You are in: eMedicine Specialties > Radiology > CHEST Pneumonia, Atypical BacterialArticle Last Updated: Mar 7, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 9
  Author: Shakeel Amanullah, MD, Consulting Staff, Pulmonary, Critical Care, and Sleep Medicine, Clarian Arnett Health Shakeel Amanullah is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine Coauthor(s): David H Posner, MD, Assistant Professor of Medicine, New York University School of Medicine; Assistant Chief of Pulmonary Diseases, Instructor, Intensive Care Unit, Education Coordinator for Pulmonary Fellowship, Lenox Hill Hospital; Mina Farhad, MD, PhD, Clinical Instructor of Radiology, New York University School of Medicine; Head of Thoracic Imaging, Department of Radiology, Lenox Hill Hospital; Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital Editors: Satinder P Singh, MD, Associate Professor of Radiology, Chief of Cardiopulmonary Radiology, Director of Cardiac CT, Director of Combined Cardiopulmonary and Abdominal Radiology, Department of Radiology, University of Alabama at Birmingham; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Eric J Stern, MD, Professor of Radiology, Adjunct Professor of Medicine, Adjunct Professor of Medical Education and Biomedical Informatics, University of Washington School of Medicine; Director of Thoracic Imaging, Harborview Medical Center; Associate Medical Staff, Seattle Cancer Care Alliance; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Kavita Garg, MD, Professor, Department of Radiology, University of Colorado Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: walking pneumonia, atypical pneumonia, Legionella pneumonia, Chlamydia pneumonia, Mycoplasma pneumonia, Mycobacterium tuberculosis, community-acquired pneumonia, CAP, Legionnaires disease, Legionnaire's disease, Legionnaires' disease, Legionella pneumophila, Legionella micdadei, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia psittaci, Chlamydia trachomatis, Chlamydia pneumoniae, TWAR agent INTRODUCTIONSection 2 of 9
  BackgroundDuring the latter half of the 19th century, by which time physicians had embraced autopsy as an essential learning tool, pneumonia diagnoses were usually made post mortem. With the discovery of x-rays (1895), chest radiography became part of the routine evaluation of pneumonia in patients with suggestive signs and symptoms. Patients who presented with fever, shaking chills, and rust-colored sputum (which under examination showed gram-positive diplococci in chains) and whose chest radiographic findings were suggestive of pulmonary infection were considered to have typical pneumonia. History In 1934, Gallagher described a disease outbreak in 16 boys living in a preparatory school. The youngsters had bronchopneumonia, which Gallagher considered to be atypical. Four years later, Reimann reported on 8 patients with chest infection but an atypical presentation, which he referred to as atypical pneumonia. As a result of Gallagher's and Reimann's work, the concept of typical and atypical pneumonia became established in medical literature. The arbitrary classification of typical versus atypical pneumonia is nonetheless of limited clinical value. Moreover, the literature now shows that a primary pathogen may coexist with a secondary one, further blurring the distinction between these terms. Related eMedicine topics: Pneumonia, Bacterial Pneumonia, Viral Pneumonia, Typical Bacterial Related Medscape Topics: Resource Center Pneumonia CME/CE What's New in Ventilator-Associated Pneumonia CME/CE Healthcare-Associated Pneumonia CME Oral Amoxicillin May Be Effective for Children Admitted to Hospital for Pneumonia CME/CE Macrolides Improve Outcomes Among Elderly With Bacteremic Pneumonia PathophysiologyPathogens Most pathogens that are responsible for community-acquired pneumonia (CAP) reach the lungs after first colonizing the oropharynx. Community respiratory pathogens that enter the lungs without oropharyngeal colonization include Mycobacterium tuberculosis, Legionella species, and certain viruses. See Clinical Details, below. Radiologic phases A phase of active hyperemia occurs, lasting approximately 24 hours before radiologic consolidation of the alveoli appears. This phase is characterized by engorgement of the arterial blood vessels. Edematous fluid, which may be seen in the alveolus, contains few exudative cells. The next stage is referred to as red hepatization. Neutrophils and fibrin material fill the alveoli, and massive extravasation of red blood cells produces a homogeneous opacity. The red hepatization phase is then followed by gray hepatization. Fibrin and exudative cells accumulate, appearing on radiographs as a clear zone adjoining the alveolar and acinar cells. If the process extends to the pleural space, associated empyema may be present. FrequencyUnited StatesCAP affects approximately 5.6 million adults in the United States each year, resulting in approximately 1.1 million hospital admissions (Garibaldi, 1985; Neiderman, 1998). Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory infections in adults and children. This organism is one of the most common atypical pathogens responsible for CAP in adults, but infection-rate figures vary, depending on the population and on the diagnostic methods used. Studies have shown that the prevalence of this agent in adults with pneumonia ranges from 2% to over 30% (Mansel, 1989; Pareja, 1992). The prevalence of Chlamydia pneumoniae infection varies by year and geographic setting. It causes 5-15% of all cases of CAP (Marrie, 1998). InternationalData are not currently available. The estimated range is 30-220 million cases per year. Mortality/MorbidityThe overall mortality rate is approximately 15%, ranging from 5% in studies including both ambulatory and hospitalized patients to 15% in studies of only hospitalized patients.
RaceIn endemic areas, certain zoonotic infections should be considered when patients present with atypical pneumonia. AgeThere is a higher incidence of atypical pneumonia in the elderly as a result of associated comorbidities, reduced immunocompetence, and an increased risk of aspiration in this population. Clinical DetailsPneumonia is predominantly a clinical syndrome. The classic etiologic agents of atypical pneumonia are Legionella species, M pneumoniae, and C pneumoniae. Many other diseases, caused by various pathogens, should be considered in the differential diagnosis. Such etiologic agents include fungi, mycobacteria, parasites, and viruses (eg, influenza virus, adenovirus, respiratory syncytial virus, human parainfluenza virus, measles, varicella zoster, Hantavirus). In immunosuppressed patients, outbreaks of isolated cases of respiratory virus infections with atypical presentations are reported. These infections can be severe and may have concomitant bacterial etiologies. In endemic areas, certain zoonotic infections should be considered when patients present with atypical pneumonia. Noninfectious etiologies must be considered in atypical and nonresolving pneumonias. Legionella pneumoniaLegionella became recognized as a pneumonia agent following an outbreak of L pneumophila infections at a 1976 American Legion convention in Philadelphia. Legionella pneumonia is responsible for 2-15% of all CAPs that require hospitalization. Outbreaks of nosocomial legionellosis (Legionnaires disease) previously occurred in tertiary care centers. More recently, however, sporadic nosocomial cases from community hospitals have predominated. Risk factors The risk factors for Legionella pneumonia include cigarette smoking, chronic lung disease, and immunosuppression (especially that caused by corticosteroid use). Surgery is a major predisposing factor in nosocomial infections; transplant patients are at highest risk. Legionnaires disease can be acquired by aerosol inhalation or by the microaspiration of water contaminated with Legionella pathogens, although aspiration remains an underrecognized mode of transmission. Sources of contaminated water include aerosol-generating systems such as cooling towers, respiratory therapy equipment, and whirlpool baths. Nasogastric tubes are implicated in some cases of nosocomial legionellosis. A high incidence of Legionella pneumonia is reported in patients who undergo head and neck surgery. Although 40 Legionella species have been identified, fewer than 20 have been implicated as human pathogens. L pneumophila is the most pathogenic, accounting for 90% of cases of human legionellosis, followed by L micdadei. Clinical manifestations Early in the course of illness, patients have nonspecific symptoms, including fever, malaise, myalgia, anorexia, and headache. Temperature often exceeds 40°C. Cough is usually only minimally productive. Pleuritic chest pain occasionally occurs and can be associated with hemoptysis, which may mistakenly suggest pulmonary embolus. Diarrhea is present in as many as 20-40% of patients and is classically described as watery, rather than bloody. Relative bradycardia is described, but this condition is most often seen in elderly patients with severe pneumonia. Hyponatremia with a serum sodium level of 125-130 mmol/L is more commonly associated with Legionella pneumonia than with other forms of pneumonia. Extrapulmonary legionellosis is rare, but the clinical manifestations can be severe. The heart is the most common extrapulmonary site. Patients with cardiac involvement may present with myocarditis, pericarditis, postpericardiotomy syndrome, and prosthetic valve endocarditis. Chest radiographs cannot be used to distinguish Legionnaires disease from other pneumonias. Details are described in Radiograph. Laboratory diagnosis Diagnostic laboratory tests for Legionnaires disease are necessary but must be specifically requested. The definitive diagnosis is made by culturing the Legionella organism. However, a specialized medium is needed for testing; a lack of this medium delayed diagnosis in the 1976 American Legion outbreak. Sputum should be cultured regardless of the quality of the specimen. Legionella has been cultured from specimens with more than 25 squamous epithelial cells and fewer than 25 leukocytes per low-power field. This procedure may be important because many patients have a minimally productive cough. The Legionella urine antigen test can be performed rapidly and relatively inexpensively. This test is commercially available as both a radioimmunoassay and an enzyme immunoassay. It detects only the serotype 1, but it should be included in the initial diagnostic work-up because this is the most common serotype that causes clinical infection. The test has a sensitivity of 70% and a specificity of approximately 95%. Direct fluorescent antibody staining is a rapid diagnostic test, but because a large number of organisms are required for visualization, it is less sensitive than are techniques employing bacterial cultures. Serologic tests are useful for epidemiologic purposes. However, they do not help the treating physician, because a convalescent measurement is required. The diagnosis is based on a 4-fold increase of antibody titer to 1:128 or higher. A single titer of 1:256 or higher during convalescence is also suggestive of Legionella infection. If antibody screening is performed, both immunoglobulin G (IgG) and immunoglobulin M (IgM) levels should be evaluated. The polymerase chain reaction (PCR) assay has been used to evaluate serum, urine, and bronchoalveolar fluid. Although PCR is highly specific, it is not more sensitive than culturing. Its primary advantage is its ability to rapidly detect Legionella or species other than L pneumophila. The sensitivity of culturing or direct fluorescent antibody staining of specimens obtained during bronchoscopy is similar to that of sputum analysis. Pleural fluid, if present, should be evaluated by staining and culturing and by performing the radioimmunoassay used to detect urinary antigen. Treatment Delayed treatment of Legionella pneumonia significantly increases the associated mortality rate. The newer macrolides, especially azithromycin, have superior in vitro activity, with greater intracellular and lung tissue penetration than erythromycin. Quinolones, in turn, have greater in vitro activity and intracellular penetration than the macrolides. In severely ill patients, rifampin may be recommended for use in combination with macrolides or quinolones. The duration of therapy is 10-14 days, with a 21-day regimen for immunosuppressed patients or those with extensive disease, as shown on chest radiographs. Mycoplasma pneumoniaM pneumoniae is a frequent cause of community-acquired respiratory infections in adults and children. This organism is one of the most common atypical pathogens responsible for CAP in adults, but infection-rate figures vary depending on the population and the diagnostic methods used. Recent studies have shown that the prevalence of this agent in adults with pneumonia ranges from 2% to over 30%. The class Mollicutes, generally referred to as the mycoplasmas, comprises 5 genera: Mycoplasma, Ureaplasma, Acholeplasma, Anaeroplasma, and Asteroleplasma. Three well-established causes of human disease are M pneumoniae, M hominis, and U urealyticum. Mycoplasmas grow on cell-free media, multiplying by means of primary fission. Because, unlike other bacteria, they lack a cell wall, these organisms are not susceptible to antibiotics that interfere with cell-wall synthesis. Mycoplasmas may be among the least frequently diagnosed respiratory pathogens in the