Pneumonia

Community-Acquired Pneumonia: A Clinical Diagnostic Approach

BURKE A. CUNHA, MD
State University of New York School of Medicine, Stony Brook

Dr Cunha is chief of the infectious disease division at Winthrop University Hospital, Mineola, NY, and is professor of medicine at the State University of New York School of Medicine, Stony Brook, New York.

ABSTRACT: Before beginning a work-up for community-acquired pneumonia (CAP), be sure to exclude noninfectious mimics. The chest film is an extremely important diagnostic tool in cases of suspected CAP. Since both zoonotic and non-zoonotic atypical CAPs are characterized by distinctive patterns of extrapulmonary manifestations, a presumptive diagnosis may be made based on the pattern of organ involvement. A clinical syndromic diagnosis is important to avoid “shotgun” laboratory testing. The rationale behind this approach is to rule out noninfectious mimics of CAP, to confirm the diagnosis of CAP, and to differentiate typical from atypical CAPs.

Key words: community-acquired pneumonia, legionnaire’s disease


 

Pneumonia is one of the most common medical problems encountered in clinical practice and is one of the leading causes of infectious disease–related death worldwide. The pathogenesis of community-acquired pneumonia (CAP) involves the inhalation of a pulmonary pathogen; the severity of pneumonia depends on inoculum size, virulence of the organism, and adequacy of the patient’s host defenses.

Pneumonia may be classified according to where it is acquired, that is, whether it is community-acquired, nursing home–acquired, or hospital-acquired. In addition, if the pneumonia is confined to the lungs only and has no extrapulmonary manifestations, it is referred to as typical bacterial CAP. Ultimately, if a patient has CAP coupled with extrapulmonary findings, then the patient is said to have an atypical CAP. If the organism causing a typical or atypical CAP is identified, then the CAP is described by both its type and the causative organism—for example, typical CAP due to Streptococcus pneumoniae or atypical CAP due to Legionella pneumophila.1-5 The atypical CAPs are further subdivided clinically and epidemiologically into 2 groups, the zoonotic atypical and non-zoonotic atypical CAPs. The non-zoonotic CAPs are caused by either Legionella species, Chlamydophila pneumoniae, or Mycoplasma pneumoniae. The zoonotic atypical CAPs are Q fever, tularemia, and psittacosis (Table 1).2,6-9 In this review, the clinical diagnostic approach is to differentiate the typical and atypical CAPs.

table 1 - CAP

CLINICAL MANIFESTATIONS OF CAP

Most patients with CAP who are immunocompetent adults present with fever and chills accompanied by a variety of pulmonary symptoms, including cough, sputum production, pleuritic chest pain, and shortness of breath. In addition, patients with atypical CAP present with a variety of pathogen-dependent extrapulmonary findings (Tables 2 and 3).1-5 Sometimes, patients with CAP may present with a complication of pneumonia, such as empyema. In addition, CAP may precipitate congestive heart failure (CHF), acute myocardial infarction, renal insufficiency, or pulmonary insufficiency.1,2

table - Cap symptoms

MIMICS OF CAP

Before beginning a work-up for CAP, the clinician should be sure to exclude noninfectious mimics. Several noninfectious medical disorders may manifest with fever, pulmonary symptoms, and pulmonary infiltrates detected by chest radiography that may mimic CAP. The chest film is an extremely important diagnostic tool in cases of suspected CAP. The chest film not only confirms whether pneumonia is present but also may suggest a noninfectious CAP mimic based on the character and distribution of the pulmonary infiltrates on the radiograph.2

table - cap findings

The disorders most likely to mimic CAP are CHF, bronchogenic carcinoma, sarcoidosis, hypersensitivity pneumonitis, drug-induced pulmonary disease, and bronchiolitis obliterans with organizing pneumonia. Systemic lupus erythematosis, pneumonitis, and sarcoidosis are also common CAP mimics. Patients with systemic diseases with pulmonary manifestations, such as systemic lupus erythematosis, sarcoidosis, and CHF, usually have a history or extrapulmonary findings that suggest the underlying systemic disorder (Table 4).10-17 When the chest film suggests the infiltrates may be due to CAP, other findings often suggest a specific CAP pathogen—for example, a right lower lobe infiltrate with a mild or moderate right lower lobe effusion is likely due to Haemophilus influenzae.2-5

table - noninfectious mimics

MILD OR MODERATE TO SEVERE CAP

The clinical severity of CAP is a function of the pathogen, underlying cardiopulmonary function, and impaired immune response of the host. In the consideration of pathogen-related severity, legionnaire’s disease, with all other things being equal, causes a more severe CAP than Moraxella catarrhalis infection. However, in a patient with chronic obstructive pulmonary disease who has limited lung reserve, M catarrhalis infection may manifest as severe CAP. Similarly, CAP in hosts with impaired splenic function (decreased humoral immunity/B-lymphocyte function) is often severe.2,18,19

