognostic variables: confusion; blood urea nitrogen concentration (>20 mg/dL); respiratory rate (>30 breaths per minute); low blood pressure (systolic, <90 mm Hg; diastolic, <60 mm Hg); and age older than 65 years. Patients with scores of 0 or 1 were thought to be appropriate for outpatient care; those with scores of 2 or 3 should be considered for admission, perhaps to the ICU; and scores of 4 or 5 mandated ICU care. A simplified version of CURB-65, termed CRB-65, drops the blood urea nitrogen measurement and thus is applicable to the outpatient office setting.³¹

The PSI and the CURB-65 have been compared in a variety of studies,^24,32,33 and both have been found to have strengths and weaknesses. The PSI is particularly good at identifying patients with a low risk of mortality but tends to underestimate severity of illness in some populations of patients. Alternatively, the CURB-65 more accurately identifies those patients with severe CAP and at high risk of death. It has been proposed that the two assessment tools may be thought of as complementary rather than competitive tests.³⁴

Treatment

The treatment of CAP at initial presentation is outlined in Figure 12-5, as described by the American Thoracic Society/Infectious Diseases Society of America, stratified by the presence or absence of modifying factors, comorbidities, and site of initial treatment.³ Data from published reports support the use of the guidelines, leading to better outcomes.^10,35–37 The timing of therapy is important, with the first dose of antibiotic given 4 to 8 hours after initial presentation. Prompt administration of therapy has been associated with improved survival.³⁸ The use of the guidelines facilitates prompt delivery of appropriate therapy. Further, although it is desirable to narrow the spectrum of administered antibiotic agents, this is not possible in up to 50% of cases because of a lack of an identifiable organism. In addition, a significant proportion of cases represent mixed polymicrobial infections. The use of these guidelines employing broad-spectrum therapy allows appropriate treatment in these patients.

Figure 12–5 Empiric therapy for community-acquired pneumonia.

(Modified from Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults; and Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults.)

Clinical decisions about duration of therapy are poorly supported in the literature. In general, most treatment regimens last 7 to 14 days; the severity of the presenting illness, the response to therapy, and the underlying comorbidities should all be considered in addressing duration of treatment. Most bacterial infections, including those due to S. pneumoniae, are treated for 7 to 10 days, provided a good clinical response is seen. Mycoplasma, Chlamydia, and Legionella infections should be treated for 10 to 14 days and perhaps longer if significant comorbidity exists.

Successful response to therapy in a patient with CAP usually follows a predictable course. Stabilization of clinical parameters often occurs by 72 hours, with gradual improvement noted thereafter. The severity of the presenting illness and the underlying disease understandably play a role in the response to therapy. The febrile response and leukocytosis typically resolve by day 4 to 5, with the radiologic findings lagging behind. In fact, the initial radiographic abnormalities may actually worsen before improvement is documented. Only 15% of chest films are clear at discharge, and many take 2 to 3 months to return to normal. With a successful response to treatment, consideration should be given to conversion to oral therapy. The American Thoracic Society describes four criteria that should be met before switching to oral therapy: improvement in cough and dyspnea; afebrile (<100°F) at two consecutive assessments 8 hours apart; resolving leukocytosis; and a functioning gastrointestinal tract with oral intake.⁴ Obviously, some leeway may be allowed in these criteria, given the clinical situation. Compliance can be an issue with oral therapy, and drug dosing schedules and side effects should be taken into account in selecting an oral regimen.³⁹

Two adjunctive therapies have been recently studied for their effects on outcome in patients with severe CAP. In a retrospective analysis, the administration of activated protein C to a subset of patients in the PROWESS study with CAP was associated with a drop in mortality rates.⁴⁰ Further studies, including prospective randomized trials, remain pending. In at least one randomized study, the continuous infusion of corticosteroids in patients with CAP was associated with lower mortality rates, shorter length of ICU stay, and shorter duration of mechanical ventilation.⁴¹ No increase in complications was associated with the use of steroids in this population of patients.

Two serum markers, C-reactive protein and procalcitonin, have been studied to assess response to CAP therapy, to determine outcome, and to guide duration of therapy. Of the two, procalcitonin seems the most promising. Procalcitonin is the precursor to calcitonin and has no hormonal effects. Serum levels of procalcitonin rise in the setting of acute bacterial infections, stimulated by cytokines, microbial toxins, and the cell-mediated immune response. One study determined that higher serum levels of procalcitonin, within 24 hours of admission to the hospital, were associated with higher PSI scores and a greater risk of mortality.⁴² Other investigators have found procalcitonin levels useful in predicting outcome and guiding duration of therapy.^43–45

Clinicians should resist the urge to switch antibiotic therapy within the first 72 hours unless marked clinical deterioration occurs. Failure to respond to initial therapy does occur in up to 10% of patients because of a variety of factors. A drug-resistant or unusual pathogen may be the cause, which may be remedied by further diagnostic tests for the etiologic agent, broadening of the antibiotic therapy, or both. A complication of the initial pneumonia may be present, either local (e.g., lung abscess, empyema) or at a distant site (e.g., meningitis, endocarditis, septic arthritis). Selected imaging such as computed tomography and echocardiography as well as sampling of fluid collections based on these studies and physical examination can often reveal the source of the persistent infection. Finally, several noninfectious illnesses can mimic pneumonia and should be ruled out. This group of disease states is extensive and includes bronchogenic cancer, lymphoma, and a variety of inflammatory and interstitial lung diseases.

Ventilator-Associated Pneumonia

Ventilator-associated pneumonia is a nosocomial pulmonary infection developing in patients receiving mechanical ventilation. Ventilator-associated pneumonia that occurs early, within 48 to 72 hours after intubation, is typically due to bacteria responsive to antibiotic therapy (e.g., pansensitive S. aureus, H. influenzae, and S. pneumoniae) and frequently results from aspiration complicating the intubation process. In contrast, late-onset ventilator-associated pneumonia is often caused by antibiotic-resistant organisms (e.g., methicillin-resistant S. aureus, Pseudomonas aeruginosa, Acinetobacter and Enterobacter species).⁵² Risk factors for ventilator-associated pneumonia include the duration of mechanical ventilation, age older than 70 years, H₂ or antacid therapy, chronic lung disease, depressed consciousness, need for reintubation, and gastric aspiration.^46,52–55 The incidence of ventilator-associated pneumonia is significantly higher in surgical ICUs as opposed to medical ICUs, according to the Centers for Disease Control and Prevention.⁵⁶

There is some controversy in the literature about optimal diagnosis of ventilator-associated pneumonia.⁵⁷ To date, there seems to be little evidence supporting the use of invasive (bronchoscopic) techniques for diagnosis compared with quantitative tracheobronchial aspirates, with no difference in subsequent mortality, length of hospital stay, or duration of mechanical ventilation.^58–62 Bronchoscopy may be of use in patients who fail to respond to initial therapy.⁶³ The treatment of ventilator-associated pneumonia consists of general supportive care and the administration of empiric broad-spectrum antibiotics, guided by the severity of the illness.^46,64 The adequacy of initial antibiotic therapy appears to be the most important determinant of outcome.^65,66 Numerous studies have examined preventive measures to limit the development of ventilator-associated pneumonia. Semirecumbent positioning, sucralfate instead of H₂ antagonists for stress ulcer prophylaxis, and selective digestive tract decontamination were found to have the strongest support in the literature.⁶⁷

Health Care–Associated Pneumonia

Health care–associated pneumonia refers to pneumonia that occurs in a nonhospitalized patient with extensive health-care contacts. Examples of such contacts include outpatient intravenous therapy, hospitalization or treatment at a hospital or dialysis unit within the past 30 days, and residence in a nursing home or other long-term care facility. The recommendations for treatment mirror those suggested for hospital-acquired pneumonia.⁴⁶

Aspiration Pneumonia

Aspiration refers to the inhalation of oropharyngeal or gastric contents into the tracheobronchial tree. This usually results in either a pneumonitis caused by a chemical injury from contact with sterile, acidic gastric contents or a pneumonia due to inhalation of infected material. Rarely, aspiration can lead to airway obstruction, lung abscess, and other findings. Aspiration pneumonia is a common problem, accounting for 5% to 15% of CAP, and is frequently seen in nursing home residents, those with swallowing disorders, and patients with altered mental states. It is also a recognized complication of general anesthesia, occurring in about 1 in 3000 operations and accounting for 10% to 30% of deaths related to anesthesia.⁶⁸

The acute lung injury or pneumonitis from gastric aspiration, termed Mendelson’s syndrome,⁶⁹ appears directly related to the acidity and volume of aspirated material. In general, a pH below 2.5 and a volume in excess of 0.3 mL/kg (about 21 mL in a 70-kg adult) are required to initiate lung injury. The injury follows a biphasic pattern; the initial insult is caused by direct damage of the acid on the delicate capillary and alveolar cells, followed several hours later by the rapid accumulation of inflammatory cells and mediators, resulting in a local and systemic inflammatory response. Progression to acute respiratory distress syndrome and multiorgan system failure may ensue. Because the gastric contents are sterile due to the acidity, infection is usually not an initial feature in these cases but may become prominent later in the course of the illness with secondary infection of the damaged lung parenchyma. Efforts to modify the gastric pH may lead to gastric colonization with gram-negative bacteria as well as with other organisms, leading to infection early after the aspiration episode. Treatment is largely supportive in nature. Particularly if the aspiration is witnessed, bronchoscopy is indicated to remove any residual fluid or debris from the airway. The use of corticosteroids in the treatment of aspiration pneumonitis has not been shown to be of benefit. Although it is common practice to initiate antibiotic therapy in these patients, this often overtreats simple pneumonitis, which may resolve with supportive measures only. Further, the use of antibiotics early may encourage the development of resistant organisms. Antibiotic therapy should be considered early in those thought to have gastric colonization and in those patients who do not improve within 48 hours of the inciting event, with evidence of ongoing lung injury, infection, or infiltrate.⁷⁰ Empiric coverage with broad-spectrum agents is recommended.

Aspiration pneumonia commonly arises from inhalation of colonized oropharyngeal bacteria, causing the signs, symptoms, and radiographic changes of pneumonia. About half of normal adults aspirate while asleep,⁷¹ and for infection to occur, the normal protective mechanisms must either fail or be overwhelmed by the volume or bacterial burden of the aspirate. In supine patients, the dependent lung segments (posterior aspects of upper lobes, superior segments of lower lobes) are affected most frequently. In upright individuals, the basilar segments, particularly on the right side, are at greatest risk of infection. The aspiration episode in patients developing pneumonia is frequently not observed, and the diagnosis is derived from the clinical picture and characteristic radiographic changes in individuals known to be at risk. Treatment with antimicrobial therapy is appropriate. Use of antibiotics with anaerobic coverage is probably overdone but appropriate in select cases in which severe periodontal disease, alcoholism, and other disorders predominate. In hospitalized patients, coverage of gram-negative bacteria is essential.