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Residual antibiotic drug concentrations in blood as a monitoring tool for evaluating population medicine usage and the impact of antibiotic stewardship interventions

English title Residual antibiotic drug concentrations in blood as a monitoring tool for evaluating population medicine usage and the impact of antibiotic stewardship interventions
Applicant Genton Blaise
Number 179273
Funding scheme Project funding (Div. I-III)
Research institution Department of Epidemiology and Public Health Swiss Tropical and Public Health Institute Universität Basel
Institution of higher education University of Basel - BS
Main discipline Infectious Diseases
Start/End 01.04.2019 - 31.03.2022
Approved amount 525'000.00
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All Disciplines (2)

Infectious Diseases
Pharmacology, Pharmacy

Keywords (9)

Fever case management; Intervention; Mapping; Drug concentration; Antibiotics; Impact; Drug resistance; Drug exposure; Drug pressure

Lay Summary (French)

There is no standardized method to reliably estimate drug use at the population level. We propose to assess drug pressure in the community by measuring antibiotic concentration in Dried Blood Spots already collected from individuals in 2015 in three districts of Tanzania using tandem mass spectrometry. In addition, the impact of an antibiotic stewardship intervention on drug pressure will be assessed using DBS prospectively collected from children in the community before and after the introduction of electronic algorithm for the management of febrile children with fever [e-POCT]. The relevance and impact of the project is to tackle the global public health threat of antimicrobial resistance (AMR), in particular improve the surveillance of antimicrobial consumption in humans using an inovative standardized and reliable approach, and to provide a new tool to assess the impact of antimicrobial stewarship interventions.
Lay summary

Il n'y a pas de méthode pour estimer de manière fiable l'utilisation des médicaments antimicrobiens dans la population. Habituellement, les estimations sont basées sur le suivi des stocks, les taux de prescription, les données de remboursement de l'assurance maladie ou l'auto-déclaration de médicaments lors d'enquêtes communautaires, toutes mesures susceptibles d'être biaisées. Une mesure objective de la concentration sanguine du médicament au niveau de la population devrait fournir une évaluation plus exacte de l’utilisation et de la pression globale des médicaments.

Le but du projet est d'évaluer la pression des antimicrobiens au niveau de la population et d'évaluer l'impact des interventions visant à une utilisation rationnelle de ceux-ci.

Le projet utilisera les informations existantes et les échantillons de sang recueillis lors d'une enquête transversale menée en 2015, qui évaluait l'utilisation d'antipaludéens chez 6 000 personnes dans trois régions de Tanzanie. Des informations sur l'utilisation d'antipaludéens et d'antibiotiques ont été collectées, ainsi que des échantillons de sang sur papier filtre (DBS). Ceux-ci seront utilisés pour mesurer la concentration en antibiotiques par la technologie de spectrométrie de masse en tandem à large spectre.

Pour évaluer l'impact d’une intervention d' ’antimicrobial stewardship’ (algorithme électronique de prise en charge des enfants fiévreux [e-POCT]) sur l'utilisation de antimicrobiens, un design ‘avant-après’ sera utilisé. U néchantillon représentatif d'enfants de moins de 10 ans sera interrogé et du  sang sera prélevé prospectivement lors de deux enquêtes transversales afin de mesurer la concentration d'antibiotiques et d'antipaludéens avant et après la mise en œuvre de l'intervention.

La pertinence et l’impact du projet sont : i) lutter contre la menace que représente la résistance aux antimicrobiens pour la santé publique en adressant une des étapes spécifiques, à savoir la surveillance de la consommation humaine d’antimicrobiens, ceci en utilisant une approche fiable pour quantifier la pression et l’utilisation effectives des antibiotiques et des antipaludéens, ii) fournir un nouvel outil permettant d’évaluer l’impact des interventions visant à améliorer l’utilisation rationnelle des antimicrobiens.