Clinically, it is useful to remember that severe CAP is most commonly due to host factors such as cardiac, pulmonary, and immune dysfunction rather than to the virulence of the pathogen per se. The clinical presentation of severe CAP should prompt a careful evaluation of these host factors to account for the severity of the pneumonia (Table 5). Viral CAPs are often severe even in normal hosts, since, except for adenoviral CAP, they are usually diffuse and often result in severe hypoxemia.20-25

The treatment of severe CAP is the same as that of nonsevere CAP, since therapy is based on the presumed pathogen, not on comorbidities.1,2

table - severe cap

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THE TYPICAL CAP PATHOGENS

The most common pulmonary pathogens causing CAP are S pneumoniae, H influenzae, and M catarrhalis. In addition, oral anaerobic bacteria cause aspiration pneumonia. Uncommon causes of CAP include group A streptococci (Streptococcus pyogenes) and Escherichia coli, among others. Importantly, Klebsiella pneumoniae manifests as CAP only in patients with alcoholic cirrhosis. Pseudomonas aeruginosa CAP occurs only virtually in those with chronic bronchiectasis or cystic fibrosis. Patients with febrile neutropenia who are undergoing chemotherapy may have P aeruginosa bacteremia but do not present with P aeruginosa CAP.1-3 

Staphylococcus aureus, either of the methicillin-sensitive or the methicillin-resistant variety, does not cause CAP. However, methicillin-sensitive or -resistant S aureus infection may occur simultaneously with influenza CAP or with an influenza-like illness.2,19 Excluding these exceptions for practical purposes, the diagnostic approach should be directed to differentiating S pneumoniae from H influenzae and both of those from M catarrhalis by microbiologic means, such as Gram staining and/or culture of the sputum and blood culture (Tables 6 and 7).1-5

table - pneumonia

The diagnosis of the typical bacterial CAPs is, in the main, microbiologic. Streptococcus pneumoniae may also be identified by culture from blood or pleural fluid or by urinary antigenuria testing for S pneumoniae. With M catarrhalis CAP, blood cultures are extremely rare and diagnosis depends on a culture of the organism from the sputum in the appropriate clinical setting, such as acute exacerbation of chronic bronchitis CAP. However, the typical pathogens also provide a variety of radiologic and other clues that may lead to a specific etiologic diagnosis. Haemophilus influenzae, like S pneumoniae, is often bacteremic, and blood cultures often provide a specific etiologic diagnosis in CAP caused by these pathogens.26-31

Streptococcus pneumoniae CAP. The onset of pneumococcal pneumonia is abrupt, occurring with high fever (102°F or higher) and a single shaking chill followed by a productive cough (purulent sputum) with or without pleuritic chest pain. Bacteremia occurs in 75% of cases. Patients with asplenia are particularly vulnerable to S pneumoniae infection1-3 and may present with overwhelming pneumococcal sepsis. Chest films usually show segmental/lobar right lower lobe consolidation or an air bronchogram. Pleural reaction is not uncommon with S pneumoniae, and empyema develops in approximately 1% to 2% of cases. Moderate to large pleural effusion argues against the diagnosis of S pneumoniae infection. Streptococcus pneumoniae CAP does not involve cavitation, and it predominantly affects the right lower lobe.1-5,32,33

table - pneumonia sputum

Haemophilus influenzae CAP. In adults, the typical presenting symptoms of H influenzae CAP include a subacute onset of fever with or without chills and productive cough. Chest films will demonstrate a patchy bronchopneumonia (most common in adults) or a unilateral focal segmental/lobar right lower lobe (the most common location) infiltrate without cavitation. Mild or moderately sized pleural effusion (exudative) on the side of the infiltrate is typical, and empyema is rare.1-3

Moraxella (Branhamella) catarrhalis CAP. Often, the onset of M catarrhalis CAP is typically subacute and follows an acute exacerbation of chronic bronchitis. Moraxella catarrhalis CAP appears with a productive cough and purulent sputum; chills are infrequent. On chest films, there is usually consolidation superimposed on findings of chronic obstructive pulmonary disease, and cavitation and pleural effusion are rare.4,5

ZOONOTIC AND NON-ZOONOTIC ATYPICAL CAP

Zoonotic atypical CAPs. The atypical CAP pathogens may be classified as either zoonotic or non-zoonotic. The zoonotic CAPs due to Q fever, psittacosis, or tularemia and are not random events but are localized epidemiologically and are always associated with recent contact with the appropriate vector. Patients do not acquire zoonotic CAP randomly or from others. If a patient has CAP with extrapulmonary findings, the clinician should determine the patient’s recent history of close vector contact. The zoonotic atypical CAPs due to psittacosis, tularemia, or Q fever are diagnosed serologically. If zoonotic pathogens are suspected, samples should not be sent to the laboratory, because they represent a biohazard to laboratory personnel. If the appropriate vector contact history is negative, then the clinician may assume the patient is not likely to have a zoonotic atypical CAP.2,9,31,34-38

