Overview of Quantitative Methodologies to Understand Antimicrobial Resistance via Minimum Inhibitory Concentration.

Abstract

Simple SummaryAn emerging threat to human and food animal health is the development of antimicrobial resistance in bacteria associated with food animals. One of the primary tools for assessing resistance levels and monitoring for changes in expressed resistance is the use of minimum inhibitory concentration tests, which expose bacterial isolates to a series of dilutions of an antimicrobial agent to identify the lowest concentration of the antimicrobial that effectively prevents bacterial growth. These tests produce a minimum inhibitory value that falls within a range of concentrations instead of an exact value, a process known as censoring. Analysis of censored data is complex and careful consideration of methods of analysis is necessary. The use of regression methods such as logistic regression that divide the data into two or three categories is relatively easy to implement but may not detect important changes in the distributions of data that occur within the categories. Models that do not simplify the data may be more complex but may detect potentially relevant changes missed when the data is categorized. As a result, the analysis of minimum inhibitory concentration data requires careful consideration to identify the appropriate model for the purpose of the study.The development of antimicrobial resistance (AMR) represents a significant threat to humans and food animals. The use of antimicrobials in human and veterinary medicine may select for resistant bacteria, resulting in increased levels of AMR in these populations. As the threat presented by AMR increases, it becomes critically important to find methods for effectively interpreting minimum inhibitory concentration (MIC) tests. Currently, a wide array of techniques for analyzing these data can be found in the literature, but few guidelines for choosing among them exist. Here, we examine several quantitative techniques for analyzing the results of MIC tests and discuss and summarize various ways to model MIC data. The goal of this review is to propose important considerations for appropriate model selection given the purpose and context of the study. Approaches reviewed include mixture models, logistic regression, cumulative logistic regression, and accelerated failure time–frailty models. Important considerations in model selection include the objective of the study (e.g., modeling MIC creep vs. clinical resistance), degree of censoring in the data (e.g., heavily left/right censored vs. primarily interval censored), and consistency of testing parameters (e.g., same range of concentrations tested for a given antibiotic).