Interpreting the results of rapid molecular diagnostic tests for carbapenem-resistant Enterobacterales infection: current clinical perspective while waiting for further evidence

ABSTRACT

Introduction

Carbapenem-resistant Enterobacterales (CRE) causing severe infections in humans have represented an important challenge for clinicians worldwide during the past two decades.

Areas covered

Novel β-lactams and β-lactam/β-lactamase inhibitor combinations have led to a shift in the first-line approach to the treatment of severe CRE infections from polymyxin-based regimens to treatment with less toxic agents. This new scenario offers the opportunity to apply rapid molecular diagnostic tests for CRE infection to identify different types of carbapenemases. Herein, the authors provide an overview of this subject and follow it with their expert perspectives.

Expert opinion

When considering studies actually measuring the clinical impact of rapid molecular tests in real-life scenarios, high certainty evidence from randomized controlled trials is still limited and not focused on CRE infections. Nonetheless, it is indisputable that rapid molecular tests have been shown to impact early therapeutic choices (in terms of both escalation and de-escalation) when used in real-life settings, thus issues in the clinical interpretation of their results are already relevant. Overall, increased expertise is required for the appropriate interpretation of rapid molecular tests for personalized antibiotic selection by understanding their strengths and limitations.

KEYWORDS:

• Molecular diagnosis
• multiplex panels
• syndromic panels
• CPE
• carbapenemases

Article highlights

• Novel β-lactams and β-lactam/β-lactamase inhibitor combinations have led to a shift in the first-line approach to treatment of severe CRE infections from polymyxin-based regimens to treatment with less toxic agents

• This new scenario offers the opportunity to apply rapid molecular diagnostic tests for CRE infection to identify different types of carbapenemases

• When considering studies actually measuring the clinical impact of RMTs in real-life scenarios, high certainty evidence from RCTs is still limited

• Nonetheless, it is indisputable that rapid molecular tests have been shown to impact early therapeutic choices when used in real-life settings, thus issues on the clinical interpretation of their results are already relevant

• Overall, increased expertise is required for the appropriate interpretation of rapid molecular tests for personalized antibiotic selection by understanding their strengths and limitations

• A collaborative, interdisciplinary approach based on integration of antimicrobial and diagnostic stewardship is needed to maximize the benefits of RMTs, in terms of implementation, appropriateness, and interpretation of results

Declaration of interest

Outside the submitted work, M Bassetti has received funding for scientific advisory boards, travel, and speaker honoraria from Cidara, Gilead Sciences, Menarini, Merck Sharp and Dohme, Mundipharma, Pfizer, and Shionogi. Outside the submitted work, DR Giacobbe reports investigator-initiated grants from Pfizer, Shionogi, BioMérieux, and Gilead Italia, and speaker/advisor fees from Pfizer, Menarini, and Tillotts Pharma. Outside the submitted work, A Marchese reports an investigator-initiated grant from Gilead Italia. Outside the submitted work, V Di Pilato reports speaker/advisor fees from the Applicazioni Diagnostiche Avanzate (ADA), BioRad, and travel grants from Arrow Diagnostics. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This manuscript was not funded.