Genotype-based diagnostics for antibiotic resistance represent a promising alternative to empiric therapy, reducing inappropriate antibiotic use. However, because such assays infer resistance based on known genetic markers, their utility will wane with the emergence of novel resistance. Maintenance of these diagnostics will therefore require surveillance to ensure early detection of novel resistance variants, but efficient strategies to do so remain undefined. We evaluate the efficiency of targeted sampling approaches informed by patient and pathogen characteristics in detecting antibiotic resistance and diagnostic escape variants in Neisseria gonorrhoeae, a pathogen associated with a high burden of disease and antibiotic resistance and the development of genotype-based diagnostics. We show that patient characteristic-informed sampling is not a reliable strategy for efficient variant detection. In contrast, sampling informed by pathogen characteristics, such as genomic diversity and genomic background, is significantly more efficient than random sampling in identifying genetic variants associated with resistance and diagnostic escape.

中文翻译：

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用于有效检测新型抗生素耐药性变异的有针对性的监测策略


基于基因型的抗生素耐药性诊断是经验性治疗的一种有前景的替代方案，可以减少抗生素的不当使用。然而，由于此类检测是根据已知的遗传标记推断耐药性，因此它们的效用将随着新型耐药性的出现而减弱。因此，维护这些诊断需要进行监测，以确保及早发现新的耐药变异，但有效的策略仍未确定。我们评估了根据患者和病原体特征确定的针对性采样方法在检测淋病奈瑟菌（一种与高疾病负担和抗生素耐药性相关的病原体）的抗生素耐药性和诊断逃逸变异以及基于基因型诊断的发展方面的效率。我们表明，基于患者特征的采样并不是有效变异检测的可靠策略。相比之下，在识别与耐药性和诊断逃避相关的遗传变异方面，根据病原体特征（例如基因组多样性和基因组背景）进行的采样比随机采样更有效。