■  PERSPECTIVE

Pneumonia is the seventh leading cause of death and the leading cause of death from infectious disease in the United States.1 The annual incidence of community-acquired pneu-monia (CAP) in the United States ranges from 2 to 4 million, resulting in approximately 500,000 hospital admissions. Most cases of CAP are managed in the outpatient setting and the mortality is low (<1%), but pneumonia requiring hospi-talization is associated with a much higher mortality rate (approximately 15%). Most deaths occur in elderly or immu-nosuppressed patients. Pneumonia remains challenging because of an expanding spectrum of pathogens, changing antibiotic resistance patterns, the availability of newer antimi-crobial agents, and increasing emphasis on cost-effectiveness and outpatient management.

The epidemiology of CAP is changing. As the percentage of the population older than age 65 years continues to increase, the incidence of pneumonia is expected to increase. An increasing number of patients are taking immunosuppressive drugs related to treatment of malignancy, transplantation, or autoimmune disease, resulting in more cases of pneumonia due to other opportunistic pathogens. Patients with acquired immunodeficiency syndrome (AIDS) are at increased risk of infection with Streptococcus pneumoniae, Mycobacterium tubercu-losis, or Pneumocystis jirovecii (previously known as Pneumocystis carinii). Antibiotic resistance is more common among S. pneu-moniae and other pathogens. In addition, the threat exists of respiratory infections due to biologic terrorism or newly recog-nized pathogens that have the potential to spread quickly through international travel.

Identification of a specific etiology of pneumonia is extremely difficult within the time frame of an emergency department (ED) visit. Even after a thorough inpatient evaluation, a spe-cific pathogen is never identified in many patients with pneu-monia. When pneumonia is diagnosed, the priorities in the ED are to initiate appropriate empirical antibiotic therapy based on the most likely pathogens, provide appropriate respiratory support, assess the severity of disease, and recognize indica-tions for hospitalization.

■  PRINCIPLES OF DISEASE

Despite the constant presence of potential pathogens in the respiratory tract, the lungs are remarkably resistant to infection. The alveolar surface of the lungs covers an area of

approximately 140 m2. Approximately 10,000 L of air passes through the respiratory tract each day, and typical ambient air can contain hundreds to thousands of microorganisms per cubic meter. Numerous potential respiratory tract pathogens may colonize the oropharynx and upper airways. Although the cough and laryngeal reflexes prevent most large particulate matter from entering the lower respiratory tract, aspiration of oropharyngeal contents may be a common occurrence during normal sleep. Despite these hazards, healthy lungs are usually a virtually sterile environment.

The development of clinical pneumonia requires a defect in host defenses, the presence of a particularly virulent organ-ism, or the introduction of a large inoculum of organisms. If the challenge of invading organisms overwhelms host defenses, microbial proliferation leads to inflammation, an immune response, and clinical pneumonia. If host defenses are weak, a minimal challenge may lead to the development of pneumonia.

The mouth normally contains numerous microorganisms. Saliva contains approximately 108 bacteria/mL, with anaerobic organisms predominating. Bacteroides and Fusobacterium spp. are the most common anaerobic organisms. Streptococci are the most common aerobic organisms, but staphylococci, Haemophilus sp., Moraxella catarrhalis, and Neisseria sp. are also found. Anything that upsets the balance of normal oral flora may permit the growth of more virulent organisms. Systemic illness may alter epithelial binding of oral flora, leading to increased colonization with aerobic gram-negative bacilli. Antimicrobial therapy can also adversely alter normal oral flora.

Host defenses can be impaired in many ways. An altered level of consciousness (e.g., intoxication, stroke, seizures, and anesthesia) can suppress protective airway reflexes and lead to aspiration of oropharyngeal contents into the lower respiratory tract. Interventions that bypass the usual defenses of the upper airways, such as endotracheal intubation, nasogastric intuba-tion, and respiratory therapy devices, predispose to infection. Cigarette smoking damages mucociliary function and macro-phage activity. Viral infections of the respiratory tract may destroy respiratory epithelium and predispose it to bacterial infection. Increased risk of bacterial pneumonia after influenza or other viral respiratory infections is well described. The elderly are at increased risk of pneumonia related to decline of mucociliary clearance, elastic recoil of the lungs, and humoral and cellular immunity. Human immunodeficiency virus (HIV) infection impairs humoral and cellular immunity.

927

Chapter 74 PneumoniaGregory J. Moran and David A. Talan

928PA

RT 

III

■ M

edic

ine

and

Surg

ery

/ Se

Cti

on

tw

o •

Pul

mon

ary

Syst

em

If an infectious organism reaches the alveoli and begins replicating, a series of host immune responses occurs that ulti-mately may lead to the development of clinical pneumonia. As antigens of the infecting organism are identified by the host, cytokines, such as interleukin-1, interleukin-8, and tumor necrosis factor, are produced that mediate the inflammatory response. Transudation of plasma fluids into the lung tissue allows entry of IgM and IgG for bacterial opsonization, com-plement activation, agglutination, and neutralization. Neutro-phils are recruited into the lung to ingest and kill the infecting organisms. Cell-mediated immunity plays an important role in defense against certain pathogens, such as viruses and intra-cellular organisms such as Mycobacterium and Legionella spp. As fluids and inflammatory cells enter the alveolar spaces to combat the infection, the patient develops the clinical and radiographic signs of pneumonia.

Etiologic Agents

The challenge with pneumonia lies in identifying the etiologic agent rather than in diagnosis of pneumonia. It is extremely difficult to determine with a high degree of certainty the spe-cific organism responsible for pneumonia, especially within the time frame of an ED evaluation. Empiric therapy must be chosen with activity against the spectrum of likely pathogens based on the overall clinical picture.

Difficulty in determining the specific etiology of pneumonia exists even with advanced microbiologic and serologic testing that is not generally available during an ED evaluation. In community-acquired pneumonia, a microbial etiology cannot be determined in one third to one half of cases, even after thorough investigation. In hospitalized adults with CAP, pathogens such as S. pneumoniae and Haemophilus influenzae, referred to as “typical” pathogens, account for approximately one fourth of cases. Legionella, Mycoplasma, and Chlamydophila spp. (previously known as Chlamydia), referred to as “atypical” pathogens, are also common.2 Testing for common viral agents reveals a viral etiology in approximately 18% of cases, with influenza and parainfluenza viruses most common.3 Adults who require intensive care unit (ICU) admission have S. pneumoniae as the most common pathogen, with even higher prevalence among fatal cases. Legionella sp., Staphylococ-cus aureus, and aerobic gram-negative bacilli also appear to be relatively more common among adults with severe CAP.4 Atypical organisms such as Mycoplasma sp. or viruses account for a relatively higher proportion of pneumonia in patients who have milder illness that is amenable to outpatient therapy.5 However, atypical organisms occur with significant frequency in patients with severe illness requiring hospitalization, particularly due to Legionella infection. Co-infection, such as with Chlamydophila pneumoniae and S. pneumoniae, is also well recognized.

Streptococcus pneumoniae is a gram-positive coccus that is the most common etiology of CAP among adults. It colonizes the nasopharynx in 40% of healthy adults. Although this organism can cause pneumonia in healthy people, patients with a history of diabetes, cardiovascular disease, alcoholism, sickle cell disease, splenectomy, and malignancy or other immunosup-pressive illness are at increased risk. A vaccine containing the 23 capsular polysaccharides of pneumococcal types most com-monly associated with pneumonia reduces the likelihood of serious pneumococcal infection. It is recommended for people at increased risk because of underlying illness or age older than 65 years.6 Many ED patients have not received pneumo-coccal vaccine, and vaccinating eligible patients in this setting seems to be feasible and effective.7 A heptavalent protein-conjugate pneumococcal vaccine effectively reduces invasive

pneumococcal disease and pneumonia in infants and young children.8

Haemophilus influenzae, the second most frequently isolated organism in CAP among adults, is a pleomorphic gram- negative rod. It is a common pathogen in adults with chronic obstructive pulmonary disease (COPD), alcoholism, malnutri-tion, malignancy, or diabetes.

Although Staphylococcus aureus remains an uncommon cause of CAP, community-associated strains of methicillin-resistant S. aureus (CA-MRSA) are emerging as a cause of severe pneu-monia in previously healthy adults and children. This is often associated with influenza.9 Staphylococcal pneumonias are often necrotizing, with cavitation and pneumatocele forma-tion. Intravenous drug users may develop hematogenous spread of S. aureus that involves both lungs with multiple small infiltrates or abscesses (e.g., tricuspid endocarditis resulting in septic pulmonary emboli). Other pyogenic bacterial etiologies include Moraxella catarrhalis, a gram-negative diplococcus that can be associated with lower respiratory tract infections in patients with COPD.

Klebsiella pneumoniae is a gram-negative rod that rarely causes disease in a normal host and accounts for a small percentage of CAPs. It may cause severe pneumonia in debilitated patients with alcoholism, diabetes, or other chronic illness. There is a high incidence of antibiotic resistance since the organism is often hospital acquired.

Mycoplasma pneumoniae is one of the most common causes of CAP in previously healthy patients younger than age 40 years. Another important organism in CAP is C. pneumoniae, an intracellular parasite that is transmitted between humans by respiratory secretions or aerosols. Seroprevalence studies indi-cate that virtually everyone is infected with C. pneumoniae at some time and that reinfection is common. Chlamydophila pneumoniae is a relatively common etiology of CAP, especially in older adults. It accounts for at least 8% of cases, although this is an underestimate due to difficulty in diagnosing infec-tion with this organism.

At least 30 species of Legionella have been isolated since the 1976 convention-related outbreak in Philadelphia, from which the organism derives its name. At least 19 are known human pathogens. Legionella is an intracellular organism that lives in aquatic environments. There is no person-to-person trans-mission. Although it is implicated in point outbreaks related to cooling towers and similar aquatic sources, the organism also lives in ordinary tap water and is underdiagnosed as an etiology of CAP. Legionella prevalence seems to vary greatly by region.

Lower respiratory infections due to anaerobic organisms generally result from the aspiration of oropharyngeal contents with large amounts of bacteria. These infections are typically polymicrobial, including Peptostreptococcus, Bacteroides, Fuso-bacterium, and Prevotella spp. Presentation is often subacute or chronic and may be difficult to distinguish clinically from other etiologies of pneumonia. Clinical factors that suggest an anaer-obic infection include risk factors for aspiration, such as central nervous system depression or swallowing dysfunction; severe periodontal disease; fetid sputum; and the presence of a pul-monary abscess or empyema.

Viral pneumonias are common in infants and young children and are recognized as an important cause of pneumonia in adults. Respiratory syncytial virus and parainfluenza viruses are the most common causes of pneumonia in infants and small children, occurring mostly during autumn and winter. Influenza viruses are the most common cause of viral pneumo-nia in adults. Winter influenza outbreaks, usually due to influ-enza type A, may cause 40,000 deaths annually in the United States. More than 90% occur in people age 65 years or older.10

Ch

apter 74 / P

neumonia

929Metapneumovirus is a paramyxovirus that seems to be an important cause of viral pneumonia in children and adults.11 Cytomegalovirus (CMV) primarily causes pneumonia in immunosuppressed patients, such as transplant recipients. Varicella-zoster virus causes pneumonia that seems to be more common and more severe in adults. Predisposing factors include smoking or pregnancy. Severe acute respiratory syn-drome (SARS) is a respiratory illness due to a coronavirus identified in Southeast Asia. SARS is associated with a high case fatality rate (approximately 10–15% overall and higher in the elderly).

Fungal infections due to organisms such as Histoplasma capsulatum, Blastomyces dermatitides, and Coccidioides immitis commonly present as pulmonary disease. These organisms are present in the soil in various geographic areas of the United States: H. capsulatum in the Mississippi and Ohio River valleys, C. immitis in desert areas of the Southwest, and B. dermatitides in a poorly defined area extending beyond that of H. capsula-tum. These infections should be considered in people in appropriate geographic areas, especially in those who are near activities that disturb the soil, such as construction or dirt bike riding. Clinical presentation varies from an acute or chronic pneumonia to asymptomatic granulomas and hilar adenopathy.

Pneumocystis pneumonia (PCP) occurs in compromised hosts, principally people with AIDS or malignancy. Although P. jir-ovecii is often classified as a protozoan, biochemical evidence indicates that it is more closely related to fungi. PCP is one of the most common presentations leading to a diagnosis of HIV infection and AIDS. Patients with pulmonary complaints should be questioned about HIV risk factors, and clinicians should search for signs of HIV-related immunosuppression, such as weight loss, lymphadenopathy, and oral thrush. PCP typically presents subacutely with fatigue, exertional dyspnea, nonproductive cough, pleuritic chest pain, and fever.

Mycobacterium tuberculosis is a slow-growing bacterium trans-mitted between people by droplet nuclei produced from coughing and sneezing. Mycobacterium tuberculosis survives within macrophages as a facultative intracellular parasite and may remain dormant in the body for many years. Active tuber-culosis (TB) develops within 2 years of infection in approxi-mately 5% of patients, and another 5% develop reactivation disease at some later time. Reactivation is more likely to occur in people with impaired cell-mediated immunity, such as patients with diabetes, renal failure, immunosuppressive therapy, malnutrition, or AIDS. Approximately one third of the world’s population is infected with M. tuberculosis. Approxi-mately 8 million new cases of active disease develop annually, resulting in 3 million deaths worldwide. An estimated 10 to 15 million people in the United States (3–5% of the population) are infected with TB. Multidrug-resistant strains of M. tuber-culosis are found in increasing numbers, especially among immigrants from Southeast Asia and AIDS patients.

Unusual Causes of Pneumonia

Hantaviruses are endemic in several areas of the United States and can cause a syndrome of severe respiratory distress and shock. Infection occurs from inhalation of aerosols contami-nated with rodent urine and feces. Patients are typically healthy adults with a prodrome of fever, myalgia, and malaise followed several days later by the onset of respiratory distress. Hypoxia may progress rapidly, requiring ventilatory support. Characteristic laboratory findings include thrombocytopenia, hemoconcentration, and leukocytosis with atypical lympho-cytes. Chest radiographs show bilateral interstitial lung infil-trates that are more pronounced in dependent areas. Treatment

is supportive, including the use of extracorporeal membrane oxygenation. There is no known effective antiviral therapy.

Plague, caused by Yersinia pestis, is endemic in many areas of the world, including the southwestern United States. It is an agent that could be used for biologic terrorism,12 but it also occurs naturally in people bitten by fleas from infected rodents or carnivores. Hematogenous spread may lead to pneumonia that is highly contagious and has a high mortality.

A number of zoonotic organisms cause pneumonia. Tulare-mia, caused by the bacterium Francisella tularensis, is spread by contact with body fluids of an infected mammal (especially rabbits) or the bite of an infected arthropod. Illness usually begins with an ulcerated skin lesion and painful regional lymphadenopathy. Some patients have a typhoidal form with only fever, malaise, and weight loss. Pneumonia may occur with either form, presenting as a nonproductive cough and patchy infiltrates on a chest radiograph. Psittacosis can spread to humans from birds infected with Chlamydophila psittaci. Illness often begins rapidly with chills, high fever, myalgias, and nonproductive cough. Severe headache is often the major complaint. Splenomegaly is often present. Q fever is caused by the rickettsial organism Coxiella burnetii. It is most common in people with occupational exposure to cattle or sheep or parturient animals, including cats. Severe headache occurs in approximately 75% of cases. Q fever is rarely fatal. Other zoo-notic pulmonary infections include Rhodococcus equi associated with exposure to horses and Bordetella bronchiseptica associated with exposure to ill dogs (“kennel cough”).

■  CLINICAL FEATURES

The ED evaluation should focus on establishing the diagnosis of pneumonia and determining the presence of epidemiologic and clinical features that would influence decisions regarding hospitalization and antibiotics. Key history includes the character and pattern of symptoms, the setting in which the pneumonia is acquired, geographic or animal exposures, and host factors that predispose to certain types of infections and are associated with outcome.

