. 2025 Jul;31(7):1126-1138.

doi: 10.1016/j.cmi.2025.02.029. Epub 2025 Mar 1.

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

Morgan K Walker¹, Emad A Chishti¹, Christina Yek², Sadia Sarzynski¹, Sahil Angelo³, Jennifer Cohn⁴, Alicia A Livinski⁵, Sameer S Kadri⁶

Affiliations

¹ 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.
² 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.
³ Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁴ Global Antibiotic Research and Development Partnership, Geneva, Switzerland.
⁵ National Institutes of Health Library, Office of Research Services, Office of the Director (OD), National Institutes of Health, Bethesda, MD, USA.
⁶ 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. Electronic address: sameer.kadri@nih.gov.

PMID: 40032082
PMCID: PMC12167685 (available on 2026-07-01)
DOI: 10.1016/j.cmi.2025.02.029

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

Morgan K Walker et al. Clin Microbiol Infect. 2025 Jul.

. 2025 Jul;31(7):1126-1138.

doi: 10.1016/j.cmi.2025.02.029. Epub 2025 Mar 1.

Authors

Morgan K Walker¹, Emad A Chishti¹, Christina Yek², Sadia Sarzynski¹, Sahil Angelo³, Jennifer Cohn⁴, Alicia A Livinski⁵, Sameer S Kadri⁶

Affiliations

¹ 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.
² 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.
³ Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁴ Global Antibiotic Research and Development Partnership, Geneva, Switzerland.
⁵ National Institutes of Health Library, Office of Research Services, Office of the Director (OD), National Institutes of Health, Bethesda, MD, USA.
⁶ 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. Electronic address: sameer.kadri@nih.gov.

PMID: 40032082
PMCID: PMC12167685 (available on 2026-07-01)
DOI: 10.1016/j.cmi.2025.02.029

Abstract

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.

Keywords: Antibiotic access; Antibiotic resistance; Clinical epidemiology; Difficult-to-treat resistance; Difficult-to-treat resistance index.

Published by Elsevier Ltd.

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Conflict of interest statement

Conflicts of interest: All authors report no conflicts of interest

References

1. Political declaration of the high-level meeting on antimicrobial resistance. 2024. United Nations General Assembly New York.
1. G. B. D. Antimicrobial Resistance Collaborators, Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet, 2024. 404(10459): p. 1199–1226. - PMC - PubMed
1. Magiorakos AP, Srinivasan A, Carey RB, et al. , Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect, 2012. 18(3): p. 268–81. - PubMed
1. Centers for Disease Control and Prevention, National Center for Emerging Zoonotic and Infectious Diseases, Viral Hepatitis National Center for HIV/AIDS, STD, and TB Prevention, and National Center for Immunization and Respiratory Diseases, Antibiotic resistance threats in the United States, 2013. 2013.
1. Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2019. 2019, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention: Atlanta, GA.

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials