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Nebulised taurolidine and B cepacia bronchiectasis
  1. M J LEDSON,
  2. C COWPERTHWAITE,
  3. M J WALSHAW
  1. Regional Adult CF Unit
  2. The Cardiothoracic Centre
  3. Liverpool L14 3PE
  4. UK
  5. Department of Medical Microbiology
  6. Liverpool University
  7. Liverpool
  8. UK
  1. Dr M J Walshaw
  1. M J GALLAGHER,
  2. T WILLIETS,
  3. C A HART
  1. Regional Adult CF Unit
  2. The Cardiothoracic Centre
  3. Liverpool L14 3PE
  4. UK
  5. Department of Medical Microbiology
  6. Liverpool University
  7. Liverpool
  8. UK
  1. Dr M J Walshaw

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We have already reported a unique case of bronchiectasis with chronic colonisation by UK epidemic (ET12)Burkholderia cepacia in a previously well woman which developed following an acute infection acquired from her two B cepacia colonised children with cystic fibrosis.1 This has intermediate sensitivity to only co-trimoxazole and ceftazidime and, despite several intravenous courses of these antibiotics, the patient has remained chronically colonised for more than four years. We have therefore looked for other antibiotics which may have action against this multidrug resistant pathogen. Taurolidine acts by disrupting the cell wall, diminishing bacterial adherence, and neutralising toxins.2 It has good in vitro anti-B cepacia activity (MIC 0.4 mg/ml) but is currently used as an antiseptic peritoneal lavage solution. We gave nebulised taurolidine to our non-cystic fibrosis patient in a randomised, double blind, placebo controlled, crossover fashion (“n-of-1 trial”) to assess its effect on her chronic respiratory B cepacia colonisation (primary outcome measure), spirometric tests, and inflammatory markers (serum and sputum concentrations of interleukins 6 and 8, C reactive protein, total white cell count, erythrocyte sedimentation rate) (secondary outcome measures). She was given 4 ml 2% taurolidine twice daily in the active arm and 4 ml 0.9% saline twice daily in the placebo arm, each for four weeks separated by a two week washout period. Every two weeks sputum counts of B cepacia (colony forming units/ml) were determined by two independent microbiologists blinded to each others' results; concordance between them was >95%. A bioassay was performed on the sputum by agar diffusion to confirm that taurolidine was no longer active.

The study was approved by the local ethics committee and the patient gave her informed consent.

B cepacia disappeared from the sputum during the taurolidine arm and did not reappear until four weeks after cessation of treatment. There was no change in the placebo arm (fig 1). The only side effects noted during taurolidine treatment were transient mild pharyngitis and cough. There was no difference in spirometric parameters or inflammatory markers between the active and control arms. No changes in medication occurred during the trial.

Figure 1

Effect of treatment with taurolidine on colonisation with Burkholderia cepacia in a non-cystic fibrosis patient.

UK epidemic (ET12) B cepacia is innately resistant to many antibiotics and therefore the discovery of a different antimicrobial agent that has activity against this organism is important. Whilst a pilot study of taurolidine in patients with cystic fibrosis suggested that it may reduce colony counts,3 in a formal double blind placebo controlled crossover trial the results were disappointing.4 However, in our non-cystic fibrosis patient B cepaciadisappeared from the sputum within two weeks of commencement of treatment and remained absent for two weeks after treatment stopped. Dilutional studies showed no taurolidine activity in the sputum samples so recurrence of the organism in sputum after cessation of treatment may reflect recolonisation from her children or spread of residual colonisation in her upper respiratory tract. The apparent difference between the effect of taurolidine in this formulation in our patient and in patients with cystic fibrosis raises interesting questions as to the mechanisms by which B cepacia survives in subjects with cystic fibrosis. These include the presence of a biofilm5 and intracellular survival of organisms allowed by the defective CFTR protein.6

The current formulation of taurolidine uses povidone as a solubilising agent which may cause an unpleasant taste. Furthermore, taurolidine is only available as a 2% solution. We believe this agent may have a part to play in B cepacia infections in patients both with and without cystic fibrosis, and reformulation of taurolidine and its derivatives to allow a higher concentration to be delivered may improve its efficacy in patients with cystic fibrosis.

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