Antibiotic stewardship for infections in patients with tuberculosis

We propose an innovative strategy analyzing the drivers of bacterial infections in TB patients. Our concept is implementing community-level interventions and antibiotic stewardship protecting humans, animals, and the environment from unnecessary antimicrobial use. New mobile app will integrate analytics with clinical guidelines identifying TB patients who really need extra-antibiotic.

Dr Andrii Dudnyk, MD, PhD - Respiratory Physician specialised in Tuberculosis

Investigator at the Innovation in Respiratory Infections and Tuberculosis Diagnosis Group

Germans Trias i Pujol Research Institute (IGTP)

Antimicrobial resistance (AMR) is one of the top 10 global public health issue, particularly in the management of tuberculosis (TB). Annually, over 10 million people fall ill with TB representing the largest population of long-term antibiotic users. About one-third of TB cases in the European Region are drug-resistant (DR). In 2023, a high prevalence of AMR was reported in some hospitals in Ukraine, where 60% of health-associated infections (HAIs) have been carbapenem-resistant.

Recently, shorter all-oral regimens for people suffering from TB were implemented in many countries. The 4-month rifapentine-based regimen is a novel (2 month shorter) treatment option for drug-susceptible(DS) TB while the 6-month BPaL/M regimen (3 fold shorter) is recommended for DR-TB. The global reduction of antibiotic consumption is recognized by WHO as a strategic priority to combat drug-resistant bacterial infections. 

Currently, there are no data representing the rate of HAIs and antibiotic consumption among TB patients leading to unregulated policy decisions. Moreover, TB patients already take a few antimicrobials. It limits appropriate isolation of pathogens, interpriting of drug susceptibility testing, and rational prescribing of antibiotics.We plan to demonstrate how misuse and overuse of antibiotics interlink between humans, animals, and the environment following One Health approach. 

Our core target audience is patients with TB and TB/HIV co-infection receiving multiple antimicrobials for long-term. Our tool is designed to provide people-centered treatment reducing the risk of antimicrobial resistance transmission in the community. Within study period we will identify all patients prescribed antimicrobials other than anti-TB medicines. We are in contact with global TB affected communities to advocate their rights for shorter fully-oral treatment. 

Other target populations are clinicians, clinical pharmacologist, medical directors and national TB program managers. We will share facility-specific reports on antibiotic susceptibility rates with prescribers, they will recieve the tool for appropriate management of health-associated infections, better planning of antibiotic purchase and “real world” data on the long-term safety and impact of TB treatment on the probability of resistance to antimicrobials in other pathogens. 

Finally, for ensuring a sustainable global access to effective antibiotic therapy for all in need we will show how shorter TB treatment may reduce the level of health-associated infections, and the direct contamination of the environment with both antibiotic residues and resistant bacteria. 

Our proposal is focused on main drivers underpinning the development of AMR - misuse of antibiotics and insufficient antimicrobial resistance control at the community-level. At present time there are no data about prevalence of HAIs in TB patients, their risk factors and efficacy of treatment. Lack of evidence limits our capacity to prevent infections and to implement effective antibiotic stewardship program in this population.

We will provide a public good in the form of knowledge and services such as  peer-review publication and free-to-use digital clinical decision support algorithms of rational antimicrobial prescribing in TB facilities. We assume that this tool will guide health-care providers on what antimicrobial to use if any. Another public good is a more powerful understanding of the role of co-morbidity (TB and other infections) in driving AMR in humans by integration of medical data that is collected daily about people in communities with bacterial AMR laboratory data sets .

Based on our findings we will suggest technological solutions to reduce environmental contamination in community settings, strengthen the
food chain and reduce transmission of resistant bacteria between humans and animals.

Our free-to-use digital decision support algorithms on rational antimicrobial prescribing will help TB patients to obtain the most appropriate treatment option. Many individuals with TB belong to underserved or vulnerable populations. Lack of appropriate inclusion in clinical studies therefore means that study results may be less generalizable to groups who would potentially benefit from the findings. This weakness has impeded the quality of available evidence for decision-making, leaving huge uncertainties related to care, most affecting the groups with the highest TB burden.

Clinicians and policy makers will recieve a useful tool to monitor, prevent and manage HAIs in TB facilities. 

First, collection of data about isolated bacterial pathogens and the rate of their resistance in hospitalised TB patients.

Secondly, comperative analysis of our findings stratified by facility, country and TB treatment regimen (drug-susceptible vs drug-resistant).

