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Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial

Pallavi Bedi, Manjit K. Cartlidge, Yang Zhang, Kim Turnbull, Samantha Donaldson, Andrea Clarke, Jane Crowe, Kadiga Campbell, Catriona Graham, Ruzanna Franguylan, Adriano G. Rossi, Adam T. Hill
European Respiratory Journal 2021 58: 2004388; DOI: 10.1183/13993003.04388-2020
Pallavi Bedi
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
4P. Bedi and M.K. Cartlidge are joint first authors
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  • For correspondence: drpallavibedi@gmail.com
Manjit K. Cartlidge
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
4P. Bedi and M.K. Cartlidge are joint first authors
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Yang Zhang
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
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Kim Turnbull
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Samantha Donaldson
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Andrea Clarke
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Jane Crowe
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Kadiga Campbell
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Catriona Graham
3Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK
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  • ORCID record for Catriona Graham
Ruzanna Franguylan
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Adriano G. Rossi
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
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Adam T. Hill
1MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
2Royal Infirmary of Edinburgh, Edinburgh, UK
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Abstract

Background There is a lack of evidence to guide the duration of intravenous antibiotics for bronchiectasis exacerbations.

Aims The aim of this study was to assess whether it is feasible, based on bacterial load, to shorten intravenous antibiotics during exacerbations and whether 14 days of treatment is superior.

Methods We recruited participants requiring intravenous antibiotics for exacerbations. Participants were randomised into two groups: to receive antibiotics for 14 days (14-day group) or to have a shorter duration of treatment based on bacterial load (bacterial load-guided group (BLGG)). Bacterial load was checked on days 0, 7, 10, 14 and 21. If the bacterial load was <106 CFU·mL−1 on day 7 or day 10 in the BLGG, antibiotics were stopped the following day.

Results A total of 47 participants were in the 14-day group and 43 were in the BLGG. 88% of participants in the BLGG were able to stop antibiotics by day 8 and potentially 81% of participants in the 14-day group could have stopped antibiotics at day 8. There was a nonsignificant trend for increased clinical improvement by day 21 in the 14-day group compared to the BLGG. However, overall group data showed the median (interquartile range) time to next exacerbation was 27.5 days (12.5–60 days) in the 14-day group and 60 days (18–110 days) in the in BLGG (p=0.0034). In a Cox proportional hazard model, participants in the 14-day group were more likely to experience exacerbations (HR 1.80, 95% CI 1.16–2.80, p=0.009) than those in the BLGG, and those with mild bronchiectasis were less likely to experience exacerbations than patients with more severe bronchiectasis (HR 0.359, 95% CI 0.13–0.99, p=0.048).

Conclusions Bacterial load-guided therapy is feasible in most exacerbations requiring intravenous antibiotics. There was a nonsignificant trend for increased clinical improvement by day 21 with 14 days of antibiotics compared with bacterial load-guided therapy but paradoxically there was a prolonged time to next exacerbation in the BLGG.

Abstract

In bronchiectasis, bacterial load-guided therapy is feasible in most exacerbations requiring intravenous antibiotic therapy https://bit.ly/33VIQuR

Footnotes

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.01416-2021

  • This study is registered at ClinicalTrials.gov as NCT02047773. Data will be available to researchers whose proposed use of the data has been approved by an independent review.

  • Author contributions: P. Bedi contributed to experimental design, interpreted the data and wrote the manuscript. M.K. Cartlidge contributed to collecting the data and performing experiments. Y. Zhang contributed to performing the experiments. K. Turnbull, S. Donaldson, A. Clarke, J. Crowe and K. Campbell collected data, performed the patient interventions, provided domiciliary antibiotic service and performed the experiments. C. Graham is the statistician for this study and carried out the statistical analysis. R. Frangulyan contributed to collecting data. A.G. Rossi contributed to experimental design, interpretation of data and writing of the manuscript. A.T. Hill provided the experimental design, interpretation of data and writing of the manuscript.

  • This article has supplementary material available from erj.ersjournals.com

  • Conflict of interest: P. Bedi has nothing to disclose.

  • Conflict of interest: M.K. Cartlidge has nothing to disclose.

  • Conflict of interest: Y. Zhang has nothing to disclose.

  • Conflict of interest: K. Turnbull has nothing to disclose.

  • Conflict of interest: S. Donaldson has nothing to disclose.

  • Conflict of interest: A. Clarke has nothing to disclose.

  • Conflict of interest: J. Crowe has nothing to disclose.

  • Conflict of interest: K. Campbell has nothing to disclose.

  • Conflict of interest: C. Graham reports grants from the Scottish Office, during the conduct of the study.

  • Conflict of interest: R. Frangulyan has nothing to disclose.

  • Conflict of interest: A.G. Rossi has nothing to disclose.

  • Conflict of interest: A.T. Hill has nothing to disclose.

  • Received December 4, 2020.
  • Accepted May 4, 2021.
  • Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
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Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial
Pallavi Bedi, Manjit K. Cartlidge, Yang Zhang, Kim Turnbull, Samantha Donaldson, Andrea Clarke, Jane Crowe, Kadiga Campbell, Catriona Graham, Ruzanna Franguylan, Adriano G. Rossi, Adam T. Hill
European Respiratory Journal Dec 2021, 58 (6) 2004388; DOI: 10.1183/13993003.04388-2020

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Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial
Pallavi Bedi, Manjit K. Cartlidge, Yang Zhang, Kim Turnbull, Samantha Donaldson, Andrea Clarke, Jane Crowe, Kadiga Campbell, Catriona Graham, Ruzanna Franguylan, Adriano G. Rossi, Adam T. Hill
European Respiratory Journal Dec 2021, 58 (6) 2004388; DOI: 10.1183/13993003.04388-2020
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