In the Journals

Phages associated with chronic infection, antibiotic resistance in patients with CF

Study findings suggest that filamentous bacteriophages may be associated with chronic Pseudomonas aeruginosa infection, antibiotic resistance and other negative outcomes in patients with cystic fibrosis.

“Phages haven’t been thought of as pathogens that affect humans,” Elizabeth B. Burgener, MD, instructor of pediatrics and pulmonary medicine at Stanford University, said in a news release. “This is a whole new paradigm of thinking about them.”

Bacteriophages — viruses that target and consume bacteria — are being studied as a last-resort treatment for patients with extensively drug-resistant bacterial infections. In a recently published study in Science Translational Medicine, Burgener and colleagues detail the examination of sputum samples from two cohorts to determine the prevalence and clinical relevance of filamentous bacteriophages (Pf phages) — which have been shown to exacerbate the severity P. aeruginosa in animal models — in patients with cystic fibrosis (CF).

“It is now well established that lung disease starts very early in the life of patients with CF, primarily as a consequence of mucus obstruction and bacterial infection,” they wrote. “Pseudomonas aeruginosa is a common pathogen recovered from CF airway secretions. Infection with P. aeruginosa likely starts as an intermittent infection progressing to a chronic stage, with eventual conversion to a biofilm-entrenched state. These communities of bacteria encased in extracellular matrix allow P. aeruginosa to effectively adapt to the airway environment and persist despite strong immune response and antibiotic therapy.”

According to Burgener and colleagues, data from a Danish study including 34 patients with CF revealed that 26.5% (n = 9) were Pf phage positive. A second cohort from a prospective cross-sectional cohort of 58 patients with CF at Stanford who underwent sputum qPCR analysis, showed that 36.2% (n = 21) were Pf phage positive.

In the Stanford cohort, researchers found that Pf phages were associated with chronic P. aeruginosa infection — specifically, more than half of respiratory cultures tested positive for P. aeruginosa in 100% of Pf phage-positive patients during a 12-month period, compared with around 35% of patients negative for Pf phage. The phages also were associated with worse lower pulmonary function during exacerbations than patients negative for Pf phage presence and older patient age, according to Burgener and colleagues. Additionally, overall results revealed that P. aeruginosa strains carrying Pf phage exhibited increased resistance to antipseudomonal antibiotics.

“We report that Pf phage is abundant in P. aeruginosa in multiple settings and that higher concentrations of Pf phage are associated with increased patient age, chronic P. aeruginosa infection, lower (forced expiratory volume) during pulmonary exacerbations, and increased antibiotic resistance profiles in a cohort of patients with CF,” the authors concluded.

“Together with the available in vitro and animal model data, these findings implicate Pf phage in the pathogenesis of CF lung disease and specifically in establishing chronic infection with P. aeruginosa. Our study identifies carriage of Pf phage as a potential biomarker for risk of antibiotic resistance and a potential therapeutic target for treatment of chronic P. aeruginosa infections in CF.” – by Caitlyn Stulpin

Disclosures: Burgener reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Study findings suggest that filamentous bacteriophages may be associated with chronic Pseudomonas aeruginosa infection, antibiotic resistance and other negative outcomes in patients with cystic fibrosis.

“Phages haven’t been thought of as pathogens that affect humans,” Elizabeth B. Burgener, MD, instructor of pediatrics and pulmonary medicine at Stanford University, said in a news release. “This is a whole new paradigm of thinking about them.”

Bacteriophages — viruses that target and consume bacteria — are being studied as a last-resort treatment for patients with extensively drug-resistant bacterial infections. In a recently published study in Science Translational Medicine, Burgener and colleagues detail the examination of sputum samples from two cohorts to determine the prevalence and clinical relevance of filamentous bacteriophages (Pf phages) — which have been shown to exacerbate the severity P. aeruginosa in animal models — in patients with cystic fibrosis (CF).

“It is now well established that lung disease starts very early in the life of patients with CF, primarily as a consequence of mucus obstruction and bacterial infection,” they wrote. “Pseudomonas aeruginosa is a common pathogen recovered from CF airway secretions. Infection with P. aeruginosa likely starts as an intermittent infection progressing to a chronic stage, with eventual conversion to a biofilm-entrenched state. These communities of bacteria encased in extracellular matrix allow P. aeruginosa to effectively adapt to the airway environment and persist despite strong immune response and antibiotic therapy.”

According to Burgener and colleagues, data from a Danish study including 34 patients with CF revealed that 26.5% (n = 9) were Pf phage positive. A second cohort from a prospective cross-sectional cohort of 58 patients with CF at Stanford who underwent sputum qPCR analysis, showed that 36.2% (n = 21) were Pf phage positive.

In the Stanford cohort, researchers found that Pf phages were associated with chronic P. aeruginosa infection — specifically, more than half of respiratory cultures tested positive for P. aeruginosa in 100% of Pf phage-positive patients during a 12-month period, compared with around 35% of patients negative for Pf phage. The phages also were associated with worse lower pulmonary function during exacerbations than patients negative for Pf phage presence and older patient age, according to Burgener and colleagues. Additionally, overall results revealed that P. aeruginosa strains carrying Pf phage exhibited increased resistance to antipseudomonal antibiotics.

“We report that Pf phage is abundant in P. aeruginosa in multiple settings and that higher concentrations of Pf phage are associated with increased patient age, chronic P. aeruginosa infection, lower (forced expiratory volume) during pulmonary exacerbations, and increased antibiotic resistance profiles in a cohort of patients with CF,” the authors concluded.

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“Together with the available in vitro and animal model data, these findings implicate Pf phage in the pathogenesis of CF lung disease and specifically in establishing chronic infection with P. aeruginosa. Our study identifies carriage of Pf phage as a potential biomarker for risk of antibiotic resistance and a potential therapeutic target for treatment of chronic P. aeruginosa infections in CF.” – by Caitlyn Stulpin

Disclosures: Burgener reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.