Preserving lung microbial diversity in cystic fibrosis

Preserving lung microbial diversity in cystic fibrosis
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Published in Scientific Reports, correct antibiotic dosage could potentially preserve lung microbial diversity in those suffering from cystic fibrosis.

Children and young adults with cystic fibrosis (CF) whose lung infections were treated with suboptimal doses of antibiotics had fewer changes in lung microbial diversity during the IV treatment, and their microbial diversity levels were higher 30 days later, a multi-institutional study that includes Children’s researchers shows.

By contrast, patients who were treated with therapeutic doses had greater decreases in lung microbial diversity and significantly lower diversity levels when the antibiotic treatment ended as well as 30 days later.

Understanding lung microbial diversity

The study clearly establishes the importance of the interplay between baseline microbial diversity and lung function and also has the potential to improve clinical practices.

Andrea Hahn, M.D., MS, an infectious disease specialist at Children’s National Health System and the study’s lead author, explains: “With the subtherapeutic treatment group, this could represent a ‘basement effect’ where it is harder to decrease diversity when it is already low to start.

“Also, patients in the subtherapeutic group had more advanced disease than those in the therapeutic group, which may influence the findings.”

What do you know about cystic fibrosis?

More than 30,000 people in the U.S. live with CF, a genetic disease that leads to recurrent lung infections that gradually deplete lung function over time.

Individuals with this disease frequently require hospitalisation for these infections, known as acute pulmonary exacerbations (APEs), which are typically treated with antibiotics.
These often include beta-lactams, a class of antibiotics that include penicillin and a host of other structurally related compounds.

Worsening lung function in CF patients has been linked to decreased microbial diversity in their lungs, a factor thought to be caused by repeated dosing of antibiotics to treat APEs.

Although it’s well known that patients frequently don’t achieve therapeutic doses of antibiotics that effectively clear their infections, it’s been unclear how microbial diversity changes in patients who receive subtherapeutic doses compared with patients who receive therapeutic doses.

Antibiotics play an important role

The researchers suspect that patients who often don’t achieve therapeutic blood levels of antibiotics may be genetically predisposed to metabolise beta-lactam antibiotics quickly.

Repeated subtherapeutic courses of antibiotics could significantly knock down microbial diversity without effectively clearing infections, leading to more lung damage that negatively impacts lung function over time.

Hahn adds that eventually it may be possible to avoid this effect by keeping closer tabs on CF patients’ antibiotic blood levels in real time to make sure that each APE is treated with therapeutic-level dosing.

“What this study shows is that levels of the antibiotics we give probably play a role in patients’ ability to recover baseline diversity,” she says.

“If we pay more attention to drug levels when using these types of antibiotics to ensure that dosing is sufficient, we could potentially improve patients’ clinical outcomes over time.”

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