Immediate Treatment of M. Abscessus Urged for Cystic Fibrosis

By Marilynn Larkin

May 11, 2021

NEW YORK (Reuters Health) - An analysis of whole genome data from cystic fibrosis patients reveals how multi-drug resistant pathogens evolve and suggests that Mycobacterium abscessus infection be treated promptly, contrary to current medical practice.

"Our study highlights how environmental bacteria can evolve into specialized human pathogens," Dr. R. Andres Floto of the University of Cambridge, UK, told Reuters Health by email. "We define a series of key steps that appear common across mycobacteria and probably led to the emergence of tuberculosis several thousands of years ago."

For the current study, published in Science, he said, "We have focused on a nontuberculous mycobacterial (NTM) species, M. abscessus, which causes devastating infections particularly in people with cystic fibrosis and other chronic inflammatory lung diseases."

The team analyzed whole genome data for 1,173 M. abscessus samples taken from 526 cystic fibrosis patients. The work identifies the following, according to Dr. Floto:

- How gene gain events, through a process called horizontal gene transfer, drive large step-changes in environmental isolates of M. abscessus, potentially enabling the pathogen to suddenly become much more virulent.

- How chronic lung infection can allow multiple subclones to evolve in parallel and become more virulent - a process called within-host evolution. The longer the infection exists, the more opportunities the subclones have to evolve, Dr. Floto explained, "with the fittest variants eventually winning out."

- That the evolved clones don't survive well on surfaces, thereby constraining their transmission.

The study has several clinical implications, he noted. "The finding of rapid parallel evolution within the lung of infected patients, making the bacteria more virulent, indicates that we may need to rapidly eradicate M. abscessus as soon as possible."

"We therefore need to consider frequent screening for M. abscessus infection in at-risk patients - and accept the increase in care costs - and immediate treatment of (infected) patients, rather than waiting for patients to fulfill the ATS/IDSA criteria for NTM pulmonary disease, as is currently recommended," he said. "Such changes to policy would need to be formally evaluated."

"Since transmission is currently indirect - probably through infectious aerosols and via fomites - increased attention needs to be paid to hospital cross-infection policies," he continued. "Conventional ward and clinic-based ventilation systems and surface cleaning are unlikely to be sufficient to prevent transmission of M. abscessus."

Further, "permitting direct transmission of M. abscessus...would allow the highly virulent subclones to directly infect another person's lungs, thereby accelerating pathogenic evolution," Dr. Floto said. "This highlights the importance of cohort and individual segregation of people in high-risk clinical groups."

The authors note in the paper, "Ultimately, we predict that opportunities for direct transmission of emergent mycobacteria (potentially through increases in population density and/or host susceptibility) will permit unconstrained, accelerated evolution into an obligate pathogen (accompanied by permanent loss of the smooth morphotype), as occurred in M. tuberculosis an estimated 4,000 to 6,000 years ago."

Drs. Rossa Brugha and Helen Spencer of Great Ormond Street Hospital in London note in an editorial, "International guidelines recommend annual surveillance for NTM species in patients with (cystic fibrosis), and a single isolate of NTM does not necessarily mean an immediate recourse to treatment."

Thus, they say, a randomized trial comparing current versus more aggressive NTM treatment is required.

The study was funded in part by Wellcome Trust grants. The authors declare no competing interests.

SOURCE: https://bit.ly/3eBo3Da and https://bit.ly/3uNMKBC Science, online April 30, 2021.

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