Direct link to Lay Summary Last update: 30.12.2018

Responsible applicant and co-applicants


Associated projects

Number Title Start Funding scheme
149587 Usefulness of antimalarial drug concentrations in blood as a monitoring tool for evaluating population drug usage in relation to diagnosis and treatment environment 01.05.2014 Project funding (Div. I-III)


Background and rationale Usually the assessment of antimicrobials use relies either on longitudinal recording of stocks, prescription rates in health facilities, and health insurance reimbursement data, or on medication use by individuals recorded in community surveys. These measures are potentially biased and do not provide accurate estimates of levels of circulating drugs at community level, which is likely the most important driver for the development of antimicrobial resistant pathogens. Objective and standardized measurements of drug blood concentration at the population level should provide more reliable assessment of overall medicine use and pressure. They would also allow evaluating the public health impact of interventions that target at improving appropriate antibiotic and antimalarial treatment.GoalTo assess antimicrobial drug pressure at the population level, and evaluate the impact of antibiotic stewardship interventions on antimicrobial drug pressure Main objectives1) To estimate the prevalence of individuals with residual antibiotic drugs in the blood in a representative sample of the population in three districts of Tanzania with different level of malaria endemicity, and to explore the factors that determine antibiotic use2) To obtain spatially explicit estimates of the burden of antibiotic use in the three districts3) To assess the impact of antimicrobial stewardship intervention (electronic algorithm for the management of children with fever [e-POCT]) on medicines (antibiotics and antimalarials) use (pressure) in the population of children<10 years MethodologyTo address objectives 1 and 2), the project will make use of existing information and blood samples. These were collected during a large cross-sectional survey in 2015 that assessed antimalarial medicine use in a population of 6000 individuals in three Tanzanian regions with different ecological zones and malaria transmission intensity. The study comprised two types of cross-sectional surveys:- Household (HH)-based survey that included i) information on self-reported rates of morbidity, diagnosis and treatment seeking behaviour, diagnostic tests performed, antimalarial and antibiotic use, and ii) collection of Dried Blood Spots (DBS) to measure residual antimalarial concentration by broad-range tandem mass spectrometry (LC-MS/MS) technology.- Health facilities (HF)-based survey of facilities that served the sampled HH; the survey included information on diagnostic tests in stock, treatment packages in stock (mainly antimalarial and antibiotics), and morbidity.Antibiotic concentration will be measured by LC-MS/MS method in the same samples (DBS) as those already assessed for antimalarial concentration. To address objective 3), a before-after design will be used. In the year prior to introduction of the e-POCT tool, a representative sample of children <10 years will be interviewed using the same questionnaire as in previous HH survey. Blood samples will also be collected. Six months after e-POCT introduction, the same survey will be conducted ‘during’ the intervention (the large-scale implementation of e-POCT intervention will be paid through another funder). Antibiotic and antimalarial residual concentration will be measured in these samples before and after e-POCT implementation.Analytical approach1) Antibiotic use and pressure at the population level will be assessed according to different explanatory factors (rural-urban, age, gender, density of health facilities, other medicine retailers, medicine in stocks, malaria endemicity etc.)2) Bayesian geostatistical logistic regression models will be used to map the spatial distribution of antibiotic use and to predict the use at non-sampled locations via Bayesian kriging 3) Antibiotic and antimalarial use and pressure at the population level (children <10 years) will be compared before and after implementation of e-POCT tool.Relevance and impact of the project- To tackle the global public health threat of antimicrobial resistance (AMR) and address one of the specific step, namely improving global surveillance of antimicrobial consumption in humans as mentioned in the national strategic programme StAR, the WHO Global Action Plan and the UK final report and recommendations on AMR- To provide an inovative standardized and reliable approach to quantify real antibiotic and antimalarial drug use and pressure at the community level- To provide a new tool to assess the impact of interventions aimed at improving the rational use of medicines (antibiotics and antimalarials)