eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Pneumonia: Differential Diagnoses & Workup

Author: Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Coauthor(s): Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University; Isabel Virella-Lowell, MD, Department of Pediatrics, Division of Pulmonary Diseases, Pediatric Pulmonology, Allergy and Immunology
Contributor Information and Disclosures

Updated: Jan 12, 2009

Differential Diagnoses

Workup

Laboratory Studies

Identifying the causative infectious agent is the most valuable step in managing a complicated case of pneumonia. Unfortunately, an etiologic agent can be difficult to identify. Therefore, in most patients with community-acquired pneumonia who are treated on an outpatient basis, treatment is empiric and based primarily on patient age and clinical presentation.

In patients with complicated pneumonia who have not responded to treatment or who require admission to the hospital, several diagnostic studies aimed at identifying the infectious culprit are warranted, including cultures, serology, and a CBC count with the differential and acute-phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]).

• Direct antigen detection
  • Although antiviral therapies are not often used, performing a nasal wash for respiratory syncytial virus (RSV) and influenza enzyme-linked immunoassay (ELISA) and viral culture can help to establish a rapid diagnosis, which may be helpful in excluding other diagnoses. In addition, correct diagnosis allows for appropriate placement of patients in the hospital. For example, if necessary, 2 infants with RSV infection may share a room, whereas such patients would normally need isolation and may unnecessarily tie up a bed.
  • Viral cultures can be obtained in 1-2 days using newer cell culture techniques and may permit discontinuation of unnecessary antibiotics.
• Sputum culture
  • Sputum is rarely produced in children younger than 10 years, and samples are always contaminated by oral flora. An adequate sputum culture should contain more than 25 polymorphonuclear (PMN) cells per field and fewer than 10 squamous cells per field.
  • The common agents that cause pneumonia may be normal oral flora. For these reasons, sputum cultures are not useful in most children with pneumonia, although a Gram stain may help.
• Bronchoscopy
  • Flexible fiberoptic bronchoscopy is occasionally useful to obtain lower airway secretions for culture or cytology.
  • This procedure is most useful in immunocompromised patients who are believed to be infected with unusual organisms (Pneumocystis, other fungi) or in patients who are severely ill.
  • Careful consideration of the diagnostic possibilities is necessary to send the samples for the appropriate tests.
  • Contamination of the bronchoscopic aspirate with upper airway secretions is common; quantitative cultures can help distinguish contamination from infection. 
• Blood culture
  • Although blood cultures are technically easy to obtain and relatively noninvasive and nontraumatic, the results are rarely positive in the presence of pneumonia and even less so in cases of pretreated pneumonia.
  • In a study of 168 patients with known pneumonia, Wubbel et al found only sterile blood cultures. In general, blood culture results are positive in 10-15% of patients with streptococcal pneumonia (Media file 1).² The numbers are even less in patients with Staphylococcus infection. A blood culture is still recommended in complicated cases of pneumonia.
• Lung aspirate
  • This test is underused and is a significantly more efficient method of obtaining a culture.
  • A study that compared the incidence of (1) positive culture results obtained with blood culture with (2) positive culture results obtained with lung aspiration in 100 children aged 3-58 months with pneumonia merits mention.³ Blood culture implicated an organism in 18% of the patients compared with 52% with lung aspirate. The organisms obtained in the blood and lung aspirate differed in 4 of the 8 children in whom both culture results were positive, suggesting that a blood culture may not always accurately reveal the lung pathogen.
  • Other studies have demonstrated lung aspirate results to be positive in 50-60% of patients with known pneumonia. In these studies, 1.5-9% of patients had a pneumothorax and 0.7-3% had transient small hemoptysis complicating their lung aspirations. Because of the possible risks associated with lung aspiration, it should be reserved for patients who are ill enough to require hospitalization, have not improved with previous empiric treatment, or are immunocompromised and an exact etiology is needed.
  • A lung aspirate should not be performed in patients who are on ventilators, patients with a bleeding diathesis, or in patients suspected of having an infection with Pneumocystis.
• Thoracentesis
  • This test is performed for diagnostic and therapeutic purposes in children with pleural effusions.
