Pleural Infection: What We Need to Know but Don't
The presence of pus and/or bacteria in pleural fluid defines empyema. Identification of the causative organism can guide antibiotics use and allow better understanding of disease cause. However, in up to 40% of patients with pleural infection, no microbes can be grown from the pleural fluid. More reliable culture methods are required to enhance microbiological diagnosis. A higher yield can be achieved with inoculation of pleural fluid into blood-culture bottles at the bedside (from 38 to 59%), instead of transporting the samples in a sterile container.
Many hypotheses have been proposed to explain the low-culture yield, but few have been formally tested in research studies. Pus is formed from degranulated leukocytes and it is possible that pleural pus results from an intense inflammatory response triggered by bacteria, which continues after the bacteria have been eradicated. Likewise, whether bacteria in the pleural cavity form biofilms is unknown. If pleural biofilm exists, it may contribute to the difficulty of isolating organisms.
The preceding use of empirical antibiotics prior to sample collection may contribute to the low yield. PCR can be more sensitive in detecting the presence of bacteria, including those that may have been killed by prior antibiotic use. Paediatric empyema studies have shown that PCR targeting 16S ribosomal DNA may increase the detection of pathogens, especially Gram-positive organisms. One study reports nearly a 10-fold increase in sensitivity using a PCR-based approach compared with pleural fluid culture for identification of S. pneumoniae in children with empyema. The use of PCR in adult empyema samples, however, has shown significant false-positive and false-negative results, limiting its clinical usefulness.
Where in the pleural cavity are the bacteria most abundant in empyema? Conventional strategies have all targeted capturing bacteria from the pleural fluid (and/or blood). Few data exist on wherein bacteria inhabit within the pleural cavity. However, in tuberculous pleuritis, culture of pleural tissue has a significantly higher yield than from pleural fluid, often by several folds. In the animal model of S. pneumoniae described above, bacteria are found in abundance in the parietal and diaphragmatic pleura. This prompts the question whether culture of pleural biopsy tissue in empyema may have additional value over standard fluid culture.
Can biomarkers help improve management? Pleural fluid pH, glucose, and lactate dehydrogenase (LDH) have remained important biochemical markers for pleural infection since 1980. A huge number of potential molecules have been evaluated in recent years (reviewed elsewhere), ranging from cytokines to inflammatory markers (e.g., procalcitonin, CRP), and bacterial-related proteins (e.g., lipopolysaccharide-binding protein). None has been shown to be superior to the currently used markers of pH, glucose, and LDH for diagnosing pleural infection. It is unlikely that any single biomarker, especially in isolation without clinical/radiological/bacteriological data, will be able to determine pleural infection with sufficient accuracy to replace current practice.
Efforts to date have concentrated on capturing the causative bacteria in empyema. It is likely that the quantity of bacteria present may also be informative on disease progress and prognosis, as shown in recent studies of quantifying pneumococci in pneumonia patients.
Diagnosing Pleural Infection
The presence of pus and/or bacteria in pleural fluid defines empyema. Identification of the causative organism can guide antibiotics use and allow better understanding of disease cause. However, in up to 40% of patients with pleural infection, no microbes can be grown from the pleural fluid. More reliable culture methods are required to enhance microbiological diagnosis. A higher yield can be achieved with inoculation of pleural fluid into blood-culture bottles at the bedside (from 38 to 59%), instead of transporting the samples in a sterile container.
Many hypotheses have been proposed to explain the low-culture yield, but few have been formally tested in research studies. Pus is formed from degranulated leukocytes and it is possible that pleural pus results from an intense inflammatory response triggered by bacteria, which continues after the bacteria have been eradicated. Likewise, whether bacteria in the pleural cavity form biofilms is unknown. If pleural biofilm exists, it may contribute to the difficulty of isolating organisms.
The preceding use of empirical antibiotics prior to sample collection may contribute to the low yield. PCR can be more sensitive in detecting the presence of bacteria, including those that may have been killed by prior antibiotic use. Paediatric empyema studies have shown that PCR targeting 16S ribosomal DNA may increase the detection of pathogens, especially Gram-positive organisms. One study reports nearly a 10-fold increase in sensitivity using a PCR-based approach compared with pleural fluid culture for identification of S. pneumoniae in children with empyema. The use of PCR in adult empyema samples, however, has shown significant false-positive and false-negative results, limiting its clinical usefulness.
Where in the pleural cavity are the bacteria most abundant in empyema? Conventional strategies have all targeted capturing bacteria from the pleural fluid (and/or blood). Few data exist on wherein bacteria inhabit within the pleural cavity. However, in tuberculous pleuritis, culture of pleural tissue has a significantly higher yield than from pleural fluid, often by several folds. In the animal model of S. pneumoniae described above, bacteria are found in abundance in the parietal and diaphragmatic pleura. This prompts the question whether culture of pleural biopsy tissue in empyema may have additional value over standard fluid culture.
Can biomarkers help improve management? Pleural fluid pH, glucose, and lactate dehydrogenase (LDH) have remained important biochemical markers for pleural infection since 1980. A huge number of potential molecules have been evaluated in recent years (reviewed elsewhere), ranging from cytokines to inflammatory markers (e.g., procalcitonin, CRP), and bacterial-related proteins (e.g., lipopolysaccharide-binding protein). None has been shown to be superior to the currently used markers of pH, glucose, and LDH for diagnosing pleural infection. It is unlikely that any single biomarker, especially in isolation without clinical/radiological/bacteriological data, will be able to determine pleural infection with sufficient accuracy to replace current practice.
Efforts to date have concentrated on capturing the causative bacteria in empyema. It is likely that the quantity of bacteria present may also be informative on disease progress and prognosis, as shown in recent studies of quantifying pneumococci in pneumonia patients.
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