Mutation Drives Persistent Pseudomonas in COPD

Heidi Splete, MDedge News

March 10, 2022

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

"Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations," Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. "This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections," the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, "the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients," they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

This article originally appeared in Chest Physician.

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