A 7-year-old with a history of cough, vomiting

A 7-year-old black boy presented to the emergency room with a two-day history of productive cough, congestion, fever, nausea and vomiting. His chest x-ray showed the presence of an early left lower lobe infiltrate and no other laboratory studies were performed at that time. He was prescribed azithromycin and sent home. During the following three days, he continued to have fevers, productive cough, congestion and shortness of breath. He was re-evaluated by his primary care physician.

Upon presentation to his primary care physician, he was found to be febrile (102° F) with a respiratory rate of 35 breaths/min, heart rate of 120 beats/min, oxygen saturation of 89% on room air and normal blood pressure. His exam was notable for tachypnea with decreased breath sounds over his left lung fields. He continued to complain of fevers, shortness of breath and left-sided pleuritic chest pain. Another chest x-ray performed at this visit showed a left lower lobe consolidation with a small effusion (Figure 1). Due to his worsening clinical status, he was transferred to the pediatric ward for further management.

He was otherwise healthy, with no significant past medical or surgical history, no current medications and no allergies to medications. All of his childhood immunizations were up to date. He lived in Maryland with his parents and 5-year old sister. Mother denied any recent travel and there were no pets at home. There were no known recent sick contacts.

After admission to the pediatric ward, he was empirically started on ceftriaxone, clindamycin and azithromycin. Despite broad-spectrum therapy and supportive care, he continued to remain febrile, tachypneic and hypoxic, requiring supplemental oxygen via nasal cannula. A chest ultrasound was performed on hospital day four, which confirmed the presence of a small parapneumonic effusion without loculations. Due to persistent fevers and little clinical improvement, he was switched to ampicillin-sulbactam and vancomycin and transferred to the pediatric intensive care unit. Over the following three days, his fevers persisted (Tmax-103° F) with continued respiratory distress. At this time, a chest CT was performed, which showed a moderate-sized left lower lobe effusion and the presence of loculations (Figure 2).

On hospital day nine, he was taken to the operating room for a video-assisted thoracoscopic surgery (VATS) procedure. During the procedure a moderate amount of purulent pleural fluid was drained and the loculations were lysed. The pleural fluid had a pH of 7.8, glucose of 89, and protein of 4.6. The ratio of pleural to serum protein was elevated. Lactate dehydrogenase (LDH) testing was not performed on the pleural fluid. Aerobic, anaerobic, and mycobacterial cultures were sent from his pleural fluid sample.

During his hospitalization, his laboratory studies were significant for an elevated white blood cell count of 24,500/m3, bands 18%, segmented neutrophils 63%, and platelets 425,000. Blood cultures, two sputum cultures, and a nasopharyngeal respiratory viral panel were negative. His basic metabolic profile was normal.

What is his diagnosis?

1. Necrotizing pneumonia
2. Uncomplicated parapneumonic effusion
3. Empyema
4. Empyema neccesitans

What is the most likely etiology?

1. Haemophilus influenzae
2. Streptococcus pneumoniae
3. Staphylococcus aureus
4. Viral illness

Case Discussion

Based on the history, laboratory, and radiological studies, this case clearly illustrates an example of a complicated parapneumonic effusion or empyema. He ultimately required surgical drainage and prolonged antibiotic therapy.

Pneumonia usually presents with fevers, fatigue, cough and upper respiratory symptoms. Many of these infections self-resolve with appropriate antimicrobial therapy within one to two weeks. Approximately 40% of bacterial pneumonias can be accompanied by a parapneumonic effusion, which is an inflammatory fluid collection adjacent to a pneumonic process. They are then subdivided into complicated or uncomplicated parapneumonic effusion based on pleural fluid pH, LDH, glucose, and protein levels. Most often, complicated parapneumonic effusions are associated with an elevated LDH, elevated pleural protein to serum protein ratio, low glucose, and low pH. Aerobic, anaerobic, and mycobacterial cultures are usually sent on pleural fluid samples. However, parapneumonic effusions are sterile in 22% to 58% of samples, with organisms rarely isolated from blood or pleural fluid.

When an effusion is filled with purulent or seropurulent material, it is referred to as an empyema. This can occur in 3.1 per 100,000 children and is usually associated with high morbidity, but low mortality. They usually begin as a simple uncomplicated parapneumonic effusion as a result of a primary bacterial pneumonia, but can also be seen in association with Mycoplasma pneumonia and viral infections such as influenza and adenovirus.

Parapneumonic effusions are usually the result of immune-mediated, inflammatory or hypersensitivity processes. Often these uncomplicated effusions are reabsorbed by the lymphatic system and resolve without long-term sequela. Sometimes, bacterial pathogens within the pulmonary parenchyma can induce an inflammatory response, resulting in endothelial damage and leakage of bacterial pathogens and inflammatory mediators into the pleural space. Replication of bacteria, toxin production, and further inflammatory response, can result in purulent material which can further organize and produce loculations within the pleural space, producing an empyema. The infected pleural space and resulting inflammatory response can also lead to deposition of fibrin, which can further complicate this infectious process. The organization of the empyema through these various stages can be categorized as follows:

Based on the radiological studies, our patient likely had a stage II empyema, with loculations and frank pus.

The most common isolates implicated in complicated parapneumonic effusions and empyemas are S. pneumoniae, S. aureus, and H. influenzae.

The implementation of protein conjugate immunizations against pneumococcus (PCV7) and H. influenzae has substantially decreased the rate of these diseases. Recently, the emergence of resistant serotypes of S. pneumoniae, especially the serotype 19A which is not prevented by the PCV7 vaccine, have emerged as important pathogens. S. aureus, more commonly community-associated methicillin-resistant S. aureus (CA-MRSA), has been increasingly recognized as a cause of empyema and complicated parapneumonic effusions. In addition, Group A beta-hemolytic streptococcus, Gram-negative bacilli, and anaerobic organisms can play a role.

Chest radiographs are a useful tool to initially assess for the presence of an effusion. However, they are limited. Lateral decubitus films in conjunction with chest radiographs are useful in determining if the fluid is free-flowing, suggesting an uncomplicated parapneumonic effusion. In addition, chest ultrasound and computed tomography (CT) have also been used to distinguish between these two processes and can help determine the extent of disease. Chest ultrasound offers the advantages of convenience, able to be performed at the bedside, and can provide information on the location and size of an effusion to assist with staging. CT scans may also provide this information, and are more helpful in determining the extent of involvement of the lung parenchyma. Studies have shown that both modalities, along with chest radiography, are useful in diagnosis and management.

Patients presenting with a complicated parapneumonic effusion/empyema, usually are ill-appearing and may have pleuritic pain that results in splinting. On physical exam, patients typically have decreased breath sounds and crackles, with dullness to percussion over the affected lung. However, the clinical presentation can vary from patient to patient, especially depending on the inciting organism.

The initial management of complicated parapneumonic effusions and empyemas is varied. Most agree with the early initiation of broad-spectrum antimicrobial therapy such as a beta-lactam agent (i.e. ceftriaxone or cefotaxime) in combination with anti-staphylococcal therapy (ie, clindamycin or vancomycin). In addition, coverage for Gram-negative organisms, anaerobes and atypical pathogens can be considered based on the clinical history.

Management of empyemas includes appropriate antimicrobial therapy and surgical intervention such as VATS or thorocotomy. However, there is controversy as to when surgical intervention is indicated. Studies that have examined this issue have found improved mortality and overall outcomes in patients who had early surgical intervention with VATS and initiation of appropriate antimicrobial therapy. Despite these findings, there are no universal consensus guidelines regarding the appropriate early management of these patients.

Mortality rate for complicated parapneumonic effusions has been reported to be 0% to 3% with early and appropriate antimicrobial therapy. Complications, although rare, are often seen when the pathogen is S. aureus (especially MRSA). However, most children have little or no long-term sequela, with complete resolution of symptoms within weeks to months.

Our patient had a complicated parapneumonic effusion/empyema, which was diagnosed four days into his hospitalization. Although he received oral antibiotic therapy with azithromycin, it failed to cover for the most common organisms, S. pneumoniae and S. aureus. Once appropriate antimicrobial therapy was initiated and he underwent a VATS procedure to drain his focus of infection, his clinical status significantly improved. His pleural fluid cultures ultimately remained negative, and no organisms were identified on Gram stain. He was ultimately discharged home in improved condition, and treated for two weeks with oral clindamycin with no long-standing complications.

Disclaimer: The opinions or assertions contained herein are private views of the authors and are not to be construed as official or as reflecting views of the Department of Defense.

For more information:

• Long S, Pickering L, Prober C. Principles and Practices of Pediatric Infectious Diseases, 3^rd Edition.
• Avansino JR, Goldman B, Sawin RS, et al. “Primary operative versus nonoperative therapy for pediatric empyema: a meta-analysis,” Pediatrics. 2005; 115: 1652-1659.
• Buckingham SC, King MD, Miller ML. “Incidence and etiologies of complicated parapneumonic effusions in children, 1996 to 2001”. Pediatr Infect Dis J. 2003; 22:499-504.
• Byington CL, Korgenski K, Daly J. Impact of the pneumococcal conjugate vaccine on pneumococcal parapneumonic empyema. Pediatr Infect Dis J. 2006. 25:250-254.
• Sonnappa S, Cohen G, Owens CM, et al. Comparison of Urokinase and VATS surgery for treatment of Childhood Empyema. Am J Resp Crit Care Medicine. 2006; 174:221-227.

Anjali Kunz, MD, is a Major in the U.S. Army. She is with the F. Edward Hebert School of Medicine, Uniformed Services University of Health Sciences in Bethesda, MD.

Michael Rajnik, MD, is a Lieutenant Colonel in the U.S. Air Force. He is currently the pediatric infectious disease fellowship director and assistant professor of pediatrics at the F. Edward Hebert School of Medicine, Uniformed Services University of Health Sciences in Bethesda, MD.