New in vitro model to study the effect of human simulated antibiotic concentrations on bacterial biofilms.
A new in vitro pharmacokinetic/pharmacodynamic simulator for bacterial biofilms utilizing flow cell technology and confocal laser scanning microscopy is described. The device has the ability to simulate the changing antibiotic concentrations in humans associated with intravenous dosing on bacterial biofilms grown under continuous culture conditions. The free drug concentrations of a single 2-g meropenem intravenous bolus dose and first-order elimination utilizing a half-life of 0.895 h (elimination rate constant, 0.776 h(-1)) were simulated. The antibacterial activity of meropenem against biofilms of Pseudomonas aeruginosa PAO1 and three clinical strains isolated from patients with cystic fibrosis was investigated. Additionally, the effect of meropenem on PAO1 biofilms cultured for 24 h versus that on biofilms cultured for 72 h was examined. Using confocal laser scanning microscopy, rapid biofilm killing was observed in the first hour of the dosing interval for all biofilms. However, for PAO1 biofilms cultured for 72 h, only bacterial subpopulations at the periphery of the biofilm were affected, with subpopulations at the substratum remaining viable, even at the conclusion of the dosing interval. The described model is a novel method to investigate antimicrobial killing of bacterial biofilms using human simulated concentrations.
Department of Civil and Environmental Engineering, Stanford University, Stanford, California, USA.
Janus A J
JA
Haagensen
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco School of Pharmacy, San Francisco, California, USA.
Davide
D
Verotta
Department of Clinical Pharmacy, University of California San Francisco School of Pharmacy, San Francisco, California, USA.
Liusheng
L
Huang
Department of Civil and Environmental Engineering, Stanford University, Stanford, California, USA.
Alfred
A
Spormann
Department of Clinical Pharmacy, University of California San Francisco School of Pharmacy, San Francisco, California, USA yangk@pharmacy.ucsf.edu.
Katherine
K
Yang
D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects*; D003550:Cystic Fibrosis / Q000382:microbiology; D005434:Flow Cytometry; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013845:Thienamycins / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem