Variability in bacteriophage and antibiotic sensitivity in serial Pseudomonas aeruginosa isolates from cystic fibrosis airway cultures over 12 months

Isaac Martin; Dervla T.D. Kenna; Sandra Morales; Eric W.F.W. Alton; Jane C. Davies

doi:10.3390/microorganisms9030660

Variability in bacteriophage and antibiotic sensitivity in serial Pseudomonas aeruginosa isolates from cystic fibrosis airway cultures over 12 months

Isaac Martin^*, Dervla T.D. Kenna, Sandra Morales, Eric W.F.W. Alton, Jane C. Davies

^*Corresponding author for this work

NIS: ARMHAI Reference Lab

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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 ex-plored 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 ques-tioned 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 as-says. 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 re-sistant. 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.

Original language	English
Article number	660
Pages (from-to)	1-12
Number of pages	12
Journal	Microorganisms
Volume	9
Issue number	3
DOIs	https://doi.org/10.3390/microorganisms9030660
Publication status	Published - Mar 2021

Bibliographical note

Funding Information:
Funding: This research was part funded by the Cystic Fibrosis Trust, UK and the Strategic Re‐ search Centre for Pseudomonas.

Funding Information:
Acknowledgments: We gratefully acknowledge funding for the Strategic Research Centre for Pseudomonas from the Cystic Fibrosis Trust, UK. The group is supported by the National Institute for Health Research through the Imperial Biomedical Research Centre, the Royal Brompton Hospi‐ tal/Imperial College London Clinical Research Facility and NIHR Senior Investigator Awards (JCD, EWFWA). We thank the staff of the clinical microbiology laboratory for their help in collect‐ ing bacterial strains. We also would like to acknowledge the work of Zoë Payne from Public Health England, and her painstaking work performing VNTR typing on the isolates in this study.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Adjunctive therapy
Antimicrobial resistance
Bacteriophage
Cystic fibrosis
Novel antimicrobials
Pseudomonas aeruginosa
Pulmonary infection

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title = "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 ex-plored 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 ques-tioned 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 as-says. 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 re-sistant. 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.",

keywords = "Adjunctive therapy, Antimicrobial resistance, Bacteriophage, Cystic fibrosis, Novel antimicrobials, Pseudomonas aeruginosa, Pulmonary infection",

author = "Isaac Martin and Kenna, {Dervla T.D.} and Sandra Morales and Alton, {Eric W.F.W.} and Davies, {Jane C.}",

note = "Funding Information: Funding: This research was part funded by the Cystic Fibrosis Trust, UK and the Strategic Re‐ search Centre for Pseudomonas. Funding Information: Acknowledgments: We gratefully acknowledge funding for the Strategic Research Centre for Pseudomonas from the Cystic Fibrosis Trust, UK. The group is supported by the National Institute for Health Research through the Imperial Biomedical Research Centre, the Royal Brompton Hospi‐ tal/Imperial College London Clinical Research Facility and NIHR Senior Investigator Awards (JCD, EWFWA). We thank the staff of the clinical microbiology laboratory for their help in collect‐ ing bacterial strains. We also would like to acknowledge the work of Zo{\"e} Payne from Public Health England, and her painstaking work performing VNTR typing on the isolates in this study. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Alton, Eric W.F.W.

AU - Davies, Jane C.

N1 - Funding Information: Funding: This research was part funded by the Cystic Fibrosis Trust, UK and the Strategic Re‐ search Centre for Pseudomonas. Funding Information: Acknowledgments: We gratefully acknowledge funding for the Strategic Research Centre for Pseudomonas from the Cystic Fibrosis Trust, UK. The group is supported by the National Institute for Health Research through the Imperial Biomedical Research Centre, the Royal Brompton Hospi‐ tal/Imperial College London Clinical Research Facility and NIHR Senior Investigator Awards (JCD, EWFWA). We thank the staff of the clinical microbiology laboratory for their help in collect‐ ing bacterial strains. We also would like to acknowledge the work of Zoë Payne from Public Health England, and her painstaking work performing VNTR typing on the isolates in this study. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/3

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N2 - 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 ex-plored 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 ques-tioned 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 as-says. 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 re-sistant. 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.

AB - 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 ex-plored 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 ques-tioned 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 as-says. 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 re-sistant. 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.

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ER -

Variability in bacteriophage and antibiotic sensitivity in serial Pseudomonas aeruginosa isolates from cystic fibrosis airway cultures over 12 months

Abstract

Bibliographical note

Keywords

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