Harvey B. Simon MD, FACP1
Associate Professor of Medicine
1Harvard Medical School; Health Sciences and Technology Faculty, Massachusetts Institute of Technology; Physician, Massachusetts General Hospital
The author has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.
Pulmonary infections span a wide spectrum, ranging from self-limited to life-threatening and from acute to chronic. This chapter details the pathophysiology, epidemiology, general features, and treatment of pulmonary infections, particularly bacterial pneumonia [see Table 1].
Table 1 Major Causes of Pulmonary Infection
Although overall hospitalization rates are declining, hospitalizations for acute lower respiratory tract infections have increased steadily since 1980, particularly in the elderly.1 Taken together, pneumonia and influenza rank as the sixth leading cause of death in the United States and lead all other infectious diseases in this respect. Antibiotics have greatly modified the natural history of pneumonia and have sharply reduced the case-fatality rate. At the same time, the widespread use of antimicrobial agents has led to the emergence of drug-resistant strains, thereby altering and expanding the range of pathogens responsible for pneumonia, especially in hospitalized patients. The growing population of patients with chronic obstructive pulmonary disease (COPD) and other debilitating illnesses and the use of respiratory therapy and immunosuppressive drugs have contributed to the increasing incidence of nosocomial and opportunistic pneumonias, which are associated with a very high mortality.
Host Defense Mechanisms
The lung is normally sterile. In healthy people, an intricate series of defense mechanisms maintain that sterility in the face of heavy bacterial colonization of the upper respiratory tract, inhalation of thousands of bacteria in droplet nuclei each day, and nearly universal aspiration of upper airway secretions during normal sleep each night.2 Defects in host defense mechanisms account for many cases of pneumonia [see Table 2]; even the use of gastric acid suppressive drugs increases risk.3
Table 2 Host Defense Mechanisms against Pulmonary Infection
Transmission of Organisms to Lungs
Inhalation of aerosols and droplets account for the transmission of respiratory viruses, such as severe acute respiratory syndrome (SARS)2and influenza virus, which cause highly contagious infections that often occur in epidemics.4 Other nonviral agents produce pneumonia through similar means of spread. Such agents include mycoplasmas, which are transmitted from person to person and cause primary atypical pneumonia; Coxiella burnetii, which is transmitted from livestock and causes Q fever; and Chlamydophila (formerly Chlamydia), which is transmitted from birds (C. psittaci) or humans (C. pneumoniae). Mycobacterium tuberculosis is spread from person to person by aerosols. The organisms that are responsible for causing the systemic mycoses are probably inhaled from sources in nature. Of bacteria that cause pneumonia, Legionella pneumophila is the species most likely to be spread by inhalation of aerosolized organisms that originate in contaminated freshwater.
Pneumococci are spread from person to person by aerosolized droplets, but pneumococcal pneumonia is not highly contagious and is caused in many cases by microaspiration of nasopharyngeal organisms, the second major mechanism of infection.4 Aspiration of nasopharyngeal organisms occurs in nearly all persons during sleep and is probably responsible for most bacterial pneumonias, including staphylococcal and gram-negative bacillary pneumonias; it certainly accounts for the necrotizing pneumonitis that results from the aspiration of mixed mouth flora.
Hematogenous seeding, the third and least common mechanism for pneumonia, accounts for occasional cases of staphylococcal pneumonia that complicate tricuspid valve endocarditis or septic thrombophlebitis. This mechanism is also responsible for various gram-negative bacillary pneumonias in patients with bacteremia.
Once organisms succeed in bypassing host defense mechanisms to arrive at the alveoli, a variety of tissue responses may ensue, depending on the nature of the pathogen and on the integrity of the host inflammatory response. Although the inflammatory response is essential for the control of infection, it can produce tissue damage, impair ciliary action, and impede phagocytosis.
The inflammatory response to Streptococcus pneumoniae or Haemophilus influenzae often produces lobar consolidation, but these infections rarely result in tissue necrosis. In contrast, staphylococci and many gram-negative bacilli often produce necrosis, which can lead to cavitation and even frank abscess formation; a peribronchial distribution is characteristic, but lobar consolidation may occur. Viruses generally produce interstitial inflammation rather than air-space exudates. The infection is usually bilateral and causes diffuse alveolar damage and interstitial edema. Similar tissue responses may be initiated by Mycoplasma, Chlamydophila, and Legionella species; by gram-negative bacteremia (shock lung); and by other causes of the acute respiratory distress syndrome. Mycobacteria and fungi typically evoke a slow granulomatous response.
Epidemiology and Etiology
Like other respiratory tract illnesses, pneumonia is most common in the winter because of the seasonal increase in viral infections and the close contact of persons confined indoors. Community-acquired pneumonias are a major problem in the United States, with an estimated four million cases occurring annually.5 About one million cases require hospitalization,5 and at least 60,000 result in death.6 The mortality of community-acquired pneumonia ranges from less than 1% in patients who are not ill enough to require hospitalization to 13.7% for hospitalized patients, 19.6% for bacteremic patients, and 36.5% for patients admitted to intensive care units.7 Clinical and laboratory data can be used to determine which patients are at greatest risk for death and thus require hospitalization and aggressive therapy. Comorbidity is the strongest risk factor, with neoplastic disease, neurologic disease, and alcoholism being particularly worrisome.8 Advanced age is another strong predictor of risk,6 in part because older patients often underreport symptoms.7,8,9 Physical findings of high fever, tachypnea, confusion, hypoxia, and hypotension also portend an adverse result.10 The presence of extensive radiographic abnormalities, especially bilateral pleural effusions, is associated with higher risk, as are laboratory abnormalities such as hypoxia, azotemia, acidosis, hyponatremia, and hypophosphatemia. Postobstructive, aspiration, gram-negative, and staphylococcal pneumonias are associated with a high mortality. Patients lacking these adverse prognostic indicators have a low risk of death and can usually be treated successfully as outpatients. Patients hospitalized for pneumonia have a greater than fivefold likelihood of requiring subsequent hospitalization for pneumonia than patients with other serious illnesses; it is important to be sure their influenza and pneumococcal immunizations are up to date before discharge.11Patients hospitalized for pneumonia also have substantially higher long-term mortality than age-matched control subjects.11,12
In the preantibiotic era, pneumonia was nearly synonymous with S. pneumoniae infection. Pneumococci still account for 30% to 60% of all community-acquired pneumonias for which an etiology can be determined.13 Pneumococci are particularly likely to be responsible for community-acquired pneumonias severe enough to require hospitalization and for pneumonia in persons older than 60 years.14
The second most common bacterial cause of community-acquired pneumonia is H. influenzae, which accounts for about 10% of cases13; patients with COPD are particularly vulnerable. Although infection with Moraxella catarrhalis is much less common than infection with H. influenzae, M. catarrhalis is being recognized increasingly as a cause of community-acquired pneumonia. Like H. influenzae, M. catarrhalishas a predilection for patients with cardiopulmonary disease. In rare cases, M. catarrhalis causes fulminant pneumonia, bacteremia, or both.
