HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Evaluation of daptomycin treatment of Staphylococcus aureus bacterial endocarditis: an in vitro and in vivo simulation using historical and current dosing strategies.

AbstractOBJECTIVES:
A failure to daptomycin therapy and subsequent emergence of a daptomycin non-susceptible isolate occurred during the 1990 clinical investigation of daptomycin for the treatment of Staphylococcus aureus bacteraemia and endocarditis. We attempted to determine if this occurrence was reproducible in vitro and if it could be prevented by various daptomycin dosing strategies.
METHODS:
The daptomycin susceptible parent strain (SA-675) and the subsequent non-susceptible derivative (SA-684) were evaluated. In the rabbit endocarditis model, daptomycin 3 mg/kg every 8 h for 4 days was administered to simulate the study patient's pharmacokinetic exposure. Daptomycin doses of 1.5 and 3 mg/kg every 12 h and 6 and 10 mg/kg every 24 and 48 h were simulated in the in vitro model with simulated endocardial vegetations (SEVs).
RESULTS:
Daptomycin significantly reduced bacterial counts of SA-675 in rabbits, but one in 10(5)-10(6) organisms from vegetations of one animal had an 8-fold increase in MIC. Daptomycin 1.5 mg/kg every 12 h in the in vitro model demonstrated no activity against either strain; reduced susceptibility emerged in SA-675 (4-fold increase in MIC). Bactericidal activity was noted with 6 and 10 mg/kg dosing against SA-675 with no resistance detected. The activity of the 6 mg/kg regimen was reduced against SA-684 but significantly improved activity was noted with 10 mg/kg daily.
CONCLUSIONS:
The emergence of resistance was successfully recreated at suboptimal dosing regimens while the current recommended regimen of 6 mg/kg/day prevented the emergence of non-susceptible mutants. Daptomycin 10 mg/kg/day demonstrated even more enhanced killing. Further investigation with daptomycin 10 mg/kg is warranted.
AuthorsWarren E Rose, Michael J Rybak, Glenn W Kaatz
JournalThe Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 60 Issue 2 Pg. 334-40 (Aug 2007) ISSN: 0305-7453 [Print] England
PMID17540670 (Publication Type: Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Culture Media
  • Indicators and Reagents
  • Daptomycin
Topics
  • Animals
  • Anti-Bacterial Agents (administration & dosage, pharmacokinetics, therapeutic use)
  • Area Under Curve
  • Colony Count, Microbial
  • Culture Media
  • Daptomycin (administration & dosage, pharmacokinetics, therapeutic use)
  • Drug Resistance, Bacterial
  • Endocarditis, Bacterial (drug therapy, microbiology)
  • Half-Life
  • Humans
  • Indicators and Reagents
  • Male
  • Microbial Sensitivity Tests
  • Rabbits
  • Staphylococcal Infections (drug therapy, microbiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: