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Review
. 2013 Jun 5;2013(6):CD008037.
doi: 10.1002/14651858.CD008037.pub3.

Antibiotic Adjuvant Therapy for Pulmonary Infection in Cystic Fibrosis

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Free PMC article
Review

Antibiotic Adjuvant Therapy for Pulmonary Infection in Cystic Fibrosis

Matthew N Hurley et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, are urgently needed.

Objectives: To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis.

Search methods: We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings.Date of most recent search: 26 July 2012.We also searched MEDLINE (all years) on 23 February 2013 and ongoing trials registers on 13 February 2013.

Selection criteria: Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis.

Data collection and analysis: The authors independently assessed and extracted data from identified studies.

Main results: We identified eighteen studies of which four are included that examined antibiotic adjuvant therapies, three studies are ongoing. The included studies involve the assessment of β-carotene, garlic and zinc supplementation and KB001 (a biological agent). No therapy demonstrated a significant effect upon pulmonary function, pulmonary exacerbations or quality of life. The study of zinc supplementation reports a reduction in the requirement of oral antibiotics but not of intravenous antibiotics, an effect that is difficult to understand.

Authors' conclusions: We could not identify an antibiotic adjuvant therapy that could be recommended for the treatment of lung infection in those with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.

Conflict of interest statement

Dr Matthew Hurley Dr Hurley has received support from the Wellcome Trust as a Wellcome Turst Clinical Research Training Fellow.

Professor Alan Smyth Professor Smyth is lead investigator on one of the studies included in the review (Smyth 2010).

He has also acted as a consultant to the pharmaceutical industry for therapies in development for pulmonary infection with Pseudomonas aeruginosa in cystic fibrosis (CF):

Novartis ‐ dry powder inhaled tobramycin

Mpex Pharmaceuticals ‐ inhaled, nebulised levofloxacin

Biocontrol ‐ bacteriophage therapy

Professor Smyth has also received payment for commercial clinical trials:

Boehringer Ingelheim, Ltd. (UK) ‐ inhaled tiotropium as a long‐acting bronchodilator in CF.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Chronic Infection: ß‐carotene supplementation, Outcome 1 Days of antibiotic consumption.
1.2
1.2. Analysis
Comparison 1 Chronic Infection: ß‐carotene supplementation, Outcome 2 Respiratory function (FEV1 % predicted).
1.3
1.3. Analysis
Comparison 1 Chronic Infection: ß‐carotene supplementation, Outcome 3 Mortality.
2.1
2.1. Analysis
Comparison 2 Chronic Infection: Garlic supplementation, Outcome 1 Respiratory function (% change FEV1).
2.2
2.2. Analysis
Comparison 2 Chronic Infection: Garlic supplementation, Outcome 2 Mortality.
2.3
2.3. Analysis
Comparison 2 Chronic Infection: Garlic supplementation, Outcome 3 Mild adverse events.
3.1
3.1. Analysis
Comparison 3 Chronic infection: Zinc supplementation, Outcome 1 Respiratory function (FEV1 % predicted).
3.2
3.2. Analysis
Comparison 3 Chronic infection: Zinc supplementation, Outcome 2 Respiratory function (FVC %predicted).
3.3
3.3. Analysis
Comparison 3 Chronic infection: Zinc supplementation, Outcome 3 Antibiotic consumption (days oral antibiotics).
3.4
3.4. Analysis
Comparison 3 Chronic infection: Zinc supplementation, Outcome 4 Antibiotic consumption (days iv antibiotics).
3.5
3.5. Analysis
Comparison 3 Chronic infection: Zinc supplementation, Outcome 5 Antibiotic consumption (days of oral and iv antibiotics).
4.1
4.1. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 1 Pulmonary exacerbations .
4.2
4.2. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 2 Decrease in respiratory function (FEV1).
4.3
4.3. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 3 Number of participants experiencing an adverse event.
4.4
4.4. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 4 Serious adverse events.
4.5
4.5. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 5 Ear and labyrinth adverse effects.
4.6
4.6. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 6 Gastrointestinal adverse events.
4.7
4.7. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 7 General adverse events.
4.8
4.8. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 8 Infections and infestations.
4.9
4.9. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 9 Injury, poisoning and procedural complications  .
4.10
4.10. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 10 Investigative adverse events.
4.11
4.11. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 11 Nervous system adverse events.
4.12
4.12. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 12 Psychiatric adverse events.
4.13
4.13. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 13 Respiratory, thoracic and mediastinal adverse events.
4.14
4.14. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 14 Skin and subcutaneous tissue adverse events.
4.15
4.15. Analysis
Comparison 4 Chronic infection: KB001‐A, Outcome 15 Vascular adverse events.

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