Comparison of ceftaroline fosamil, daptomycin and tigecycline in an experimental rabbit endocarditis model caused by methicillin-susceptible, methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus

Université de Nantes, Nantes Atlantique Universités, Thérapeutiques Cliniques et Expérimentales des Infections, EA3826, F-44000 Nantes, France.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.34). 03/2011; 66(4):863-6. DOI: 10.1093/jac/dkr019
Source: PubMed

ABSTRACT The aim of this study was to compare the in vivo activities of the new antistaphylococcal drugs ceftaroline fosamil, daptomycin and tigecycline at projected human therapeutic doses against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains in a rabbit model of endocarditis.
The efficacy of therapeutic regimens in our model was evaluated following 4 days of treatment by determining colony counts of infected vegetations. Emergence of resistant variants during therapy was assessed.
Using this model of infective endocarditis, ceftaroline fosamil and daptomycin demonstrated high bactericidal in vivo activity (reduction of >5 log(10) cfu/g of vegetation) after a 4 day treatment against MSSA, MRSA and GISA strains. Both drugs were more efficacious than tigecycline, which showed moderate activity but failed to exhibit a bactericidal effect. Ceftaroline was superior to daptomycin in terms of sterilization of the vegetations. Emergence of resistant variants during daptomycin therapy was observed in two animals (one in the MSSA group and one in the MRSA group) but was not observed in ceftaroline- or tigecycline-treated animals.
The novel β-lactam agent ceftaroline fosamil was the most active bactericidal drug in this model and is a promising therapeutic option for the treatment of severe S. aureus infections, including those caused by MRSA and GISA strains.

  • [Show abstract] [Hide abstract]
    ABSTRACT: We compared the efficacy of daptomycin (doses equivalent to 8-10mg/kg/d in humans) and cloxacillin alone, and the cloxacillin-rifampin and -daptomycin combinations using a tissue cage MSSA infection model. Monotherapies were less effective than combinations (P<0.05) and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin, and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of PJI.
    Antimicrobial Agents and Chemotherapy 06/2014; 58(9). DOI:10.1128/AAC.02681-14 · 4.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ceftaroline fosamil is a new subclass of cephalosporins with high intrinsic activity against various multi-resistant Gram-positive organisms, including Staphylococcus aureus and Streptococcus pneumoniae, as well as against Enterobacteriaceae causing bacteremia and infective endocarditis. Because of its pharmacokinetic profile and pharmacodynamic characteristics, this drug is a good therapeutic option for these infections. Experimental studies have shown good clinical efficacy for the treatment of endocarditis caused by S. aureus, regardless of their sensitivity to methicillin or vancomycin. Clinical experience is limited, although clinical trials and case series have reported a favorable clinical response in patients with bacteremia associated with skin and soft tissue infections, pneumonia, or infective endocarditis. Future studies should define more precisely the role of this new antibiotic in the treatment of these infections.
    Enfermedades Infecciosas y Microbiología Clínica 03/2014; 32:44–53. DOI:10.1016/S0213-005X(14)70158-2 · 1.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.
    12/2013; 2(2):95-110. DOI:10.1007/s40121-013-0010-x


Available from
Jun 3, 2014