An Easy and Rapid Test to Detect Infections Caused by Antibiotic-Resistant Bacteria in the Clinic

The BL-DetecTool is a rapid and reliable diagnostic test for the detection of antibiotic resistance mechanisms directly from clinical samples, according to a multicentre study in which the Barcelona Institute for Global Health (ISGlobal), an institution supported by "la Caixa" Foundation, participated together with the Hospital Clínic de Barcelona. This test will make it possible to rapidly identify and treat multidrug-resistant infections, thus preventing them from spreading.

Antibiotic resistance is one of the world's most worrying public health problems, with significant clinical and economic implications. Tackling this problem requires the development of strategies at different levels (e.g. increasing surveillance, speeding up diagnosis and/or finding new treatments). The BL-DetecTool project, funded by the European Institute of Innovation and Technology (EIT-Health) and in which ISGlobal participated, was launched four years ago with the aim of validating a rapid test to detect two types of molecules that cause antibiotic resistance: extended-spectrum beta-lactamases (bacterial enzymes capable of degrading cephalosporins) and carbapenemases (capable of degrading last-line carbapenem antibiotics). The emergence and spread of multi-resistant bacteria carrying multiple carbapenemases in recent years is a cause for concern.

 "Early detection of these enzymes would help to improve the treatment of patients with infections caused by multi-resistant bacteria and thus prevent their spread," says Jordi Vila, Director of the Antimicrobial Resistance Initiative at ISGlobal and coordinator of the study.

One test, two resistance mechanisms, nine European centres and more than 20,000 clinical specimens

BL-DetecTool is a rapid and simple test based on a lateral flow immunoassay (similar to pregnancy or COVID-19 tests) to detect a range of extended-spectrum beta-lactamases (ESBL) and/or five of the major carbapenemases produced by multi-resistant bacteria (enterobacteria such as Escherichia coli or Klebsiella pneumoniae, as well as Pseudomona aeruginosa). The test provides results in 35 minutes, directly from positive blood cultures or urine, as well as from rectal swabs.

Nine European centres - in Spain (including Hospital Clínic), France, Hungary, Greece, Italy and Germany - participated in this study to evaluate the test on a total of 22,010 biological specimens.

High sensitivity directly from urine and blood

The prevalence of BLEE-producing bacteria ranged from 6% to 29%, depending on the hospital, and the test proved to be highly sensitive for positive blood culture samples (sensitivity over 90%) and urine (over 94%, with the exception of one hospital where eight samples were false positives). For rectal specimens, specificity was more variable but increased to over 75% if the sample was pre-treated with an enrichment step.

As expected, the prevalence of carbapenemase-producing bacteria was lower: between 1.9 and 20% in five hospitals, while none were detected in the other four. Excluding the hospital with the lowest prevalence, the sensitivity of the test was 75-100% for blood or urine samples. Again, rectal samples required pre-treatment to increase sensitivity above 66%. 

"The sensitivity observed is slightly lower than previously reported for the BL-DetecTool, but this is due to the high number of samples in our cohort and the multicentre study design," says Mariana Fernandez-Pittol, researcher at the Hospital Clínic and first author of the study. 

The results confirm that the BL-DetecTool allows rapid and reliable detection of extended-spectrum beta-lactamases and carbapenemases directly from positive blood cultures or urine, as well as from enriched rectal specimens. "This technique is easy to implement and will greatly facilitate work in clinical microbiology laboratories," he adds.

Reference

Fernandez-Pittol M, Bosch J, Ballesté-Delpierre C et al. Multicentre study to assess the use of BL-DetecTool for the detection of CTX-M-type ESBLs and carbapenemases directly from clinical specimens. JCM. DOI: 10.1128/jcm.01136-23