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Activity of serum concentrations of daptomycin vs. vancomycin against vancomycin-susceptible and resistant Enterococcus faecium in the presence of albumin physiological concentrations: an in vitro pharmacodynamic simulation

  • L. Alou
  • L. Aguilar
  • M. J. Giménez
  • M. Torrico
  • D. Sevillano
Brief Report

Killing curves with daptomycin (56 μg/ml, the Cmax after 4 mg/kg) in media containing albumin physiological concentrations showed bactericidal activity against Enterococcus faecium, but due to its high protein binding (91.7%), cidal activity was delayed when compared to that in media without albumin [1]. This study explores the activity over 24 h of simulated serum concentrations of daptomycin (after 6 mg/kg od regimen) vs. vancomycin (1,000 mg bid regimen) against two vancomycin-susceptible but tolerant and one resistant E. faecium in an in vitro pharmacodynamic device using media containing albumin physiological concentrations. A one-compartment dynamic model was used to expose bacteria to changing study drug concentrations [2] using Mueller Hinton broth supplemented with albumin (4 g/dl). In daptomycin simulations, media was calcium-adjusted by adding 100 μg/ml of Ca2+ [3]. Albumin concentrations were determined by the bromcresol green method, ionized calcium concentrations were...

Keywords

Vancomycin Daptomycin Initial Inoculum Bromcresol Bromcresol Green 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

To N. González for her technical assistance and J. Prieto for his critical review of the manuscript.

This study was supported by an unrestricted grant from Novartis Farmacéutica S.A., Barcelona, Spain.

References

  1. 1.
    Cafini F, Aguilar L, González N, Giménez MJ, Torrico M, Alou L, Sevillano D, Vallejo P, Prieto J (2007) In vitro effect of the presence of human albumin or human serum on the bactericidal activity of daptomycin against strains with the main resistance phenotypes in Gram-positives. J Antimicrob Chemother 59:1185–1189PubMedCrossRefGoogle Scholar
  2. 2.
    Cha R, Grucz RG Jr, Rybak MJ (2003) Daptomycin dose–effect relationship against resistant gram-positive organisms. Antimicrob Agents Chemother 47:1598–1603PubMedCrossRefGoogle Scholar
  3. 3.
    Hanberger H, Nilsson LE, Maller R, Isaksson B (1991) Pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis and Staphylococcus aureus demonstrated by studies of initial killing and postantibiotic effect and influence of Ca2+ and albumin on these drugs. Antimicrob Agents Chemother 35:1710–1716PubMedGoogle Scholar
  4. 4.
    Rybak MJ, Bailey EM, Lamp KC, Kaatz GW (1992) Pharmacokinetics and bactericidal rates of daptomycin and vancomycin in intravenous drug abusers being treated for gram-positive endocarditis and bacteremia. Antimicrob Agents Chemother 36:1109–1114PubMedGoogle Scholar
  5. 5.
    Dvorchik BH, Brazier D, DeBruin MF, Arbeit RD (2003) Daptomycin pharmacokinetics and safety following administration of escalating doses once daily to healthy subjects. Antimicrob Agents Chemother 47:1318–1323PubMedCrossRefGoogle Scholar
  6. 6.
    Sader HS, Watters AA, Fritsche TR, Jones RN (2007) Daptomycin antimicrobial activity tested against methicillin-resistant staphylococci and vancomycin-resistant enterococci isolated in European medical centers (2005). BMC Infect Dis 7:29PubMedCrossRefGoogle Scholar
  7. 7.
    Saribas S, Bagdatli Y (2004) Vancomycin tolerance in enterococci. Chemotherapy 50:250–254PubMedCrossRefGoogle Scholar
  8. 8.
    Moellering RC, Eliopoulos GM (2005) Principles of anti-infective therapy. In: Mandell GL, Bennett JE, Dolin R (eds) Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 6th edn. Elsevier Churchill Livingstone, Philadelphia, pp 242–253Google Scholar
  9. 9.
    Alou L, Giménez MJ, Sevillano D, Aguilar L, Cafini F, Echeverría O, Pérez-Trallero E, Prieto J (2006) A pharmacodynamic approach to antimicrobial activity in serum and epithelial lining fluid against in vivo-selected Streptococcus pneumoniae mutants and association with clinical failure in pneumonia. J Antimicrob Chemother 58:349–358PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • L. Alou
    • 1
  • L. Aguilar
    • 1
  • M. J. Giménez
    • 1
  • M. Torrico
    • 1
  • D. Sevillano
    • 1
  1. 1.Microbiology Department, School of MedicineUniversity ComplutenseMadridSpain

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