Staphylococci and gram-negative bacilli are much less common but more serious causes of community-acquired respiratory infections. Significant predisposing conditions are required for these organisms to produce pneumonia. In the community setting, staphylococcal pneumonia usually follows influenza. Gram-negative pneumonias in the community setting are most common in patients who have recently been hospitalized and treated with antibiotics, in smokers and others with chronic lung disease, and in immunosuppressed patients.2,15,16Exposure to aerosols of contaminated water is an additional risk factor for infection with Pseudomonas aeruginosa,17 and alcoholism predisposes to Klebsiella pneumonia. Meningococcal pneumonia is rare.18 A variety of other bacteria, including L. pneumophila, can cause pneumonia in the community setting.14 Aspiration of mixed mouth flora is responsible for infection in some patients.
In about half the patients with community-acquired pneumonia, the etiologic agent cannot be identified.19 Especially in younger patients, many of these infections result from so-called atypical agents, which lack the cell wall structure that characterizes ordinary bacteria. In a study of patients with a mean age of 41 years, for example, M. pneumoniae accounted for 22.8% of community-acquired pneumonias, and C. pneumoniae for 10.7%; in addition, influenza A accounted for 2.7%.19 C. pneumoniae is also increasingly being recognized as a cause of community-acquired pneumonia in adults with COPD [see 14:III Chronic Obstructive Diseases of the Lung]. Respiratory tract viruses, including respiratory syncytial virus, adenoviruses, and influenza or parainfluenza viruses,20 can also cause community-acquired pneumonias in persons of all ages.1,14
Pneumonia is the second most common nosocomial infection in the United States21; about 200,000 cases occur annually, accounting for 17.8% of all hospital-acquired infections and 40,000 to 70,000 deaths. Risk factors for nosocomial infections include aspiration, COPD or other chronic severe illnesses, thoracic and upper abdominal surgery, and treatment in an ICU. Patients who require mechanical ventilation are particularly at risk; pneumonia develops in 9% to 24% of patients who require intubation for more than 48 hours.22 Ventilated patients who acquire nosocomial pneumonia have a much higher mortality (54%) than comparably ill ventilated patients who do not acquire pneumonia (27%).
The bacterial etiologies of hospital-acquired pneumonias are very different from those of community-acquired pneumonias. Many nosocomial pneumonias are polymicrobial; gram-negative bacilli are isolated in 47% of patients, anaerobes in 35%, and Staphylococcus aureus in 26%. In contrast, pneumococci account for no more than 10% of hospital-acquired pneumonias. Other organisms that are associated with community-acquired infections can occasionally cause pneumonia in the hospital setting; such organisms include Legionella species, M. pneumoniae, and C. pneumoniae.23
Pseudomonas, Klebsiella, and Escherichia coli are the most commonly implicated causes of gram-negative pneumonias. Nosocomial gram-negative pneumonias often occur in patients with serious underlying diseases; as a result, mortality is as high as 30% to 50%. Previous antibiotic administration, respiratory therapy, chronic illness, and confinement to bed predispose to oropharyngeal colonization with gram-negative bacilli, which occurs in up to 45% of ICU patients and precedes pneumonia in most cases. Upper intestinal colonization has also been implicated, but its importance is uncertain. The 2005 guidelines of the American Thoracic Society and the Infectious Diseases Society of America consider health care-associated pneumonia to be part of the spectrum of hospital-acquired pneumonias.24 Patients who develop pneumonia within 90 days of being hospitalized in an acute care hospital for 2 or more days should be approached as if they had hospital-acquired pneumonia, as should residents of long-term care facilities, hemodialysis patients, and patients who received I.V. antibiotics, wound care, or chemotherapy within 30 days of developing pneumonia.25
Pneumonia in Immunosuppressed Patients
Immunosuppressed patients, particularly those with AIDS,26,27 are vulnerable to a broad range of pulmonary pathogens. In addition to being susceptible to the many organisms that produce community- and hospital-acquired pneumonias, these patients are susceptible to many opportunistic microbes that are unlikely to cause pneumonia in immunologically competent hosts.28 Such organisms include bacteria (e.g.,Pseudomonas, Nocardia, and Legionella), mycobacteria (e.g., M. avium complex), viruses (e.g., cytomegalovirus and herpesvirus), fungi (e.g., Candida, Aspergillus, Mucor, and Pneumocystis jiroveci [formerly P. carinii]), and protozoa (e.g., Toxoplasma gondii). As a result, immunosuppressed patients require an aggressive approach to diagnosis and therapy [see 7:X Infections Due to Haemophilus, Moraxella, Legionella, Bordetella, and Pseudomonas, 7:XI Infections Due to Brucella, Francisella, Yersinia pestis, and Bartonella, and 7:XXXVIII Mycotic Infections in the Compromised Host].
Classic signs and symptoms of pneumonia include cough, sputum production, chest pain, fever, chills, hypoxia, and dyspnea. Although the results of physical examination in patients with typical pneumonias are often nonspecific, the examination may reveal rales, rhonchi, or bronchial breath sounds, as well as percussion dullness over the involved segments of the lung. Pleural effusions may accompany pneumonia. The chest x-ray shows infiltrates.
Nonbacterial and bacterial pneumonias have differing clinical presentations. Although both types of pneumonia can affect persons of all ages, nonbacterial pneumonias are most common in older children and young adults. Patients with viral, mycoplasmal, or chlamydial pneumonias will often complain of a severe hacking cough, but substantial sputum production is unusual. Sputum production is also minimal in patients with Legionnaires disease, but these patients are usually sicker than those with nonbacterial pneumonias [see 7:X Infections Due to Haemophilus, Moraxella, Legionella, Bordetella, and Pseudomonas].
Patients with bacterial pneumonias are more likely to have copious sputum production—as well as an abrupt onset of illness, high temperatures, chills, and development of significant pleural effusions—than are patients with nonbacterial pneumonias.
On physical examination, a patient with bacterial pneumonia generally looks sicker than a patient with nonbacterial pneumonia, and chest examination of patients with bacterial pneumonia often reveals signs of consolidation or at least localized rales and rhonchi. In contrast, the chest examination of patients with nonbacterial pneumonias typically shows only fine rales, and often, the physical findings are less extensive than the radiologic abnormalities.
Patients with bacterial pneumonias are more likely to have polymorphonuclear leukocytosis. If the chest x-ray reveals lobar or segmental consolidation, abscess formation, or significant pleural effusion, bacterial pneumonia is more likely. A patchy infiltrate can occur in either process, but a true interstitial infiltrate suggests a nonbacterial etiology. The absence of radiographic abnormalities should not supersede clinical judgment in managing patients with suspected pneumonia.14,29 Computed tomography is extremely helpful in diagnosing complex infections.
Although the sputum examination has been the traditional key to the etiologic diagnosis of pneumonia, the high success rate of empirical therapy for uncomplicated community-acquired pneumonia has diminished the importance of, as well as the use of, the sputum examination. Still, microscopic examination and culture of a good sputum specimen30 can be helpful, particularly in complicated or unusual cases. The sputum of patients with bacterial pneumonia is typically thick and either green or brownish and is sometimes blood tinged. If the patient cannot expectorate spontaneously, pulmonary physiotherapy, intermittent positive pressure ventilation with humidified air, or nasotracheal suction may be used to obtain the specimen. The Gram stain of sputum from patients with bacterial pneumonia usually reveals abundant polymorphonuclear leukocytes and will often disclose the primary pathogens. Patients with nonbacterial pneumonias or Legionnaires disease generally produce only scant quantities of thin sputum. In influenzal pneumonia, the sputum may be bloody. The Gram stain of sputum from patients with pneumonia from atypical agents reveals an absence of bacteria and a scant cellular response; in patients with mycoplasmal pneumonia, mononuclear cells may predominate.31 It can be difficult to determine the etiology in patients with nosocomial pneumonias; prolonged hospitalization, antibiotic administration, and ventilatory therapy predispose to colonization with organisms that contaminate sputum specimens but can also cause pneumonia. Bronchoalveolar lavage is effective in identifying the responsible pathogen.32
Kits for the detection of nucleic acids from Legionella, Mycoplasma, and mycobacterial species in sputum are currently available, and polymerase chain reaction tests may soon be available for the detection of other pathogens.33 Urinary antigen assays may assist in the diagnosis of Legionella34 and pneumococcal35 pneumonias. Although blood cultures are of limited value in the management of patients with community-acquired pneumonias, they should be obtained in patients who are ill enough to require hospitalization.36
In immunocompromised patients, numerous opportunistic agents can cause pneumonia, and aggressive techniques may be required to obtain a satisfactory specimen. Although invasive procedures rarely are necessary in immunocompetent patients, they may be required in patients who present with unusual features, are critically ill, or fail to respond to conventional therapy. Procedures such as transtracheal aspiration, bronchoscopy (sometimes including transbronchial biopsies), bronchial brushing, and percutaneous lung taps may be necessary; bronchoalveolar lavage is a particularly useful technique and is generally well tolerated.37 If these less invasive techniques fail to produce a diagnosis, open lung biopsy should be considered.
Diagnosis of Ventilator-Associated Pneumonia
The diagnosis of ventilator-associated pneumonias may be based on clinical criteria, Gram stains and cultures of tracheal aspirates, and pulmonary infection scores or invasive techniques.38,39 Even with bronchoscopy and lavage, the diagnosis can be difficult; the detection of a marker called soluble triggering receptor expressed on myeloid cells (sTREM-1) in lavage fluid may be an indication of ventilator-associated pneumonia.40
Noninfectious diseases can be mistaken for infections of the respiratory tract. Asthmatic bronchitis and hypersensitivity pneumonitis are common examples. COPD, including emphysema and bronchiectasis, may be misleading if previous x-rays are not available. Atelectasis, pulmonary infarction, pulmonary edema, and lung tumors may also be confused with pneumonia. Hypersensitivity reactions and toxins—in the form of aerosols, systemic drugs, or chemicals—produce clinical illnesses and pulmonary infiltrates simulating those of infectious pneumonia. Radiation pneumonitis, sarcoidosis, vasculitis, uremic pneumonitis, pulmonary hemorrhage, eosinophilic pneumonia, organizing pneumonia, and lipoid pneumonitis are included in the differential diagnosis [see 14:V Chronic Diffuse Infiltrative Lung Disease].
One of the primary considerations in patients with a lower respiratory tract infection is to distinguish between acute bronchitis and pneumonia. The distinction is anatomic rather than etiologic because the same basic range of organisms can cause the two syndromes. As a result, these conditions often overlap clinically, but bronchitis requires less intensive therapy [see Acute Bronchitis, below].
Certain general principles are useful in the care of all patients with pneumonia. Adequate hydration is important to help clear secretions; hydration can be achieved by systemic administration of fluids and local airway humidification. Expectorants such as guaifenesin may be helpful in loosening the sputum. Although clinical trials have demonstrated that chest physiotherapy does not hasten the resolution of pneumonia, this traditional therapeutic modality may provide symptomatic benefit to patients with copious airway secretions. In general, the cough reflex should not be suppressed in patients with bacterial infections, because coughing is an important mechanism for clearing secretions. If severe paroxysms of coughing produce respiratory fatigue or harsh pain, however, temporary relief may be obtained with small doses of codeine. Chest pain should be treated with analgesics that do not suppress cough. If hypoxia is present, oxygen should be administered. Persons who have COPD and retain carbon dioxide must be monitored very closely because oxygen therapy can lead to respiratory depression.
Specific antimicrobial therapy depends on the etiologic agent. Whereas culture and sensitivity testing require at least 24 to 48 hours to provide definitive information, the clinical setting, chest x-ray, and sputum Gram stain usually enable the physician to make a reasonable presumptive diagnosis and to initiate therapy at once. Treatment can then be modified as necessary on the basis of culture results. Because antibiotics penetrate sputum by passive diffusion, it is important to maintain adequate blood levels of these drugs. The administration of antibiotics by aerosol is not indicated for most cases of pneumonia but may help patients with cystic fibrosis and endobronchialPseudomonas infections.41
It is best to choose an antibiotic regimen directed specifically at organisms seen on Gram stain and, after 24 to 48 hours, identified from sputum or blood cultures. Even if these data are lacking, however, a reasonable choice of initial antimicrobial therapy can be made on the basis of the epidemiologic setting and clinical features.
Several factors are responsible for rapid changes in the empirical treatment of community-acquired pneumonias: the emergence of drug-resistant pneumococci; the increasing population of elderly or chronically ill patients who are vulnerable to infections caused by H. influenzae and M. catarrhalis; the increased importance of atypical pathogens such as M. pneumoniae, C. pneumoniae, and L. pneumophila; and the availability of new fluoroquinolones with enhanced activity against gram-positive cocci (including penicillin-nonsensitive pneumococci) and anaerobes (including mouth flora). For patients who do not require hospitalization, several therapeutic options are available [see Tables 3 and 4].42 Erythromycin is cost-effective, but the so-called advanced macrolides clarithromycin and azithromycin may be preferable because of their better gastrointestinal tolerability and their activity against Haemophilus and Moraxella species.43,44Doxycycline is an effective and inexpensive alternative.45 However, because of the increasing prevalence of drug-resistant pneumococci, use of one of the so-called respiratory fluoroquinolones (i.e., levofloxacin, moxifloxacin, and gemifloxacin) is recommended.46 These agents have excellent activity against the major causes of community-acquired pneumonia, and prospective trials have been very favorable.47 They are a particularly good choice for patients who have recently received antibiotic therapy.48 The use of high-dose levofloxacin (750 mg a day) may enable short-course (5-day) therapy, potentially improving compliance and reducing costs.49 The respiratory fluoroquinolones may also emerge as drugs of choice for patients with community-acquired pneumonia who require hospitalization; levofloxacin and moxifloxacin are available in preparations for intravenous administration [see Table 5]. Levofloxacin-resistant pneumococci are still uncommon, but their emergence is a concern.50,51 In addition, dual therapy may be preferable for patients with severe pneumococcal pneumonia.52,53 For that reason, patients with moderate to severe community-acquired pneumonia may benefit from cefotaxime or ceftriaxone in combination with a macrolide or a fluoroquinolone.42 Because vancomycin is active against virtually all pneumococci, it can be substituted for the third-generation cephalosporin in patients allergic to β-lactam antibiotics; linezolid is another alternative.54 When aspiration is suspected, penicillin, clindamycin, or metronidazole is useful; amoxicillin-clavulanate, imipenem, meropenem, and respiratory fluoroquinolones are also active against oral anaerobes [see Table 6].
Table 3 Initial Empirical Antibiotic Therapy in Patients with Suspected Community-Acquired Pneumonia*†42
Table 4 Initial Antibiotic Therapy for Community-Acquired Pneumonia in Outpatients*
Table 5 Initial Antibiotic Therapy for Community-Acquired Pneumonia in Patients Who Require Hospitalization*
Table 6 Antibiotic Choices for Aspiration Pneumonia*
In all cases, antibiotic therapy should be tailored to the results of culture and sensitivity, the clinical response, and the occurrence of side effects. Many patients who require intravenous antibiotics initially can be switched to oral therapy within 3 days,55 facilitating early hospital discharge.56 In most patients with uncomplicated pneumococcal pneumonia, antibiotics can be discontinued after 3 afebrile days; most patients with other bacterial pneumonias are treated for 7 to 14 days, and most with atypical pneumonias are treated for 10 to 21 days.
Immunizations may help prevent community-acquired pneumonia. Each fall, influenza vaccine should be offered to patients 50 years of age and older and to other vulnerable persons [see 7:XXV Respiratory Viral Infections]. Pneumococcal polysaccharide vaccine should be offered to persons 65 years of age and older and to others who are at increased risk57 [see 7:I Infections Due to Gram-Positive Cocci]. Patients who have recovered from one bout of pneumonia may benefit from both vaccines.11
Because gram-negative bacilli and S. aureus cause many nosocomial pneumonias, patients with hospital-acquired pneumonias require broad antimicrobial coverage until the results of Gram stains, cultures, and sensitivity tests permit focused therapy. Options for the initial treatment of hospital-acquired pneumonia include ticarcillin-clavulanate or piperacillin-tazobactam; meropenem or imipenem-cilastatin; a third-generation cephalosporin plus nafcillin or vancomycin; a first-generation cephalosporin plus an aminoglycoside; or vancomycin plus an aminoglycoside. The prevalence of resistant bacteria in a particular hospital or patient care unit should help guide the initial therapy; for example, if methicillin-resistant staphylococci are common, vancomycin is a desirable component of the initial therapy, and when multidrug-resistant Klebsiella organisms are common, meropenem or imipenem-cilastatin should be considered. Linezolid is an effective alternative to vancomycin for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.58 Patients with ventilator-associated nosocomial pneumonia may respond as well to 8 days of antibiotics as they do to 15 days of therapy.59 Because of the high mortality associated with pneumonias in the intensive care unit, strategies to prevent pneumonia in the ICU have been studied,60 and comprehensive guidelines are available.61
Infections Caused by Legionella Species
Epidemiology and Etiology
Since it was first identified in 1976, Legionnaires disease has become recognized as a common cause of both community-acquired and hospital-acquired pneumonias. Worldwide, it accounts for between 2% and 15% of all community-acquired pneumonias severe enough to require hospitalization.62 It is estimated that 10,000 to 25,000 cases occur in the United States each year, but only 1,200 to 1,500 are reported annually.63 Legionnaires disease is caused by L. pneumophila, a fastidious, filamentous, flagellated, aerobic gram-negative bacillus. The organism can be grown on charcoal-yeast extract agar; optimal growth occurs at 35° C in 5% carbon dioxide, but growth is slow, and a period of 3 to 6 days is required for colonies to form.
At least nine serogroups of L. pneumophila exist; most clinical isolates belong to serogroup 1. By special staining techniques, large numbers of the organism can be identified in tissue sections of alveoli, both within macrophages and extracellularly. Virulence factors of L. pneumophila and various extracellular enzymes that the organism secretes have been identified. L. pneumophila is able to survive intracellularly in host leukocytes. Antibody is not protective, but cell-mediated immunity does promote recovery and prevent reinfection.
In nature, L. pneumophila survives principally in water and, to a lesser extent, in soil. Human disease is acquired primarily by inhalation of aerosols contaminated with organisms; person-to-person transmission has not been documented. Contaminated water systems have been responsible for both community-acquired and hospital-acquired outbreaks [see 7:X Infections Due to Haemophilus, Moraxella, Legionella, Bordetella, and Pseudomonas].
The attack rate for Legionnaires disease appears to be higher in elderly persons and persons with underlying conditions such as COPD, neoplastic disease, organ transplants, and renal failure. Although L. pneumophila is a relatively uncommon pathogen in persons infected with HIV, it can cause severe disease in them.
Legionnaires disease is characterized by a 1-day prodrome of myalgias, malaise, and slight headache after an incubation period of 2 to 10 days. Acute onset of high fever, shaking chills, nonproductive cough, tachypnea, and, often, pleuritic pain ensues. The cough may subsequently become slightly productive, but the sputum is not purulent. Obtundation or toxic encephalopathy is common, but frank meningitis is not a feature. Abdominal pain, vomiting, and, especially, diarrhea may be present. Signs of consolidation on lung examination are present infrequently, but rales are commonly heard. Chest radiographs show patchy or interstitial infiltrates, which often progress to areas of nodular consolidation in a single lobe or multiple lobes; minimal effusions are present in up to one third of cases. Abscess formation is uncommon but has been observed. Pulmonary fibrosis may occur in some survivors.
Although pneumonia is present in nearly all patients with Legionnaires disease, extrathoracic symptoms can be the presenting or predominant features. Central nervous system, GI, and renal manifestations are especially common. L. pneumophila has been isolated from blood cultures, and the organism can be found in many organs both in immunosuppressed patients and in previously normal patients who are afflicted with severe disease. Extrapulmonary manifestations include ocular and pericardial involvement, perirectal abscess, wound infection, peritonitis, cellulitis, rhabdomyolysis and acute renal failure, neutropenia, hemolytic anemia, and thrombotic thrombocytopenic purpura. Implanted devices such as heart valves and hemodialysis fistulas can become colonized.
A nonpneumonic form of legionellosis called Pontiac fever has a short incubation period and a low mortality. It has been responsible for at least four outbreaks of illness, including several related to whirlpools and hot tubs.
The peripheral white blood cell count is mildly elevated to between 8,000 and 16,000/mm3. Cold agglutinins are negative. Other laboratory findings may include an elevated erythrocyte sedimentation rate, hypoxia, abnormal liver function test results, and elevated creatine phosphokinase levels.64 Proteinuria and microscopic hematuria have been observed, and acute renal failure may complicate the course on occasion.
Gram stains of the sputum or tracheal secretions will not reveal L. pneumophila, but the organism can occasionally be isolated from sputum and other specimens by using charcoal-yeast extract agar. The diagnosis can be established rapidly in about 20% of cases by demonstrating the organism with direct immunofluorescent staining of sputum specimens; bronchoalveolar lavage may be helpful in immunosuppressed patients. A kit that uses radiolabeled complementary DNA is commercially available, but clinical experience is still limited. A very promising polymerase chain reaction assay has been developed.65
Another method of rapid diagnosis involves detection of L. pneumophila antigen in the urine; this radioimmunoassay test is highly specific and has a sensitivity of about 80% to 90%.65 However, the test is available only for L. pneumophila serogroup 1, which is the most common cause of Legionnaires disease. Most often, however, the diagnosis is established serologically by an indirect fluorescent antibody technique involving staining of the causative bacterium. With this technique, a fourfold or greater rise in antibody titer during the illness or a stable titer of 1:256 or greater is considered diagnostic. The clinical picture and radiologic findings in Legionnaires disease are not specific. The diagnosis should be considered in patients with segmental, lobar, or interstitial pneumonia in which the etiologic agent is not evident on Gram stains of sputum or tracheal secretions. A mild case may resemble Mycoplasma pneumonia or other types of atypical pneumonia.
On in vitro susceptibility testing, L. pneumophila has been shown to be susceptible to a variety of antimicrobial agents, including erythromycin, clarithromycin, azithromycin, tetracycline, rifampin, and the fluoroquinolones. Current evidence indicates that azithromycin66or levofloxacin67 is the treatment of choice. Occasionally, patients may experience a relapse if antibiotics are discontinued prematurely; recovery occurs during a second, more prolonged course of treatment. A combination of rifampin and either azithromycin or levofloxacin may be considered in patients who fail to respond to monotherapy and in immunologically impaired patients with overwhelming disease. Improvements in diagnosis and therapy have produced a dramatic decline in the case-fatality rate of L. pneumophila infection, from 34% in 1980 to 12% in 1998.68
Infections Caused by Other Legionella Species
Since 1943, unusual, fastidious Rickettsia-like organisms have been identified as causes of isolated cases of pneumonia. Long considered medical curiosities, these organisms were named after their discoverers or the patients from whom they were isolated. Such obscure nomenclature (e.g., TATLOCK, OLDA, HEBA, and WIGA) reflected the absence of knowledge concerning these agents. Subsequent studies of these organisms led to their reclassification as Legionella species. Of the more than 30 Legionella species that have been identified, at least 19 have been recognized as causes of pneumonia, particularly in immunosuppressed hosts.
The clinical picture is not distinctive. Fever is the most common feature, cough is variable in severity, and sputum production is absent or scant. Pleurisy or dyspnea may develop, and chest x-rays show a patchy or nodular, progressive bronchopneumonia. L. micdadei is the most important of these organisms. Previously known as TATLOCK and HEBA, L. micdadei was rediscovered as the Pittsburgh pneumonia agent that caused acute suppurative pneumonia in eight immunosuppressed patients from two centers in 1979.69 L. micdadei can also cause pneumonia in immunologically intact hosts and extrathoracic infections in immunologically impaired hosts. It has been isolated from hospital water supplies and can cause nosocomial infections in immunosuppressed patients.70
In the first 13 patients with Pittsburgh pneumonia, the diagnosis was established through a lung biopsy or autopsy that revealed acute alveolar inflammation and short, weakly acid-fast, gram-negative bacilli. More recent cases have been diagnosed by culturing the agent on charcoal-yeast extract agar or by serologic means. Erythromycin has been used with success. Unlike L. pneumophila, L. micdadei is susceptible to penicillins and cephalosporins in vitro; however, there are no data on the use of these drugs in clinical L. micdadei infection.
Many other Legionella species have been identified as causes of pneumonia. These organisms grow on charcoal-yeast extract agar. Some cases in which Legionella species have been implicated share common features: patients have been exposed to infected water and have COPD or are immunosuppressed.71 Therapy with erythromycin, alone or with rifampin, has been suggested.
Infections Caused by Chlamydophila (Chlamydia) Pneumoniae
Unlike psittacosis, which is a true zoonosis that spreads only from animals to humans,73 C. pneumoniae spreads from person to person via respiratory droplets. The incubation period of C. pneumoniae is long. Unlike C. trachomatis, which causes neonatal pneumonia, C. pneumoniae infects mainly older children and young adults; however, older patients (especially those with COPD) can also be affected.
Clinically, C. pneumoniae pneumonia in young patients resembles M. pneumoniae pneumonia74; after a prodrome of pharyngitis that lasts no more than 2 weeks, nonproductive cough and fever occur. Pulmonary infiltrates are mild. The infection is usually self-limited. In older patients with underlying COPD, C. pneumoniae can cause bronchitis that may be mild or very persistent. Bronchospasm may be prominent.75This organism can sometimes cause severe pneumonia in patients with COPD, and fatalities have been reported in debilitated patients. A macrolide, a tetracycline, or a fluoroquinolone is recommended for therapy.
Patients with recurrent pneumonia present a diagnostic and therapeutic challenge. Anatomic abnormalities should be carefully sought in all such patients and should be suspected particularly when the infections recur in one bronchopulmonary segment. Examples of anatomic abnormalities include cysts, blebs, abscess cavities, bronchiectasis, and bronchial obstruction by tumors, foreign bodies, or bronchiostenosis. If shifting locations are involved, systemic abnormalities may be present. Examples include defects of leukocyte function, immunoglobulin deficiencies, α1-antitrypsin globulin deficiency, and cystic fibrosis. Recurrent aspiration may be responsible, in which case a carefully performed neurologic examination and a barium swallow may reveal the proper diagnosis. It is important to remember that noninfectious processes may produce recurrent pulmonary infiltrates that may be accompanied by cough and fever [see 14:V Chronic Diffuse Infiltrative Lung Disease]. Examples of such processes include organizing pneumonia, eosinophilic pneumonia, hypersensitivity pneumonitis, vasculitis, pulmonary hemosiderosis, and pulmonary emboli.
Often, bacterial pneumonias exhibit delayed resolution, in which radiographic abnormalities persist for weeks or even months after clinical recovery. Infrequently, pyogenic infection pursues a slow but progressively destructive course despite antibiotic therapy; K. pneumoniae and other gram-negative bacilli have been implicated in some patients with such chronic bacterial pneumonias. Mycobacteria and Actinomycesare common causes of chronic pulmonary infection; fungi are particularly common in patients treated with corticosteroids. Persistent infiltration caused by neoplasia, sarcoidosis, pulmonary hemorrhage, vasculitis, fibrosing alveolitis, alveolar proteinosis, lipoid pneumonia, toxins, and other processes may mimic chronic pulmonary infection. Fiberoptic bronchoscopy is very useful for diagnosis, but lung biopsy may be needed.
Epidemiology and Etiology
Although aspiration is probably the mechanism responsible for most bacterial pneumonias, the term aspiration pneumonia is best reserved for infection caused by mixed mouth flora. In clinical practice, aspiration pneumonia most often occurs in persons with depressed consciousness, which may result from alcoholism, drug abuse, administration of sedatives or anesthesia, head trauma, and seizures or other neurologic disorders. Seventy percent of patients with depressed consciousness have demonstrable pharyngeal aspiration, often involving much larger volumes of material than that aspirated by healthy persons. Because of the larger volumes of aspirated material, underlying diseases impairing host defenses, and alterations in oropharyngeal flora, patients with altered consciousness are most prone to developing aspiration pneumonia. In addition, aspiration of GI contents is more frequent in patients with abnormalities of deglutition or esophageal motility resulting from placement of nasogastric tubes, esophageal carcinoma, bowel obstruction, or repeated vomiting from any cause. Poor oral hygiene and periodontal disease predispose to aspiration pneumonia because of the increased bacterial flora in these patients.
The clinical results of pulmonary aspiration depend in large part on the nature and volume of material aspirated. Aspiration of gastric contents is a common problem that may produce Mendelson syndrome, a fulminating illness, if a large volume of acidic gastric juice is aspirated.76 Aspiration of particulate material can produce acute airway obstruction and death by asphyxiation; aspiration of smaller particles may produce atelectasis of a pulmonary segment or even of an entire lung, resulting in dyspnea, wheezing, and cyanosis. Characteristic pulmonary injuries and distinctive clinical syndromes are produced by aspiration of smoke, freshwater or saltwater, and fats or oils (lipoid pneumonitis).
Patients with mixed aspiration pneumonia may present with an acute febrile illness, or the illness may follow a more indolent course, extending over many days or even weeks. Fever, cough, and sputum production are the dominant symptoms; the sputum may be copious, foul smelling, or both. Physical examination typically discloses rales and signs of pulmonary consolidation. An evaluation of dental hygiene and of the gag reflex is helpful; disordered pharyngeal sensation is a better predictor of vulnerability than is an absent gag reflex.
Radiographically, infiltrates are most common in dependent areas of the lung, especially the apical segments of the lower lobes and the posterior segments of the upper lobes. Tissue necrosis can occur. Without treatment, aspiration pneumonia may produce multiple small cavities, which reflect a necrotizing pneumonitis. Lung abscesses or empyemas may ensue.
The sputum of patients with classic aspiration pneumonia contains abundant polymorphonuclear leukocytes and mixed mouth flora. If specimens are obtained by transtracheal aspiration or other procedures that avoid contamination of sputum by organisms from the oral cavity, aerobic and anaerobic bacteriologic techniques can reveal the specific causative bacteria. Because anaerobes are the dominant flora of the upper respiratory tract (outnumbering aerobic or facultative bacteria by 10 to 1), it is not surprising that anaerobes are the dominant organisms in aspiration pneumonia. Of particular importance are Prevotella melaninogenica and other Prevotella (formerly, oral strains ofBacteroides) species (slender, pleomorphic, pale gram-negative rods), Fusobacterium nucleatum (slender gram-negative rods with pointed ends), and anaerobic or microaerophilic streptococci and Peptostreptococcus (small gram-positive cocci in chains or clumps). As expected, multiple organisms are recovered from most patients.
Although penicillin has been the traditional drug of choice for aspiration pneumonia, clindamycin has surpassed it in clinical trials77,78 and is now the preferred treatment; the usual dosage is 600 mg every 8 to 12 hours I.V. until a clinical response is evident, followed by oral administration of 300 mg four times a day for 10 to 14 days. Alternative treatments include amoxicillin-clavulanate and the combination of penicillin and metronidazole [see Table 6]. Parenteral therapy is advisable initially, but a 10- to 14-day course of treatment can be concluded with orally administered antibiotics if the patient responds well.
Hospitalization or antibiotic therapy alters the usual oropharyngeal bacterial flora, so that staphylococci, facultative gram-negative bacilli, or both may be identified in patients. As a result, aspiration pneumonia in hospitalized patients often involves pathogens that are uncommon in community-acquired pneumonias. Gram stains and cultures of sputum are especially important for identifying gram-negative bacilli and staphylococci in the hospital setting. Broad antimicrobial coverage is required until specific pathogens have been identified by culture and sensitivity testing. Although tube feedings are often recommended to prevent aspiration pneumonia, there is no evidence that they are effective.76
Other Pulmonary Infections
Cough is the chief complaint responsible for an estimated 30 million physician office visits in the United States annually. For about 12 million of these patients, the clinical diagnosis is acute bronchitis.79
Acute bronchitis is commonly defined as an acute respiratory tract infection in which cough, with or without sputum production, is a prominent feature. In most cases, an etiologic diagnosis is not established. When sputum is absent or scant, the illness is often attributed to a respiratory tract virus; when purulent sputum is present, the bacteria that cause community-acquired pneumonias are considered likely causes.
Most otherwise healthy persons recover from acute bronchitis in 1 to 3 weeks, but the cough can linger for more than a month in up to 20% of patients.80 Although 70% to 90% of patients are treated with antibiotics, published trials demonstrate little clinical benefit, even if purulent sputum is present.80,81 Guidelines of the Infectious Disease Society of America, the American College of Physicians-American Society of Internal Medicine, and the American Academy of Family Physicians state that routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough.82 Suspected cases of pertussis constitute an exception.83 Clinicians who are confronted with demands for antibiotics may use a strategy of delayed prescription,84 whereby the physician offers the patient a prescription but suggests that it be filled only if symptoms fail to resolve without antibiotics. Patients with high fever, chills, respiratory distress, underlying pulmonary or immunosuppressive disorders, or physical signs of pulmonary parenchymal infection should be evaluated for pneumonia and treated according to the guidelines for community-acquired pneumonia (see above).
