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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number660
Pages (from-to)1-12
Number of pages12
JournalMicroorganisms
Volume9
Issue number3
DOIs
Publication statusPublished - 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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