Ceftaroline Restores Daptomycin Activity against Daptomycin-Nonsusceptible Vancomycin-Resistant Enterococcus faecium

@article{Sakoulas2013CeftarolineRD,
  title={Ceftaroline Restores Daptomycin Activity against Daptomycin-Nonsusceptible Vancomycin-Resistant Enterococcus faecium},
  author={George Sakoulas and Warren E. Rose and Poochit Nonejuie and Joshua Olson and Joe Pogliano and Romney M. Humphries and Victor Nizet},
  journal={Antimicrobial Agents and Chemotherapy},
  year={2013},
  volume={58},
  pages={1494 - 1500}
}
ABSTRACT 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… 

A combination of ceftaroline and daptomycin has synergistic and bactericidal activity in vitro against daptomycin nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA)

Daptomycin and ceftaroline combinations may be promising against persistent MRSA bacteremia in patients with methicillin-resistant Staphylococcus aureus who have failed conventional therapy.

Ceftobiprole and ampicillin increase daptomycin susceptibility of daptomycin-susceptible and -resistant VRE.

Ceftobiprole appears to offer a similar degree of synergistic activity to ampicillin when combined with daptomycin against VRE, and further research should explore the genetic and phenotypic qualities of strains that respond preferentially to ceftoiprole as opposed to ispicillin.

In Vitro Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci

Ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the liaFSR system, adding support to the growing body of evidence indicating that therapy combining daptomecin and ampicillin may be helpful in eradicating refractory VRE infections.

Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with β-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions

Combinations of DAP with AMP, CPT, or ERT demonstrated enhanced eradication and reduced potential for resistance, allowing de-escalation of the DAP dose and pave the way for testing these approaches in humans.

Fosfomycin Enhances the Activity of Daptomycin against Vancomycin-Resistant Enterococci in an In Vitro Pharmacokinetic-Pharmacodynamic Model

The combination of DAP plus FOF may provide improved killing against VRE (including DAP-resistant strains) through modulation of cell surface charge.

β-Lactam combinations with daptomycin provide synergy against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium.

The data support the potential use of daptomycin/BL combination therapy in infections caused by VRE and demonstrate that combination regimens, other than those involving cefazolin and cefotaxime, provide better kill compared with d aptomycin alone.

Whole-Genome Analyses of Enterococcus faecium Isolates with Diverse Daptomycin MICs

The presence of changes in 43 predicted proteins previously associated with DAP resistance in enterococci and staphylococci using the genomes of 19 E. faecium using DAP MICs above the susceptibility breakpoint suggests that genotypic information may be crucial to predict response to DAP plus β-lactam combinations.

β-Lactams Enhance Daptomycin Activity against Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium in In Vitro Pharmacokinetic/Pharmacodynamic Models

Compared to DAP alone, combination regimens provide better killing and prevent resistance, and clinical research involving DAP combinations is warranted.
...

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