Correlation between mutations in liaFSR of enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints

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dc.contributor.authorMunita, José
dc.contributor.authorPanesso, Diana
dc.contributor.authorDiaz, Lorena
dc.contributor.authorTran, Truc
dc.contributor.authorReyes, Jinnethe
dc.contributor.authorWanger, Audrey
dc.contributor.authorMurray, Barbara
dc.contributor.authorArias, Cesar
dc.date.accessioned2017-05-29T15:52:51Z
dc.date.available2017-05-29T15:52:51Z
dc.date.issued2012
dc.description.abstractMutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 μg/ml (the DAP breakpoint is 4 μg/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 μg/ml might harbor mutations in liaFSR, we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 μg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 μg/ml), 5 had mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC of ≤2 μg/ml harbored mutations in this system (P < 0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of ≥16 μg/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated.
dc.format.extent6
dc.identifier.citationAntimicrobial Agents and Chemotherapy, 2012 Aug;56(8):4354-9
dc.identifier.urihttp://hdl.handle.net/11447/1352
dc.identifier.urihttp://dx.doi.org/10.1128/AAC.00509-12
dc.language.isoen_US
dc.publisherAmerican Society for Microbiology
dc.subjectAnti-Bacterial Agents/pharmacology
dc.subjectDaptomycin/pharmacology
dc.subjectDrug Resistance, Bacterial/genetics
dc.subjectEnterococcus faecium/drug effects
dc.subjectVancomycin/pharmacology
dc.titleCorrelation between mutations in liaFSR of enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints
dc.typeArtículo

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