Antibiotic interactions that select against resistance

Remy Chait, Allison Craney and Roy Kishony ()
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Remy Chait: Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Allison Craney: Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Roy Kishony: Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

Nature, 2007, vol. 446, issue 7136, 668-671

Abstract: Resistance movement It's the 'catch-22' of antimicrobial treatments: the use of any drug inherently generates selection for resistant mutants. But a new study has come up with a result that holds out the tantalizing prospect that it might be possible to bias selection against resistance. Sensitive growth rate measurements and competition assays between drug-sensitive and drug-resistant strains were performed for a range of combined drug dosages. At certain sublethal concentrations, a mixture of doxycycline and ciprofloxacin preferentially selected for wild-type Escherichia coli in favour of a resistant strain in a lab culture. This paradox can be understood theoretically by a simple geometrical argument. Sublethal concentrations, of course, are not clinically relevant, but this work does suggest that further research might lead to antimicrobial combinations with improved selection against resistance.

Date: 2007
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DOI: 10.1038/nature05685

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