One System for All: Is Mass Spectrometry a Future Alternative for Conventional Antibiotic Susceptibility Testing?

Abstract

The two main pillars of clinical microbiological diagnostics are the identification of potentially pathogenic microorganisms from patient samples and the testing for antibiotic susceptibility (AST) to allow efficient treatment with active antimicrobial agents. While routine microbial species identification is increasingly performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), routine AST still largely relies on conventional and molecular techniques such as broth microdilution or disk and gradient diffusion tests, PCR and automated variants thereof. However, shortly after the introduction of MALDI-TOF MS based routine identification, first attempts to perform AST on the same instruments were reported. Today, a number of different approaches to perform AST with MALDI-TOF MS and other MS techniques have been proposed, some restricted to particular microbial taxa and resistance mechanisms while others being more generic. Further, while some of the methods are in a stage of proof of principles, others are already commercialized. In this review we discuss the different principal approaches of mass spectrometry based AST and evaluate the advantages and disadvantages compared to conventional and molecular techniques. At present, the possibility that MS will soon become a routine tool for AST seems unlikely – still, the same was true for routine microbial identification a mere 15 years ago.

Development of a Rapid, Antimicrobial Susceptibility Test for E. coli Based on Low-Cost, Screen-Printed Electrodes

“…In contrast to genotypic antibiotic resistance tests (ART) calling for prior knowledge of resistance determinants, phenotypic AST suggests antibiotics that would be effective against the micro-organisms tested [ 36 , 37 ]. The gel-modified electrodes enable different types of bacterial infections to be detected and the effect of antibiotics in their presence.…”

Rapid Methods for Antimicrobial Resistance Diagnostics

“…Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can be used for the detection of AMR, alternatively to traditional genotypic or phenotypic bacterial characterization [ 107 , 108 , 109 , 110 , 111 ]. MALDI-TOF MS relies on the cellular proteome and is capable of profiling proteins (mainly ribosomal, 2–20 kD) from whole bacterial cell extracts creating a bacterial spectral fingerprint or profiles that discriminates microorganisms at a genus, species, and subspecies level [ 112 , 113 ].…”

Mass spectrometry-based microbiological testing for blood stream infection

“…Although MALDI-TOF MS is now an essential tool for rapid bacterial ID of pathogens that cause blood stream infection, another important task of microbiology laboratories is antimicrobial susceptibility testing of the causative agents. Although increasing numbers of reports have described applications of MALDI-TOF MS for detection of bacterial resistance to antibiotics [72][73][74][75][76][77][78], its contribution is still limited. Three main approaches are used, including detection of antibiotic modifications due to the enzymatic activity of bacteria, detection of antimicrobial resistance based on the specific mass peaks or analysis of mass peak profiles, and detection of resistance with semiquantification of bacterial growth in the presence of a given antibiotic [72].…”

“…Three main approaches are used, including detection of antibiotic modifications due to the enzymatic activity of bacteria, detection of antimicrobial resistance based on the specific mass peaks or analysis of mass peak profiles, and detection of resistance with semiquantification of bacterial growth in the presence of a given antibiotic [72]. Assessment of antimicrobial resistance with MALDI-TOF MS is beyond the scope of this review and has been reviewed elsewhere [72][73][74][75][76][77][78].…”