NORCAP

Rapid molecular testing for the diagnosis of community-acquired pneumonia

Lower respiratory tract infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. Researchers in the NORCAP project have investigated whether comprehensive molecular testing can be used to improve the microbiological diagnosis of CAP and potentially improve clinical outcomes, as Professor Harleen Grewal explains.

Several different viruses and bacteria can be involved in the development of community-acquired pneumonia (CAP), including Streptococcus pneumoniae and Haemophilus influenzae, and it is difficult to identify the specific agent or agents involved. A reliable method of identifying the cause of CAP could help clinicians treat the condition more effectively. As coordinator of the NORCAP project, Professor Harleen Grewal is part of the team that has investigated whether using a commercial, syndromic polymerase chain reaction (PCR)-based panel to rapidly test patients hospitalised with suspected CAP can lead to faster, more accurate microbiology-resultbased treatment. “We are interested in providing a definitive diagnosis, in terms of the microbial agent involved,” she outlines. This would then

NORCAP

The Impact of Molecular Point-of-Care Testing on Improved Diagnosis, Treatment and Management of Community Acquired Pneumonia in Norway: a pragmatic randomised controlled trial

Harleen Grewal MD PhD DTMH

Professor, Department of Clinical Science Faculty of Medicine, University of Bergen, Norway Senior Consultant, Department of Microbiology Haukeland University Hospital, Norway

T: +47 99450554/+47 55974631

E: Harleen.Grewal@uib.no

W: www.uib.no

Harleen Grewal, Coordinator NORCAP funded by the Research Council of Norway, is a Professor of Microbiology (2002) and Global Health (2013) at the University of Bergen, Norway and a Consultant Physician at the Haukeland University Hospital, also in Bergen. Elling Ulvestad, Coordinator of the related RESPNOR project funded by the Trond Mohn Foundation, is the head of Microbiology at Haukeland University Hospital and a Professor at the University of Bergen, Norway

Haukeland University Hospital Trial

The randomised trial 1, conducted at the emergency department of Haukeland University Hospital, compared the effects of utilising a syndromic PCR-based panel for rapid testing against standard care procedures. The study demonstrated that the patients randomised to rapid molecular testing were three times more likely to receive targeted treatment, and the time to the administration of that treatment was significantly reduced.

“Through this study, we observed that adding rapid molecular testing into the care process could help doctors make quicker treatment decisions, potentially improving outcomes for patients with communityacquired pneumonia,” says Senior consultant and researcher Dagfinn Markussen.

provide the basis for more tailored treatment of individual cases and avoid unnecessary antibiotics. Professor Grewal explains that incorporating rapid molecular testing alongside clinical decision-making tools and antimicrobial stewardship programs holds promise in curbing unnecessary antibiotic prescriptions.

NORCAP project

The project’s work represents an important contribution to this wider goal, where researchers at the University of Bergen and Haukeland university hospital (HUS) have conducted a pragmatic randomised controlled superiority trial on CAP patients recruited at HUS in Bergen. A multiplex, polymerase chain reaction (PCR) test is used on patients hospitalised with mild to moderate CAP, who are typically treated with empirical antibiotics. “This PCR test has 27 different agents, including bacteria and viruses, and some antibiotic-resistant genes. It’s designed for use in lower respiratory tract infections,” says Professor Grewal. The test results are available in just 1.5 hours, providing feedback that can inform treatment and improve the likelihood of positive clinical outcomes.

This research could help increase the proportion of CAP patients who can be put on microbiology-directed treatment, as well as reduce the time taken before such treatment is administered. This work holds relevance beyond Norway, with CAP a major cause of death across the world, although Professor Grewal says the

PCR test would need to be modified to reflect local circumstances if it is to be applied more widely eventually. “Antibiotic resistance varies across populations and regions, so you would need to tailor the device to accommodate genes of interest relevant to a particular region,” she explains. Reducing the number of target agents to those relevant to a particular geographical region could help bring down the overall cost of the device, which is a significant consideration in the project. “If this approach is to be used for testing in low- and middle-income countries, then we would need to pilot cheaper point-ofcare tests,” acknowledges Professor Grewal. A further topic of interest in the project is the identification of biomarkers, with researchers looking to build a deeper picture of the host response to infection, which is an important consideration in guiding treatment. In cases of co-infection with a virus and bacteria, Professor Grewal and co-researchers are interested in looking at read-outs in the blood in terms of signatures based on protein and RNA transcripts. “We want to see if the patient has a viral or a bacterial response,” she outlines. This would then enable the development of more intelligent tests, where the host response is married with the microbial result. “The objective is to distinguish between a viral and bacterial response in the patient. We also aim to pave the way for developing more sophisticated tests where the intricacies of the host response are integrated with the microbial result,” says Professor Grewal.

1 Markussen DL, Serigstad S, Ritz C, et al. Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(3):e240830. doi:10.1001/ jamanetworkopen.2024.0830

NORCAP is supported by funding from the Research Council of Norway (NORCAP; 288718), which is the principal funder of the trial; Co-ordinator of the NORCAP project, Prof. Harleen Grewal

Co-funding was obtained from:

a) Trond Mohn Foundation which funds the COVID-19 CAPNOR project (TMS2020TMT07); Co-ordinator Prof. Harleen Grewal

b) Trond Mohn Foundation, which funds the RESPNOR project (TMS2019TMT06): Coordinator Prof. Elling Ulvesatd

c)Intra-mural funding from the University of Bergen

d)Intra-mural funding from the Haukeland University Hospital.