MacKinnon Melissa C, Pearl David L, Carson Carolee A, Parmley E Jane, McEwen Scott A
Department of Population Medicine, Ontario Veterinary College, University of Guelph, 50 Stone Rd E, Guelph, Ontario, N1G 2W1, Canada.
Department of Population Medicine, Ontario Veterinary College, University of Guelph, 50 Stone Rd E, Guelph, Ontario, N1G 2W1, Canada.
Prev Vet Med. 2018 Nov 15;160:123-135. doi: 10.1016/j.prevetmed.2018.08.009. Epub 2018 Aug 25.
Statistical modelling of antimicrobial resistance (AMR) data is an important aspect of AMR surveillance programs; however, minimum inhibitory concentration (MIC) data can be challenging to model. The conventional approach is to dichotomize data using established breakpoints, then use logistic regression modelling for analysis. A disadvantage of this approach is a loss of information created by dichotomizing the data. The objectives of the study were to compare the performance and results of different regression models for the analysis of annual variation in susceptibility of generic Escherichia coli (E. coli) isolates to ceftiofur, ampicillin and nalidixic acid from retail chicken meat surveillance samples. E. coli susceptibility data for the three antimicrobials from retail chicken samples from 2007 to 2014 were obtained from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). Annual variation in susceptibility for each antimicrobial was evaluated using multivariable linear, tobit, logistic, multinomial, ordinal and complementary log-log regression models (clog-log). MIC (log), censored MIC (log), resistant/susceptible, and categorized MIC (3 or 4 categories) data were used as outcome variables for the appropriate statistical models. Year and region were modelled as categorical predictor variables. Random intercepts were included in the ceftiofur and ampicillin models to account for clustering by retail establishment. The model assumptions evaluated for the mixed models included homoscedasticity and normality of residuals (linear and tobit), homoscedasticity and normality of best linear unbiased predictions (all models), proportional odds (ordinal), and proportional hazards (clog-log). Fixed effects models were used for the nalidixic acid models. The model assumptions evaluated for the fixed effects models included homoscedasticity and normality of residuals (linear and tobit), goodness-of-fit test (logistic and multinomial), proportional odds (ordinal), and proportional hazards (clog-log).Only logistic and multinomial models met model assumptions. Significant annual variation in susceptibility to all three antimicrobials was identified by the multinomial regression models, whereas the logistic regression models only identified significant annual variation in susceptibility to ceftiofur. The multinomial regression model consistently identified additional significant annual variation in susceptibility compared to the logistic regression model. The multinomial modelling approach was able to identify differences between MIC categories within susceptible MIC values, which were below the breakpoint (R) detection level. Given the convention of dichotomizing susceptibility data, the logistic regression approach is likely to remain the standard method of analysis for AMR surveillance data; however, the results of this study demonstrate that multinomial regression should be considered for the analysis of AMR surveillance data.
抗菌药物耐药性(AMR)数据的统计建模是AMR监测项目的一个重要方面;然而,最低抑菌浓度(MIC)数据建模具有挑战性。传统方法是使用既定的断点将数据二分,然后使用逻辑回归模型进行分析。这种方法的一个缺点是二分数据会导致信息丢失。本研究的目的是比较不同回归模型在分析零售鸡肉监测样本中普通大肠杆菌(E. coli)分离株对头孢噻呋、氨苄西林和萘啶酸敏感性年度变化时的性能和结果。2007年至2014年零售鸡肉样本中三种抗菌药物的大肠杆菌敏感性数据来自加拿大抗菌药物耐药性综合监测项目(CIPARS)。使用多变量线性、托比特、逻辑、多项、有序和互补对数-对数回归模型(clog-log)评估每种抗菌药物敏感性的年度变化。MIC(对数)、截尾MIC(对数)、耐药/敏感以及分类MIC(3或4类)数据用作适当统计模型的结果变量。年份和地区被建模为分类预测变量。在头孢噻呋和氨苄西林模型中纳入随机截距以考虑零售机构的聚类情况。对混合模型评估的模型假设包括残差的同方差性和正态性(线性和托比特模型)、最佳线性无偏预测的同方差性和正态性(所有模型)、比例优势(有序模型)以及比例风险(clog-log模型)。对萘啶酸模型使用固定效应模型。对固定效应模型评估的模型假设包括残差的同方差性和正态性(线性和托比特模型)、拟合优度检验(逻辑和多项模型)、比例优势(有序模型)以及比例风险(clog-log模型)。只有逻辑和多项模型符合模型假设。多项回归模型确定了对所有三种抗菌药物敏感性的显著年度变化,而逻辑回归模型仅确定了对头孢噻呋敏感性的显著年度变化。与逻辑回归模型相比,多项回归模型一致地确定了敏感性方面额外的显著年度变化。多项建模方法能够识别低于断点(R)检测水平的敏感MIC值内MIC类别之间的差异。鉴于将敏感性数据二分的惯例,逻辑回归方法可能仍将是AMR监测数据的标准分析方法;然而,本研究结果表明,在分析AMR监测数据时应考虑多项回归。