clinical setting, because of a lack of standardized, specific diagnostic tests for them. M pneumoniae infection tends to be endemic, punctuated by epidemics occurring at 4- to 7-year intervals. When these epidemics develop, M pneumoniae may be responsible for up to 50% of all pneumonia cases. The overall incidence depends on the prevalence and appears to be related to age. The highest prevalence is observed in children aged 5-9 years. Outbreaks may occur in institutional settings, such as military bases, summer camps, and schools. Clinical features M pneumoniae infections may be symptomatic or asymptomatic. The onset is usually gradual, with a prodrome of flu-like symptoms, including headache, malaise, and low-grade fever, occurring. Chills are common, but rigors are not. Objective abnormalities on physical examination are minimal in contrast to the patient's reported symptoms. Symptoms are best divided into pulmonary and extrapulmonary manifestations. M pneumoniae is most frequently responsible for the pulmonary manifestation tracheobronchitis, which is 30 times as common as pneumonia. This pathogen is best known as the primary cause of walking pneumonia. Typical symptoms include sore throat, headaches, chills, and coryza. Myringitis, including hemorrhagic bullous myringitis and otitis, may be present, and transient bronchial hyperreactivity can occur as well. The cough associated with Mycoplasma infection is usually nonproductive or minimally productive. Extrapulmonary manifestations involve the central nervous system (CNS), blood, skin, heart, joints, or gastrointestinal (GI) tract. CNS manifestations include aseptic meningitis, cranial nerve palsies, cerebral ataxia, meningoencephalitis, peripheral neuropathy, and transverse myelitis. These symptoms are infrequent, and when seen, they are usually found in children. They are most often associated with increased morbidity and mortality rates and are thought to represent an immune-mediated reaction of the host to the M pneumoniae infection or to an extrapulmonary manifestation of it. An antecedent respiratory infection is not always present. Hematologic manifestations include the presence of IgM antibodies to the erythrocyte membrane I antigen. Their appearance produces a cold agglutinin response that leads to hemolysis. Dermatologic manifestations include rash, which may be maculopapular or vesicular, and Stevens-Johnson syndrome. Antimicrobials are known to potentiate the dermatosensitive potential of M pneumoniae. Cardiac involvement may include myocarditis, pericarditis, congestive heart failure, hemopericardium, and various heart blocks. Joint manifestations are occasionally described. Various GI symptoms can include nausea, vomiting, diarrhea, and pancreatitis. Diagnosis Culturing, serologic analysis, PCR testing, and determination of cold agglutinin titers can aid in diagnosing an M pneumoniae infection. However, because each of these tests has certain drawbacks, therapy must be empirical. Because of M pneumoniae's fastidious growth requirements and long incubation period, culturing has limited utility, and most laboratories do not offer it. IgM and IgG titers are elevated in most cases, but the response is often delayed. Therefore, antibody tests also have limited usefulness. Some authorities consider PCR to be particularly promising. However, amplification techniques have some technical problems because of differences in sample-collection and preparation methods. Cold agglutinin titers higher than 1:64 support the diagnosis, and the cold agglutinin response is correlated with the severity of pulmonary symptoms. However, the test lacks both sensitivity and specificity. The antibody response develops approximately 7-10 days after the onset of symptoms and peaks at approximately 3 weeks. Treatment In most cases, the recommended treatment includes tetracycline or a macrolide. Fluoroquinolones also may be used. Two to three weeks of therapy is generally recommended to reduce the risk of relapse. Chlamydia pneumoniaThe genus Chlamydia includes 3 species that infect humans: C psittaci, C trachomatis, and C pneumoniae (formerly called the TWAR agent). C trachomatis is seen in newborn infants during delivery. It has also been associated with pneumonia in adults. Ornithosis is a systemic infection that is often accompanied by pneumonia and caused by C psittaci, which is common in birds and some domestic animals. The incubation period is approximately 5-15 days. Pet-shop employees and poultry workers