Method and system for rapidly testing antimicrobial susceptibility
Inventors
DEBSKI, Pawel • Garstecki, Piotr
Assignees
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Publication Number
US-11891648-B2
Publication Date
2024-02-06
Expiration Date
Abstract
Disclosed are methods and systems for rapidly testing antimicrobial susceptibility, wherein the qualitative and quantitative susceptibility of an inoculated microorganism against an antimicrobial agent or a combination of antimicrobial agents is determined as a function of one or more slopes of linear trends α of data of readouts.
Core Innovation
The invention relates to a computer-implemented method for determining the qualitative or quantitative susceptibility of a microorganism inoculum in a phenotypic antimicrobial susceptibility test (AST) using broth dilution. The method uses a carrier with compartments in which at least part of the compartments comprise respectively a single antimicrobial agent or a combination of antimicrobial agents to create one or more test assays, and a sample containing the diluted inoculum is dispensed into the compartments and incubated so that each inoculated compartment houses a respective test assay.
During incubation, the method repeatedly measures at least n times for each test assay with constant or inconstant frequency Δt a signal derived from a chemical or physical property of the inoculated microorganism. The signal is characterized as representing an essentially monotonic function of the number of microorganisms in the measured test assay, with corresponding values {x_i} recorded at recording times {t_i}, where n is a full integer of 13 or more measurements.
The susceptibility is determined from one or more slopes of linear trends α derived from the time-series readouts. One or more slopes of linear trends α are estimated in data as a function of a distribution of a difference formed from the subtraction of constituents of a pair of the readout values {x_i} and {x_j} (with j>i), divided by the time interval δt_ij between taking readouts indexed i and j.
The invention also describes a rapid antimicrobial susceptibility testing system with an incubation assembly, an interrogation and readout assembly, and a computing assembly. The interrogation and readout assembly facilitates measuring at least n times (n≥13) a signal derived from a chemical or physical property that is essentially monotonic with microorganism number, and the computing assembly estimates slopes of linear trends α using distributions of pairwise differences over time intervals and determines qualitative or quantitative susceptibility based on the estimated slopes.
Claims Coverage
The partial content provides two independent claims: a computer-implemented method for determining qualitative or quantitative susceptibility in phenotypic broth-dilution AST, and a rapid antimicrobial susceptibility testing system for performing the same type of phenotypic broth-dilution AST. Across the independent claims, the inventive features center on repeated time-series readouts (n≥13) of an essentially monotonic signal during incubation, estimation of one or more linear-trend slopes α using a distribution of pairwise differences over time intervals, and mapping those slopes to qualitative or quantitative susceptibility for single or combined antimicrobial agent compartments.
Broth-dilution phenotypic AST susceptibility determination via time-series monotonic signals and slope estimation
Determining the qualitative or quantitative susceptibility of a microorganism inoculum in a phenotypic antimicrobial susceptibility test using broth dilution by measuring, during incubation, at least n (n≥13) times with constant or inconstant frequency Δt a signal derived from a chemical or physical property of the inoculated microorganism, wherein the signal represents an essentially monotonic function of the number of the microorganisms in the measured test assay, reading out corresponding values {x_i} at recording times {t_i}, estimating one or more slopes of linear trends α in data as a function of distribution of a difference from the subtraction of constituents of a pair of readout values {x_i} and {x_j} divided by the time interval δt_ij, using at least 13 or more readout values {x_i}, and determining susceptibility as a function of the one or more slopes of linear trends α.
Carrier compartments for single or combination antimicrobial agents in broth-dilution AST
Providing a carrier comprising one or more compartments suitable for broth dilution AST, wherein at least part of the compartments comprise respectively a single antimicrobial agent or a combination of antimicrobial agents, dispensing a sample containing the diluted inoculum into the compartments so that the inoculated compartments comprise the respective test assays, and incubating the carrier comprising the respective test assays.
Rapid ast system with incubation assembly, interrogation/readout assembly, and computing assembly
Providing an incubation assembly adapted to house at least one carrier having one or more compartments for receiving a sample of a microorganism inoculum diluted in a growth medium, and configured to provide an incubation and/or measuring environment; an interrogation and readout assembly configured to interrogate and readout the one or more test assays during incubation and facilitate measuring at least n times (n≥13) for each test assay a signal derived from a chemical or physical property wherein the signal represents an essentially monotonic function of the number of microorganisms, reading out corresponding values {x_i} at corresponding recording times {t_i}; and a computing assembly receiving the number n of readouts, the values {x_i} and the corresponding recording times {t_i}, estimating one or more slopes of linear trends α as a function of distribution of a difference from subtraction of constituents of a pair of readout values {x_i} and {x_j} (j>i) divided by the time interval δt_ij, using at least 13 or more readout values, and determining the qualitative or quantitative susceptibility of the inoculated microorganism against the single antimicrobial agent or the combination of antimicrobial agents as a function of the one or more slopes of linear trends α.
Across the independent claims, the core claimed coverage is directed to phenotypic broth-dilution AST in which repeated measurements (n≥13) of an essentially monotonic chemical or physical signal are taken during incubation, one or more slopes of linear trends α are estimated from distributions of pairwise differences over time intervals, and qualitative or quantitative susceptibility is determined as a function of those slopes for single or combination antimicrobial agent test assay compartments.
Stated Advantages
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