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Journal of Antimicrobial Chemotherapy (1996) 38, 757-769
© 1996 The British Society for Antimicrobial Chemotherapy

other

Mathematical model of ß-lactam penetration into a biofilm of Pseudomonas aeruginosa while undergoing simultaneous inactivation by released ß-lactamases

George H. Dibdina,*, Stephen J. Assindera, Wright W. Nicholsb and Peter A. Lambertc

aMedical Research Council Dental Group, University of Bristol Lower Maudlin Street, Bristol BS1 2LY bZeneca Pharmaceuticals, Mereside, Aston University Birmingham, UK cDepartment of Pharmaceutical and Biological Sciences, Aston University Birmingham, UK

Received 22 December 1995; returned 27 March 1996; accepted 31 May 1996

*Tel: +44-(ll7)-928-4332; Fax: +44-(117)-928-4778; Email: George.Dibdin@Bristol.ac.uk

We present a mathematical model that describes penetration of an antibacterial agent into a bacterial biofilm and, in particular, the penetration of a ß-lactam compound into a biofilm of Pseudomonas aeruginosa. As well as dealing with this penetration, and the consequent bacterial lysis, the model considered diffusion of the released ß-lactamases in the extracellular space and the consequent inactivation there of further incoming antibiotic; it also allowed for any chosen fraction of the total ß-lactamase to be permanently accessible to exogenous substrate. The modelling scheme was validated against analytical solutions under appropriately simplified conditions. Using published experimental data we show here that lysis of cells in the surface layers of a film could have an important protective effect on the viability of underlying bacteria, especially in thick biofilms.


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