Document Detail

Emergence and spread of antibiotic resistance following exposure to antibiotics.
MedLine Citation:
PMID:  21722146     Owner:  NLM     Status:  Publisher    
Within a susceptible wild-type population, a small fraction of cells, even <10(-9) , is not affected when challenged by an antimicrobial agent. This subpopulation has mutations that impede antimicrobial action allowing their selection during clinical treatment. Emergence of resistance occurs in the frame of a selective compartment termed mutant selection window (MSW). The lower margin corresponds to the MIC of the susceptible cells, whereas the upper boundary, named mutant prevention concentration (MPC), restricts the growth of the whole population, including that of the resistant mutants. By combining pharmacokinetic/pharmacodynamic concepts and an MPC strategy, the selection of resistant mutants can be limited. Early treatment avoiding an increase of the inoculum size as well as a regimen restricting the time within the MSW can reduce the probability of emergence of the resistant mutants. Physiological and, possibly, genetic adaptation in biofilms and a high proportion of mutator clones that may arise during chronic infections influence the emergence of resistant mutants. Moreover, a resistant population can emerge in a specific selective compartment after acquiring a resistance trait by horizontal gene transfer, but this may also be avoided to some extent when the MPC is reached. Known linkage between antimicrobial use and resistance should encourage actions for the design of antimicrobial treatment regimens that minimize the emergence of resistance.
Rafael Cantón; María-Isabel Morosini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-1
Journal Detail:
Title:  FEMS microbiology reviews     Volume:  -     ISSN:  1574-6976     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8902526     Medline TA:  FEMS Microbiol Rev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Servicio de Microbiología and CIBER en Epidemiología y Salud Pública (CIBERESP), Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain Unidad de Resistencia a Antibióticos y Virulencia Bacteriana Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
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