Diagnostic Utility of Pleural Infection-specific Multiplex PCR Panel

NCT07077096 | Not Yet Recruiting

• 1 other identifier: PRISM
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pleural Infection

Keywords

Parapneumonic effusion; Pleural effusion; Empyema

Outcome Measures

Primary Outcomes (1)

• Diagnostic sensitivity and specificity of the PRISM PCR panel

  The diagnostic performance (sensitivity and specificity ) of the PRISM PCR panel and conventional bacterial culture in diagnosing pleural infection

  24 months

Secondary Outcomes (2)

• the effect of antibiotic on the diagnostic sensitivity and specificity of PRISM PCR panel

  24 months

• the effect of pleural fluid pH on the diagnostic sensitivity and specificity of PRISM PCR panel

  24 months

Study Arms (2)

Pleural infection

Patients with pleural infection

Diagnostic Test: PRISM PCR panel; Diagnostic Test: Conventional bacterial culture

Non-pleural infection

Patients without pleural infection

Diagnostic Test: PRISM PCR panel; Diagnostic Test: Conventional bacterial culture

Interventions

PRISM PCR panel DIAGNOSTIC_TEST

Comparing the diagnostic accuracy between conventional bacterial culture and multiplex PCR on diagnosing pleural infection

Non-pleural infection; Pleural infection

Conventional bacterial culture DIAGNOSTIC_TEST

Comparing the diagnostic accuracy between conventional bacterial culture and multiplex PCR on diagnosing pleural infection

Non-pleural infection; Pleural infection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with pleural infection will be recruited as positive control. Patients without pleural infection will be recruited as negative control.

You may qualify if:

• Patients hospitalized for new-onset pleural effusion requiring thoracentesis
• Aged 18 years old or above

You may not qualify if:

• History of tuberculous pleuritis and bacterial pleural infection in the ipsilateral pleural space
• History of intrapleural therapy (including talc and fibrinolytic) in the ipsilateral pleural space
• History of surgical decortication or pleurodesis in the ipsilateral pleural space
• Eczematous or infected cutaneous conditions at the site of planned pleural procedure that may increase the risk of contamination during the procedure
• Failed to obtain informed consent due to the patient's refusal or cognitive impairment

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Biospecimen

Retention: SAMPLES WITH DNA

Pleural fluid

MeSH Terms

Conditions

Pleural Effusion; Empyema

Condition Hierarchy (Ancestors)

Pleural Diseases; Respiratory Tract Diseases; Suppuration; Infections; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Ka Pang Chan, MBChB

CONTACT

35052211; chankapang@cuhk.edu.hk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: July 22, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)