DEPARTMENT FOR SCIENCE, INNOVATION AND TECHNOLOGY

INTERCEPT: INTerrupting prolifERation of Carbapenem resistance in Indonesia: clinical and genomic Evaluation of Pathways of Transmission

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Description

Bacteria that are resistant to last-line antibiotics of the carbapenem class are a global public health threat, and classified as critical priority pathogens by the World Health Organisation. In Indonesia, they are a serious problem and common disease-causing bacteria are frequently resistant to carbapenems. The routes by which people acquire these bacteria are unknown, but scarce data from Indonesia and experience in other settings suggests that transmission in hospitals is likely common: strategies to block transmission are needed. Infection prevention and control (IPC) and antimicrobial stewardship provide tools to do just that; the principles of these disciplines have been established in high-income settings since the 1950s, yet despite sporadic attempts to deploy them in Indonesia, carbapenem resistance has emerged and proliferated. This mirrors the earlier rapid spread of extended-spectrum beta-lactamase (ESBL) producing bacteria: these bacteria – problematic to treat in their own right - confer resistance to older antibiotics of the beta-lactam class. Carbapenems are commonly used to treat, which in turn has driven carbapenem resistance. To break this vicious cycle, new interventions to block transmission of resistant bacteria that are locally-adapted and sustainable are required. But understanding transmission is complex. Bacteria can resist antibiotics by acquiring genes that confer resistance, but these acquired genes can be transported by many vehicles, often nested, like a Matryoshka Russian doll: “jumping genes” (transposons) can jump to and from bacterial chromosomes and replicating genetic fragments (mobile genetic elements like plasmids), which can themselves jump between bacteria. Bacteria can move between animals, the environment, and humans, living harmlessly in the human gut (so-called colonisation) prior to causing invasive disease when they escape into (for example) the bloodstream. At the health system level, humans carry resistance genes with them as they move between health facilities and the community; travel disseminates them globally. INTERCEPT brings together UK and Indonesian researchers to tackle this problem, using cutting-edge techniques to identify key transmission routes across this complex system, then co-designing and piloting interventions to block them. At different levels of the Indonesian health care system, we will test humans and the environment for colonisation with carbapenem-resistant bacteria, as well as community members and hospital wastewater, defining flow of resistance genes into and out of health facilities. We will recruit a cohort of patients with bloodstream infection to properly define current treatments and outcomes of people with carbapenem-resistant infection, and identify and interview key stakeholders to understand perceived barriers to the implementation of effective antimicrobial stewardship and IPC interventions. Whole-genome sequencing techniques will fully describe bacteria and resistance genes and mobile genetic elements, tracking them through this system; mathematical models will identify key transmission routes. We will take clinical strains into the laboratory where molecular biology techniques developed at the Liverpool School of Tropical Medicine will allow us to understand mechanisms of resistance and the capability of carbapenemase genes to transfer within and between bacteria. Ultimately, insights from these analyses will inform design of locally-adapted interventions. We will convene workshops of key institutional and government stakeholders to co-design interventions, and pilot them whilst ongoing sampling assesses the impact on transmission. INTERCEPT will provide practical data to guide interventions aligned with national and international AMR-control priorities, suitable for scale-up and larger scale assessment, but also insights into transmission of carbapenem resistance that will benefit hospitalised patients in Indonesia, and worldwide.

Objectives

Bacteria that are resistant to last-line antibiotics of the carbapenem class are a global public health threat, and classified as critical priority pathogens by the World Health Organisation. In Indonesia, they are a serious problem and common disease-causing bacteria are frequently resistant to carbapenems. The routes by which people acquire these bacteria are unknown, but scarce data from Indonesia and experience in other settings suggests that transmission in hospitals is likely common: strategies to block transmission are needed. Infection prevention and control (IPC) and antimicrobial stewardship provide tools to do just that; the principles of these disciplines have been established in high-income settings since the 1950s, yet despite sporadic attempts to deploy them in Indonesia, carbapenem resistance has emerged and proliferated. This mirrors the earlier rapid spread of extended-spectrum beta-lactamase (ESBL) producing bacteria: these bacteria – problematic to treat in their own right - confer resistance to older antibiotics of the beta-lactam class. Carbapenems are commonly used to treat, which in turn has driven carbapenem resistance. To break this vicious cycle, new interventions to block transmission of resistant bacteria that are locally-adapted and sustainable are required. But understanding transmission is complex. Bacteria can resist antibiotics by acquiring genes that confer resistance, but these acquired genes can be transported by many vehicles, often nested, like a Matryoshka Russian doll: “jumping genes” (transposons) can jump to and from bacterial chromosomes and replicating genetic fragments (mobile genetic elements like plasmids), which can themselves jump between bacteria. Bacteria can move between animals, the environment, and humans, living harmlessly in the human gut (so-called colonisation) prior to causing invasive disease when they escape into (for example) the bloodstream. At the health system level, humans carry resistance genes with them as they move between health facilities and the community; travel disseminates them globally. INTERCEPT brings together UK and Indonesian researchers to tackle this problem, using cutting-edge techniques to identify key transmission routes across this complex system, then co-designing and piloting interventions to block them. At different levels of the Indonesian health care system, we will test humans and the environment for colonisation with carbapenem-resistant bacteria, as well as community members and hospital wastewater, defining flow of resistance genes into and out of health facilities. We will recruit a cohort of patients with bloodstream infection to properly define current treatments and outcomes of people with carbapenem-resistant infection, and identify and interview key stakeholders to understand perceived barriers to the implementation of effective antimicrobial stewardship and IPC interventions. Whole-genome sequencing techniques will fully describe bacteria and resistance genes and mobile genetic elements, tracking them through this system; mathematical models will identify key transmission routes. We will take clinical strains into the laboratory where molecular biology techniques developed at the Liverpool School of Tropical Medicine will allow us to understand mechanisms of resistance and the capability of carbapenemase genes to transfer within and between bacteria. Ultimately, insights from these analyses will inform design of locally-adapted interventions. We will convene workshops of key institutional and government stakeholders to co-design interventions, and pilot them whilst ongoing sampling assesses the impact on transmission. INTERCEPT will provide practical data to guide interventions aligned with national and international AMR-control priorities, suitable for scale-up and larger scale assessment, but also insights into transmission of carbapenem resistance that will benefit hospitalised patients in Indonesia, and worldwide.

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Location

The country, countries or regions that benefit from this Programme.

Indonesia

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