title: Effect of antibiotic co-administration on young and mature biofilms of cystic fibrosis clinical isolates: the importance of the biofilm model.
abstract: The prognosis of patients with cystic fibrosis (CF) has improved dramatically over the last three decades although the majority of patients still die in early adulthood. Infection with Pseudomonas aeruginosa has generally been associated with declining lung function and increased mortality in patients. This study aimed to investigate the in vitro activity of tobramycin/clarithromycin combination on biofilms of clinical isolates of P. aeruginosa, meticillin-susceptible and -resistant Staphylococcus aureus, and Burkholderia cepacia. First, the impact of antibiotic co-administration on biofilms at different stages of maturation, i.e. during early formation and on 24-h-old and 12-day-old biofilms, was compared. The 24-h-old biofilms were found to behave differently compared with those aged 12 days, which were more resistant to antibiotics. A kinetic study of antibiotic co-administration twice a day for 9 days on 12-day-old P. aeruginosa biofilms was then performed to simulate the effect of treatment of CF patients by inhaled tobramycin through aerosolisation (TOBI). The results obtained support a synergistic activity of tobramycin/clarithromycin combination on biofilms of P. aeruginosa PY02 and PA01, with a logarithmic bacterial decrease of 3.37 and 3.96, respectively. On the other hand, increased resistance to each of the antibacterial agents used alone was observed. This study highlights the importance of the biofilm stage for in vitro investigations and enabled the development of an in vitro model of mature biofilm that is more appropriate to mimic in vivo conditions in CF patients.
authors.affiliation: Pharmaceutical Microbiology Laboratory, Institute of Pharmacy, Université Libre de Bruxelles, CP 205/02, Boulevard du Triomphe, 1050 Brussels, Belgium. marie.tre-hardy@ulb.ac.be
authors.forename: Marie
authors.initials: M
authors.lastname: Tré-Hardy
authors.forename: Camille
authors.initials: C
authors.lastname: Macé
authors.forename: Naïma
authors.initials: N
authors.lastname: El Manssouri
authors.forename: Francis
authors.initials: F
authors.lastname: Vanderbist
authors.forename: Hamidou
authors.initials: H
authors.lastname: Traore
authors.forename: Michel Jean
authors.initials: MJ
authors.lastname: Devleeschouwer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D016956:Burkholderia cepacia / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D017291:Clarithromycin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000382:microbiology*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D013997:Time Factors; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D017291:Clarithromycin; D014031:Tobramycin