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Antibiotic adjuvants: multicomponent anti-infective strategies

Published online by Cambridge University Press:  23 February 2011

Lindsay Kalan  and
Gerard D. Wright
Lindsay Kalan
Affiliation:
Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, McMaster University Hamilton, ON, Canada.
Gerard D. Wright*
Affiliation:
Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, McMaster University Hamilton, ON, Canada.
*
*Corresponding author: Gerard D. Wright, Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, McMaster University Hamilton, ON, Canada L8N 3Z5. E-mail: [email protected]
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Abstract

The unremitting emergence of multidrug-resistant bacterial pathogens highlights a matching need for new therapeutic options. For example, new carbapenemases such as KPC (class A Klebsiella pneumoniae) and NDM-1 (New Delhi metallo-β-lactamase 1) are surfacing, resulting in almost total resistance to β-lactam antibiotics. Furthermore, resistance is quickly disseminated, not only in the healthcare sector, but also within the community at large, because many resistance determinants are carried on mobile genetic elements readily shared among pathogens. The absence of new antibiotics has led to a growing reliance on older, more toxic drugs such as colistin, but resistance to these is already arising. One approach to combat this growing problem is the use of combination drug antibiotic adjuvant therapy, which potentiates the activity of antibiotics. Here, we review the current situation and discuss potential drug combinations that may increase the potency of antibiotics in the future. Adjuvant therapies include antibiotic combinations, synergy between antibiotics and nonantibiotics, inhibition of resistance and molecules that alter the physiology of antibiotic-insensitive cells, such as those in biofilms. We provide a rationale for these multicomponent strategies, highlighting current research and important considerations for their clinical use and pharmacological properties.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e5
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts

Pillai, S., Moellering, R.C. and Eliopoulos, G.M. (2005) Antimicrobial combinations. In Antibiotics in Laboratory Medicine (Lorian, V. ed.), Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
Torella, J.P., Chait, R. and Kishony, R. (2010) Optimal drug synergy in antimicrobial treatments. PLoS Computational Biology 6, e1000796Google Scholar
De Pascale, G. and Wright, G.D. (2010) Antibiotic resistance by enzyme inactivation: from mechanisms to solutions. Chembiochem 11, 1325-1334Google Scholar
Piddock, L.J. (2006) Multidrug-resistance efflux pumps – not just for resistance. Nature Reviews. Microbiology 4, 629-636Google Scholar