  • If the Gram stain or the culture result from the pleural fluid is positive or the WBC is higher than 1000 cells/mL, by definition, the patient has an empyema, which may require drainage for complete resolution.
  • Other therapeutic decisions can be made based on the properties of the effusion (see Complications).
• Serology
  • Because of the relatively low yield of cultures, more efforts are underway to develop quick and accurate serologic tests for common lung pathogens, such as M pneumoniae.
  • In a Finnish study, 278 patients diagnosed with community-acquired pneumonia underwent extensive testing for Mycoplasma infection.⁴
    • Acute and convalescent serum samples were collected and tested using enzyme immunoassay for M pneumoniae immunoglobulin M (IgM) and IgG antibodies. Nasopharyngeal aspirates were tested using PCR and cultured with a Pneumofast kit.
    • Positive results were confirmed with Southern hybridization of PCR products and an IgM test with solid-phase antigen. A total of 24 (9%) confirmed diagnoses of Mycoplasma infection were made. All 24 cases had positive results with IgM-capture test with convalescent-phase serum. Using an IgM-capture test in acute-phase serum, 79% of results were positive, 79% were positive using IgG serology, 50% positive using PCR, and 47% positive using culture.
    • The authors of this study concluded that IgM serologic studies for Mycoplasma infection were not only quick but also sensitive and were the most valuable tools for diagnosis of M pneumoniae infection in any age group. IgM serology is much more sensitive than cold agglutinin assessments, which are more commonly used to aid in the diagnosis of Mycoplasma infection and demonstrate positive results in only 50% of cases.
• Polymerase chain reaction
  • This test shows promise of being useful in diagnosing streptococcal pneumonia.
  • PCR is noninvasive, an advantage over lung aspirate or bronchoalveolar lavage (BAL) cultures. Similarly, C pneumoniae infection is diagnosed more readily with PCR than with culture; however, positive test results must correlate with acute symptoms to have any validity because 2-5% of the population may be asymptomatically infected with C pneumoniae.
  • Although new serologic and PCR tests for common lung pathogens hold definite promise for making rapid, accurate, and noninvasive diagnosis, they are not widely available, and the results may not return until after the patient has already completed a course of antibiotics.
  • Direct fluorescent antibody and serologic tests for RSV and influenza, as well as a PCR test for tuberculosis (TB), are widely available and have proven to be of considerable benefit in the treatment of hospitalized patients.
• Skin tests
  • These tests are used in diagnosing TB. Mantoux skin test (intradermal inoculation of 5 TU of purified protein derivative) results should be read 48-72 hours after placement.
  • In children older than 4 years without any risk factors, test results are positive if the induration (not the area of erythema, which may be larger) is 15 mm or larger. Among children younger than 4 years, those who have an increased environmental exposure to TB or other medical risk factors (eg, lymphoma, diabetes mellitus, malnutrition, renal failure), results are positive if the induration is 10 mm or larger. In immunosuppressed children or those in close contact with others who have known or suspected cases of TB, test results are positive if the induration is 5 mm or larger.
  • Even if the child has received the Bacillus Calmette-Guérin (BCG) vaccine, Mantoux test results should be interpreted using the criteria outlined above.
  • Chest radiography helps to confirm the diagnosis of a child with positive Mantoux test results. If the chest radiography findings are positive or if the child has other symptoms consistent with the diagnosis of TB, an attempt should be made to isolate the tubercle bacilli from early-morning gastric aspirates, cerebrospinal fluid, sputum, urine, pleural fluid, or biopsy specimen.
  • In a child with suspected pulmonary TB, the cough may be scarce or nonproductive. Therefore, the best test for diagnosis is an early-morning gastric aspirate sent for acid-fast bacilli (AFB) stain, culture, and, if available, PCR. Gastric aspirates should be obtained by first placing a nasogastric (NG) tube the night before sample collection; a sample is aspirated first thing the following morning, before ambulation and feeding. This should be repeated on 3 consecutive mornings.
• CBC count: Testing should include a CBC count with differential and evaluation of acute-phase reactants (ESR, CRP, or both) and sedimentation rate. The total WBC and differential may aid in determining if an infection is bacterial or viral, and, together with clinical symptoms, chest radiography and ESR can be useful in monitoring the course of pneumonia.
• ABG: This test is indicated in any patient with significant respiratory distress to determine the degree of respiratory insufficiency.

Imaging Studies

• Radiography
• This is the primary imaging study used to confirm the diagnosis of pneumonia. Radiography is often performed when diagnosing pneumonia; however, it is not always necessary or useful in determining the etiology of the infection.
• Chest radiography is indicated in an infant or toddler who presents with fever and any of the following: tachypnea, nasal flaring, retractions, grunting, rales, decreased breath sounds, or respiratory distress. In older children and adolescents, the diagnosis of pneumonia is often based on clinical presentation.
• Chest radiography is primarily indicated in complicated cases in which treatment fails to elicit a response, in patients with respiratory distress, or in those who require hospitalization. Obtain both frontal and lateral radiographs, particularly in cases in which the clinical examination findings are equivocal. In complicated cases of pneumonia, perform chest radiography 6 weeks after treatment to verify resolution of the pneumonia and to screen for any underlying predisposing conditions, such as sequestration.
• Although trends in radiographic findings may prove useful, chest radiography findings frequently do not correlate with the infectious agent involved. Chest radiography findings may be negative in the presence of pneumonia, particularly early in the course. A lobar infiltrate can be seen with viral infections, foreign body aspirations, and mucous plugging that results in atelectasis. Furthermore, pleural effusions, although usually parapneumonic (80%), may be observed in numerous disease processes.
• Several studies have demonstrated that chest radiography is 42-73% accurate in predicting the etiology of a case of pneumonia. In one study of 168 children with pneumonia, 2 radiologists who independently evaluated all chest radiographs were unable to distinguish whether the agent involved was bacterial, viral, or unidentified.² Given the frequency of nonspecific findings obtained with imaging, clinical presentation and other laboratory findings must be considered in the diagnosis of pneumonia and the determination of the etiologic agent.
• In general, viral pneumonias are associated with a patchy perihilar infiltrate, hyperinflation, and atelectasis on chest radiography.
• In patients with bacterial pneumonia, typical findings include a lobar consolidation with air bronchograms occasionally accompanied by a pleural effusion (Media files 2-3). Pneumatoceles and abscesses are less commonly found but may indicate an S aureus, gram-negative, or complicated pneumococcal pneumonia.
• The radiographic appearance of Mycoplasma infection varies. Early in the infection, the pattern tends to be reticular and interstitial; as the infection progresses, patchy and segmental areas of consolidation are noted, along with hilar adenopathy and pleural effusions.
• Except for patients with sickle cell disease (SCD), a significant pleural effusion usually indicates a bacterial etiology. Although these patterns are typical, the etiology cannot be reliably identified based solely on chest radiography findings.
• Ultrasonography
• These studies are indicated primarily in children with complications such as pleural effusions and in those in whom antibiotic treatment fails to elicit a response.
• Ultrasonography is used to effectively differentiate between a low-grade (nonfibrinopurulent) effusion and one that is high-grade (fibrinopurulent and organizing). In a study of children whose effusions were characterized as high grade based on ultrasonography findings, hospital stay was reduced by nearly 50% after surgery.
• Ultrasonography may also prove useful for guidance in thoracentesis of a loculated effusion. In addition to a pleural effusion or empyema, other suppurative complications of pneumonia include cavitary necrosis or abscess and purulent pericarditis. A significant number of these complications are not evident using radiography.
• Contrast CT scanning
• This test is also indicated in children with complications such as pleural effusions and in those in whom antibiotic treatment fails to elicit a response.
• ContrastCT scanning is often more sensitive and demonstrates changes typical for these complications. This information is beneficial when making treatment decisions (eg, whether to perform surgical debridement of organized empyemas or loculated effusions) and in outlining the projected course of the patient's illness.

Procedures

• Bronchoscopy with BAL
• Lung biopsy (guided with CT scanning or ultrasonography, as part of a video-assisted thorascopic surgery [VATS] procedure, or during bronchoscopy) to assist in the diagnosis of infection with rare or unusual organisms

Histologic Findings

No specific histologic findings are reported in most patients with pneumonias beyond evidence of inflammation and cellular infiltration and exudation into alveolar spaces and the interstitium. Sputum, lavage, or biopsy material may yield diagnostic findings.

• In patients with TB, acid-fast bacilli are present and can be detected using the Ziehl-Neelsen stain or can be grown on the Lowenstein-Jensen medium. Caseating granulomas are highly suspicious, even in the absence of detectable organisms.
• Findings of foamy alveolar casts are practically diagnostic for Pneumocystis jiroveci pneumonia, and the cup-shaped organisms are often found using Gomori methenamine silver staining or direct immunofluorescence.
• Fungal elements may be seen using Gomori methenamine silver staining or periodic acid-Schiff staining. Aspergillus and Zygomycetes species may be seen using simple hematoxylin and eosin staining. The specific morphology of the organisms may be diagnostic, but, occasionally, culture or immunostaining is required.

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