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Antimicrobial Agents and Chemotherapy, December 2008, p. 4344-4350, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.00574-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bacteriophage Therapy and the Mutant Selection Window{triangledown}

Benjamin J. Cairns* and Robert J. H. Payne

School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, United Kingdom

Received 2 May 2008/ Returned for modification 3 August 2008/ Accepted 28 September 2008

We use kinetic models to investigate how to design antimicrobial phage therapies to minimize emergence of resistant bacteria. We do this by modifying the "mutant selection window" hypothesis in a way that accounts for the ongoing self-replication of the phage. We show that components of combination phage therapies need to be appropriately matched if treatment is to avoid the emergence of resistant bacteria. Matching of components is more easily achieved when phage dosages are high enough that ongoing phage replication is not needed for the clearance of the bacteria. Theoretical predictions such as ours need to be tested experimentally if applications of phage therapy are to avoid the problems of widespread resistance that have beset chemical antibiotics.

* Corresponding author. Present address: Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. Phone: 44 1865 289673. Fax: 44 1865 289610. E-mail: ben.cairns{at}ceu.ox.ac.uk

{triangledown} Published ahead of print on 6 October 2008.

Antimicrobial Agents and Chemotherapy, December 2008, p. 4344-4350, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.00574-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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