期刊
JOURNAL OF INFECTIOUS DISEASES
卷 225, 期 11, 页码 1886-1895出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab102
关键词
cystic fibrosis; Pseudomonas aeruginosa; antibiotic eradication therapy; neutrophil phagocytosis
资金
- Cystic Fibrosis Canada [559985]
- Cystic Fibrosis Foundation [WATERS17G0]
- Meakins Christie Studentship
- Fonds de Recherche en Sante du Quebec (FRQS)
This study found that PA isolates from new-onset CF infections exhibit strain-specific susceptibility to neutrophil antibacterial functions, and PA isolates resistant to neutrophil phagocytosis are independent risk factors for failed tobramycin eradication. Experimental results on neutrophil phagocytosis and intracellular killing showed that isolates from persistent infections were more resistant compared to those from eradicated infections.
Background. Antibiotics, such as inhaled tobramycin, are used to eradicate new-onset Pseudomonas aeruginosa (PA) infections in patients with cystic fibrosis (CF) but frequently fail due to reasons poorly understood. We hypothesized that PA isolates' resistance to neutrophil antibacterial functions was associated with failed eradication in patients harboring those strains. Methods. We analyzed all PA isolates from a cohort of 39 CF children with new-onset PA infections undergoing tobramycin eradication therapy, where 30 patients had eradicated and 9 patients had persistent infection. We characterized several bacterial phenotypes and measured the isolates' susceptibility to neutrophil antibacterial functions using in vitro assays of phagocytosis and intracellular bacterial killing. Results. PA isolates from persistent infections were more resistant to neutrophil functions, with lower phagocytosis and intracellular bacterial killing compared to those from eradicated infections. In multivariable analyses, in vitro neutrophil responses were positively associated with twitching motility, and negatively with mucoidy. In vitro neutrophil phagocytosis was a predictor of persistent infection following tobramycin even after adjustment for clinical risk factors. Conclusions. PA isolates from new-onset CF infection show strain-specific susceptibility to neutrophil antibacterial functions, and infection with PA isolates resistant to neutrophil phagocytosis is an independent risk factor for failed tobramycin eradication.
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