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2014 ; 35
(12
): 664-74
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Resistance-resistant antibiotics
#MMPMID25458541
Oldfield E
; Feng X
Trends Pharmacol Sci
2014[Dec]; 35
(12
): 664-74
PMID25458541
show ga
New antibiotics are needed because drug resistance is increasing while the
introduction of new antibiotics is decreasing. We discuss here six possible
approaches to develop 'resistance-resistant' antibiotics. First, multitarget
inhibitors in which a single compound inhibits more than one target may be easier
to develop than conventional combination therapies with two new drugs. Second,
inhibiting multiple targets in the same metabolic pathway is expected to be an
effective strategy owing to synergy. Third, discovering multiple-target
inhibitors should be possible by using sequential virtual screening. Fourth,
repurposing existing drugs can lead to combinations of multitarget therapeutics.
Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation
and boosting innate immunity may also lead to decreased susceptibility to
resistance. Although it is not possible to eliminate resistance, the approaches
reviewed here offer several possibilities for reducing the effects of mutations
and, in some cases, suggest that sensitivity to existing antibiotics may be
restored in otherwise drug-resistant organisms.
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