Parapneumonic empyema occurs most commonly in previously healthy children under five years of age and is associated with considerable morbidity and need for institutional care. The majority of children in this study at all centers required pain medication (78%), supplemental oxygen (77%) and had placement of a chest drain (75%). Over half were transferred from their home communities to a tertiary care facility for relatively prolonged admissions, although in most children the length of stay was 9 days or less. Empyema appears to exact a disproportionate burden in aboriginal children, who comprised 18% of these patients, despite representing less than 3.3% percent of the overall Canadian population (census 2001, Statistics Canada). Over 75% of aboriginal children were transferred from their home community for acute care. Although empyema is associated with considerable morbidity and lengthy hospital stays, only one death occurred within two weeks of diagnosis. We were not able to look at long term pulmonary function but previous studies have shown that restrictive lung function patterns are seen in up to 90% of children with parapneumonic empyema three months after discharge, but normal lung function is present at one year follow-up.
Marked variation in patient management was observed in this multi-center study. Consultation to pulmonology, infectious diseases, and surgical services appears to be routine in all centers, but diagnostic and therapeutic interventions vary. As has been noted in a recent review by the British Thoracic Society, wide practice variation in the management of empyema is likely due to the lack of good evidence available to inform best management, which results in treatment based on physician experience and local bias. Of over 50 recommendations considered in that review, only four had high quality evidence . The only randomized controlled clinical trials of therapy for pediatric empyema have examined intrapleural installation of fibrinolytics compared to video-assisted thorascopy or installation of normal saline [18–20]. A number of case series suggest that this therapy is associated with increased pleural drainage and avoidance of surgery  but the evidence from the three randomized trials is conflicting. We cannot make conclusions about the efficacy of different interventions in this non-randomized observational study, but it is nonetheless interesting to note that no difference in length of stay was observed in children with and without chest tube placement, and that time to chest tube placement did not appear to alter length of stay. Development of consensus guidelines or critical care pathways by inter-disciplinary multicenter group could improve standardization of care until better quality data to guide decision making is available.
The most common organism isolated from parapneumonic effusions during this three-year period was S. pneumoniae, followed by S. pyogenes, Staphylococcus aureus and S. milleri. In contrast with most studies, we found S. pyogenes as important a cause of empyema as S. aureus . Based on available serotyping data from this study some empyema is potentially vaccine-preventable by heptavalent pneumococcal conjugate vaccines (PCV7). In the large randomized controlled efficacy trial of PCV7 vaccine a 17% efficacy in the prevention of a positive chest radiograph was observed in the intent-to-treat group as was a 70% decrease in consolidative pneumonia (consolidation on CXR 2.5 cm or greater)[10, 22–24]. Post-licensure surveillance indicates that invasive pneumococcal disease among children in the US has declined following universal vaccination . PCV7 infant vaccine programs were not yet in place in most provinces in Canada at the beginning of the study period. In two of the six provinces infant immunization programs began 3 and 16 months, respectively, before the study ended. Thus in one province the vaccine could have prevented S. pneumoniae associated empyema in infants 6–18 months of age who would have been eligible for the study. At the time of writing almost all jurisdictions have implemented infant conjugate pneumococcal vaccine programs. The observation of an increasing incidence of empyema due to pneumococcus in some jurisdictions with universal vaccine programs, particularly due to strains not covered in the vaccine , is concerning, and highlights the importance of surveillance to detect changes in the epidemiology of disease following the implementation of vaccine programs. We plan to repeat this study following the more widespread introduction of pneumococcal vaccine in Canada.
Children with S. aureus-associated infection had longer length of stay than children with S. pneumoniae or S. pyogenes. Methicillin-resistant S. aureus (MRSA)infection was not common in Canadian children during the years of this study, and we did not identify this organism in our population.
Definitive microbiologic diagnosis was obtained in only 32% of children in this study and so most children were exposed to unnecessarily broad-spectrum antibiotics for many weeks. S. pneumoniae has been reported in over 70% of culture-negative empyema fluids when molecular diagnosis is systematically used, and increased detection with 16SrDNA PCR . This testing should become standard practice for care of children with culture-negative empyema in order follow the effect of universal vaccine programs on the serotype epidemiology of invasive disease. If detection of antibiotic resistant genes is included in the molecular testing, use of broad spectrum antimicrobials may be avoided. In the United Kingdom an enhanced surveillance program for pediatric empyema is planned for England and Wales which will include molecular diagnosis of culture-negative cases . Given the evidence that S. pneumoniae causes most empyema in children in this study, and that a larger percentage may be found when rigorous diagnosis is pursued[27, 28], we recommend more systematic use of molecular techniques to determine microbiologic etiology of empyema. These techniques should also be considered in the implementation of surveillance programs for invasive bacterial disease so that vaccine and non-vaccine serotypes of S. pneumoniae can be documented following introduction of childhood vaccine.
One limitation of this study is that it was not population-based and thus the incidence of parapneumonic empyema for the whole country cannot be determined from this data. However, each hospital is the only referral center for pediatric care in each region and therefore we likely captured all cases in the participating sites. Secondly, we did not define a specific pleural fluid white blood cell count required for the diagnosis of empyema, rather allowing each center to define normal/abnormal fluid obtained by thoracentesis. The condition of empyema has been used variably21, but usually denotes a complicated effusion associated with an adjacent pneumonic process, which is distinguished from a pleural effusion, and from an uncomplicated parapneumonic effusion associated with pneumonia. We expect that the search strategy for this review, extraction of all records with ICD-9 CODE 510 or the ICD-10 CODE J869 (empyema), would have minimized this misclassification error. As well, each patient was seen by infectious disease, surgical and respiratory specialist physicians who agreed with the diagnosis of empyema. However, the lack of data on the white blood cell count in the pleural fluid could mean that uncomplicated parapneumonic effusions could have been included in our sample. This misclassification would have increased the number of cases.