Using a difficult-to-treat resistance index to gauge imbalance between countries' antibiotic resistance prevalence and access to antibiotics: a scoping review and concept proposal.

Background: 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.

Objectives: 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.

Methods: Data sources: Data sources included Agricola, Embase, Global Index Medicus, PubMed, Scopus, Web of Science: BIOSIS and Core Collection.

Study eligibility criteria: 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: Assessment of risk of bias included Joanna Briggs Institute critical appraisal tool.

Methods of data synthesis: 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.

Results: 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.

Conclusions: 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.