Daptomycin is effective for treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus epidermidis.
This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.
García-de-la-Mària
C
C
Microbiology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain.
Marco
F
F
Armero
Y
Y
Soy
D
D
Moreno
A
A
del Río
A
A
Almela
M
M
Cervera
C
C
Ninot
S
S
Falces
C
C
Mestres
C A
CA
Gatell
J M
JM
Jiménez de Anta
M T
MT
Miró
J M
JM
D000818:Animals; D017576:Daptomycin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004696:Endocarditis / Q000188:drug therapy*; D006020:Glycopeptides / Q000627:therapeutic use*; D006801:Humans; D016106:Methicillin Resistance / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000472:pathogenicity; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D006020:Glycopeptides; D014640:Vancomycin; D017576:Daptomycin