Maurizio Sanguinetti
Professor of Microbiology, European Society of Clinical Microbiology and Infectious Diseases, ESCMID President
In the last decades, the problem of antimicrobial resistance (AMR) has reached critical proportions to induce global health authorities to regard AMR as a today’s “serious threat” worldwide.
Targeting AMR has important clinical implications, not only related to diagnosis and management, but also prevention of infectious diseases, particularly those causing sepsis. Factors associated with death due to antimicrobial resistant pathogens known as causative agents of community – and hospital – acquired bloodstream infections (BSIs) are not completely elucidated. However, in a meta-analysis of sepsis treatment studies, the mortality rate in patients who were receiving inappropriate empiric antibiotic therapy was higher than among patients who were appropriately treated1.
The need for new diagnostic techniques
New infectious diseases diagnostic approaches, increasing the laboratory’s capability for rapid identification and characterisation of pathogens, allow us to define the phenotypic and genotypic characteristics of antimicrobial resistant organisms, in order to ensure optimal impact on the patient management2.
This is particularly important for Gram-negative bacteria (e.g. Enterobacteriaceae). It causes difficult-to-treat infections in both immunosuppressed and hospitalised patients, due to multiple resistance mechanisms contributing to the several observed phenotypes in antibiotic resistant isolates. In some settings, clinicians are normally obliged to treat patients with broad-spectrum antibiotics – even when bacterial infection is microbiologically absent – thereby determining the selection and emergence of antibiotic resistant bacterial organisms.
Adopting techniques into decision making process
We agree that the new “precision medicine” paradigm – which has extensively been used in cancer chemotherapy – should be ever increasingly applied to antimicrobial chemotherapy3. Therefore, the information available from rapid diagnostic testing (as for carbapenemase testing) should be immediately incorporated into clinical decision-making pathways regarding the therapy of Gram-negative bacterial BSIs.
Specifically, algorithms for the interpretation of AMR testing and treatment of BSIs may be adopted to achieve a rapid, effective and “molecularly-targeted” antimicrobial chemotherapy regimen for any individual patient4.
The use of rapid diagnostic tests for AMR detection will provide critical means to achieve the balance between administration of new and existing antibiotics and emergence of antimicrobial-resistant BSI and not-BSI pathogens. Studies that measure the impact of rapid diagnostics-based interventions on both antimicrobial utilisation and time to effective treatment, as well as that determine if use of rapid diagnostics improves BSI patients’ outcomes are urgently needed.
References:
1 Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54(11):4851-4863. doi:10.1128/AAC.00627-10
2 Buehler SS, Madison B, Snyder SR, et al. Effectiveness of practices to increase timeliness of providing targeted therapy for inpatients with bloodstream infections: a laboratory medicine best practices systematic review and meta-analysis. Clin Microbiol Rev. 2016;29(1):59-103. doi:10.1128/CMR.00053-14
3 Perez F, El Chakhtoura NG, Papp-Wallace KM, Wilson BM, Bonomo RA. Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply “precision medicine”
4 Giacobbe DR, Giani T, Bassetti M, Marchese A, Viscoli C, Rossolini GM. Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications. Clin Microbiol Infect. 2020;26(6):713-722. doi:10.1016/j.cmi.2019.09.023