A non-linear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance

Mamoon Aldeyab

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Balancing access to antibiotics with the control of antibiotic resistance is a global public health priority. At present, antibiotic stewardship is informed by a ‘use it and lose it’ principle, in which antibiotic use by the population is linearly related to resistance rates. However, theoretical and mathematical models suggest that use–resistance relationships are nonlinear. One explanation for this is that resistance genes are commonly associated with ‘fitness costs’ that impair the replication or transmissibility of the pathogen. Therefore, resistant genes and pathogens may only gain a survival advantage where antibiotic selection pressures exceed critical thresholds. These thresholds may provide quantitative targets for stewardship—optimizing the control of resistance while avoiding over-restriction of antibiotics. Here, we evaluated the generalizability of a nonlinear time-series analysis approach for identifying thresholds using historical prescribing and microbiological data from five populations in Europe. We identified minimum thresholds in temporal relationships between the use of selected antibiotics and incidence rates of carbapenem-resistant Acinetobacter baumannii (Hungary), extended-spectrum β-lactamase-producing Escherichia coli (Spain), cefepime-resistant E. coli (Spain), gentamicin-resistant Pseudomonas aeruginosa (France) and methicillin-resistant Staphylococcus aureus (Northern Ireland) in different epidemiological phases. Using routinely generated data, our approach can identify context-specific quantitative targets for rationalizing population antibiotic use and controlling resistance. Prospective intervention studies that restrict antibiotic consumption are needed to validate these thresholds.

LanguageEnglish
Pages1160-1172
Number of pages13
JournalNature Microbiology
Volume4
Issue number7
Early online date8 Apr 2019
DOIs
Publication statusPublished - 1 Jul 2019

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Anti-Bacterial Agents
Population
Spain
Theoretical Models
Escherichia coli
Health Priorities
Acinetobacter baumannii
Northern Ireland
Carbapenems
Hungary
Health Services Needs and Demand
beta-Lactamases
Methicillin-Resistant Staphylococcus aureus
Microbial Drug Resistance
Gentamicins
Pseudomonas aeruginosa
Genes
France
Public Health
Prospective Studies

Cite this

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abstract = "Balancing access to antibiotics with the control of antibiotic resistance is a global public health priority. At present, antibiotic stewardship is informed by a ‘use it and lose it’ principle, in which antibiotic use by the population is linearly related to resistance rates. However, theoretical and mathematical models suggest that use–resistance relationships are nonlinear. One explanation for this is that resistance genes are commonly associated with ‘fitness costs’ that impair the replication or transmissibility of the pathogen. Therefore, resistant genes and pathogens may only gain a survival advantage where antibiotic selection pressures exceed critical thresholds. These thresholds may provide quantitative targets for stewardship—optimizing the control of resistance while avoiding over-restriction of antibiotics. Here, we evaluated the generalizability of a nonlinear time-series analysis approach for identifying thresholds using historical prescribing and microbiological data from five populations in Europe. We identified minimum thresholds in temporal relationships between the use of selected antibiotics and incidence rates of carbapenem-resistant Acinetobacter baumannii (Hungary), extended-spectrum β-lactamase-producing Escherichia coli (Spain), cefepime-resistant E. coli (Spain), gentamicin-resistant Pseudomonas aeruginosa (France) and methicillin-resistant Staphylococcus aureus (Northern Ireland) in different epidemiological phases. Using routinely generated data, our approach can identify context-specific quantitative targets for rationalizing population antibiotic use and controlling resistance. Prospective intervention studies that restrict antibiotic consumption are needed to validate these thresholds.",
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A non-linear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance. / Aldeyab, Mamoon.

In: Nature Microbiology, Vol. 4, No. 7, 01.07.2019, p. 1160-1172.

Research output: Contribution to journalArticle

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