PMID- 24366742
OWN - NLM
STAT- MEDLINE
DCOM- 20141028
LR  - 20231213
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 58
IP  - 3
DP  - 2014
TI  - Ceftaroline restores daptomycin activity against daptomycin-nonsusceptible 
      vancomycin-resistant Enterococcus faecium.
PG  - 1494-500
LID - 10.1128/AAC.02274-13 [doi]
AB  - Daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium (VRE) strains 
      are a formidable emerging threat to patients with comorbidities, leaving few 
      therapeutic options in cases of severe invasive infections. Using a previously 
      characterized isogenic pair of VRE strains from the same patient differing in 
      their daptomycin susceptibilities (Etest MICs of 0.38 mg/liter and 10 mg/liter), 
      we examined the effect of ceftaroline, ceftriaxone, and ampicillin on membrane 
      fluidity and susceptibility of VRE to surface binding and killing by daptomycin 
      and human cathelicidin antimicrobial peptide LL37. Synergy was noted in vitro 
      between daptomycin, ampicillin, and ceftaroline for the daptomycin-susceptible 
      VRE strain, but only ceftaroline showed synergy against the 
      daptomycin-nonsusceptible VRE strain ( approximately 2 log10 CFU reduction at 24 h). 
      Ceftaroline cotreatment increased daptomycin surface binding with an associated 
      increase in membrane fluidity and an increase in the net negative surface charge 
      of the bacteria as evidenced by increased poly-l-lysine binding. Consistent with 
      the observed biophysical changes, ceftaroline resulted in increased binding and 
      killing of daptomycin-nonsusceptible VRE by human cathelicidin LL37. Using a pair 
      of daptomycin-susceptible/nonsusceptible VRE strains, we noted that VRE is 
      ceftaroline resistant, yet ceftaroline confers significant effects on growth rate 
      as well as biophysical changes on the cell surface of VRE that can potentiate the 
      activity of daptomycin and innate cationic host defense peptides, such as 
      cathelicidin. Although limited to just 2 strains, these finding suggest that 
      additional in vivo and in vitro studies need to be done to explore the 
      possibility of using ceftaroline as adjunctive anti-VRE therapy.
FAU - Sakoulas, George
AU  - Sakoulas G
AD  - University of California San Diego School of Medicine, La Jolla, California, USA.
FAU - Rose, Warren
AU  - Rose W
FAU - Nonejuie, Poochit
AU  - Nonejuie P
FAU - Olson, Joshua
AU  - Olson J
FAU - Pogliano, Joseph
AU  - Pogliano J
FAU - Humphries, Romney
AU  - Humphries R
FAU - Nizet, Victor
AU  - Nizet V
LA  - eng
GR  - R37 AI052453/AI/NIAID NIH HHS/United States
GR  - U54 HD071600-01 09/26/2011-06/30/2016/HD/NICHD NIH HHS/United States
GR  - R01GM073898/GM/NIGMS NIH HHS/United States
GR  - AI057153/AI/NIAID NIH HHS/United States
GR  - R01 AI052453/AI/NIAID NIH HHS/United States
GR  - R01 GM073898/GM/NIGMS NIH HHS/United States
GR  - U54 AI057153/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131223
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cephalosporins)
RN  - NWQ5N31VKK (Daptomycin)
SB  - IM
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Cell Wall/drug effects
MH  - Cephalosporins/*pharmacology
MH  - Daptomycin/*pharmacology
MH  - Drug Synergism
MH  - Enterococcus faecium/*drug effects
MH  - In Vitro Techniques
MH  - Membrane Fluidity/drug effects
MH  - Microbial Sensitivity Tests
MH  - Vancomycin Resistance/*drug effects
MH  - Ceftaroline
PMC - PMC3957885
EDAT- 2013/12/25 06:00
MHDA- 2014/10/29 06:00
PMCR- 2014/09/01
CRDT- 2013/12/25 06:00
PHST- 2013/12/25 06:00 [entrez]
PHST- 2013/12/25 06:00 [pubmed]
PHST- 2014/10/29 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - AAC.02274-13 [pii]
AID - 02274-13 [pii]
AID - 10.1128/AAC.02274-13 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2014;58(3):1494-500. doi: 10.1128/AAC.02274-13. Epub 
      2013 Dec 23.