PMID- 17369277
OWN - NLM
STAT- MEDLINE
DCOM- 20080102
LR  - 20131121
IS  - 0305-7453 (Print)
IS  - 0305-7453 (Linking)
VI  - 59
IP  - 5
DP  - 2007 May
TI  - Daptomycin-reversible rifampicin resistance in vancomycin-resistant Enterococcus 
      faecium.
PG  - 1017-20
AB  - OBJECTIVES: In a previous study, we observed marked synergy between daptomycin 
      and rifampicin against 73% of rifampicin-resistant, vancomycin-resistant 
      Enterococcus faecium (VRE), with approximately 100-fold reductions in rifampicin 
      MICs observed at one-eighth to one-fourth daptomycin MIC. The purpose of this 
      study was to determine whether the synergy between daptomycin and rifampicin 
      could be explained by enhanced entry of rifampicin into the cell or was related 
      to amino acid substitutions in the rifampicin-binding site in the beta subunit 
      (rpo beta) of the RNA polymerase. METHODS: We developed a bioassay for rifampicin 
      to measure cell-bound rifampicin levels as well as metabolic inactivation of 
      rifampicin. In addition, we sequenced the rifampicin-binding site in the rpo beta 
      of VRE strains with and without synergy between daptomycin and rifampicin. 
      RESULTS: Cell-bound rifampicin levels were the same in rifampicin-susceptible VRE 
      as in rifampicin-resistant VRE showing daptomycin synergy and were not affected 
      by the presence of daptomycin. In contrast, rifampicin-resistant VRE without 
      daptomycin synergy had undetectable cell-bound rifampicin. Sequencing the rpo 
      beta rifampicin-binding site revealed that the synergistic strains had the same 
      sequence as rifampicin-susceptible wild-type E. faecium. The daptomycin 
      synergy-resistant strains all had mutations in known rifampicin-binding sites. 
      CONCLUSIONS: Daptomycin is able to reverse rifampicin resistance in some strains 
      of VRE, but the mechanism could not be explained by an effect of daptomycin on 
      entry of rifampicin into or transport out of the cell, by inactivation of 
      rifampicin or by mutation involving the rifampicin-binding site.
FAU - Rand, Kenneth H
AU  - Rand KH
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida, Gainesville, FL 32610, USA. rand@pathology.ufl.edu
FAU - Houck, Herbert J
AU  - Houck HJ
FAU - Silverman, Jared A
AU  - Silverman JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070316
PL  - England
TA  - J Antimicrob Chemother
JT  - The Journal of antimicrobial chemotherapy
JID - 7513617
RN  - 0 (Anti-Bacterial Agents)
RN  - 6Q205EH1VU (Vancomycin)
RN  - EC 2.7.7.6 (DNA-Directed RNA Polymerases)
RN  - NWQ5N31VKK (Daptomycin)
RN  - VJT6J7R4TR (Rifampin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Anti-Bacterial Agents/*pharmacology
MH  - DNA-Directed RNA Polymerases/metabolism
MH  - Daptomycin/*pharmacology
MH  - *Drug Resistance, Multiple, Bacterial
MH  - Enterococcus faecium/*drug effects/metabolism
MH  - Molecular Sequence Data
MH  - Rifampin/metabolism/*pharmacology
MH  - Vancomycin/pharmacology
MH  - *Vancomycin Resistance
EDAT- 2007/03/21 09:00
MHDA- 2008/01/03 09:00
CRDT- 2007/03/21 09:00
PHST- 2007/03/21 09:00 [pubmed]
PHST- 2008/01/03 09:00 [medline]
PHST- 2007/03/21 09:00 [entrez]
AID - dkm045 [pii]
AID - 10.1093/jac/dkm045 [doi]
PST - ppublish
SO  - J Antimicrob Chemother. 2007 May;59(5):1017-20. doi: 10.1093/jac/dkm045. Epub 
      2007 Mar 16.