Inhaled antibiotics in bronchiectasis

I've just been listening to a talk on this topic from the 2009 ATS conference.  Dr Diana Bilton, from the Royal Brompton Hospital was the speaker.

Dr Bilton pointed out that although many of the habits we have developed with regard to the administration of antibiotics in patients with bronchiectasis really mimic what we do in patients with cystic fibrosis, these two conditions are not entirely analagous. That is, although patients with cystic fibrosis CF do develop bronchiectasis (i.e. they have thickened, dilated airways which become chronically infected by bacteria), patients who have bronchiectasis but do not have CF are different in many ways from patients with both conditions. 

For example:

1.  Patients with bronchiectasis and CF do have more variable lung function.  FEV1 tends to drop with exacerbations. The same is not true of patients with bronchiectasis.  Lung function is not a helpful indicator of 'severity' of exacerbation
2.  Lung function in patients with bronchiectasis does not often improve after treatment courses of antibiotics (once again, in contrast to patients with CF).

As the talk was particularly with regard to the impact of antibiotics in patients with bronchiectasis, and in particular antibiotics effective against Pseudomonas aeruginosa, this second point is pertinent.  One of the markers of clinical efficacy of antibiotic treatment in CF is improvement in lung function.  How do we assess whether antibiotics help in bronchiectasis?

Patients with bronchiectasis know when they are becoming unwell.  Usually they are aware that their sputum changes from being easy to cough up and clear or white, to being sticky and green.  Green sputum has been compared with white in the lab, and found to contain markers of inflammation (increased neutrophils (white blood cells) and increased myeloperoxidase, for example). My favourite point of Dr Bilton's talk was when she pronounced.....

"It is quite a good thing to make the sputum white from green."

The question, then, is how does one manage this. Between 15 and 44% of patients with bronchiectasis have Pseudomonas aeruginosa in their airways.  After a couple of courses of oral ciprofloxacin, the only oral antibiotic effective against that bug, usually that medication stops being quite so beneficial.  Do we have to admit our patients for intraveinous antibiotics at that point?  Or is there an alternative? 

The possibility of administering inhaled antibiotics - either nebulised or in powder form - in patients with bronchiectasis is appealing. This is done in CF, with clinical benefit.  The idea is that antibiotics can be delivered to where they are needed in very high concentrations, to overcome any partial antibiotic resistance and to minimise side effects. 

However, to date in bronchiectasis although such an approach has been demonstrated to greatly reduce bacterial concentration in sputum, and to reduce sputum quantity, no benefit has been demonstrated with regard to frequency of exacerbation or lung function, let alone survival.

There are no nebulised antibiotics licenced on the pharmaceutical benefits scheme for delivery in this way in this patient population in Australia.  Tobramycin and gentamicin, along with colistin, have been used in CF patients and spilled over into the population of patients with bronchiectasis.  Studies looking at tobramycin have demonstrated a benefit in clearing bacteria from the airways, and a beneficial clinical impact that is difficult to define.  Patients do feel better.  Tobramycin does have, however, have significant side effects in this group of patients.  One study of Dr Bilton's, published in Chest journal in 2006, demonstrated that ciprofloxaxin + nebulised tobramycin did have a beneficial impact compared with ciprofloxacin + placebo when given in exacerbations of bronchiectasis.  This benefit was, however, entirely overshadowed by the side effects of tobramycin. 

There are new aerosolised and powder form antibiotics in development.  Some of them will hopefully be of relevance to clinical practice within the next couple of years. These include liposomal ciprofloxacin and inhaled ciprofloxacin, liposomal amikackin and aztronam lysine.

Dr Bilton pointed out that the goal of use of these antibiotics will probably be to reduce frequence and severity of exacerbations, and to keep people out of hospital.  Although that's not a life-prolonging goal, admissions are extremely detrimental to quality of life, and also provide an opportunity for sharing bacteria.  Any treatment that significantly reduces the requirement for hospital admission is a worthy treatment.