How to accelerate antimicrobial susceptibility testing

Abstract

Background: Antimicrobial susceptibility testing (AST) results are crucial for timely administration of effective antimicrobial treatment, and, thus, should be made available to clinicians as fast as possible. In particular, increasing rates of multidrug-resistant organisms emphasize the need for rapid AST (rAST).

Objectives: This article aims to provide microbiologists and clinicians with a critical overview of the current state of possibilities to accelerate AST. We also intend to discuss technical and strategic aspects of rAST, which may be helpful to academic researchers and assay developers in the industry.

Sources: We have reviewed literature on rAST methods and their implementation in routine diagnostics.

Content: Phenotypic rAST is universal, mechanism-independent and allows exact categorization, but it demands time for the microorganisms to start the growth and to express the response to antibiotics. Detection of selected resistance mechanisms is more rapid, but the interpretation of its clinical impact is limited. Technical challenges of phenotypic rAST include inoculum effect, delayed expression of resistance, lag phase and initial biomass increase in susceptible isolates. Criteria for a successful rAST assay are ease of use, random access, capacity for simultaneous testing of multiple specimens, affordability and financial attractiveness for industry. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based AST seems to be particularly promising, as it can optimally be combined with MALDI-TOF MS identification. Direct testing from clinical specimens provides particularly early findings, with positive blood cultures being the most suitable specimen type. Polymicrobial samples and inoculum effect are serious obstacles for direct AST from other clinical specimens. Next to the technology improvement, optimization of pre-analytics and laboratory organization is essential.

Implications: It appears feasible to generate an AST report within the same working shift; however, only affordable and easy-to-use rAST technologies have a chance to enter broad diagnostic routine. Efforts should be made by industry, authorities and academia to enable wide dissemination of rAST in clinical diagnostics.

Keywords: Antibiotic; Direct susceptibility testing; Inoculum effect; Lag phase; MALDI-TOF mass spectrometry; Phenotypic susceptibility testing; Rapid antimicrobial susceptibility testing; Rapid diagnostics.