University of Toronto, Division of Infectious Diseases, Toronto, Ontario, Canada
Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
J Clin Microbiol. 2019 May 24;57(6). doi: 10.1128/JCM.01780-18. Print 2019 Jun.
Rapid diagnostic tests for antibiotic resistance that identify the presence or absence of antibiotic resistance genes/loci are increasingly being developed. However, these approaches usually neglect other sources of predictive information which could be identified over shorter time periods, including patient epidemiologic risk factors for antibiotic resistance and markers of lineage. Using a data set of 414 isolates recovered from separate episodes of bacteremia at a single academic institution in Toronto, Ontario, Canada, between 2010 and 2015, we compared the potential predictive ability of three approaches (epidemiologic risk factor-, pathogen sequence type [ST]-, and resistance gene identification-based approaches) for classifying phenotypic resistance to three antibiotics representing classes of broad-spectrum antimicrobial therapy (ceftriaxone [a 3rd-generation cephalosporin], ciprofloxacin [a fluoroquinolone], and gentamicin [an aminoglycoside]). We used logistic regression models to generate model receiver operating characteristic (ROC) curves. Predictive discrimination was measured using apparent and corrected (bootstrapped) areas under the curves (AUCs). Epidemiologic risk factor-based models based on two simple risk factors (prior antibiotic exposure and recent prior susceptibility of Gram-negative bacteria) provided a modest predictive discrimination, with AUCs ranging from 0.65 to 0.74. Sequence type-based models demonstrated strong discrimination (AUCs, 0.83 to 0.94) across all three antibiotic classes. The addition of epidemiologic risk factors to sequence type significantly improved the ability to predict resistance for all antibiotics ( < 0.05). Resistance gene identification-based approaches provided the highest degree of discrimination (AUCs, 0.88 to 0.99), with no statistically significant benefit being achieved by adding the patient epidemiologic predictors. In summary, sequence type or other lineage-based approaches could produce an excellent discrimination of antibiotic resistance and may be improved by incorporating readily available patient epidemiologic predictors but are less discriminatory than identification of the presence of known resistance loci.
快速诊断测试可识别抗生素耐药基因/位的存在与否,目前这类测试方法越来越多。然而,这些方法通常忽略了其他预测信息来源,而这些信息可以在更短的时间内确定,包括患者对抗生素耐药的流行病学危险因素和谱系标记。我们使用了加拿大安大略省多伦多市的一家学术机构在 2010 年至 2015 年期间从单独的菌血症发作中分离出的 414 株分离株的数据集,比较了三种方法(流行病学危险因素、病原体序列型[ST]和耐药基因鉴定)对三种抗生素表型耐药的潜在预测能力,这三种抗生素分别代表广谱抗菌治疗的类别(头孢曲松[第三代头孢菌素]、环丙沙星[氟喹诺酮]和庆大霉素[氨基糖苷类])。我们使用逻辑回归模型生成模型接收者操作特性(ROC)曲线。使用明显和校正(自举)曲线下面积(AUC)来衡量预测的区分能力。基于两个简单风险因素(先前的抗生素暴露和革兰氏阴性菌最近的药敏性)的基于流行病学危险因素的模型提供了适度的预测区分能力,AUC 范围为 0.65 至 0.74。序列型模型在所有三种抗生素类别中均表现出很强的区分能力(AUC 为 0.83 至 0.94)。将流行病学危险因素添加到序列型中可显著提高所有抗生素的耐药预测能力( < 0.05)。基于耐药基因鉴定的方法提供了最高程度的区分能力(AUC 为 0.88 至 0.99),添加患者流行病学预测因素并没有统计学上的显著获益。总之,序列型或其他谱系方法可以极好地区分抗生素耐药性,通过纳入现成的患者流行病学预测因素可以进一步提高区分能力,但不如鉴定已知耐药基因座的方法具有区分能力。