Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients

Adv Drug Deliv Rev. 2015 May;85:7-23. doi: 10.1016/j.addr.2014.11.017. Epub 2014 Dec 2.

Abstract

Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms of biofilm formation and antimicrobial tolerance and resistance are reviewed. Potential anti-biofilm therapeutic targets such as weakening of biofilms by quorum-sensing inhibitors or antibiotic killing guided by pharmacokinetics and pharmacodynamics of antibiotics are presented. The vicious circle of adaptive evolution of the persisting bacteria imposes important therapeutic challenges and requires development of new drug delivery systems able to reach the different niches occupied by the bacteria in the lung of cystic fibrosis patients.

Keywords: Biofilm; Cystic fibrosis; Pseudomonas aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Biofilms / drug effects
  • Biofilms / growth & development*
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / microbiology*
  • Drug Resistance, Bacterial* / genetics
  • Gene Expression Regulation, Bacterial
  • Humans
  • Lung / microbiology*
  • Microscopy, Confocal
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / growth & development
  • Quorum Sensing / drug effects
  • Quorum Sensing / genetics
  • Respiratory Tract Infections / drug therapy
  • Respiratory Tract Infections / microbiology*

Substances

  • Anti-Bacterial Agents