Thirdly, integratation of results with existing database on drug-drug interactions, optimal spectrum coverage and  national quidelines to manage HAIs. 

The impact of AMR on health and economy in the EU well described here https://www.oecd.org/health/he...

Summary of antimicrobial prescribing guidance – managing common infections /https://elearning.rcgp.org.uk/...

 Evidence supporting the possibility to reduce antibiotic consumption provided here https://www.hmpgloballearningn...

There is no systematic analysis on routinely collected data about HAIs in TB patients in European Region. However, MDR-TB strains become as common as pan-susceptible strains in Eastern Europe and Central Asia due to high rate of hospital-focused TB healthcare.

The study has measurable and sustained impact. We will collect important evidence to save lives of TB patients and related costs in resourse-limiting settings facilitating transition to ambulatory TB care. Over the next year the study will be able to demostrate the situation with HAIs in TB patients living in target countries. That will be a clear indicator for policy makers and clinicians to implement antibiotic stewardship programs. We will also create alarm points to inform clinicians about optimal periods for HAIs preventive interventions, including vaccinations.

We plan to demonstrate how new collection tools and mobility data can help to map antimicrobial resistance spread and what types of antimicrobials are the main drivers of the process.

Over the next 3 years we will publish the  article in peer-review journal and will continue to work under development and implementation of our digital tool to make selection of antibiotic beneficial for TB patients and public health.

Acceptance of article in any of journals represented in Q1 Scientific Journal Rankings will indicate professional recognizing of our study findings.

The rate of national antibiotic stewardship programes implemented/changed after initiation of the project will represent study dissemination impact.

Implementation of HAIs monitoring in TB facilities will be direct indicator of operational changes to current practices.

Release of digital tool and the number of installations will represent the public interest to our solutions.

Reducing the rate of HAIs and improving of their treatment outcomes in TB patients will be the most important metric in our project.

There are a number of barriers that prevent effective responses to AMR in TB facilities. Current poplicy regulations doesn't request data about HAIs and the level of acquired resistance to antimicrobials. Technically these data are not available in e-health system requiring long-term work with other data sets or paper hard-copies of medical documents. In Eastern Europe and Central Asia countries policy makers and management team of hospitals may restrict an access to this sensitive information to avoid any publications of unfavorable findings.

All these factors may limit our impact in the next year and the next three years. However, we have a practical experience of working in target environment with deep understanding of culture and bureaucratic specifics.

We have a research consortium and professional network aiming to improve TB management. The expertise of our team in area of drug-resistance, microbiology and clinical management of tuberculosis could be confirmed by proof of practical working in high TB burden countries, successfully realized previous projects and high-cited publications.

With financial support of The Trinity Challenge we will be able to develop effective interventions to combat AMR by predetermined deadlines.

The Trinity Challenge on Antimicrobial Resistance supports innovative solutions with high potential to be implemented. We have identified the main gaps in the evidence and clinical quidelines that could be eliminated by our solution. We need to motivate our international partners to collect the data synthesizing the evidence and then, to be able integrate them with analytical data sets. 

The Trinity Challenge is a great opportunity for our team to analyse new sources of data other than formally collected. TB patients should be considered as a key populations driving drug-resistance spread at the community and environmental levels.

We highly appreciate the possibility to integrate our data sets with broader health delivery efforts for implementation into the continuum of
care in resource-constrained health care settings. We will be grateful for unparalleled support by global leaders from the private, academic and public sectors.

If selected, our project will identify areas for improvement and formulate  an action plan to combat antimicrobial resistace with global impact on public health. As a result of the project we will be able to answer - what could we do better to support rational selection of antimicrobials in low-middle income countries.

This project provides an excellent opportunity for collaborative research and  for technology transfer.

Green Light Committee for the WHO European Region (GLC/Europe) was established to address the need for scaling up the programmatic management of drug-resistant tuberculosis in the Region. We would extend our current contacts with WHO representatives to coordinate activities against AMR in TB patients.

Stop TB Partnership brings together expertise from a broad spectrum of country, regional, and global partners in our shared mission to revolutionize the TB space and end TB by 2030. This organization takes bold and smart risks to serve the needs and amplify the voices of the people, communities, and countries affected by TB. Our consolidated efforts could be more effective to get a paradigm shift for rational antibiotic prescribtion in TB patients.

European Centre for Disease Prevention and Control (ECDC)

Wellcome

Patrick J McGovern Foundation

Ineos Oxford Institute for Antimicrobial Research

The expertize of above mentioned organization will help to develop our solutions and to maximize the effect of their implementation.