Ultrasensitive and rapid identification of ESRI developer- and piperacillin/tazobactam-resistant Escherichia coli by the MALDIpiptaz test

Abstract

The excessive use of piperacillin/tazobactam (P/T) has promoted the emergence of P/T-resistant Enterobacterales. We reported that in Escherichia coli, P/T contributes to the development of extended-spectrum resistance to β-lactam/β-lactamase inhibitor (BL/BLI) (ESRI) in isolates that are P/T susceptible but have low-level resistance to BL/BLI. Currently, the detection of P/T resistance relying on conventional methods is time-consuming. To overcome this issue, we developed a cost-effective test based on MALDI-MS technology, called MALDIpiptaz, which aims to detect P/T resistance and ESRI developers in E. coli. We used automated Clover MS Data Analysis software to analyse the protein profile spectra obtained by MALDI-MS from a collection of 248 E. coli isolates (91 P/T-resistant, 81 ESRI developers and 76 P/T-susceptible). This software allowed to preprocess all the spectra to build different peak matrices that were analysed by machine learning algorithms. We demonstrated that MALDIpiptaz can efficiently and rapidly (15 min) discriminate between P/T-resistant, ESRI developer and P/T-susceptible isolates and allowed the correct classification between ESRI developers from their isogenic resistance to P/T. The combination of excellent performance and cost-effectiveness are all desirable attributes, allowing the MALDIpiptaz test to be a useful tool for the rapid determination of P/T resistance in clinically relevant gram-negative bacteria.

A high-resolution genomic and phenotypic analysis of resistance evolution of anEscherichia colistrain from a critical care patient treated with piperacillin/tazobactam

“…Scores for BL/BLI resistance prediction from genomic data have been developed (72) in addition to β-lactamase copy number calculators (73) and tools like these will be vital to support decisions for use of new BL/BLI combinations and ensure their future efficacy is safeguarded. Alternative diagnostic methods, based on protein detection, such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) technology, may provide an alternative strategy to rapidly detect β-lactamase hyperproduction (74).…”