Diagnostic Utility of Pleural Infection-specific Multiplex PCR Panel to Identify Causative Microorganisms in Pleural Infection

Pleural effusion is a common cause of hospitalization. Pleural infection ranked third among the pleural effusions requiring hospitalization in the United States. Pleural infection, including complicated parapneumonic effusion and empyema, is associated with a 30-day mortality of 10%. Approximately 20-57% of patients with pneumonia have an associated pleural effusion at presentation, of which 5-7% progress to pleural infection. Analyses of several nation-wide healthcare databases in the United States, France and the United Kingdom have showed an increasing incidence of pleural infection in the past decade.

Adequate antibiotic coverage and fluid drainage are the two pillars of treatment for pleural infection. The empirical use of antibiotics should be based on the local spectrum of causative microorganisms and the source of infection. Subsequent targeted antibiotic regimen can be guided by the culture results and sensitivity pattern of the cultured microorganisms. The use of blood culture bottles as the transfer medium can improve the culture positivity from 30-40% to 60%. An explorative study of culturing pleural tissue can increase the microbiological yield from 20% to 45%. Despite these methods, the culture positivity rates are far from 100% although clinical evidence of pleural infection. Peripheral blood cultures may occasionally be the only positive source of culture (12%). Occasionally, complicated malignant pleural effusion (MPE) can mimic pleural infection, by sharing similar biochemical features of high neutrophil counts and lactate dehydrogenase in the pleural fluid. This would subject the patients with MPE to unnecessary prolonged course of antibiotic and delay of chemotherapy. Prolonged course of broad-spectrum antibiotics (BSA) is commonly required for culture-negative pleural infection or MPE with complicated features, but it could lead to various antibiotic-related adverse events, including kidney and liver injuries, opportunistic infections (e.g. Clostridioides difficile colitis). These are clinical unmet needs of identifying causative microorganisms in pleural infection.

The application of multiplex bacterial polymerase chain reaction (PCR) panel has transformed the care of patients with respiratory infection. Incorporating multiplex bacterial PCR test of bronchoalveolar lavage in hospitalized patients with pneumonia at risk of Gram-negative bacterial infection can significantly shorten the duration of inappropriate antibiotic therapy. For patients with suspected lower respiratory tract infection, this platform allows early antibiotic adjustment (faster antibiotic escalations for Gram-negative or Gram-positive bacteria, and faster antibiotic de-escalations directed at Gram-positive bacteria). The use of multiplex PCR panel designed for pneumonia has been applied to patients with parapneumonic effusion with successful identification of non-culturable microorganism. However, the use of pneumonia multiplex PCR panels has not been fully validated in the clinical management of pleural infection. More importantly, these panels only detect common microorganisms included on their panels specifically designed for pneumonia. Therefore, a dedicated pleural infection-specific multiplex (PRISM) PCR panel is required to enhance the identification for microorganisms in patients presenting with pleural infection.

A syndromic real-time PCR panel for diagnosing community-acquired pleural infection has been established by a Norway group, with its components constructed based on the next-generation sequencing results using prior pleural infection samples. Their panel showed a higher diagnostic sensitivity than that of conventional culture-based methods. For bacterial species included in the PCR panel, it had a sensitivity of 99.5%. However, it lacks clinical performance data and may not be applicable in the South-East Asian region as the microbiological spectrum of pleural infection differs geographically, with pneumococci and viridans streptococci the most commonly reported isolates from tropical and temperate regions, respectively. Therefore, a PRISM PCR panel dedicated for South-East Asian population is highly warranted. The investigators has developed a PRISM PCR panel dedicated for local population. The investigators hypothesize that this new PRISM PCR panel has higher diagnostic sensitivity than conventional culture-based methods in identifying causative microorganisms in prospectively collected real-world pleural fluid specimens.