Mass treatment with the antibiotic azithromycin can lead to increased drug resistance

Mass treatment with the antibiotic azithromycin can lead to increased drug resistance

Efforts to reduce child mortality in Africa through mass treatment with the antibiotic azithromycin (AZM) may lead to increased drug resistance in bacteria that often leads to pneumonia and meningitis, highlighting the need for careful monitoring, a new study led by UCL finds.

The study, published in the Lancet Infectious Diseases, is a collaboration with researchers from the Malawi Liverpool Wellcome program, the University of Liverpool, the London School of Hygiene & Tropical Medicine, the Wellcome Sanger Institute and Yale University.

It provides the first data on mass antibiotic drug administration (MDA) for infectious diseases – whereby all eligible members of an at-risk population are treated with a specific drug to reduce childhood mortality – affecting bacterial populations over time and facilitating the evolution and spread of strains with antimicrobial resistance (Amr).

Based on their findings, the study authors call for long-term genomic surveillance, used to track changes in pathogen DNA, to monitor trends in antibiotic resistance in places where MDA is used. This would allow the risks of AMR to be appropriately weighed against the benefits of MDA and interventions implemented where appropriate.

Dr. Akuzike Kalizang'oma, lead researcher on the study from the UCL Department of Infection and Immunity and the Malawi Liverpool Wellcome program, said: "Our findings highlight the potential trade-offs between MDA to improve childhood survival and increased AMRs to treat common infections. It is important to achieve the balance.

"In high mortality regions where this type of program is implemented, mortality surveillance is needed to assess the benefits of the intervention so that the risks of AMR can be appropriately weighed against the benefits of MDA. Careful surveillance using robust genomic approaches to monitor the impact of MDA.

In the study, researchers compared samples from 452 children who lived in areas that received repeated rounds of AZM MDA with 453 samples from children who lived in areas that received a placebo. Both areas were in Mangochi, a largely rural district near Lake Malawi.

Regarding bacteria called Streptococcus pneumoniae (Pneumococcus), which is commonly carried in children's background but also commonly causes life-threatening pneumonia, meningitis and sepsis, the team used genome sequencing techniques to read the genetic information that identifies the bacteria in the bacteria and the differences. they wore.

The researchers found that in areas that received MDA, resistance to AZM and similar antibiotics increased from 21.7% to 32.1% three and a half years after completing treatment, and that this resistance also spread to children born in these communities.

However, resistance also increased in areas that had received a placebo, from 21% to 30.9% three and a half years after treatment, suggesting that AMR appeared to be spreading throughout communities.

Additionally, S. pneumoniae strains were identified that had acquired resistance to several other antibiotics, including the frontline antibiotic penicillin, which is widely used.

The prevailing view for many years has been that resistance to macrolide antibiotics like AZM disappears once you stop using them. We show that pneumococcal AZM resistance persists and spreads to children who are not exposed to the antibiotic.

There is also a view that in Africa, since macrolides are not a first line treatment for most serious infections, some resistance is not as important. However, macrolides are used to treat pneumonia and are the first line treatment for cholera and drug-resistant typhoid fever. We show that the emergence of AZM resistance in pneumococci is often associated with resistance to other important antibiotics.

Without timely detection of resistant strains and interventions, these trends may be difficult to reverse. “

Professor Robert Heyderman, senior author of the study from UCL's Department of Infection & Immunity

After several large clinical trials, the World Health Organization (WHO) published a guideline in 2020 recommending MDA, consisting of two doses per year of AZM, in children aged one to 11 months in areas where there is high childhood mortality.

The authors emphasize that AZM-MDA programs remain an important tool for improving child survival in populations where mortality is unacceptably high. However, the study's results raise questions about the long-term public health impact of MDA. Without timely detection and intervention, they say these trends have the potential to make common serious infections much more difficult to treat and potentially reverse the benefits of the MDA program.

Professor Neil French, author of the University of Liverpool study, said: "Antimicrobial resistance is a major global threat, particularly among those most at risk. The exact population of children who will benefit from AZM-MDA. It is important that the balance between early benefits and long-term harm and statements of efficient monitoring of these mass drug programs is."

This research was primarily funded by the Gates Foundation.

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