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Therapeutic possibilities for diffuse panbronchiolitis
H Kobayashi1, N Ohgaki, H Takeda
1Kyorin University School Medicine, Tokyo, Japan.
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.
Insights
14-membered macrolides, like clarithromycin, effectively treat diffuse panbronchiolitis by disrupting Pseudomonas aeruginosa biofilms. This improves patient outcomes by targeting persistent bacterial infections.
Area of Science:
- Microbiology
- Pulmonology
- Pharmacology
Background:
- Diffuse panbronchiolitis is a biofilm disease associated with persistent Pseudomonas aeruginosa infections.
- Historically, 5-year survival rates were low (37% in 1982), but have improved with macrolide treatment.
- The mechanism of macrolide efficacy in diffuse panbronchiolitis remains unclear.
Purpose of the Study:
- To investigate the effect of macrolides on Pseudomonas aeruginosa biofilms.
- To understand the mechanism behind macrolide's clinical success in diffuse panbronchiolitis.
Main Methods:
- An in vitro model of P. aeruginosa biofilm was established on Teflon.
- The efficacy of various antibiotics, including macrolides, against the biofilm was assessed.
- P. aeruginosa adherence to murine tracheal cells was evaluated after clarithromycin treatment.
Main Results:
- Meropenem, ciprofloxacin, tosufloxacin, and cefoperaxone were ineffective against biofilm bacteria.
- Ciprofloxacin combined with azithromycin or clarithromycin eradicated bacteria within the biofilm.
- Clarithromycin disrupted the biofilm structure and reduced bacterial adherence to host cells.
Conclusions:
- 14-membered macrolides, particularly clarithromycin, demonstrate potent anti-biofilm activity against P. aeruginosa.
- Macrolides may exert their beneficial effects in diffuse panbronchiolitis by increasing biofilm permeability.
- These findings provide a potential explanation for the clinical effectiveness of macrolides in treating this condition.
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