Non-antibiotic agents to assist antibiotic treatment for lung infection in cystic fibrosis

People with cystic fibrosis suffer lung infections due to thick secretions and commonly suffer infections caused by unusual bacteria, including the bacteria Pseudomonas aeruginosa. These bacteria become resistant to treatment with antibiotics. Long-term infection leads to a poorer quality of life and reduced lung function. There are no new antibiotics currently in development that use a new type of action. New agents - antibiotic adjuvants - are needed to make bacteria more sensitive to either antibiotics or to the immune system, and to interfere with the formation of colonies of bacteria in the lungs.

We identified seven approaches for enhancing antibiotic action including sugars, garlic, monoclonal antibodies (many copies of one type of antibody, each made in a laboratory from a single copy of a human antibody), chick yolk antibodies, bacteriophages (viruses that infect bacteria), beta-carotene and zinc supplementation. We included four trials of these therapies in our review (one each of beta-carotene, garlic, zinc and a monoclonal antibody). All trials compared the active treatment to a placebo and looked at continuing long-term treatment rather than treatment for a short-term severe infection (the shortest trial was for 28 days and the longest was for one year). Neither beta-carotene or garlic showed a significant improvement in clinical state or the number of infections. The study of zinc supplementation showed fewer oral antibiotics were needed, but the same was not true for intravenous antibiotics. It is difficult to explain this discrepancy and so the significance of the effect of zinc remains uncertain. The zinc study published only selected results, however the authors have kindly provided additional data. The monoclonal antibody study (KB001) demonstrated safety and tolerability.

We were unable to identify any therapy to enhance the actions of antibiotics which showed a significant benefit for either lung function, rate of infection or quality of life. Further randomised controlled trials are required before the routine use of any of these therapies can be recommended.

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.

Read the full 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 strategy: 

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. 

Share/Save