Pneumonia generally presents as a cough productive of purulent sputum, shortness of breath, and fever. In most healthy older children and adults, the diagnosis can be reason-ably excluded on the basis of history and physical examination, with suspected cases confirmed by chest radiography. The absence of any abnormalities in vital signs or chest auscultation substantially reduces the likelihood of pneumonia. However, no single isolated clinical finding is highly reliable in establish-ing or excluding a diagnosis of pneumonia.13

Elder or debilitated patients with pneumonia often present with nonspecific complaints but not the classic symptoms. Pneumonia commonly presents in the elderly as acute confu-sion or a deterioration of baseline function. Elder patients are more likely to have advanced illness at the time of presenta-tion and may present with sepsis in the absence of a previous syndrome suggestive of pneumonia. Rarely, patients with lower lobe pneumonia present with a complaint of abdominal or back pain. The diagnosis may be more difficult in infants and small children who are unable to give an adequate history. Pneumonia may present in infants as a fever associated with irritability, tachypnea, tachycardia, intercostal retractions, nasal flaring, or grunting. Cough may be minimal or absent.

Pneumonia can be divided based on clinical patterns into typical pneumonia caused by pyogenic bacteria, such as S. pneumoniae or H. influenzae, and atypical pneumonia caused by organisms such as Mycoplasma and Chlamydophila spp. This division is artificial, and a clear differentiation between these two types of pneumonia on clinical grounds alone is impossi-

930PA

RT 

III

■ M

edic

ine

and

Surg

ery

/ Se

Cti

on

tw

o •

Pul

mon

ary

Syst

em

ble. Certain clinical factors are often said to be suggestive of atypical organisms. Factors studied prospectively and found not to be more frequent with atypical pneumonias than with pyogenic bacterial etiologies include gradual onset, viral pro-drome, absence of rigors, nonproductive cough, lower degree of fever, absence of pleurisy or consolidation, low leukocyte count, and an ill-defined infiltrate on a chest radiograph.2 Although it is impossible to determine with a high degree of certainty the specific etiology of pneumonia without results of microbiologic or serologic tests, certain clinical factors suggest that a specific pathogen should be considered.

The classic presentation of pneumococcal pneumonia is the abrupt onset of a single shaking chill followed by fever, cough productive of rust-colored sputum, and pleuritic chest pain. Many patients do not exhibit the classic pattern. Patients often have a preceding upper respiratory illness, and the onset of pneumonia may be insidious, especially in the elderly or with underlying lung disease. Patients with a history of asplenia, sickle cell disease, AIDS, multiple myeloma, or agammaglobu-linemia are at increased risk of pneumococcal bacteremia and sepsis with high mortality rates. Extrapulmonary complica-tions (e.g., meningitis, endocarditis, or arthritis) may rarely be present. Adults with chronic lung disease who develop pneu-monia due to H. influenzae typically present with an insidious worsening of baseline cough and sputum production, and bacteremia is rare. Klebsiella pneumoniae may cause severe pneumonia in elderly or debilitated patients. Sputum is often described as “currant jelly” because of the necrotizing, hemorrhagic nature of the infection. Abscess formation, empyema, and bacteremia are common with this organism, and mortality is high.

Atypical pneumonia is caused by organisms such as M. pneu-moniae, C. pneumoniae, viruses, Legionella sp., or rickettsiae such as C. burnetii. Mycoplasmal infection usually begins as a flulike illness with headache, malaise, and fever. Cough is usually nonproductive but may sometimes produce clear or purulent sputum. Skin lesions, including maculopapular, vesicular, urti-carial, or erythema multiforme-type rashes, are common, especially in younger patients. Although bullous myringitis is described as a classic finding, it is not specific for mycoplasmal infection and is present in only a few cases. Common physical findings include pharyngeal erythema, cervical adenopathy, and scattered rales and rhonchi. Rare extrapulmonary manifes-tations include pericarditis, glomerulonephritis, aseptic men-ingitis, and Guillain-Barré syndrome. Patients generally do not appear toxic, and most can be treated as outpatients. Although mucopurulent sputum generally indicates the presence of pyo-genic bacterial pneumonia or bronchitis, it may also be present with mycoplasmal or viral pneumonia. Viral pneumonia in adults is often preceded by symptoms of upper respiratory infection, such as rhinitis or sore throat. Cough is usually non-productive, and pleuritic chest pain is less common than with bacterial pneumonia.

Most C. pneumoniae infections in young adults cause a minor, self-limited upper respiratory illness that is subacute in onset. This organism is also associated with bronchitis, wheezing, sinusitis, pharyngitis, and atherosclerosis. Development of radiographically evident pneumonia is more common in the elderly, in contrast to the common perception that atypical pneumonias occur in the young.

Some patients with Legionella infection have a mild, self-limited atypical pneumonia presentation. Older patients, smokers, and those with chronic disease or immunosuppres-sion are more prone to develop the more acute and severe systemic illness of legionnaires’ disease. Gastrointestinal symptoms, such as diarrhea and abdominal cramping, are sometimes prominent.

In addition to age, the presence of underlying illness, and presenting symptoms, the setting of acquisition of pneumonia may provide clues to likely etiologies. CAP that occurs in otherwise healthy individuals is likely to be due to viruses, Mycoplasma sp., or S. pneumoniae. Staphylococcus aureus, includ-ing CA-MRSA, can cause severe pneumonia associated with influenza. Hospitalized patients may develop pneumonia due to agents that are uncommon in CAP, such as Enterobacteria-ceae, Pseudomonas aeruginosa, and S. aureus. Healthy patients in an institutional setting, such as a dormitory or military bar-racks, are likely to have pneumonia due to Mycoplasma sp. or viruses.

Patients with underlying lung disease, especially COPD, constitute an important group likely to develop pneumonia. The lower respiratory tract of these patients is commonly colo-nized with organisms such as S. pneumoniae, H. influenzae, and M. catarrhalis. Cystic fibrosis patients are prone to pneumonia due to P. aeruginosa or S. aureus. Defective mucociliary clear-ance in both of these groups makes them highly susceptible to repeated episodes of pneumonia.

Patients with immunosuppression due to hematologic malignancy, patients receiving chemotherapy for malignancy, and transplant recipients are prone to pulmonary infections with a wide variety of organisms. In addition to the usual pathogens, these patients may develop pneumonia secondary to viruses such as CMV, varicella, or herpes simplex virus. They are also more likely to develop pneumonia due to aerobic gram-negative bacilli, fungi such as Candida sp. or H. capsula-tum, and P. jirovecii.

Patients in nursing homes or other extended-care facilities are at increased risk for infection with resistant organisms such as P. aeruginosa, K. pneumoniae (including strains produc-ing extended-spectrum β-lactamases), Acinetobacter species, and hospital-associated strains of MRSA. Other risk factors for infection with multidrug-resistant pathogens include (1) hos-pitalization for 2 or more days in an acute care facility within 90 days of infection; (2) patients who attended a hemodialysis clinic; and (3) patients who received intravenous antibiotic therapy, chemotherapy, or wound care within 30 days of infec-tion. Any patient with pneumonia that fulfills any one of these historical features, including patients from a nursing home or long-term care facility, is designated as having health care–associated pneumonia (HCAP). HCAP is associated with a greater likelihood of resistant pathogens such as Pseudomonas and MRSA, and mortality is higher than that for CAP.14

■  DIAGNOSTIC STRATEGIES

Although many chest radiographs are obtained unnecessarily for patients with upper respiratory tract infections or bronchi-tis, it is difficult to identify a set of specific criteria to direct test ordering that is better than the clinical judgment of an experienced physician. A routine chest radiograph for all patients who present with cough is not necessary; chest radi-ography may be reserved for patients who have other sugges-tive findings (e.g., fever, tachycardia, oxygen desaturation, or an abnormal lung examination). Among patients suspected to have pneumonia, these clinical findings are prospectively vali-dated and are better predictors of a radiographic infiltrate than physician judgment.15 Patients with serious underlying disease, patients with severe sepsis or shock, and patients in whom hospitalization is considered should have chest radiography performed. Computed tomography (CT) of the chest is more sensitive than plain radiography for detecting the presence of pulmonary consolidation, although the natural history of CT-positive, plain radiograph-negative pneumonia is not clear.16 Young, healthy adults with a presumptive diagnosis of pneu-

Ch

apter 74 / P

neumonia

931

monia, who will be treated as outpatients, may have a chest radiograph deferred unless there is a suspicion of immunocom-promise or other unusual features of disease. A chest radio-graph should be obtained subsequently if there is a poor initial response to treatment. Routine performance of chest radiog-raphy for patients with exacerbation of chronic bronchitis or COPD is of low yield and may be limited to patients with other signs of infection or congestive heart failure. Studies of infants with fever show that a routine chest radiograph is of low yield in the absence of other symptoms or signs of lower respiratory tract infection (e.g., abnormal auscultation or ele-vated respiratory rate).17

Although the causative agent cannot be determined solely by the results of chest radiography, certain radiographic pat-terns may suggest the possibility of specific pathogens. In pyogenic bacterial pneumonias, radiographs usually show an area of segmental or subsegmental infiltration and air broncho-grams (Fig. 74-1). Lobar consolidation is present in a few cases of bacterial pneumonia, often due to pneumococcus or Klebsi-ella. A dense lobar infiltrate with a bulging fissure appearance on a chest radiograph is often described with pneumonia due to Klebsiella, but this finding is nonspecific, and most cases present as a subtler bronchopneumonia. Pneumonia resulting from spread of infection along the intralobular airway results in fluffy or patchy infiltrates in the involved areas of the lung. A wide variety of bacteria and agents such as Chlamydophila sp., Mycoplasma sp., Legionella sp., viruses, and fungi may cause this pattern.

An interstitial pattern on a chest radiograph (Fig. 74-2) typi-cally is caused by Mycoplasma sp., viruses, or P. jirovecii. Tiny nodules disseminated throughout both lungs represent a miliary pattern typical of granulomatous pneumonias, such as TB or fungal disease. The location of infiltrates may also give a clue to the etiology. Aspiration pneumonia occurs in depen-dent areas of the lung, most commonly the superior segments of the lower lobes or posterior segments of the upper lobes. Pneumonias produced by hematogenous spread (e.g., S. aureus) tend to be peripheral. Apical infiltrates suggest TB.

The presence of additional radiographic features in associa-tion with infiltrates may suggest a specific etiology. An infil-trate associated with hilar or mediastinal adenopathy suggests the presence of TB or fungal disease or may indicate pneumo-

Figure 74-1. Posteroanterior chest radiograph reveals a left upper lobe pneumonia. A variety of organisms can produce this pattern, most commonly S. pneumoniae, H. influenzae, or gram-negative bacilli, but also C. pneumoniae, Mycoplasma, or Legionella sp.

Figure 74-2. Posteroanterior chest radiograph reveals patchy interstitial infiltrates. Viruses and Mycoplasma are the most likely etiologies in an otherwise healthy patient, but many bacterial organisms may also produce this pattern.

nia associated with a neoplasm. Bacteria most likely associated with cavitation (Fig. 74-3) are anaerobes, aerobic gram-negative bacilli, and S. aureus. Cavitation also may be present in fungal disease or TB and with noninfectious processes (e.g., malignancy and pulmonary vascular disease). Pneumato-

932PA

RT 

III

■ M

edic

ine

and

Surg

ery

/ Se

Cti

on

tw

o •

Pul

mon

ary

Syst

em

Figure 74-3. Posteroanterior (A) and lateral (B) chest radiographs reveal a lung abscess in the left lower lobe with a distinct air-fluid level.

A B

celes or spontaneous pneumothorax may be seen in AIDS patients with PCP. Pleural effusions occur with a wide variety of organisms, including many types of pyogenic bacterial pneumonias, Chlamydophila sp., Legionella sp., and TB. Anaero-bic infections associated with an effusion are especially prone to development of empyema. The diagnosis and aspiration of pleural effusions can be aided by use of ED bedside ultrasonography.

Radiographic findings are nonspecific for predicting a par-ticular infectious etiology. Mycoplasma pneumonia may present as a dense infiltrate, or pneumococcal pneumonia may present as a diffuse interstitial infiltrate. Immunocompromised patients are particularly prone to having atypical radiographic appear-ances. Rarely, patients with a clinical picture strongly sugges-tive of pneumonia have a normal chest radiograph, and some are found to have an infiltrate within the next 24 to 48 hours. The absence of findings on a chest radiograph should not preclude the use of antimicrobial therapy in appropriate patients with a clinical diagnosis of pneumonia. Whether the state of hydration can affect the radiographic appearance of pneumonia is controversial. Although severe dehydration theoretically could result in a diminished exudative response by decreasing blood volume and hydrostatic pressure, this has not been shown experimentally.18,19

Laboratory studies also are nonspecific for identifying the etiology of pneumonia. Although the finding of a white blood cell count (WBC) greater than 15,000/mm3 increases the prob-ability of the patient having a pyogenic bacterial etiology rather than a viral or atypical etiology, the predictive value of this finding depends on the stage of the illness and likely prevalences of various etiologies. This is neither sensitive nor specific enough to aid decisions regarding therapy in an indi-vidual patient. A WBC may be helpful if it yields evidence of immunosuppression, such as neutropenia, or if it reveals lym-phopenia that may indicate immunosuppression from AIDS. Basic metabolic panels may help identify patients with renal or hepatic dysfunction or metabolic acidosis associated with sepsis. These findings predict a complicated course and influ-ence decisions regarding disposition, choice of antimicrobial agents, and dosages.

The assessment of respiratory function with pulse oximetry is important in the evaluation of patients with pneumonia since clinical assessment of oxygenation can be inaccurate.20 Pulse oximetry should be obtained in any patient suspected to have pneumonia.

Sputum Gram’s stain rarely results in a change in therapy or outcome. Correlation between identification of pneumococ-cus on Gram’s stain and sputum culture results is poor, even when commonly used criteria for an adequate sputum speci-men (<5 squamous epithelial cells and >25 WBC/high-power field) are applied. Gram’s stains are even less likely to show gram-negative pathogens, such as H. influenzae, and should not be relied on to rule out a gram-negative etiology. Empirical antimicrobial agents are usually highly clinically effective if chosen based on clinical information without sputum analysis. Guidelines for management of CAP from the Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) support limiting sputum Gram’s stain and culture to those patients with more severe disease or risk factors for unusual pathogens.1

Routine blood cultures are of essentially no value in nonim-munocompromised adults with pneumonia, in whom there is a very low prevalence of noncontaminant bacteremia, and management is rarely changed based on the results.21,22 The follow-up of false-positive blood cultures is costly and labor-intensive, and it may lead to unnecessary use of antibiotics such as vancomycin or linezolid when results are initially reported as gram-positive cocci. Blood cultures should be obtained from immunocompromised patients, those with severe sepsis or shock, or those with risk factors for endovas-cular infection (e.g., prosthetic valves, intravenous drug use, or cavitary infiltrates).1 When cultures are drawn, they should be obtained prior to the initiation of antibiotics (although anti-biotics should not be delayed for this reason).

Patients with a pleural effusion greater than 5 cm on lateral upright posterior-anterior chest radiograph should have a diagnostic thoracentesis performed,1 with fluid sent for cell count, differential, pH (pH < 7.2 predicts the need for a tho-racostomy tube), Gram’s stain, and culture. For most patients, thoracentesis can be safely deferred until after hospital admis-

Ch

apter 74 / P

neumonia

933sion. Patients in significant respiratory distress, however, or with evidence of tension and mediastinal shift require emer-gent diagnostic and therapeutic thoracentesis.

