Emerging strategies for the noninvasive diagnosis of nosocomial pneumonia

ABSTRACT

Introduction: Hospital-acquired pneumonia is a common and therapeutically challenging diagnosis that can lead to severe sepsis, critical illness, and respiratory failure. In this review, we focus on efforts to enhance microbiological diagnosis of hospital-acquired pneumonia, including ventilator-associated pneumonia.

Areas covered: A systematic literature review was conducted by searching Medline from inception to December 2018, including hand-searching of the reference lists for additional studies. The search strategy comprised the following common search terms: hospital pneumonia OR nosocomial pneumonia OR noninvasive OR molecular diagnostic tests (OR point-of-care systems OR VOC [i.e. volatile organic compounds]) OR rapid (or simple or quick test), including brand names for the most common commercial tests.

Expert opinion: In recent years, the microbiological diagnosis of respiratory pathogens has improved significantly by the development and implementation of molecular diagnostic tests for pneumonia. Real-time polymerase chain reaction, hybridization, and mass spectrometry-based platforms dominate the scene, with microarray-based assays, multiplex polymerase chain reaction, and MALDI-TOF mass spectrometry capable of detecting the determinants of antimicrobial resistance (mainly β-lactamase genes). Introducing these assays into routine clinical practice for rapid identification of the causative microbes and their resistance patterns could transform the care of pneumonia, improving antimicrobial selection, de-escalation, and stewardship.

KEYWORDS:

• Nosocomial pneumonia
• noninvasive
• diagnosis
• molecular
• VOC
• mass spectrometry

Article highlights

• Current clinical approaches for pneumonia surveillance, early detection, and conventional culture-based microbiology in critically ill patients are inadequate for targeted antibiotic treatment and stewardship.

• Molecular diagnosis in hospital-acquired pneumonia and ventilator-associated pneumonia can provide accuracy and rapidity in pathogen detection.

• Rapid microbiological diagnostics, including multiplex polymerase chain reaction, nucleic acid amplification, mass spectrometry, fluorescence microscopy-based technologies, and exhaled breath biomarkers (including volatile organic compounds) represent promising approaches for the future.

• Molecular tests can help to detect multiple bacterial pathogens simultaneously, but novel approaches are needed to distinguish infection from colonization. This may include the use of quantitative methods and the identification of discriminating cut-off levels.

• We anticipate further studies of molecular tests to focus on the methods required to help interpret the significance of positive results and their application in clinical practice.

• The research agenda should place greater focus on next-generation sequencing and microbiome research.

Acknowledgments

The authors are indebted to all medical and nursing colleagues for their assistance and cooperation in this study. Dr Cillóniz is the recipient of a Postdoctoral Grant (Strategic plan for research and innovation in health-PERIS 2016-2020).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by Centro de Investigaciones biomedicas En Red-Enfermedades Respiratorias (CibeRes CB06/06/0028)-ISCIII, Barcelona, Spain, and 2009 Support to Research Groups of Catalonia 911; IDIBAPS.