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Predictors of Failed Pseudomonas aeruginosa Eradication in Children With Cystic Fibrosis

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May 25, 2021
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Predictors of Failed Pseudomonas aeruginosa Eradication in Children With Cystic Fibrosis
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Pseudo Aeruginosa Infection has been found as a risk factor for failure of ablation treatment in patients with cystic fibrosis who are resistant to antibacterial neutrophil functions, according to results of a study published in The Journal of Infectious Diseases.

Infections it causes Aeruginosa P In patients with cystic fibrosis it is often treated with antibiotics, such as tobramycin, which often fail to clear the infection. So a team of investigators analyzed Aeruginosa P From a group of 39 children with cystic fibrosis and newborns Aeruginosa P Infection to determine factors that may contribute to treatment failure.

All patients were undergoing ablation therapy with tobramycin, with 30 of them achieving ablation and 9 having persistent infections. A total of 52 isolates from erosive infections and 19 isolates from chronic infections were analyzed. Several patients were infected with multiple isolates, so the neutrophil assay data for all phenotypes in the patient sample were collected and analyzed.


Read on

Compared with the excised infection, the median phagocytosis index for chronic infection was twice as low (9.1% versus 19.5%, s = .0003), and metrics for bacterial killing were 2.5 times lower (2.6% versus 6.7%, s = .018). When characterizing the flagellum movement, twitching movement, and mucosa (excessive gene production), the researchers found that the twitching movement (r = 0.27, s = .02) and mucosa (r = -5.60, s = .04) was significantly associated with neutrophil phagocytosis. For each 1 mm increase in twitching, there was an increase in phagocytosis of 0.27%, while mucosal presence was associated with a mean decrease in phagocytosis of 5.6%.

After adjusting for covariates, an important indicator of persistent infection was phagocytosis in vitro neutrophils (odds ratio, 0.76; 95% CI, 0.62-0.94; s = .01). The researchers reported that each increase in phagocytosis was thus associated with a 24% decrease in the odds of persistent infection. After modification, in vitro phagocytosis was an important indicator of infection eradication failure.

The investigators noted that it is chronic Aeruginosa P The infection in the lungs of patients with cystic fibrosis is very diverse, and may overlook some of the phenotypic variety. Persistent infection was determined using positive sputum culture after completion of treatment, and new infections were not excluded with whole genome sequencing. The results of the study were not validated in primary human neutrophils because this study used HL-60 cell lines to obtain robust and reproducible measurements in the face of large numbers of isolates. The researchers stated that the small sample size, especially in persistent infections, also limited the study.

According to the researchers in the study, the results indicated, however, a decrease in neutrophilic phagocytosis in Aeruginosa P As an independent predictor of failure to eliminate tobramycin. The study also provided biological insights into the failure of ablation therapy in cystic fibrosis patients and highlighted the possibility of using non-antibiotic therapies that target interactions between Aeruginosa P And neutrophils or that enhance the antibacterial function of neutrophils.

Disclosure: Valerie Waters has announced its affiliation with AstraZeneca. None of the other study authors announced any affiliations with the pharmaceutical industry.

Reference

Kwong K, Benedetti A, Yau Y, Waters V, Nguyen D.. The ablation treatment failed from a fresh start Pseudomonas aeruginosa Infection in children with cystic fibrosis is associated with bacterial resistance to neutrophil functions. J Infect Dis. Posted online February 19, 2021. doi: 10.1093 / infdis / jiab102

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