eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Congenital Pneumonia: Differential Diagnoses & Workup

Author: Roger G Faix, MD, Professor, Department of Pediatrics (Neonatology), University of Utah School of Medicine
Contributor Information and Disclosures

Updated: Oct 5, 2009

Differential Diagnoses

Other Problems to Be Considered

Other problems to consider include the following:

• Alveolar-capillary dysplasia
• Arrhythmia
• Asphyxia
• Bronchial duplication
• Chest wall injury or anomaly
• Choanal atresia
• Chylothorax
• Diaphragmatic eventration
• Heart block
• Intracranial hemorrhage
• Laryngeal cleft
• Laryngeal nerve injury
• Mutation of ABCA3 gene (for surfactant phospholipid transport)
• Neuromuscular disorders
• Phrenic nerve injury
• Pulmonary hemorrhage
• Pulmonary hypoplasia
• Pulmonary lymphangiectasia
• Spinal injury
• Surfactant-related protein B deficiency
• Tachycardia syndromes
• Tracheoesophageal fistula
• Transplacental medications
• Vascular catheter accident
• Other causes of airway obstruction
• Other congenital heart diseases
• Other inborn errors of metabolism
• Other neuromuscular diseases

Consider any other diseases that may present with respiratory dysfunction in the first 24 hours of life and consider that any of the conditions listed above may have superimposed pneumonia as well.

Workup

Laboratory Studies

The most useful laboratory tests for congenital pneumonia facilitate the identification of an infecting microorganism. Results can be used for therapeutic decisions as well as prognostic and infection control considerations.

