Resistant typhoid pathogens are spreading – new mutations are making bacteria increasingly immune to modern antibiotics

Concern: In recent years, typhus bacteria have increasingly developed new antibiotic resistance, as revealed by genetic analysis. Mutations make pathogens immune to modern emergency antibiotics and are now spreading from India. This development is worrying, scientists point out in “The Lancet Microbe”. In extreme cases, this may mean that no oral typhus medicine is working.

More than 11 million people suffer from typhoid fever each year and around 100,000 die from it, mainly in South Asia and Africa. The cause of this bacterial infection, Salmonella enterica serovar Typhi, is usually transmitted by contaminated water or food. Although the infection can be easily treated with antibiotics, antibiotic-resistant strains are spreading more and more.

From South Asia to the world

Kesia Esther da Silva of Stanford University and her colleagues have now investigated how widespread and where so resistant and multidrug-resistant typhus bacteria are now widespread. For their study, they analyzed bacterial DNA from 3,489 samples of pathogens taken from South Asia between 2014 and 2019. In addition, they evaluated 4,169 other samples from more than 70 countries and collected over the past 100 years.

Analyzes have revealed that multi-resistant strains of this type of pathogen, which are immune to older classes of antibiotics, have been circulating in South Asia for decades. Most of them come from India and since 1990 they have been introduced to other countries and regions more than 197 times, according to the team. The most common transmissions were within South Asia or Southeast Asia, but resistant typhus strains also spread to Africa, North America and Europe.

New resistances on the rise

However: In the meantime, in addition to these “classic” multi-resistant typhus bacteria, newer resistant forms are spreading. They have mechanisms in place that also make them immune to modern classes of antibiotics, such as cephalosporins, quinolones, and macrolides. Strains of fluoroquinolone-resistant bacteria already existed in the 1990s. In 2010, these already accounted for 95 percent of specimens from India, Pakistan and Nepal, according to da Silva and colleagues.

Typhoid routes
Extended type variants (FQ-NS: fluoroquinolone resistant; MDR: multidrug resistant; XDR: extremely multidrug resistant) © da Silva et al. / The Lancet Microbe, CC-by 4.0

In the last 20 years, at least seven bacterial lines have developed resistance to azithromycin, a commonly used macrolide antibiotic. The research team also identified several cephalosporin strains with corresponding resistance genes. As with early multidrug-resistant typhoid bacteria, most of these new strains have developed in India.

“A real cause for concern”

“The speed with which highly resistant Salmonella Typhi strains have evolved and spread in recent years is a real problem,” said lead author Jason Andrews of Stanford University. “This underlines the urgent need to expand and intensify prevention efforts, especially in the most vulnerable countries.”

Researchers see a particular danger that pathogens may exchange newly acquired resistance genes. This can then result in bacterial strains that are not sensitive to both the older active ingredients and the new quinolone and macrolide antibiotics. “Such organisms would avoid any treatment with established oral antimicrobials,” writes da Silva and colleagues. “This would lead to an increase in hospitalizations and increased morbidity and mortality.”

Global problem

According to the research team, their results are also a clear indicator that India remains an important point for the emergence of antibiotic resistance – more needs to be done here. “The fact that resistant strains of typhus have so often been able to spread internationally also underscores that typhoid control and resistance should be seen as a global problem, not a local problem,” says Andrews. (The Lancet Microbe, 2022; doi: 10.1016 / S2666-5247 (22) 00093-3)

What: Lancet

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