Abstract
Antibiotic treatment for Pseudomonas aeruginosa (Pa) in cystic fibrosis is limited in efficacy and may lead to multi-drug resistance (MDR). Alternatives such as bacteriophages are being explored but well designed, and controlled trials are crucial. The rational selection of patients with bacteriophage susceptible infections is required for both safety and efficacy monitoring. We questioned whether bacteriophage susceptibility profiles were constant or variable over time, variability having been reported with antibiotics. Serial Pa isolates (n = 102) from 24 chronically infected cystic fibrosis (CF) patients over one year were investigated with plaque and antibiotic disc diffusion assays. Variable number tandem repeat (VNTR) analysis identified those patients with >1 isolate. A median (range) of 4 (3–6) isolates/patient were studied. Twenty-one (87.5%) individuals had a single VNTR type; three (12.5%) had two VNTR types at different times. Seventy-five percent of isolates were sensitive to bacteriophage at ≥ 1 concentration; 50% of isolates were antibiotic multidrug resistant. Serial isolates, even when representing a single VNTR type, varied in sensitivity to both bacteriophages and antibiotics. The rates of sensitivity to bacteriophage supports the development of this therapy; however, the variability in response has implications for the selection of patients in future trials which must be on the basis of current, not past, isolate testing.
Highlights
Cystic fibrosis (CF) is an autosomal recessive condition in which affected individuals are at an increased risk of bacterial lung infection with opportunistic pathogens
Pseudomonas aeruginosa (Pa) is the pathogen leading to the greatest burden of lung disease in CF, as a majority of patients are infected with this ubiquitous Gram-negative bacterium by the time they reach adulthood
We have previously reported in a murine model that antipseudomonal bacteriophages resulted in a reduction in both bacterial load and inflammatory response [20]
Summary
Cystic fibrosis (CF) is an autosomal recessive condition in which affected individuals are at an increased risk of bacterial lung infection with opportunistic pathogens. Repeated and chronic airway infections result in a decline in lung function, decreased quality of life and increased mortality. Pseudomonas aeruginosa (Pa) is the pathogen leading to the greatest burden of lung disease in CF, as a majority of patients are infected with this ubiquitous Gram-negative bacterium by the time they reach adulthood. The natural history of infection is typically through initial acquisition of the bacteria, to intermittent infection, and eventually to chronic colonization [2,3]. Though nosocomial infection with epidemic strains—often associated with increased rates of antimicrobial resistance (AMR)—is well documented [4,5,6], early
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