Serologic tests are available for the diagnosis of many organ-isms, including C. pneumoniae, Legionella sp., and fungi. The use of serologic tests to determine the etiology of pneumonia may be helpful retrospectively, but they usually require acute and convalescent serum titers and are of little use in the ED. Urine antigen tests for S. pneumoniae and Legionella are avail-able, and in some facilities results can be obtained within the time frame of an ED evaluation. It is not clear, however, that a positive result should prompt a change of empirical treat-ment.1 Rapid diagnostic tests for viral antigens are available for several viruses, including RSV and influenza. These tests may be useful for infection control decisions in hospitalized patients, and they may provide an indication for influenza therapy and family prophylaxis. In the future, rapid testing using technology such as the polymerase chain reaction may provide emergency physicians with a reliable method to deter-mine the specific etiology of pneumonia.

Pneumonia Associated with Human Immunodeficiency Virus Infection

The approach to an HIV-infected patient with pulmonary complaints must consider the likelihood of opportunistic lung infections. Although the use of highly active antiretroviral therapy (HAART) is decreasing the incidence of opportunistic infections among HIV-infected patients, individuals who are not under regular care often present to the ED. In the setting of a patient with risk factors for HIV but an unknown serologic status, a decision must be made as to the likelihood of AIDS and the need to search aggressively for opportunistic pathogens.

Respiratory infections are the most common type of oppor-tunistic infection in AIDS patients. In addition to P. jirovecii, there is also an increased incidence of pneumonia due to M. tuberculosis and common bacterial pathogens such as S. pneumoniae and H. influenzae. The incidence of pneumococ-cal pneumonia is 7 to 10 times higher in HIV-infected people and the incidence of H. influenzae pneumonia is approximately 100 times higher than in non-HIV-infected individuals. Other less important causes of pneumonia in HIV-infected patients include Mycobacterium avium complex, CMV, aerobic gram-negative bacilli, Cryptococcus neoformans, and Rhodococcus equi.

Although some patients have known HIV infection or AIDS, many patients are unaware of their HIV status, and many are reluctant to volunteer that they have risk factors for HIV. The first crucial step in the diagnosis of PCP is the recognition that a patient may be at risk. If the possibility of HIV infection is established, the likelihood of immunosuppression must be determined. The potential for opportunistic pulmonary infec-tion can be predicted by a recent absolute CD4 lymphocyte count less than 200/mm3. This count is often known by patients with recognized HIV infection or may be surmised by a periph-eral total lymphocyte count less than 1000/mm3.23 In patients who do not know their HIV status, the presence of findings such as weight loss, hairy leukoplakia, and oral candidiasis strongly suggests immunosuppression.

Although patients with PCP may present with typical features of subacute onset of nonproductive cough, fever, shortness of breath, diffuse interstitial infiltrates on chest radi-ography, and arterial hypoxemia, 10 to 20% of patients subse-quently proven to have PCP lack these findings. PCP usually has a subacute presentation characterized by nonproductive

cough, exertional dyspnea, and weight loss. Tachypnea and tachycardia are usually present.

The classic radiographic findings in PCP are bilateral inter-stitial infiltrates that begin in the perihilar region. Radiographic manifestations of PCP can vary considerably, however, ranging from a normal appearance to dense consolidation. Lobar infiltrates, pleural effusions, hilar adenopathy, parenchymal nodules, and cavitary disease are also described. Hypoxemia, hypocapnia, and an increased arterial-alveolar oxygenation gradient are usually present. Serum lactate dehydrogenase is significantly elevated in AIDS patients with PCP compared to patients with non-PCP pneumonia. The demonstration of oxygen desaturation with mild exercise may be helpful in patients with more subtle presentations. Confirmation of the diagnosis of PCP requires sputum induction and staining and, in some cases, further invasive procedures, such as bronchos-copy with bronchoalveolar lavage or biopsy. In most settings, patients suspected to have PCP are admitted to the hospital and given presumptive therapy against PCP.

There is a broad differential diagnosis for pulmonary infil-trates in AIDS patients (Fig. 74-4). The bacterial pathogens most commonly responsible for pneumonia in these patients are the same pathogens most frequently encountered in immu-nocompetent individuals with CAP, but they may have an atypical appearance on chest x-ray. Because AIDS patients with pulmonary TB cannot be distinguished reliably from AIDS patients with other pulmonary infections at presenta-tion, consider TB in all HIV-infected patients with respiratory complaints and initiate respiratory isolation. AIDS patients are also at risk for pneumonia due to other mycobacterial species (e.g., M. avium complex). Nevertheless, the finding of acid-fast bacilli in the sputum should prompt empirical therapy against M. tuberculosis until another mycobacterial species is defini-tively identified. AIDS patients are also at increased risk for pneumonia due to Cryptococcus neoformans or other fungi associated with geographic exposure. Kaposi’s sarcoma may also present with pulmonary infiltrates.

■  DIFFERENTIAL DIAGNOSIS CONSIDERATIONS

The differentiation between upper and lower respiratory tract infections may be difficult. A chest radiograph helps differenti-ate between upper respiratory tract infection or bronchitis and pneumonia, but it is probably not necessary for all patients with cough and sputum production unless other factors are present that suggest the possibility of pneumonia or obscure its clinical diagnosis (e.g., toxic appearance, extremes of age, underlying illness, and abnormal chest examination).

Many noninfectious etiologies may result in inflammatory lung processes, including exposure to mineral dusts (e.g., silicosis), chemical fumes (e.g., chlorine and ammonia), toxic drugs (e.g., bleomycin), radiation, thermal injury, or oxygen toxicity. Immunologic diseases (e.g., sarcoidosis, Goodpas-ture’s syndrome, and collagen vascular disease) or hypersensi-tivity to environmental agents (e.g., farmer’s lung disease) may also result in pneumonia. Tumors may be confused with pneu-monia radiographically or may present initially as a postob-structive infection or adenopathy with peripheral infiltrates. Lymphangitic spread of lung malignancy may resemble inter-stitial pneumonia.

Aspiration

It is important to recognize the distinction between the acute aspiration of gastric contents or other liquids and bacterial pneumonia that may develop later as a complication of

934PA

RT 

III

■ M

edic

ine

and

Surg

ery

/ Se

Cti

on

tw

o •

Pul

mon

ary

Syst

em

Figure 74-4. Posteroanterior chest radiograph of an HIV-infected patient reveals interstitial disease mixed with patchy alveolar infiltrates. Pneumocystis jirovecii is the most common etiology, but bacterial pathogens and tuberculosis must also be considered.

aspiration. Aspiration of liquids into the lung disrupts surfac-tant and causes an inflammatory response that may lead to hypoxia and respiratory failure. Aspiration of acidic gastric con-tents is particularly damaging to lungs and is common in patients who are unconscious from intoxication or anesthesia or who have neurologic deficits. Patients may present initially with coughing or shortness of breath or may appear well ini-tially and then develop respiratory dysfunction during the next several hours.

Acute aspiration of acidic fluid into the lungs may produce fever, leukocytosis, purulent sputum, and radiographic infil-trates that mimic bacterial pneumonia. Although many of these patients go on to develop bacterial pneumonia, prophy-lactic administration of antibiotics is controversial. Some studies indicate that prophylactic antibiotics do not seem to be beneficial and may select for resistant organisms.24 Antibiot-ics should be initiated if the patient develops signs of bacterial pneumonia, including new fever, expanding infiltrate appear-ing more than 36 hours after aspiration, or unexplained dete-rioration. Systemic corticosteroids for acute aspiration are of no benefit.

■  MANAGEMENT

The possibility of communicable disease should suggest early isolation.25 Patients with a history of TB exposure, suggestive symptoms (e.g., persistent cough, weight loss, night sweats, and hemoptysis), or belonging to a group at high risk for TB (e.g., homeless, intravenous drug user, alcoholic, HIV risk, and immigrant from high-risk area) should be given a mask and placed in respiratory isolation before evaluation, including chest radiography.26 EDs that frequently care for patients at risk for TB should consider triage protocols to identify these individuals rapidly before patients, visitors, or staff are unnec-essarily exposed.27

Antimicrobials should be administered in the ED for patients who are being admitted to the hospital. Timely administration of antimicrobials has been associated with improved outcomes for hospitalized pneumonia patients28, although confounding factors limit the conclusions of these studies. A rush to treat-ment without a diagnosis of pneumonia, however, can result

in inappropriate antibiotic use. Although the Centers for Medicare and Medicaid Services have used specific time cutoffs for antibiotic administration as a quality measure, the IDSA/ATS guidelines for management of pneumonia do not support the use of a specific time cutoff. The antibiotics selected should cover the likely etiologies based on clinical, laboratory, radiologic, and epidemiologic information. However, the regimen should also be as selective as possible to avoid drug toxicity, emergence of resistance to broad-spectrum agents, and excessive cost.

The prevalence of drug-resistant S. pneumoniae (DRSP) is increasing. In most areas of the United States, high-level penicillin resistance occurs in approximately 15 to 20% of outpatient pneumococcal sputum isolates. DRSP that is resistant to penicillin is usually resistant to other β-lactams, macrolides, tetracyclines, and trimethoprim-sulfamethoxazole (TMP-SMX). Many extended-spectrum or “respiratory” fluo-roquinolones are available, such as levofloxacin, moxifloxacin, and gemifloxacin. Because oral bioavailability of fluoroquino-lones is high, oral therapy provides serum and tissue levels essentially equivalent to parenteral therapy.29 These agents are active against DRSP and other typical or atypical pneumo-nia pathogens. It is not clear, however, that in vitro resistance is related to adverse clinical outcome. Most cephalosporins and macrolides achieve adequate levels in serum and tissues to successfully treat S. pneumoniae respiratory tract infections, even if the laboratory reports that the organism is resistant.

CA-MRSA has rapidly emerged as the most common patho-gen isolated in community-acquired skin and soft tissue infec-tions. It is also increasingly recognized as a cause of severe, rapidly progressing pneumonia with sepsis, often in children or healthy young adults with influenza.9 Antimicrobials with consistent in vitro activity against CA-MRSA isolates include vancomycin, TMP-SMX, daptomycin, tigecycline, linezolid, ceftaroline, and ceftobipirole. Although vancomycin is used most often for documented MRSA infections, there is concern that vancomycin may be losing efficacy in light of increasing minimum inhibitory concentrations for vancomycin.30 Dapto-mycin is inactivated by pulmonary surfactant and would not be appropriate for empiric therapy. Empirical coverage of

Ch

apter 74 / P

neumonia

935

Table 74-1  Community-Acquired Pneumonia in Older Children and Adults: Outpatient Treatment

CLINICAL SETTING ANTIBIOTIC REGIMEN* COMMENTS

Previously healthy, no antimicrobials in last 3 mo

Doxycycline 100 mg PO bid Preferred for adolescent/young adult when likelihood of mycoplasma is high; variable activity vs. S. pneumoniae.

Azithromycin Treats common typical bacterial and atypical pathogens. Variety of dosing regimens: 500 mg once followed by 250 mg daily for 4 days; 500 mg PO daily for 3 days; 2 g PO extended-release suspension once. Can substitute clarithromycin.

Comorbidities, or antimicrobials in last 3 mo

Levofloxacin 750 mg PO daily for 5 days

Can substitute moxifloxacin or gemifloxacin.

Treats common typical and atypical bacterial pathogens; active vs. DRSP. Use if recently received β-lactam or macrolide.

Cefpodoxime 200 mg PO bid + azithromycin 500 mg PO daily

Use if recently received fluoroquinolones. Can substitute cefdinir, cefprozil, or amoxicillin/clavulanate for cefpodoxime. Variable activity against DRSP.

*Doses are for 70-kg adult with normal renal and hepatic function.DRSP, Drug-resistant S. pneumoniae.

MRSA should be strongly considered for patients with severe pneumonia associated with sepsis, especially those with con-current influenza, contact with someone infected with MRSA, or radiographic evidence of necrotizing pneumonia.

Appropriate agents for outpatient treatment of adults with CAP include macrolides, doxycycline, and fluoroquinolones with enhanced activity against S. pneumoniae (Table 74-1).1 In patients properly identified at low risk for complications and who will have careful outpatient follow-up, use of a macrolide or doxycycline is reasonable. For patients at higher risk of DRSP due to recent antibiotic use or comorbidities such as chronic heart, lung, liver, or renal disease, a respiratory fluoro-quinolone should be considered.

For patients who have received a fluoroquinolone within the previous few months, a combination of a macrolide plus a β-lactam agent (e.g., high-dose amoxicillin [1 g three times daily], amoxicillin-clavulanate [2 g orally twice daily], or cefpodoxime) is appropriate. Except for the administration of fluoroquinolones, these recommendations also apply to school-age children and adolescents, in whom mycoplasmal infection is common.

For patients whose illness is severe enough to require hos-pital admission and parenteral antibiotics, options include a combination of a β-lactam agent (e.g., ceftriaxone, cefotaxime, ampicillin-sulbactam, or ertapenem) and a macrolide (e.g., intravenous or oral azithromycin) or an extended-spectrum fluoroquinolone alone. These regimens are associated with lower mortality in elderly patients hospitalized for CAP compared with monotherapy with a third-generation cephalo-sporin. These regimens treat the most common bacterial pathogens, such as S. pneumoniae, M. catarrhalis, and H. influ-enzae, and atypical pathogens, such as Mycoplasma, Chla-mydophila, and Legionella spp. Intravenous azithromycin alone is another option, although this drug does not achieve signifi-cant serum levels and lacks significant activity against many aerobic gram-negative bacilli and DRSP. Azithromycin alone might be an appropriate choice for people with milder illness who are less likely to be bacteremic. If anaerobic organisms are suspected (e.g., aspiration), clindamycin or metronidazole could be added to the regimen, or the regimen could include an antibiotic with anaerobic activity, such as ertapenem, ampicillin-sulbactam, or piperacillin-tazobactam. Some quino-lones, such as moxifloxacin, are also active against anaerobes (Table 74-2).

Seriously ill patients who present with severe sepsis or septic shock require aggressive fluid resuscitation and may

benefit from more intensive management with vasopressors, transfusion, and inotropic agents as part of early goal-directed therapy.31 Severely ill and compromised patients are at rela-tively greater risk of infection due to S. pneumoniae, aerobic gram-negative bacilli, S. aureus (including MRSA), and, in some areas, Legionella sp. For pneumonia patients admitted to an ICU, adequate activity against DRSP may be more impor-tant. Outcomes with severe pneumococcal pneumonia may be better with combination therapy compared with a single agent such as a fluoroquinolone alone.32 A third-generation cephalo-sporin or β-lactam/β-lactamase inhibitor can be combined with a fluoroquinolone. Addition of an aminoglycoside should be considered if septic shock is present.

Patients with recent hospitalization, neutropenia, or under-lying bronchiectasis are at increased risk of infection with P. aeruginosa. Empirical therapy should include two agents with extended gram-negative activity, including P. aeruginosa. Empirical regimens include cefepime, imipenem, merope-nem, or piperacillin-tazobactam, plus either ciprofloxacin (high dose) or an aminoglycoside and a macrolide. For life-threatening pneumonia in populations at risk for MRSA, and for patients recently exposed to fluoroquinolones who may have fluoroquinolone-resistant S. pneumoniae, consider vanco-mycin or linezolid. The regimen should also cover atypical pathogens and gram-negative bacilli.

