Treating Fungal Infection in Cystic Fibrosis Patients Can Harm Lungs, Study Reports

Treating patients with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD), infected with the fungus Aspergillus fumigatus, with antifungal therapies may contribute to the adaptation and resistance of this microorganism, and exacerbate lung infection, a new study reported.

This finding, in a report by medical researchers in the Netherlands, underscores the challenge facing clinicians, who must choose between administering drugs that may increase fungal resistance in these patients — or not treating and allowing the fungus to settle in their lungs. The study, “In-Host Adaptation And Acquired Triazole Resistance In Aspergillus Fumigatus: A Dilemma For Clinical Management,” was published in the journal The Lancet Infectious Diseases.

Many fungi species have the ability to adapt to rapidly changing environments. These microorganisms have developed several physiological and gene mutation mechanisms that allow them to adapt to adverse conditions. One example is A. fumigatus, a fungus associated with many diseases.

In nature, this pathogen decomposes organic materials in compost heaps. In the human lung, it adjusts easily to the environment, posing a particular problem for people with weakened immune systems, such as CF and COPD patients.

Given that any change in the fungus’ environment can stimulate adaptation, the start of a new treatment, the substitution of one antifungal drug for another, or even halting a treatment can be a contributing mechanism, the researchers reported. This is a real problem for doctors who have to choose between two unwelcome options in eliminating the infection: treat the fungus and increase its adaptive skills, or not treat it and allow the pathogen to settle in the lungs.

“We hypothesise that the current diagnostic tools and treatment strategies do not take into account the biology of the fungus and might result in an increased likelihood of fungal persistence in patients,” they wrote.

Researchers also reported that treatment with triazoles, a group of antifungal medications, allow the occurrence of mutations that confer resistance. Substituting one triazole-based treatment for another, or even stopping a treatment, only helps A. fumigatus become resistant, as the fungus accumulates mutations that allow it to survive multiple treatments.

“[O]ver time the fungus will become increasingly adapted to the lung environment, thereby limiting the probability of eradication. Our hypothesis challenges current management strategies, and future research should investigate the genomic dynamics during infection to understand the key factors facilitating adaptation of Aspergillus,” the research team concluded.