There is considerable interest in the use of
azithromycin for the treatment of
lung disease in patients with
cystic fibrosis (CF). Although its mechanism of action as an inhibitor of
bacterial protein synthesis has been well-established, it is less clear how
azithromycin ameliorates the
lung disease associated with Pseudomonas aeruginosa, which is considered to be resistant to the
drug. We tested the effects of
azithromycin on clinical isolates (CIs) from CF patients and compared them with laboratory reference strains to establish how this
drug might interfere with the production of bacterial
virulence factors that are relevant to the pathogenesis of airway disease in CF patients.
Azithromycin inhibited P aeruginosa PAO1
protein synthesis by 80%, inhibiting bacterial growth and the expression of immunostimulatory exoproducts such as
pyocyanin, as well as the gene products necessary for biofilm formation. In contrast, the effects of
azithromycin on CIs of P aeruginosa were much more variable, due in large part to their slow growth and limited exoproduct expression. Culture supernatants for two of three clinical strains induced appreciable CXCL8 expression from cultured epithelial cells.
Azithromycin treatment of the organisms inhibited 65 to 70% of this induction;
azithromycin had no direct effect on the ability of either normal cells or CF epithelial cells to produce CXCL8.
Azithromycin does decrease the P aeruginosa synthesis of immunostimulatory exoproducts and is likely to be most effective against planktonic, actively growing bacteria. This effect is less predictable against CIs than the prototypic strain PAO1.