Therapeutic possibilities for diffuse panbronchiolitis

Abstract

Diffuse panbronchiolitis can be thought of as one of the biofilm diseases of which cystic fibrosis is another example. The patient often has persistent infection with Pseudomonas aeruginosa and, in 1982, the survival rate to 5 years in these patients was only 37%. Recently, the prognosis of these patients has remarkably improved by using long-term treatment with 14-membered macrolides. However, the reason for the effect of macrolides in these patients is still obscure. To try to understand this pneumonia, some experiments were performed to assess the effect of macrolides on P. aeruginosa biofilm. An in vitro biofilm of P. aeruginosa was prepared on Teflon after 6 days' incubation and the effects of antibiotics on the biofilm were assessed. Floating, but not biofilm bacteria were killed by meropenem, ciprofloxacin, tosufloxacin and cefoperaxone. Ciprofloxacin with either azithromycin or clarithromycin killed bacteria within the biofilm, whereas ciprofloxacin with clindamycin, josamycin or other 16-membered macrolides was ineffective. Clarithromycin destroyed the biofilm, releasing the bacteria into the medium. The ability of P. aeruginosa to adhere to murine tracheal cells was also reduced by clarithromycin. These kinds of macrolides may have some sort of permeability effect on the biofilm surface and this may bear some relation to the good clinical performance of macrolides in diffuse panbronchiolitis.