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Review
. 2024 Dec 30;28(1):440.
doi: 10.1186/s13054-024-05224-3.

The role of rapid multiplex molecular syndromic panels in the clinical management of infections in critically ill patients: an experts-opinion document

Affiliations
Review

The role of rapid multiplex molecular syndromic panels in the clinical management of infections in critically ill patients: an experts-opinion document

Francisco Javier Candel et al. Crit Care. .

Abstract

Rapid multiplex molecular syndromic panels (RMMSP) (3 or more pathogens and time-to-results < 6 h) allow simultaneous detection of multiple pathogens and genotypic resistance markers. Their implementation has revolutionized the clinical landscape by significantly enhancing diagnostic accuracy and reducing time-to-results in different critical conditions. The current revision is a comprehensive but not systematic review of the literature. We conducted electronic searches of the PubMed, Medline, Embase, and Google Scholar databases to identify studies assessing the clinical performance of RMMSP in critically ill patients until July 30, 2024. A multidisciplinary group of 11 Spanish specialists developed clinical questions pertaining to the indications and limitations of these diagnostic tools in daily practice in different clinical scenarios. The topics covered included pneumonia, sepsis/septic shock, candidemia, meningitis/encephalitis, and off-label uses of these RMMSP. These tools reduced the time-to-diagnosis (and therefore the time-to-appropriate treatment), reduced inappropriate empiric treatment and the length of antibiotic therapy (which has a positive impact on antimicrobial stewardship and might be associated with lower in-hospital mortality), may reduce the length of hospital stay, which could potentially lead to cost savings. Despite their advantages, these RMMSP have limitations that should be known, including limited availability, missed diagnoses if the causative agent or resistance determinants are not included in the panel, false positives, and codetections. Overall, the implementation of RMMSP represents a significant advancement in infectious disease diagnostics, enabling more precise and timely interventions. This document addresses relevant issues related to the use of RMMSP on different critically ill patient profiles, to standardize procedures, assist in making management decisions and help specialists to obtain optimal outcomes.

Keywords: Critically ill patient; Infection; Multidrug resistant pathogens; Septic shock, sepsis, bloodstream infection; Syndromic molecular diagnosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Francisco Javier Candel has received (in the last three years) honoraria for lectures and advisory boards from Advanz Pharma, Angelini, Biomerieux, Gilead, Meiji, Menarini, MSD, Pfizer, Shionogi, and Viatris. Miguel Salavert Lletí has received (in the last three years) honoraria for lectures and advisory boards from Advanz Pharma, Angelini, Janssen, Menarini, MSD, Pfizer, Shionogi, and Viatris, and educational grants from Gilead and Tedec-Meiji. Rafael Cantón has participate in educational programs sponsored by BioMeieux, Pfizer, Menarini, MSD, Shionogi, and Tedec-Meiji and participate in research studies funded by BD, BioMerieux, Cepheid, MSD, and Shionogi. Jose Luis del Pozo has received honoraria for lectures and advisory boards from Advanz Pharma, Angelini, Menarini, MSD, Pfizer, Shionogi, and GSK, and educational grants from Pfizer. Fátima Galán-Sánchez has received honoraria for lectures and advisory boards from MSD, Pfizer, Shionogi and bioMerieux, and grants from Pfizer and Menarini. Montserrat Rodríguez-Aguirregabiria has conducted consulting work for Viatris and Shionogi. MR-A has served as a speaker for Pfizer, Gilead Sciences, and Shionogi. Rafael Zaragoza has received (in the last three years) honoraria for lectures and advisory boards from Advanz Pharma, BiomeMeieux, Gilead science, MSD, Mundipharma, Pfizer, Shionogi, and Viatris, David Navarro; Alejandro Rodríguez; Juan Carlos Rodríguez;L and Borja Suberviola declare that they have no competing interests. Jose Luis del Pozo has received honoraria for lectures and advisory boards from Advanz Pharma, Angelini, Menarini, MSD, Pfizer, Shionogi, and GSK, and educational grants from Pfizer. Fátima Galán-Sánchez has received honoraria for lectures and advisory boards from MSD, Pfizer, Shionogi and bioMerieux, and grants from Pfizer and Menarini. Montserrat Rodríguez-Aguirregabiria has conducted consulting work for Viatris and Shionogi. MR-A has served as a speaker for Pfizer, Gilead Sciences, and Shionogi. Rafael Zaragoza has received (in the last three years) honoraria for lectures and advisory boards from Advanz Pharma, BiomeMeieux, Gilead science, MSD, Mundipharma, Pfizer, Shionogi, and Viatris, David Navarro; Alejandro Rodríguez; Juan Carlos Rodríguez;L and Borja Suberviola declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Severe Community-acquired pneumonia. Adapted from Martin-Loeches et al. [87]. *Risk factors for Multiresistant drug bacteria (MDRB) at admission: Prior contact or hospital admission; stay in chronic health center; Chronic obstructive pulmonary disease; Cystic fibrosis; Bronchiectasis; Immuno-depression; Previous antibiotic treatment; Underweight; High severity illness; Endemic areas; Diabetes mellitus; Chronic alcoholism; Prior hospitalization; Prior colonization; Intravenous drug use; Post influenza or Severe-acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. **With or without shock. MDRB Multiresistant drug bacteria
Fig. 2
Fig. 2
Algorithm for the use of the rapid multiplex molecular syndromic platforms in bacteremia. 1Syndromic PCR panels that detects at least: Streptococcus pyogenes, Streptococcus pneumoniae, Genus Streptococcus, Enterococcus faecalis, Enterococcus faecium, vanA/vanB. 2Perform directly from the blood culture sample. Assess techniques to be carried out according to microorganism and local epidemiology. As a guide, the following instructions can be followed: Escherichia coli: Colorimetric test for the detection of 3rd generation cephalosporin hydrolyzing enzymes. If it is negative and there is clinical suspicion of infection with an extended-spectrum beta-lactamase-producing strain or the patient is very serious/vulnerable: immunochromatography or PCR to detect CTX-M production/gene. Klebsiella spp: Colorimetric test for the detection of enzymes hydrolyzing 3rd generation cephalosporins and carbapenemases. If they are negative and there is clinical suspicion of multidrug-resistant strain infection or the patient is very serious/vulnerable: immunochromatography or PCR for detection of CTX-M production/gene and immunochromatography or PCR for detection/production of genes VIM, NDM, OXA-48, and KPC. Proteus spp: Colorimetric test for the detection of 3rd generation cephalosporin hydrolyzing enzymes. If it is negative and there is clinical suspicion of infection with an extended-spectrum beta-lactamase-producing strain or the patient is very serious/vulnerable: immunochromatography or PCR to detect CTX-M production/gene. Enterobacter spp: Colorimetric test for the detection of carbapenemases. If they are negative and there is clinical suspicion of infection with a multidrug-resistant strain or the patient is very serious/vulnerable: immunochromatography or PCR for detection of production/genes of VIM, NDM, OXA-48 and KPC. Pseudomonas aeruginosa: According to local epidemiology, colorimetric test for the detection of carbapenemases, immunochromatography or PCR for detection of VIM and NDM production/genes. Acinetobacter baumanii: According to local epidemiology, colorimetric test for detection of carbapenemases, immunochromatography or PCR for detection of VIM and NDM production/genes (ideally include OXA-23, OXA-24 and OXA-58). 3Syndromic PCR panels that detects at least: Species-level identification of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumanii and the resistance genes blaCTX-M, blaVIM, blaNDM, blaOXA-48 and blaKPC. 4Syndromic PCR panles that has targets to detect at least: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Genus Streptococcus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumanii, Listeria spp, mecA/C, vanA/vanB, blaCTX-M, blaVIM, blaNDM, blaOXA −48 and blaKPC. *See corresponding sections of the current Experts’ opinion Document. **If polymicrobial infection: directly perform syndromic PCR
Fig. 3
Fig. 3
Algorithm for the use of the rapid multiplex molecular syndromic platforms in Candida infection. 1Syndromic PCR that detects at least: Candida albicans, C. parapsilosis, C. glabrata, C. tropicalis and C. krusei. According to local epidemiology, consider C. auris detection
Fig. 4
Fig. 4
Diagnostic algorithm for meningoencephalitis. PCR Polymerase chain reaction

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