Abstract
Due to the importance of a rapid determination of patients infected by multidrug resistant bacteria, we evaluated two rapid diagnostic tests for the detection of third-generation cephalosporins (3GC)-resistant Enterobacterales directly from positive blood cultures within 1 h: BL-REDTM (electrochemical method) and β-LACTATM test (chromogenic method). A panel of 150 clinical strains characterized for their resistance profiles (e.g., penicillinases, extended-spectrum beta-lactamases (ESBLs), overproduction of cephalosporinase, carbapenemases, impermeability) was tested. Approximately 100 CFU of each isolate was spiked into sterile blood culture bottles and incubated in a BD BACTECTM FX automated system (Becton Dickinson, USA). Positive blood cultures were examined to parallel testing using the BL-REDTM and β-LACTATM tests and conventional susceptibility method (disc diffusion following EUCAST recommendations). For all phenotypes combined, the sensitivity, specificity, positive predictive value, and negative predictive value in the detection of 3GC resistance were, respectively (i) with BL-REDTM: 45.7, 100, 100, and 54.2% and (ii) with β-LACTATM test: 52.2, 100, 100, and 56.9%. The positivity of tests allows to adapt antibiotic treatment whereas the negative result requires other tests. Moreover, these tests detect most Ambler class A-producing Enterobacterales (KPC, ESBL, extended-spectrum OXY) with sensitivities and specificities of 87.5 and 99% for BL-REDTM, respectively and both 100% for β-LACTATM test (47/47 isolates). These two rapid tests failed to detect AmpC overexpressed (sensitivities of 2.7% for BL-REDTM and 0% for β-LACTATM test) and Ambler class B-producing Enterobacterales (sensitivities of 40% for both tests) notably strains without ESBLs associated (sensitivities of 0% for both tests). BL-REDTM and β-LACTATM tests are easy-to-use and mainly attractive when a positive result is obtained notably to detect most of the Ambler class A-producing Enterobacterales in <1 h after the positivity of the blood culture, allowing a rapid adaptation of the antibiotic therapy in patients.
Highlights
The spread of multidrug resistant (MDR) Enterobacterales is a major public health problem notably related to the misuse and overuse of antibiotics (Laxminarayan et al, 2013; World Health Organisation, 2014)
The diffusion of 3GC-resistance among Enterobacterales, resulting from the spread of ESBL- and carbapenemase-producing isolates represents a serious problem worldwide. This is true for life-threatening infections such as Bloodstream infections (BSI), for which inappropriate first-line antibiotic therapy has a dramatic impact on short-term mortality (Kumar et al, 2009; Zilberberg et al, 2014)
We evaluated two rapid and easy-to-use methods: BL-REDTM and β-LACTATM tests
Summary
The spread of multidrug resistant (MDR) Enterobacterales is a major public health problem notably related to the misuse and overuse of antibiotics (Laxminarayan et al, 2013; World Health Organisation, 2014). Over the last couple of years, the improvement of available rapid diagnostic tests directly from positive blood cultures has changed approaches for identification and AST (Maugeri et al, 2019) These tests have the advantage of providing fast results, optimizing antibiotic therapy, improving survival, and reducing the length of hospitalization (Perez et al, 2013). These new techniques promote the proper use of antibiotics by limiting the antimicrobial resistance and decreasing the medico-economic impact by (de)-escalation of the antibiotic therapy and reduction of hospital stay (Farfour et al, 2019). They include molecular biology tests identifying the MDR encoding genes (pathogen-specific real-time or multiplex PCR), spectrometry assays detecting β-lactamase hydrolytic activity (MALDI TOF-MS), biochemical tests, β-lactamases inhibitorbased tests, chromogenic tests and electrochemical test (Buchan et al, 2013; Renvoise et al, 2013; Bogaerts et al, 2016; Salimnia et al, 2016; Faron et al, 2017; Pantel et al, 2018)
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