Trikafta seen to diminish number of P. aeruginosa in patients’ sinuses
Infections due to opportunistic bacteria are major cause of lung disease in CF
Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor, lowered the number of Pseudomonas aeruginosa bacteria in the nose and sinuses of people with cystic fibrosis (CF) taking part in a small study.
Mucus from the sinuses — air-filled pockets in the skull — can enter the lungs, so reducing the number of bacteria there may help to prevent infections with P. aeruginosa, a major contributor to poorer lung health in people with CF.
The study, “Elexacaftor–tezacaftor–ivacaftor decreases pseudomonas abundance in the sinonasal microbiome in cystic fibrosis,” was published in the International Forum of Allergy & Rhinology.
Trikafta shown to ease chronic rhinosinusitis, common with cystic fibrosis
Bacteria and other germs can enter the sinuses by breathing them in, causing inflammation. Usually, such inflammation diminishes as the sinuses produce mucus to flush away the germs.
In people with CF, however, a faulty or absent CFTR protein causes mucus to become abnormally thick and sticky. Instead of flushing germs away, this mucus traps them. Chronic rhinosinusitis, quite common among people with CF, occurs when the nose and sinuses keep getting infected and inflamed, causing pain and a blocked or runny nose.
Trikafta, a CFTR modulator marketed as Kaftrio in Europe, has been shown to relieve rhinosinusitis’ symptoms in people with CF, including those with advanced lung disease.
To find out how Trikafta, by Vertex Pharmaceuticals, changes the type and number of bacteria in the nose and sinuses, a team of researchers in the U.S. collected samples from 29 adults and adolescents, ages 12 and older, with a CF diagnosis and being followed at pulmonary clinics for the disease.
The median age of these patients, 17 males and 12 females, was 27. Eighteen (62.1%) had allergic rhinitis, inflammation of the nose caused by an allergen such as pollen, and 23 (79.3%) previously had undergone sinus surgery.
A method called 16S rRNA sequencing was used to identify which types of bacteria were present in samples of sinus swabs collected before and a median of nine months after starting treatment with Trikafta.
A total of 23 pairs of swap samples were available for analysis, excluding six patients with only one available sample. At baseline (the study’s start), the most abundant genus (type) of bacteria was Staphylococcus.
P. aeruginosa no longer evident in six infected patients with Trikafta’s use
Alpha diversity, a measure of the diversity within the set of bacteria present in a sample, was low compared with a reference group of patients without rhinosinusitis. It also was lower for patients who had prior sinus surgery than for those who hadn’t.
An analysis of beta diversity, which compares samples to see how much they differ from each other, revealed that Staphylococcus bacteria were more abundant in patients who also had allergic rhinitis.
After treatment with Trikafta, no significant change was seen in alpha diversity. However, the number of bacteria of the Pseudomonas and Burkholderia/Caballeronia/Paraburkholderia types decreased significantly.
Patients who tested positive for Pseudomonas had significantly poorer lung function at baseline, as seen by lower predicted forced expiratory volume in 1 second (FEV1).
Using a method called quantitative PCR, P. aeruginosa was detected in the sinus swabs of six patients at the study’s start. Nine months after starting treatment with Trikafta, this species could no longer be detected.
“Treatment with [Trikafta] leads to a reduction in Pseudomonas abundance within the sinonasal microbiome [the set of germs in a particular environment] of individuals with Pseudomonas at baseline,” the researchers concluded.
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