Variability in Bacteriophage and Antibiotic Sensitivity in Serial Pseudomonas aeruginosa Isolates from Cystic Fibrosis Airway Cultures over 12 Months

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.

Phage therapy in lung infections caused by multidrug-resistant Pseudomonas aeruginosa – A literature review

“…The combination of phages and antibiotics considered, the isolates showed notable variability in susceptibility over time. For instance, a pronounced variability in sensitivity of the bacterial isolates towards tobramycin and meropenem was found in 14% and 29% of 21 patients, respectively [ 27 ].…”

Respiratory Viruses and Cystic Fibrosis

“…154 Further work by Martin and colleagues has shown that the susceptibility to bacteriophages of P. aeruginosa isolates from people with CF displays considerable variability when samples are collected longitudinally. 155…”

“…154 Further work by Martin and colleagues has shown that the susceptibility to bacteriophages of P. aeruginosa isolates from people with CF displays considerable variability when samples are collected longitudinally. 155 The literature supporting the use of phage therapy in CF is currently limited to a small number of case reports, only. In the 1990s, a small study was conducted in Moscow involving five children with CF who received phage therapy administered by nebulization.…”

Lytic Bacteriophage Is a Promising Adjunct to Common Antibiotics across Cystic Fibrosis Clinical Strains and Culture Models of Pseudomonas aeruginosa Infection

“…There is an expanding body of evidence demonstrating the potential of bacteriophage (phage or phages) to combat Pa infection in CF lungs. We have previously shown increased survival and lowered inflammatory response in a model of murine Pa lung infection [ 10 ] and demonstrated phage sensitivity over time for many MDR strains (including the Liverpool Epidemic Strain) in patients at our hospital [ 11 ]. Although these and other studies provide a promising evidence base, as this therapy makes the leap from laboratory to human therapy in several ongoing human trials [ 12 , 13 , 14 , 15 ], there is no reason that the interactions between antibiotics, phage and bacteria should be consistent across the concentrations or type of bacterial growth encountered in the lung.…”