• Culture
  • Conventional bacteriologic culture is used most widely and is currently most helpful.
  • Aerobic processing is sufficient for recovery of most responsible pathogens.
  • Although the foul smell of amniotic fluid in the setting of maternal chorioamnionitis is often attributable to anaerobes, these organisms are seldom shown to be causative.
  • Culture of fungi, viruses, U urealyticum, U parvum and other nonbacterial organisms often requires different microbiologic processing but may be warranted in suggestive clinical settings.
• Blood culture
  • Blood culture with at least 1 mL of blood from an appropriately cleaned and prepared peripheral venous or arterial site is essential because many neonatal pneumonias are hematogenous in origin and others serve as a focus for secondary seeding of the bloodstream.
  • Blood culture samples drawn through freshly placed indwelling vascular catheters may be helpful, but the possibility of contamination rises the longer the catheter is in place.
  • Multiple cultures of blood from different sites and/or those drawn at different times may increase culture yield, but limited circulating blood volume precludes this as the standard of care in neonates on the first day of life.
• Culture of specimens from lumbar puncture
  • Routine culture and analysis of spinal fluid in infants in whom congenital pneumonia is suspected is controversial because the yield is low and many infants with respiratory support requirements do not tolerate lumbar puncture well.
  • Spinal fluid may yield a pathogen when blood does not, especially following maternal antibiotic pretreatment.¹⁴
  • Presence of a pathogen in the spinal fluid may indicate the need for alteration in the selection, dosage, and duration of antibiotic therapy even if cultures from other sites yield the same organism.
• Urine culture: During the first 3 days of life, urine culture is unlikely to be helpful because most urinary tract infections at this age are hematogenous.
• Culture of specimens from endotracheal aspiration
  • Culture and Gram stain of an endotracheal aspirate obtained by aseptic technique as soon as possible after intubation may be useful.
  • Under typical circumstances, airway commensals take as long as 8 hours to migrate down the trachea. At least one study demonstrated that culture of endotracheal aspirates obtained within 8 hours of birth correlates very well with blood culture results and probably reflects aspirated infected fluid.¹⁵ The longer the tube has been in place, the greater the likelihood that recovered organisms represent colonizing organisms rather than invasive pathogens; nonetheless, recovery of a single recognized pathogen in large quantities may be helpful in the selection of antibiotic therapy, especially if culture results from normally sterile sites are negative.
  • The absence of significant inflammatory cells in an endotracheal aspirate or other respiratory specimen suggests that organisms recovered from that site are unlikely to be truly invasive (unless the infant is markedly leukopenic). Thus, the organism represents colonization of the respiratory tract and not infection.
• Culture from extrapulmonary sites
  • Detection of microorganisms at inflamed extrapulmonary sites may be helpful because concurrent involvement of the lungs is not rare.
  • Studies of abscesses, conjunctivitis, skin lesions, and vesicles may be fruitful.
  • Take care to ensure that the specimen submitted is as free of contamination as possible. Tests such as organism-specific DNA probe or polymerase chain reaction (PCR)–based assay are less likely to be affected by such factors.
• Culture from other respiratory sites
  • Pleural fluid: In the presence of radiographically visible fluid, careful positioning of the infant and thoracentesis after sterile preparation of the sampling site may yield diagnostic findings on Gram stain, direct microscopy, and/or culture. Ultrasonography may reveal smaller fluid pockets and facilitate safer sampling under direct visualization. Although data from neonates are insufficient to draw conclusions, studies in older populations suggest a very high correlation with culture of lung tissue and/or blood.
  • Bronchoscopic alveolar lavage: Quantitative culture techniques have been assessed in non-neonatal populations and reported to offer a specificity of >80% depending on the threshold selected (values from >100 to 100,000 cfu/mL have been used).^16,17 Data from studies of neonates with suspected congenital pneumonia are lacking.
  • Nonbronchoscopic protected specimen brush:¹⁸ Nondirected specimens have been obtained through endotracheal tubes 3 mm or greater internal diameter and intuitively appear to offer decreased probability of contamination. Data from neonates are sparse at present. Unlike bronchoscopically obtained specimens, ensuring sampling from a particular involved site is more difficult.
  • Lung puncture: Although used much less frequently than in previous decades, this technique may still be useful in circumstances in which pleural and subpleural lung surfaces are visibly involved and can be well-localized.¹⁹ Risk-benefit ratio merits careful consideration given the risk of such complications as pneumothorax, broncho-pleural fistula, hemothorax, and sampling a nondiagnostic site. This is a high-risk procedure and should not be considered a routine procedure in the diagnosis or treatment of pneumonia in the neonate.
• Limitations of cultures
  • A number of factors may interfere with the ability to grow a likely pathogen from the sites noted, including (but not limited to) the following: (1) pretreatment with antibiotics that limit in vitro but not in vivo growth, (2) contaminants that overgrow the pathogen, (3) pathogens that do not replicate in currently available culture systems, and (4 ) patients in whom the process is inflammatory but not infectious, such as meconium aspiration.
  • Techniques that may help overcome some of these limitations include antigen detection, nucleic acid probes, PCR-based assays, or serologic tests.
  • Although once widely used, tests such as latex agglutination for detection of group B streptococcal antigen in urine, serum, or other fluids have fallen into disfavor because of poor predictive value; however, new generations of non–culture-based technologies continue to undergo development and may be more accurate and widely available in the future.
• Serologic tests
  • Serologic tests have limited use but may offer some insights in congenital pneumonia secondary to cytomegalovirus or toxoplasmosis.
  • Serologic tests for syphilis may suggest or confirm the presence of pneumonia alba, particularly in high-risk populations.
  • Giacoia and colleagues espoused the value of assessing antibody responses in acute and convalescent sera from infants using flora recovered from endotracheal aspirates.²⁰ This usually permits diagnosis only retrospectively, but may be useful in infants who fail to adequately respond to empiric therapy or for epidemiologic purposes.
  • Concerns persist regarding the specificity of such tests in distinguishing invasion from colonization.
• Markers of inflammation
  • The use of markers of inflammation to support a diagnosis of suspected infection, including pneumonia, remains controversial.
  • Various indices derived from differential leukocyte counts have been used most widely for this purpose, although noninfectious causes of such abnormal results are numerous. Many reports have been published regarding infants with proven infection who initially had neutrophil indices within reference ranges.
  • Quantitative measurements of C-reactive protein, procalcitonin, cytokines (eg, interleukin-6), interalpha inhibitor proteins,²¹ and batteries of acute-phase reactants have been touted to be more specific but are limited by suboptimal positive predictive value.
    • Lag time from infection to abnormal values are noted.
    • Serial measurements are often necessary and do offer a high negative predictive value.
  • These tests may be useful in assessing the resolution of an inflammatory process, including infection, but they are not sufficiently precise to establish a diagnosis without additional supporting information. Decisions about antimicrobial therapy should not be based on inflammatory markers alone.

Imaging Studies

• Radiography
  • Numerous radiographic patterns are consistent with neonatal pneumonia and a multitude of other pathologic processes.²² A synthesis of all available information and careful consideration of the differential diagnosis is essential to establishing the diagnosis, although empiric antimicrobial treatment usually cannot be deferred because of inability to prospectively exclude the diagnosis.
  • A well-centered, appropriately penetrated, anteroposterior chest radiography is essential, although other views may be warranted to clarify anatomic relationships and air-fluid levels.
  • Be aware that any image reflects conditions only at the instant when the study was performed. Because neonatal lung diseases, including pneumonia, are dynamic, initially suggestive images may require reassessment based on subsequent clinical course and findings in later studies.
  • When considering pneumonia, devote particular attention to the following:
    • Costophrenic angles
    • Pleural spaces and surfaces
    • Diaphragmatic margins
    • Cardiothymic silhouette
    • Pulmonary vasculature
    • Right major fissure
    • Air bronchograms overlying the cardiac shadow
    • Lung expansion
    • Patterns of aeration
  • Diffuse relatively homogeneous infiltrates that resemble the ground-glass pattern of respiratory distress syndrome are suggestive of a hematogenous process, although aspiration of infected fluid with subsequent seeding of the bloodstream cannot be excluded.
  • Patchy irregular densities that obscure normal margins are suggestive of antepartum or intrapartum aspiration, especially if such opacities are distant from the hilus.
  • Patchy irregular densities in dependent areas that are more prominent on the right side are more consistent with postnatal aspiration.
  • Generalized hyperinflation with patchy infiltrates suggests partial airway obstruction from particulate or inflammatory debris, although the contribution of positive airway pressure from respiratory support must be considered.
  • Pneumatoceles (especially with air-fluid interfaces) and prominent pleural fluid collections also support the presence of infectious processes.
  • Single or multiple prominent air bronchograms 2 or more generations beyond the mainstem bronchi reflect dense pulmonary parenchyma (possibly an infiltrate) highlighting the air-filled conducting airways.
  • A well-defined dense lobar infiltrate with bulging margins is unusual.
  • Lateral or oblique projections may help to better define structures whose location and significance are unclear.
• Ultrasonography: Ultrasonography may be helpful in selected circumstances. Ultrasonography is particularly useful for identifying and localizing fluid in the pleural and pericardial spaces. However, the presence of air within the lungs limits the use of ultrasonography.
• CT scanning or MRI: These imaging modalities may be helpful in selected circumstances. CT or MRI may be helpful for evaluating suspected tumors, aberrant vessels, sequestered lobes, or other primary pulmonary anomalies and for establishing the presence of infiltrate, atelectasis or other acquired processes. Such studies may be particularly useful for localizing infiltrates, abscesses, or infected fluid before percutaneous sampling attempts.

Procedures

• Thoracentesis
  • If significant pleural fluid is detected radiographically or sonographically, consider thoracentesis for Gram stain, culture, and biochemical tests.
  • The risk of pneumothorax or laceration of intercostal vessels is real but can be minimized by the use of proper technique, including use of the Z-technique (stretching the skin down over the entry site, so that release after the procedure will permit the return of tissues to their usual location with occlusion of the path of the needle), entry over the superior rib margin (to minimize inadvertent puncture of intercostal vessels) at a dependent site where fluid is most likely to collect, continuous aspiration once the skin is penetrated, and no further advancement once fluid is obtained.
  • This procedure may be therapeutic as well as diagnostic if the pleural fluid is impinging on lung or cardiac function.
  • Sonographic guidance may facilitate performance.
• Bronchoscopy: Transbronchial biopsy and guided aspiration or brush specimens obtained via direct bronchoscopy may be advantageous in some circumstances. The technique of direct rigid bronchoscopy may be used in larger infants; fiberoptic technique is occasionally possible in smaller infants or infants in whom the site is not easily reached using the rigid technique. Both this technique and protected brush tracheal aspirate sampling may not be well tolerated in infants with significant lung disease and poor gas exchange who are very dependent on continuous positive pressure ventilation.
• Protected brush tracheal aspirate sampling¹⁸
  • Sites distant from the larger bronchi often cannot be sampled.
  • Specimens may have an increased risk of contamination with oral or airway commensals compared with bronchoscopic sampling but are thought to be more accurate than a conventional endotracheal aspirate.
• Lung aspiration
  • If a prominent infiltrate can be adequately localized in multiple planes, direct aspiration of the infected lung may be performed for culture or biopsy. Lung CT may facilitate such localization.
  • Lung aspiration is associated with a greater risk of postprocedural air leak and usually requires a larger-bore needle than is used to obtain pleural fluid.
  • Because the risk associated with this procedure is high, this technique is usually reserved for circumstances in which empiric therapy is failing, less invasive cultures and detection tests are unrewarding, and/or the infant continues to deteriorate.
  • With advances in surgical techniques and increased experience, many clinicians prefer to seek open surgical biopsy or thoracoscopic sampling in such circumstances, especially because success and specimen size are greater and the ability to deal directly with any complication is enhanced.

Histologic Findings

• Tissue samples of lung tissue in human infants have typically been obtained from an unrepresentative population. The sample population usually includes only infants with severe pulmonary disease that results in death or threatens to do so or infants who die of other causes and have coincidental sampling of the lung. Consequently, direct observations regarding histologic changes in mild or moderate pneumonia are sparse and are often supplemented by extrapolation from animal disease models, human adults with similar diseases, or more severe cases in human infants that resulted in death or biopsy. Despite these limitations, certain observations in congenital pneumonia recur, whether or not a specific pathogen is implicated.²³
• Macroscopically, the lung may have diffuse, multifocal, or very localized involvement with visibly increased density and decreased aeration. Frankly hemorrhagic areas and petechiae on pleural and intraparenchymal surfaces are common. Airway and intraparenchymal secretions may range from thin and watery to serosanguineous to frankly purulent and frequently are accompanied by small-to-moderate pleural effusions that display variable concentrations of inflammatory cells, protein, and glucose.
• Frank empyema and abscesses are unusual in newborn infants. Particulate meconium or vernix may be visible, especially in the more proximal airways, following aspiration episodes. Superimposed changes, such as air leak, emphysema, and sloughed airway mucosa, may be seen as a consequence of volutrauma, pressure-related injury, oxygen toxicity, and other processes that reflect the vigorous respiratory support often provided to these infants in an attempt to manage derangements of gas exchange caused by the underlying illness.
• With conventional microscopy, inflammatory cells are particularly prominent in alveoli and airways. Mononuclear cells (macrophages, natural killer cells, small lymphocytes) are usually noted early, and granulocytes (eosinophils, neutrophils) typically become more prominent later. Microorganisms of variable viability or particulate debris may be observed within these cells. If systemic neutropenia is present, the number of inflammatory cells may be reduced. Alveoli may be atelectatic from surfactant destruction or dysfunction, partially expanded with proteinaceous debris (often resembling hyaline membranes), or hyperexpanded secondary to partial airway obstruction from inflammatory debris or meconium.
• Microscopic examination of tissue following immunohistochemical staining or other molecular biologic techniques can identify the herpes virus and an increasing number of other organisms.
• Hemorrhage in the alveoli and in distal airways is frequent. Vascular congestion is common; vasculitis and perivascular hemorrhage are seen less frequently. Inflammatory changes in interstitial tissues are less common in newborns than in older individuals.
• Examination of the placenta may be useful. An unusually large placenta with a thick umbilical cord or necrotizing funisitis is suggestive of congenital syphilis, with an increased risk of congenital pneumonia alba. Although results of early maternal serologic screening may have been negative, false-negative results from the prozone phenomenon or infection later in pregnancy may occur. Careful microscopic examination for trophozoites may establish a diagnosis of congenital toxoplasmosis long before other confirmatory tests become available. Other evidence of inflammation or infection derived from gross inspection, microscopy, or specific microbiologic testing may also be useful.

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