Since HCAP is associated with higher mortality and a greater likelihood of unusual pathogens, it is appropriate to give broader spectrum empirical therapy, usually with a combina-tion of antimicrobials to increase the chance that at least one antibiotic will be active against the causative pathogen. Appro-priate combinations include an antipseudomonal β-lactam agent, such as piperacillin-tazobactam, cefepime, imipenem, or meropenem, with either an aminoglycoside or a fluoroqui-nolone and vancomycin or linezolid for MRSA.33

For patients with AIDS, it is important to treat P. jirovecii and bacterial pathogens such as S. pneumoniae. TMP-SMX is the treatment of choice; the usual regimen is 20 mg/kg of TMP and 100 mg/kg of SMX daily in four divided doses, to be continued for 21 days.34 For most adult patients, a regimen of three ampules (80 mg of TMP and 400 mg of SMX per ampule) every 6 hours is appropriate. For patients allergic to sulfa, pentamidine can be given, 4 mg/kg over 1 hour. Toxici-ties of pentamidine include acute hypotension and hypogly-cemia. Because pentamidine has no activity against S. pneumoniae or other bacterial pathogens, it is important to add a cephalosporin or other antibacterial agent to the initial

936PA

RT 

III

■ M

edic

ine

and

Surg

ery

/ Se

Cti

on

tw

o •

Pul

mon

ary

Syst

em

Table 74-2  Community-Acquired Pneumonia in Older Children and Adults: Inpatient Antimicrobial Treatment

CLINICAL SETTING ANTIBIOTIC REGIMEN* COMMENTS

Community-acquired, nonimmunocompromised

Ceftriaxone 1 g q24h + azithromycin 500 mg q24h IV or PO

Could substitute cefotaxime, ampicillin-sulbactam, or ertapenem for ceftriaxone.

Respiratory fluoroquinolone (levofloxacin 750 mg IV q24h or moxifloxacin 400 mg IV q24h)

Treats most common bacterial and atypical pathogens. Active vs. DRSP.

Severe pneumonia (ICU) Ceftriaxone 1 g IV q24h + levofloxacin 750 mg IV q24h + vancomycin 1 g IV q12h

Can substitute cefotaxime, cefepime, ertapenem, or β-lactam/β-lactamase inhibitor for ceftriaxone. Can substitute moxifloxacin for levofloxacin. Can substitute linezolid for vancomycin.

Health care–associated pneumonia or severe pneumonia with neutropenia, bronchiectasis (risk for Pseudomonas)

Cefepime 2 g IV q12h + ciprofloxacin 500 mg IV q12h + vancomycin 1 g IV q12h

Can substitute other antipseudomonal β-lactam, such as piperacillin-tazobactam, imipenem, or meropenem, for cefepime. Can substitute aminoglycoside plus macrolide for ciprofloxacin.

Presumed PCP Trimethoprim-sulfamethoxazole 240/1200 mg IV q6h

Add ceftriaxone to TMP/SMX if severe, until PCP confirmed. Alternatives for sulfa allergy include pentamidine + third-generation cephalosporin; clindamycin + primaquine; or atovaquone + ceftriaxone.

*Doses are for a 70-kg adult with normal renal and hepatic function.DRSP, drug-resistant S. pneumoniae; ICU, intensive care unit; PCP, Pneumocystis pneumonia.

empiric regimen. Other options include clindamycin, 900 mg intravenously every 8 hours, plus primaquine, 15 mg orally daily; atovaquone; trimetrexate; or TMP plus dapsone. The addition of steroids (prednisone, 40 mg orally twice daily) reduces mortality and clinical deterioration in patients with partial arterial oxygen tension (Pao2) less than 70 mm Hg or alveolar-arterial gradient greater than 35 mm Hg. Myco-plasma, Legionella, and Chlamydophila spp. are uncommon eti-ologies of severe pneumonia in AIDS patients, so empirical therapy with erythromycin or doxycycline is not routinely recommended.

Many EDs initiate outpatient therapy in moderately ill patients, for whom hospitalization might be considered, with an initial parenteral dose of a long-acting antibiotic, such as ceftriaxone, and employ extended observation (i.e., 12–24 hours) while administering supportive care, such as hydration, antipyretics, and bronchodilators, before discharge on an oral regimen. Certain patients may also be brought back to the ED for follow-up in 24 hours and receive a second parenteral or observed oral dose of antibiotics. An extended-spectrum fluo-roquinolone (oral or parenteral) is another option that may be advantageous due to additional activity against atypical patho-gens and DRSP.

There is little experimental evidence that directly addresses the question of duration of therapy for pneumonia. Outpatient treatment for pneumonia is generally 10 to 14 days. A 5-day treatment course is possible with azithromycin or levofloxacin (750 mg daily).

Patients with a positive influenza antigen test or culture may benefit from antiviral treatment. Empirical antiviral treatment is reasonable with compatible clinical findings when influenza is in the community, and it may be associated with reduced mortality when started early in the course of influenza.35 Neur-aminidase inhibitors such as oseltamivir are recommended instead of amantadine and rimantadine because they are active against influenza A and B and because many circulating strains are resistant to these older agents.36 Inhaled zanamavir is not recommended for patients with underlying reactive airway disease because of concern about induced bronchospasm.

■  DISPOSITION

There is tremendous variability in physician admission decisions for pneumonia. The more common tendency is overestimation of disease severity, leading to hospitalization of patients at low risk for death or serious complications. The decision to hospitalize a patient with pneumonia does not necessarily mean that a prolonged inpatient stay is required. Observation for 12 to 24 hours in the ED or hospital may allow the early discharge of certain moderate-risk patients. Inpatient treatment of pneumonia is 15 to 20 times more expensive per patient than outpatient treatment, and most patients are more comfortable in a home environment.

Although no firm guidelines exist regarding hospital admis-sion, a scoring system may assist with hospitalization decisions. One commonly used system is based on the Pneumonia Patient Outcomes Research Team study, a prospectively vali-dated predictive rule for mortality among immunocompetent adults with CAP.37 This model (also known as the Pneumonia Severity Index [PSI]) suggests a two-step approach to assess risk. Patients in the lowest risk class who are recommended for outpatient management are those younger than age 50 years, without significant comorbid conditions (neoplasm, congestive heart failure, cerebrovascular disease, renal disease, liver disease, and HIV), and without the following findings on physical examination: altered mental status, pulse 125 beats/min or greater, respiratory rate 30 breaths/min or greater, systolic blood pressure less than 90 mm Hg, or temperature less than 35° C or 40° C or greater. Patients who do not fit the lowest risk category are classified into categories based on a scoring system that accounts for age, comorbid illness, physical examination findings, and laboratory abnormalities (Table 74-3). Hospitalization is recommended for patients with a score greater than 91, and brief admission or observation may be considered for patients with a score of 71 to 90. Although this method of assessing the likelihood of successful outpatient management is helpful, it can be cumbersome, is not modeled to predict acute life-threatening events, does not take into account dynamic evaluation over time, and has many

Ch

apter 74 / P

neumonia

937

Table 74-3  Scoring System for Pneumonia Mortality Prediction

PATIENT CHARACTERISTICS POINTS

Demographic factor Age Male No. years of age Female No. years of age −10 Nursing home resident 10Comorbid illness Neoplastic disease 30 Liver disease 20 Congestive heart failure 10 Cerebrovascular disease 10 Renal disease 10Physical examination finding Altered mental status 20 Respiratory rate ≥ 30 20 Systolic blood pressure ≤90 mm Hg 20 Temperature < 35° C or > 40° C 15 Pulse ≥ 125 beats/min 10Laboratory or radiographic finding Arterial pH < 7.35 30 Blood urea nitrogen >30 mg/dL 20 Sodium <130 mEq/L 20 Glucose > 250 mg/dL 10 Hematocrit < 30% 10 Arterial Po2 < 60 mm Hg 10 Pleural effusion 10

Adapted from Mandell LA, et al: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 37:1405, 2003.

important exceptions (e.g., an otherwise low-risk patient with severe hypoxia would be discharged by strict interpretation of this rule). Clinical judgment should supersede a strict inter-pretation of this scoring system. However, a study in which physicians were educated and provided the patient’s risk score revealed a significantly lower overall admission rate, cost savings, and similar quality-of-life scores compared to those for patients conventionally managed by their physicians.38 Addi-tional discharge criteria include improving and stable vital signs over a several-hour observation period, ability to take oral medications, an ambulatory pulse oximetry greater than 90%, home support, and access to follow-up.

A similar tool that is easier to use is the CURB-65 rule.39 This rule uses only five simple criteria to determine patients at lower risk for adverse events: confusion, uremia (blood urea nitrogen >20 mg/dL), respiratory rate greater than 30, blood pressure less than 90 systolic or greater than 60 diastolic, and age 65 or greater. The risk of 30-day mortality increases with a greater number of these factors present: 0.7% with zero factors, 9.2% with two factors, and 57% with five factors. Patients with zero or one feature can receive outpatient care, those with two should be admitted, and ICU care should be considered for those with three or more. No randomized trials of hospital admission strategies directly compare the PSI to the CURB-65 score. In a comparison of scores in the same population of CAP patients, the PSI yields a slightly higher percentage of patients in the low-risk category, with a similar low mortality rate.40

The disposition of HIV-infected patients with possible PCP is dictated by the likelihood of progression to severe disease and by the feasibility of close outpatient follow-up. Factors associated with decreased survival in AIDS patients with PCP include a history of prior PCP, anemia, hypoxemia, and medical

Table 74-4  Criteria for Severe Community-Acquired Pneumonia

Minor criteria* Respiratory rate ≥30 breaths/min†

Pao2/Fio2 ratio ≤250†

Multilobar infiltrates Confusion/disorientation Uremia (BUN level, ≥20 mg/dL) Leukopenia‡ (WBC count, <4000 cells/mm3) Thrombocytopenia (platelet count, <100,000 cells/mm3) Hypothermia (core temperature, <36° C) Hypotension requiring aggressive fluid resuscitationMajor criteria Invasive mechanical ventilation Septic shock with the need for vasopressors

*Other criteria to consider include hypoglycemia (in patients who do not have diabetes), acute alcoholism/alcoholic withdrawal, hyponatremia, unexplained metabolic acidosis or elevated lactate level, cirrhosis, and asplenia.

†A need for noninvasive ventilation can substitute for a respiratory rate >30 breaths/min or a Pao2/Fio2 ratio <250.

‡As a result of infection alone.

Adapted 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. Clin Infect Dis 44:S27, 2007.

BUN, blood urea nitrogen; Pao2/Fio2, arterial oxygen pressure/fraction of inspired oxygen.

comorbidity.41 Patients without multiple poor prognostic factors may be discharged from the ED with close outpatient follow-up, ideally within 2 or 3 days. Because of the potential toxicity of TMP-SMX, empirical treatment with this agent for well-appearing patients with a low probability of disease is not recommended. An empirical trial of a macrolide may be indi-cated for treatment of bronchitis or mild CAP in a patient at low risk for PCP (e.g., recent CD4 count >350/mm3). Any deterioration on outpatient oral antibiotics should prompt admission for a more extensive evaluation. Some clinicians initiate oral outpatient therapy with TMP-SMX or an alternate drug for patients with a high probability of PCP and favorable clinical parameters, but this should be done only if the patient can be followed closely.

The decision to admit a patient to the ICU is straightfor-ward when patients are intubated or require vasopressors. It is more difficult to identify patients who do not require these interventions initially but may be at greater risk for deteriora-tion and require a level of monitoring that may be beyond that available on the typical hospital ward. Objective criteria using the PSI (class V) and CURB-65 are proposed but have not been prospectively validated for the ICU admission decision.42 When similar criteria were retrospectively studied in a cohort of CAP patients, they did not perform better than actual physi-cian decisions.43 IDSA/ATS guidelines include criteria for defining severe CAP (Table 74-4), but these have not been validated.1 The decision to admit a patient to the hospital largely reflects the potential for acute deterioration. Likewise, some rate of floor to ICU transfer is inevitable.

Most patients with CAP do not need respiratory isolation. Patients who could pose a threat of transmission to other patients (e.g., influenza, varicella, TB, and plague) should be isolated. People with fever and respiratory symptoms who have been traveling in an area with SARS or avian influenza should also be isolated. Neutropenic patients generally are placed in reverse isolation. HIV-infected patients who present with pneumonia should be isolated until TB can be evaluated by sputum acid-fast bacilli smears; this is particularly true for

938PA

RT 

III

■ M

edic

ine

and

Surg

ery

/ Se

Cti

on

tw

o •

Pul

mon

ary

Syst

em

patients with other risk factors for TB. The chest radiograph cannot exclude TB in AIDS patients because it often does not have the typical appearance of TB. Isolation should be strongly considered for others at high risk for TB, such as inner-city homeless people and intravenous drug users.

■  ACUTE RESPIRATORY DISTRESS SYNDROME

Acute respiratory distress syndrome (ARDS) is a form of non-cardiogenic pulmonary edema that is a result of the nonspecific response of the lung to a variety of insults. ARDS is defined as respiratory failure indicated by a requirement for mechani-cal ventilation and Pao2/fraction of inspired oxygen ratio 200 or less in the appropriate clinical setting with one or more recognized risk factors. This presentation is accompanied by new, bilateral, diffuse, patchy or homogeneous pulmonary infiltrates on the chest radiograph, with no clinical evidence of heart failure, fluid overload, or chronic lung disease (pulmo-nary artery occlusion pressure ≤18 mm Hg).44

Respiratory failure results from damage to the region of alveolar-capillary oxygen exchange with increased permeabil-ity to plasma fluid and protein. ARDS can be caused by a direct injury to the lungs (e.g., aspiration of liquids or inhaled toxins)

or may result from circulating inflammatory mediators associated with multisystem trauma, sepsis, or numerous drugs (Box 74-1). A variety of mediators are implicated in the devel-opment of ARDS, including neutrophil production of prote-ases and oxygen radicals, interleukins and other cytokines, tumor necrosis factor, and complement factors. This syndrome most often develops in patients already seriously ill in the hospital.

Treatment of ARDS is primarily supportive. High inspira-tory pressures and positive end-expiratory pressure are often required to maintain oxygenation, so it is difficult to avoid barotrauma. Peak airway pressures should be kept at less than 35 cm H2O if possible. Outcome is improved with use of reduced tidal volumes, allowing permissive hypercapnia.45 Other ventilator techniques that may be beneficial include inverse-ratio ventilation with prolonged inspiratory time and use of a high-frequency oscillatory ventilator.46 Fluid balance must avoid increased pulmonary capillary pressure while maintaining organ perfusion. Prone positioning during ventila-tion may improve distribution of perfusion to ventilated lung regions, but improvement in oxygenation is variable. Inhaled nitric oxide, N-acetylcysteine, prostaglandin E1, ketoconazole, and nonsteroidal anti-inflammatory drugs produce variable results.47 Corticosteroids do not reduce mortality in early ARDS but may have benefit in the late fibroproliferative phase. Although mortality is high, most survivors recover normal or near-normal lung function. Research is focusing on preventive measures for ARDS that may be used in the ED for patients at risk. Agents under study include aerosolized surfactant, free radical scavengers, prostaglandin inhibitors, and agents that can modify interleukins and other inflamma-tory mediators.

SepsisShockToxic gas or smoke inhalationAspiration

Gastric contentsNear-drowningHydrocarbons/solvents

PneumoniaDrug reaction

SalicylatesOpiatesTricyclic antidepressantsCyclosporineAmiodaroneCancer chemotherapeutic agents (e.g., bleomycin)Hydrochlorothiazide

TraumaBurnsTransfusion reactionRadiation injuryPancreatitisThromboembolismFat embolismAir embolismAmniotic fluid embolismEclampsiaNeurogenic (e.g., subarachnoid hemorrhage, head trauma)Disseminated intravascular coagulationHigh-altitude exposureOxygen toxicityCardiopulmonary bypass

BOX 74-1 Conditions AssoCiAted with ACute RespiRAtoRy distRess syndRome

KEY CONCEPTS

■ Empirical antimicrobial therapy should be started in the ED for patients admitted with pneumonia. Empirical therapy should treat the most likely pathogens, including S. pneumoniae, H. influenzae, M. pneumoniae, and C. pneumoniae.

■ HIV or other immunosuppressive conditions should be considered in all patients in whom pneumonia is suspected.

■ Communicable diseases should be considered and isolation initiated when appropriate, including suspected TB, SARS, or influenza.

■ The disposition of patients with pneumonia is dictated by the patient’s underlying medical conditions, the severity of illness and likelihood of clinical deterioration, and the feasibility of home care and outpatient follow-up.

■ Mycoplasma pneumonia may present as a dense infiltrate, or pneumococcal pneumonia may present as a diffuse interstitial infiltrate.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.