are at particular risk, and this organism should be considered when these individuals present with pneumonia. Besides the lungs, other major organs and systems that may be affected by C psittaci infection include the CNS (meningoencephalitis, cranial nerve deficits) and the cardiovascular system (culture-negative endocarditis). The prevalence of C pneumoniae infection varies by year and geographic setting. It causes 5-15% of all cases of CAP. Repeat infection is common. Chlamydia pneumonia may be associated with acute upper-airway infection, sinusitis, bronchitis, and bronchiolitis. Infection by C pneumoniae can cause prolonged, acute bronchitis with reactive airway disease. Bronchiolitis may be seen as a restrictive pattern on pulmonary-function tests. Pneumonia usually tends to be mild. When C pneumoniae is found in association with other pathogens, particularly Streptococcus pneumoniae, the clinical severity is usually determined by the secondary pathogen. The cough associated with C pneumoniae tends to be nonproductive and prolonged despite appropriate antibiotic therapy. Most patients report headache. Diagnosis Results of C pneumoniae cultures, PCR, and serologic tests can suggest the diagnosis. Cell culture is not routinely available except in research laboratories. PCR technology has not been standardized, and serology is problematic because of its nonspecificity. The preferred diagnostic result is a 4-fold increase in titers from the acute stage to convalescence, with supporting evidence from PCR or culture tests. Therefore, most laboratories cannot confirm the diagnosis in a timely fashion; the treatment of Chlamydia pneumonia should be empirical. Treatment C pneumoniae may be treated with doxycycline, a macrolide, or a fluoroquinolone. DIFFERENTIALSSection 3 of 9
Acute Respiratory Distress Syndrome Bronchiolitis Obliterans Organizing Pneumonia Empyema Lung, Drug-Induced Disease Lung, Nontuberculous Mycobacterial Infections Lung, Postprimary Tuberculosis Lung, Primary Tuberculosis Pneumonia, Atypical Bacterial Pneumonia, Pneumocystis Carinii Pneumonia, Typical Bacterial Pneumonia, Viral Other Problems to Be ConsideredHypersensitivity pneumonitis RADIOGRAPHSection 4 of 9
FindingsLegionella pneumonia Legionella species are implicated in 2-15% of CAP cases. These organisms usually cause a patchy, localized infiltrate in the lower lobes. Associated hilar adenopathy may be present. Pleural effusion is seen in up to 30% of cases. In rare instances, Legionella infection is associated with cavitation and a masslike appearance. Radiologic resolution of Legionella pneumonia may take 6-12 months. Permanent residual fibrosis is observed in as many as 25% of patients. An early progression of infiltrates can occur despite clinical improvement. Mycoplasma pneumonia M pneumoniae is implicated in 2-30% of all cases of CAP. Mycoplasma pneumonia is usually mild and results in a rapid resolution of any radiologic findings. However, it tends to be more severe in patients with sickle cell anemia. Radiographic resolution in 40% of patients occurs in 4 weeks, and 80% of cases resolve by 8 weeks. Residual radiographic abnormalities are uncommon. The infiltrates in Mycoplasma pneumonia can be unilateral, multilobar, or bilateral. In about 20% of patients, pleural effusion or hilar adenopathy may be present. Chlamydia pneumonia The infiltrates may be subsegmental or more extensive in elderly patients; pleural effusions are rarely seen. Chest radiographs show 50% resolution in 4 weeks. In 20% of cases, resolution takes longer than 9 weeks. Degree of ConfidenceRadiologic findings alone are not reliable in differentiating pneumonia into typical or atypical forms. Therefore, the radiographic findings described above should be used along with clinical and laboratory data to narrow the possibilities. Structural lung disease with abnormal lung parenchyma affects the pattern of infiltrates. In cases of severe emphysematous lung disease, clinicians may tend to underestimate the presence of infiltrates on chest radiographs. CT SCANSection 5 of 9
FindingsCT scans are increasingly being used in clinical practice. Various authors have questioned CT scanning's usefulness in evaluating consolidations, suggesting that the value of CT in the diagnosis of pneumonia is limited to specific cases involving (1) an indistinct, abnormal opacity on chest radiographs; (2) patchy, ground-glass, linear, or reticular opacities on chest radiographs; (3) possible pleural effusion; and (4) neutropenia and fever of unknown origin (for which ultra–thin-section CT scanning may be helpful). High-resolution CT findings in CAP Tanaka et al (1996) compared high-resolution CT (HRCT) scan findings in CAP with pathologic findings and evaluated the role of HRCT scanning in differentiating between bacterial and atypical pneumonias in 32 patients with CAP (18 with bacterial pneumonia, 14 with atypical pneumonia). Bacterial pneumonia often resulted in airspace consolidation with a segmental distribution (72%) that typically occurred toward the middle and outer zones of the lungs. Atypical pneumonias included Mycoplasma and Chlamydia pneumonias, as well as influenza viral pneumonia. These conditions frequently caused a centrilobular shadow (64%), an acinar shadow (71%), and/or airspace consolidation (57%) and ground-glass attenuation (86%) with a lobular distribution. The lesions were often distributed to the inner, middle, and outer layers of the lung (86%). Legionella pneumonia Mild Legionella pneumonia may manifest with bilateral involvement of the lung parenchyma. Multiple segments are affected, and peripheral lung consolidation with ground-glass opacity and pleural effusion may be seen. With more severe infection, lung cavitation and bulging of the fissure have been reported. Residual lung parenchymal scarring can be found, even after the acute infection resolves. Mycoplasma pneumonia In 2000, Reittner et al examined 28 patients, identifying ground-glass attenuation in 24 (86%) and airspace consolidation in 22 (79%). In 13 of the latter 22 patients (59%), the areas of consolidation had a lobular distribution. Nodules were more common on HRCT scans (89%) than on radiographic images (50%), and in 24 of 28 patients (86%), the nodules had a predominantly centrilobular distribution on CT scans. Thickening of bronchovascular markings were more often found with CT scanning (82%) than with radiography (18%). Degree of ConfidenceCoinfection with several organisms is not uncommon. Underlying parenchymal lung abnormalities usually predispose patients to pneumonia. Therefore, in patients with pneumonia, the overall clinical and radiologic picture must be considered in place of an independent, dichotomous view. ULTRASOUNDSection 6 of 9
FindingsThe literature suggests that ultrasonography can help in differentiating between consolidation and effusion. Consolidated lung tissue may appear as hypoechoic areas with blurred margins. The texture varies with the amount of aeration, being more heterogeneous with aeration and more homogeneous with dense consolidation. The literature also reports that sonography may aid in the diagnosis of empyema and abscesses. However, the current authors believe that in clinical practice, sonography's usefulness is limited to the identification and quantification of parapneumonic effusions. Once found, the area where an effusion occurs can be marked for subsequent diagnostic or therapeutic thoracentesis. INTERVENTIONSection 7 of 9
Legionella pneumonia Delay in the treatment of Legionella pneumonia is associated with a significantly increased mortality rate. The newer macrolides, especially azithromycin, have superior in vitro activity, with more intracellular and lung tissue penetration than erythromycin. Quinolones have even greater in vitro activity and better intracellular penetration than the macrolides. In severely ill patients, rifampin may be used in combination with the macrolides or quinolones. The duration of therapy is 10-14 days, with a 21-day regimen for immunosuppressed patients or those with extensive disease, as shown on chest radiographs. Chest radiographic findings may continue to deteriorate despite clinical improvement. Mycoplasma pneumonia In most cases, recommended treatment for Mycoplasma pneumonia includes tetracycline or a macrolide. Fluoroquinolones also may be used. Two to three weeks of therapy is generally recommended to lessen the risk of relapse. Chlamydia pneumonia Chlamydia pneumonia may be treated with doxycycline, a macrolide, or a fluoroquinolone. The preferred diagnostic result is a 4-fold increase in titers from the acute stage to convalescence, with supporting evidence from PCR or culture tests. Therefore, most laboratories cannot confirm the diagnosis in a timely fashion; the treatment of this pneumonia should be empirical. MULTIMEDIASection 8 of 9
REFERENCESSection 9 of 9
Pneumonia, Atypical Bacterial excerpt Article Last Updated: Mar 7, 2008 | |||||||||||||||||||||||||||||||||||||||||||||||||
