Why Stubborn Lung Infections Persist Despite Therapy - European Medical Journal Why Stubborn Lung Infections Persist Despite Therapy - AMJ

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Why Stubborn Lung Infections Persist Despite Therapy

Middle-aged woman touching her neck while appearing uncomfortable, suggesting respiratory or throat symptoms related to a stubborn lung infection.

STUBBORN lung infection can evolve within patients and develop traits that help it persist over time. Chronic pulmonary disease caused by Mycobacterium avium complex remains difficult to manage and incidence is rising among vulnerable individuals. Researchers are working to understand how these organisms persist in the lung despite prolonged treatment.

Genomic Analysis of Long-Term Infection

This analysis included 287 isolates from 56 patients with chronic M. avium infection. Fifty newly sequenced samples from Ireland were compared with isolates from two European cohorts. This approach enabled the team to study whether international strain similarities exist and how M. avium populations change during disease progression.

Two isolates from Ireland closely matched strains from continental Europe within a small single nucleotide polymorphism threshold. This supports previous observations that dominant clones are circulating internationally, which may indicate common environmental sources affecting high-risk patient groups.

Within-Host Evolution of Mycobacterium Avium

Across all cohorts, M. avium communities changed significantly during the course of infection. New strain acquisition was frequent, suggesting that reinfection plays a substantial role in the ongoing clinical challenge. Importantly, positive selection pressure was detected in 13 genes linked to virulence, including those that may support resistance to antibiotics and host immune defense.

Adaptive evolution within the lung may worsen treatment resistance over time. These findings highlight the importance of monitoring pathogen response not only at diagnosis but throughout long-term therapy.

Clinical Relevance and Future Directions

As M. avium adapts to its environment in the host, management of chronic pulmonary disease may require targeted strategies to reduce reinfection and address persistence mechanisms. Whole genome analysis offers opportunities to identify new therapeutic targets and tailor surveillance for emerging resistance.

The researchers emphasized that ongoing sequencing efforts could help clinicians better anticipate treatment challenges in stubborn lung infections and support more effective patient care.

Reference: Walsh AM et al. Genomic characterisation of recurrent Mycobacterium avium isolates from chronically infected patients reveals patterns of within-host evolution. Genome Medicine. 2025; doi:10.1186/s13073-025-01549-y.

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