Non-zoonotic atypical CAPs. If the zoonotic vector history is negative, the clinician should focus on differentiating or identifying Legionella species from C pneumoniae and both of those from M pneumoniae. As with the non-zoonotic atypical CAPs, the diagnosis is usually serologic for Legionella species, M pneumoniae, and C pneumoniae. The diagnosis of legionnaire’s disease may be confirmed by elevated serum titers. Legionella pneumophila infection may also be diagnosed by urinary antigen testing. However, it should be remembered that the Legionella urinary antigen only tests for L pneumophila (serogroups 01-06) but does not detect Legionella species that are not of this serogroup or species.2,3,6-9,39,40

Mycoplasma pneumoniae CAP. The onset of M pneumoniae CAP is subacute with a characteristic dry or nonproductive cough that lasts for weeks and is accompanied by low-grade fever and chills with or without mild myalgias. Other findings pointing to M pneumoniae CAP include sore throat (nonexudative pharyngitis), bullous myringitis, otitis media, rhinorrhea and/or watery loose stools or diarrhea. Ruling against the diagnosis of M pneumoniae CAP are high fever (higher than 102°F), relative bradycardia, laryngitis, abdominal pain, elevated glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels, or a low serum phosphorus level. Chest films will show ill-defined unilateral infiltrates without pleural effusion, consolidation, or cavitation.1,2,6-9,41-45

Chlamydophila (Chlamydia) pneumoniae CAP. Chlamydophila pneumoniae CAP presents as a “Mycoplasma-like” illness, except hoarseness is often present. The body temperature is usually 102° F or higher and relative bradycardia is not present. Chest films will show a unilateral ill-defined infiltrate without consolidation, cavitation, or pleural effusion.2,46,47

Legionnaire’s disease. Most patients with Legionella CAP require hospitalization, as Legionella CAP is more severe than M pneumoniae or C pneumoniae CAP. Its onset is usually acute, occurring with high fevers (102°F or higher) and relative bradycardia. Myalgias and chills are not uncommon. Legionella CAP has a characteristic pattern of extrapulmonary manifestations. Legionella CAP may be suspected with worsening or unresponsiveness to beta-lactam therapy.

On chest films, the appearance of Legionella is not diagnostic, but the behavior of infiltrates on chest films, marked by asymmetric and rapidly progressive infiltrates, is characteristic of legionnaire’s disease. There is no lobar predilection, and bilateral involvement is usual. Consolidation and pleural effusion are not uncommon, but cavitation is rare. Mental confusion is common, as are watery diarrhea, abdominal pain, relative lymphopenia, mild or transient elevations of SGOT/SGPT, early or transient decreased serum phosphorus levels, highly elevated ferritin levels (more than 2 times normal), a highly elevated erythrocyte sedimentation rate (higher than 100 mm/h), an elevated creatine phosphokinase level, and an elevated C-reactive protein level (higher than 30 mg/dL) (Table 8).2,48-56

table - legionnaire's

THE CLINICAL SYNDROMIC DIAGNOSTIC APPROACH

Since both zoonotic and non-zoonotic atypical CAPs are characterized by distinctive patterns of extrapulmonary manifestations, a presumptive diagnosis may be made based on the pattern of organ involvement with each of these organisms. While individual findings are not specific and overlap with those of other pathogens when the findings are combined together, a syndromic presumptive diagnosis is almost always possible. Although all patients do not have all of the characteristic findings of each atypical CAP pathogen, there is almost always a sufficient number upon which to base a presumptive clinical syndromic diagnosis. Viral CAPs, particularly influenza CAP, have a distinctive clinical presentation (Table 9).2,6,7,48,56

A clinical syndromic diagnosis is important to avoid “shotgun” laboratory testing. The clinical syndromic diagnosis suggests the most likely pathogen and as importantly eliminates other CAP pathogens from further diagnostic consideration. For example, for a patient with a non-zoonotic atypical CAP who has an otherwise unexplained mild elevation of serum transaminase, C pneumoniae and M pneumoniae are virtually excluded, because they rarely, if ever, include the liver. In contrast, transaminitis due to legionnaire’s disease is such a common finding that otherwise unexplained mild or moderate elevations of serum transaminase in a non-zoonotic atypical CAP should suggest the diagnosis of legionnaire’s disease.2,9,47-56

table - influenza a

EMPIRIC THERAPY IS DIAGNOSIS DEPENDENT

The rationale behind the clinical syndromic diagnostic approach is to rule out noninfectious mimics of CAP, to confirm the diagnosis of CAP, and to differentiate typical from atypical CAPs. Typical CAPs may be treated with a beta-lactam or doxycycline or a “respiratory quinolone.” If a patient has an atypical CAP, then the clinician may treat it with doxycycline or a respiratory quinolone. Either is effective against both zoonotic and non-zoonotic causes of atypical CAP. However, with atypical CAPs, the problem is not deciding what is appropriate empiric therapy but rather trying to differentiate and identify the atypical pathogen responsible for the CAP. For this, the clinician relies on a variety of clues from the history, physical examination, and nonspecific laboratory tests. By narrowing the diagnostic possibilities, the work-up for the atypical CAPs is streamlined, enabling a focused, presumptive working diagnosis that will serve as the basis for determining appropriate empiric antibiotic therapy.1-4

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