Walker Morgan K, Chishti Emad A, Yek Christina, Sarzynski Sadia, Angelo Sahil, Cohn Jennifer, Livinski Alicia A, Kadri Sameer S
Clinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
Clinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA; International Center of Excellence in Research Cambodia, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia.
Clin Microbiol Infect. 2025 Jul;31(7):1126-1138. doi: 10.1016/j.cmi.2025.02.029. Epub 2025 Mar 1.
Inferring the impact of antimicrobial resistance on patient outcomes is challenging, given the variability in antibiotic access across countries and over time. By denoting resistance to all highly safe and effective antibiotics, the difficult-to-treat resistance (DTR) definition offers a framework for such assessments globally.
This study aims to conduct a scoping review to understand the international adoption, scalability, and prognostic utility of DTR and enable solutions to incorporate antibiotic access into the DTR framework.
Data sources: Data sources included Agricola, Embase, Global Index Medicus, PubMed, Scopus, Web of Science: BIOSIS and Core Collection.
Study eligibility criteria included original research publications occurring after January 2018 using the term 'difficult-to-treat resistance' to describe antimicrobial-resistant bacterial isolates demonstrating resistance to all first-line antibiotics (i.e. all β-lactam and fluoroquinolone antibiotics).
Assessment of risk of bias included Joanna Briggs Institute critical appraisal tool.
We assessed the overall themes of the included studies and classified them into epidemiological, mortality, or antibiotic effectiveness/efficacy studies. Semiquantitative results among studies evaluating the prevalence of resistant bacterial isolates and mortality were reported. We propose a 'DTR index' (DTRi) that extends beyond gram-negative bacteria and complements DTR by estimating national proportions of bacterial isolates resistant to all first-line antibiotics available specifically in that country.
DTR was utilized in 57 studies spanning 94 countries. The DTR definition was predominantly applied unmodified and retained prognostic utility in 70% of studies. The variability in access to first-line antibiotics and emergence of newer agents across countries and over time influence practical treatment options that cannot be captured by 'fixed' DTR definitions underscoring the value of the proposed DTRi.
The DTRi could appraise the clinical impact of introducing new agents in a country, identify hot zones of resistance-access imbalance, and optimize resource allocation to improve antibiotic resistance outcomes, especially in under-resourced populations.
鉴于各国抗生素可及性随时间变化存在差异，推断抗菌药物耐药性对患者预后的影响具有挑战性。通过定义对所有高度安全有效的抗生素的耐药性，难治性耐药（DTR）定义为全球此类评估提供了一个框架。
本研究旨在进行一项范围综述，以了解DTR的国际采用情况、可扩展性和预后效用，并促成将抗生素可及性纳入DTR框架的解决方案。
数据来源：数据来源包括农业与生物科学数据库、Embase、全球医学索引、PubMed、Scopus、科学引文索引：BIOSIS和核心合集。
研究纳入标准包括2018年1月之后发表的使用“难治性耐药”一词描述对所有一线抗生素（即所有β-内酰胺类和氟喹诺酮类抗生素）耐药的抗菌药物耐药性细菌分离株的原创性研究出版物。
偏倚风险评估包括乔安娜·布里格斯循证卫生保健中心批判性评价工具。
我们评估了纳入研究的总体主题，并将其分为流行病学、死亡率或抗生素有效性/疗效研究。报告了评估耐药性细菌分离株患病率和死亡率的研究中的半定量结果。我们提出了一个“DTR指数”（DTRi），该指数超越了革兰氏阴性菌的范畴，通过估计特定国家对所有可用一线抗生素耐药的细菌分离株的国家比例来补充DTR。
94个国家的57项研究使用了DTR。DTR定义主要未经修改应用，70%的研究保留了其预后效用。各国及不同时间一线抗生素可及性的差异以及新型药物的出现影响了实际治疗选择，而“固定的”DTR定义无法涵盖这些情况，这凸显了所提出的DTRi的价值。
DTRi可以评估在一个国家引入新药的临床影响，识别耐药性 - 可及性失衡的热点地区，并优化资源分配以改善抗生素耐药性结果，特别是在资源匮乏人群中。