Patients with chronic bronchitis characteristically produce sputum on most days for at least 3 months each year for more than 2 years. The sputum is frequently colonized by H. influenzae (nontypable), S. pneumoniae, or M. catarrhalis, singly or in combination. Although it is not certain whether the bacteria themselves produce additional airway damage, heavy bacterial loads correlate with increased inflammation.85Patients who acquire a new or potentially pathogenic strain of bacteria are at increased risk for symptomatic exacerbations of their chronic bronchitis.86 The role of long-term prophylactic antibiotic therapy in chronic bronchitis is controversial. Long-term antibiotic therapy may provide symptomatic relief in certain patients who experience multiple exacerbations of bronchitis during the winter, but it is not useful in improving or preserving pulmonary function. However, short-term antibiotic therapy is effective in treating acute exacerbations of chronic bronchitis.87
True saccular, or cystic, bronchiectasis involves both dilatation of the bronchi and destruction of the bronchial walls. Bronchiectasis results most often from neglected or recurrent infection, especially in childhood; therefore, bronchiectasis has become much less common since the introduction of antibiotics. Aggressive medical therapy has greatly improved the prognosis.
Symptoms include cough that may be dry or productive of copious foul sputum, recurrent lower respiratory tract infection, and hemoptysis. In rare instances, bronchiectasis can present as pleuritic chest pain. In advanced cases, fibrosis can lead to corpulmonale and respiratory failure. The chest x-ray may show increased lung markings, honeycombing, atelectasis, or pleural changes, but high-resolution or helical chest CT is required for definitive diagnosis88 [see 14:III Chronic Obstructive Diseases of the Lung].
Epidemiology and Etiology
In the antibiotic era, lung abscesses have become less common and less serious. The most common variety has been termed the primary, simple, nonspecific, or putrid abscess. Primary lung abscess accounts for about 60% of all lung abscesses and originates from a necrotizing suppurative bronchopneumonia caused by the aspiration of mixed oropharyngeal bacteria. Thus, both the predisposing factors and the causative organisms are similar to those identified in aspiration pneumonia. Patients with primary lung abscesses typically have alterations of consciousness because of underlying problems such as alcoholism and neurologic disorders; periodontal disease is often present. The organisms causing the abscess are much more reliably identified by bronchoscopic aspiration using a protected brush than by sputum cultures, which are invariably contaminated with anaerobes and other mouth flora. Bronchoalveolar lavage, transtracheal aspiration, and percutaneous lung aspiration may also be useful for bacteriologic diagnosis. Mixed anaerobic bacteria are seen in most cases; F. nucleatum, P. melaninogenica, Peptostreptococcus, and anaerobic or microaerophilic streptococci predominate. B. fragilis is recovered with other organisms in 15% of cases.
Many other conditions can lead to lung abscess. Necrotizing bacterial pneumonias caused by S. aureus, K. pneumoniae, or other gram-negative bacilli can lead to abscess formation. In other patients, abscess develops as a result of bronchial obstruction caused by tumors, foreign bodies, or bronchial stenosis. Septic pulmonary embolization is a cause of abscess formation. Pulmonary tuberculosis, fungal infection, or actinomycosis often leads to cavity formation. In the immunosuppressed host, Nocardia and other opportunistic organisms may also produce cavitation. Lung abscesses in patients with AIDS are caused by a wide array of organisms and respond poorly to therapy.
The clinical presentation of the patient with a lung abscess depends on the type of abscess. Patients with abscesses resulting from necrotizing staphylococcal or gram-negative bacillary pneumonias are usually acutely ill and exhibit clinical features of the underlying pneumonia. Although patients with primary lung abscess may also present acutely with aspiration pneumonia, they more often experience insidiously progressive symptoms for weeks or even months before diagnosis. Cough is present in almost all patients; when the abscess drains into the bronchial tree, production of copious foul-smelling sputum is characteristic. Hemoptysis is present in approximately one third of cases and may occasionally reach life-threatening proportions. Chest pain consisting of either a dull ache or a true pleurisy is common. Most patients have fever, but frank rigors are unusual. Often, patients with a chronic course of lung abscess lasting many weeks have anorexia, weight loss, and debility.
Physical Examination and Imaging
Physical examination of a patient with a lung abscess may disclose pulmonary rales, signs of consolidation, or, rarely, clubbing of the nails. These findings are not diagnostic, however, and chest x-rays or CT scans are required to establish the presence of an abscess. Although any lung segment may be involved, abscesses are most common in the posterior segments of the upper lobes and the apical segments of the lower lobes, because these areas are dependent when a person is recumbent. Abscesses may be single or, less often, multiple. The finding of air-fluid levels signifies rupture into the bronchial tree.
Laboratory Studies and Invasive Procedures
As is the case with other pulmonary infections, examination of the sputum is crucial to the diagnosis of lung abscess. In patients with primary lung abscesses, the sputum is often putrid and contains numerous polymorphonuclear leukocytes and an abundant mixed microbial flora. Sputum cultures reveal only normal mouth flora. Meaningful anaerobic bacteriology depends on obtaining, either by bronchoscopy or transtracheal aspiration, specimens that have not traversed the oropharynx. Percutaneous needle aspiration can also be very helpful, both diagnostically and therapeutically. In a typical case of aspirational putrid lung abscess, these invasive procedures may not be necessary. They are important, however, if the diagnosis is uncertain. At one time, bronchoscopy was advocated for all patients with lung abscess; however, it is now typically reserved for patients in whom there is a suspicion of bronchial obstruction by a foreign body or tumor, for patients who fail to respond to medical therapy, and for patients from whom specimens are required to rule out tuberculosis, fungal infection, or carcinoma.89 Bronchoscopy may be helpful therapeutically by promoting bronchial drainage from cavities that incompletely communicate with the bronchial tree.
Noninfectious processes can produce cavitary lung lesions. Primary and metastatic tumors, bullae, cysts, intralobar pulmonary sequestration, pulmonary infarcts, vasculitis (including Wegener granulomatosis), and rheumatoid lung disease must be considered in the differential diagnosis of lung abscess.
If specific pathogens such as S. aureus or Klebsiella are present in reliable specimens, therapy should be directed at the causative pathogen. In primary lung abscesses caused by mixed oral flora, penicillin was traditionally the drug of choice. However, prospective studies comparing penicillin therapy with clindamycin therapy in patients with lung abscess found clindamycin to be the superior agent.90 Relatively few clinical trials are available on the treatment of anaerobic lung abscesses because of the infrequency of this presentation and the difficulty in establishing a microbial diagnosis; nevertheless, other drugs that appear to be useful are amoxicillin and a β-lactamase inhibitor. Despite its excellent bactericidal activity against anaerobic bacteria, metronidazole appears to be less effective in treating lung abscess, probably because of poor activity against streptococci.91 Parenteral therapy is often required for 2 to 4 weeks before the occurrence of defervescence, diminished sputum production, and reduction in cavity size. The duration of therapy depends on the clinical course, but prolonged treatment for 4 to 8 weeks is usually required.
In addition to administration of antibiotics, adequate drainage is essential and can usually be achieved with intensive pulmonary physiotherapy and postural drainage. Bronchoscopy can be very useful in promoting drainage and for excluding the diagnosis of cancer.89Although surgery was once the mainstay of treatment for lung abscess, antibiotics are now almost always able to control infection, and surgery is needed only when complications occur. Massive hemoptysis is an indication for lung resection. Uncontrolled sepsis may occasionally necessitate lobectomy. CT-guided percutaneous tube drainage may be very helpful in patients who are too ill to tolerate thoracotomy and may be the treatment of choice for lung abscesses that are refractory to medical management. Empyema, another complication of lung abscess, requires external drainage by thoracentesis, chest tube, or rib resection. The persistence of a thin-walled cavity after otherwise successful medical treatment, however, is not an indication for surgery. Recurrent or persistent infection, recurrent hemoptysis, or the suspicion of tumor may mandate operative intervention. Shaggy, thick-walled cavities may be suggestive of tumor. Complications of lung abscess that have become uncommon because of antibiotic therapy include bronchogenic spread of infection to other pulmonary segments, bronchiectasis, and bacteremia with metastatic infection such as brain abscess.
Whereas patients with gram-negative or staphylococcal bacillary pneumonias or serious underlying diseases have a substantial mortality, the prognosis for patients with primary lung abscess is quite good. It is important to prevent recurrent pulmonary infection by treating dental disease and by avoiding factors that predispose to pulmonary aspiration.
Bacteria can reach the pleural space by many routes. Most often, empyema results from the direct spread of bronchopulmonary infections, including pneumonias, lung abscesses, and bronchiectasis.92 Less often, empyema develops as a complication of thoracotomy or, rarely, thoracentesis. Open chest trauma provides another means for the direct introduction of microorganisms. Intra-abdominal infections, especially subphrenic abscesses, can penetrate the diaphragm to cause empyemas. Uncommonly, esophageal rupture can cause spread of infection from the mediastinum to the pleural space. Finally, hematogenous seeding is an infrequent mechanism of empyema formation.
In most patients, the clinical presentation of empyemas includes fever, dyspnea, chest pain, and cough. Hemoptysis is less common than these other symptoms. If diagnosis and treatment are delayed, weight loss and debility may be prominent. The physical findings in patients with empyemas are no different from those in other patients with pleural effusions. In addition, chest wall tenderness may be present, and there may be signs of an underlying pneumonia or intra-abdominal infection. Tachypnea and respiratory distress may occur, and septic shock may complicate advanced cases. Polymorphonuclear leukocytosis is common; other laboratory findings may include anemia and hypoxia. Chest x-rays reveal pleural effusions that are free flowing in early disease but frequently loculated in late cases. Ultrasonography may be necessary to distinguish fluid from pleural fibrosis. Unless surgery or thoracentesis has been performed, air-fluid levels in the pleural space suggest a bronchopleural fistula.
In the differential diagnosis of empyema, it is important to consider the many causes of noninfected pleural effusions.94 Most important is the distinction between sterile parapneumonic effusions and true empyemas. Thoracentesis is mandatory for the diagnosis of empyema [see14:XIII Invasive Diagnostic and Therapeutic Techniques in Lung Disease]. Several thoracenteses may be needed if the fluid is loculated; CT or ultrasound guidance is very helpful in these circumstances. Gross purulence is diagnostic for empyema, but the absence of frank pus does not rule out infection. Like other inflammatory effusions, empyema fluids have the characteristics of exudates: protein levels greater than 3 g/dl and lactic dehydrogenase values in excess of 550 units. Pleural fluid acidosis is characteristic of empyemas, but alkalosis can occur if the infection is caused by a urea-splitting organism such as Proteus. Pleural fluid glucose levels are depressed in empyemas, and although white cell counts are variable, counts above 5,000/mm3 are common, with polymorphonuclear leukocytes predominating. Gram stains of the pleural fluid will often reveal the causative organisms. Both aerobic and anaerobic cultures are mandatory; a foul odor suggests anaerobic infection. Stains and cultures for mycobacteria and fungi are important in selected cases.
Treatment of empyemas involves both antibiotics and drainage. Antibiotics should be selected on the basis of the causative pathogens. High-dose parenteral therapy is required, and prolonged courses of 3 weeks or more are often needed. Adequate drainage is of paramount importance. In acute empyemas, the pleural cavity is lined by acute fibrinous inflammation, and percutaneous drainage of free-flowing fluid may be possible by repeated thoracentesis or tube thoracostomy. Closed chest tube drainage is the traditional method for draining empyemas, but image-guided catheter drainage is also effective, particularly when the fluid is loculated. Resolution of fever generally signifies satisfactory drainage. If complete drainage cannot be achieved with chest tubes, video-assisted thoracoscopic surgery (VATS) can often disrupt intrapleural adhesions and achieve excellent drainage of loculated effusions95; although VATS requires endotracheal intubation and general anesthesia, it is less invasive than the next alternative, rib resection with thoracotomy for decortication. Enzymatic debridement with streptokinase has proved ineffective.96
Septic Pulmonary Embolism
Although once uncommon, septic pulmonary embolism is now encountered because of I.V. drug abuse, which accounts for more than 75% of cases; tricuspid valve endocarditis and direct injection of infected material cause most of these cases. S. aureus and gram-negative bacilli are the predominant etiologic agents in I.V. drug abusers. Septic pulmonary embolism may also develop in patients with septic phlebitis of peripheral veins (especially phlebitis related to I.V. lines or pelvic infections), abscesses, or other bacteremic infections.
Unlike bland emboli, septic pulmonary emboli produce pulmonary infarction in most instances. Small emboli produce flame-shaped or patchy infiltrates that may shift in location; these manifestations generally resolve with antibiotic therapy. Larger emboli often cavitate and may lead to lung abscess, empyema, or bronchopleural fistula formation. In addition to antibiotics, surgical drainage may be required for such complications. Operative intervention may be needed to control the source of emboli in some patients. Heparin can be useful in patients with septic phlebitis.
Editors: Dale, David C.; Federman, Daniel D.