Skip Navigation



JAC Advance Access published online on April 5, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm078
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
59/6/1185    most recent
dkm078v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Cafini, F.
Right arrow Articles by Prieto, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cafini, F.
Right arrow Articles by Prieto, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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

F. Cafini, L. Aguilar, N. González, M. J. Giménez, M. Torrico, L. Alou, D. Sevillano, P. Vallejo and J. Prieto*

Microbiology Department, School of Medicine, Universidad Complutense, Avda. Complutense s/n, 28040 Madrid, Spain

Received 15 December 2006; returned 8 February 2007; revised 15 February 2007; accepted 22 February 2007

* Corresponding author. Tel: +34-91-3941508; Fax: +34-91-3941511; E-mail: jprieto{at}med.ucm.es

Objectives: Bactericidal activity depends on antibiotic–bacteria couples, resistance phenotype and theoretically on protein binding. This work explores the influence of protein binding on the bactericidal activity of two antibiotics, daptomycin versus vancomycin, that exhibit, respectively, different Cmax (56 versus 25.5 mg/L), protein binding (91.7% versus 36.9%) and thus theoretical free-drug fractions (4.7 versus 16.1 mg/L).

Methods: The effect of the presence of physiological concentrations of human albumin (4 g/dL) or human serum (90%) on the bactericidal activity of daptomycin was studied against Gram-positive isolates with troublesome resistance phenotypes [multidrug-resistant Streptococcus pneumoniae (MDRSP), methicillin-resistant Staphylococcus aureus (MRSA), heterogeneous vancomycin-intermediate MRSA (MRSA-hVI) and vancomycin-resistant Enterococcus faecium]. Killing curves (final inocula of ~107 cfu/mL) were performed using daptomycin and vancomycin concentrations similar to the Cmax obtained in serum.

Results: Daptomycin was rapidly bactericidal (≥3 log10 initial inocula reduction) against S. pneumoniae and S. aureus, regardless of the strain tested or the presence of albumin or human serum (that slightly delayed bactericidal activity). Against vancomycin-susceptible or -resistant enterococci, daptomycin exhibited rapid bactericidal activity, delayed to 8 and 24 h, respectively, by human albumin. Vancomycin exhibited much slower bactericidal activity against MDRSP and methicillin-susceptible or -resistant S. aureus, but was never bactericidal against MRSA-hVI and vancomycin-susceptible or -resistant E. faecium.

Conclusions: Daptomycin exhibited rapid bactericidal activity against the strains of the three Gram-positive species tested, regardless of resistance phenotype or the presence of physiological concentrations of albumin.

Key Words: protein binding , killing curves , enterococci , streptococci , staphylococci


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
L. Alou, M.-J. Gimenez, F. Cafini, L. Aguilar, D. Sevillano, N. Gonzalez, M. Torrico, J. Prieto, C. Garcia-Rey, and N. Garcia-Escribano
In vitro effect of physiological concentrations of human albumin on the antibacterial activity of tigecycline
J. Antimicrob. Chemother., December 1, 2009; 64(6): 1230 - 1233.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
K. L. LaPlante and S. Woodmansee
Activities of Daptomycin and Vancomycin Alone and in Combination with Rifampin and Gentamicin against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Isolates in an Experimental Model of Endocarditis
Antimicrob. Agents Chemother., September 1, 2009; 53(9): 3880 - 3886.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
N. Gonzalez, L. Aguilar, L. Alou, M.-J. Gimenez, D. Sevillano, M. Torrico, F. Cafini, P. Coronel, and J. Prieto
Influence of different resistance traits on the competitive growth of Haemophilus influenzae in antibiotic-free medium and selection of resistant populations by different {beta}-lactams: an in vitro pharmacodynamic approach
J. Antimicrob. Chemother., June 1, 2009; 63(6): 1215 - 1222.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
G. A. McKay, S. Beaulieu, F. F. Arhin, A. Belley, I. Sarmiento, T. Parr Jr, and G. Moeck
Time-kill kinetics of oritavancin and comparator agents against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium
J. Antimicrob. Chemother., June 1, 2009; 63(6): 1191 - 1199.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. Schmidt, K. Rock, M. Sahre, O. Burkhardt, M. Brunner, M. T. Lobmeyer, and H. Derendorf
Effect of Protein Binding on the Pharmacological Activity of Highly Bound Antibiotics
Antimicrob. Agents Chemother., November 1, 2008; 52(11): 3994 - 4000.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
M. Torrico, L. Aguilar, N. Gonzalez, M. J. Gimenez, O. Echeverria, F. Cafini, D. Sevillano, L. Alou, P. Coronel, and J. Prieto
Influence of TEM-1 {beta}-Lactamase on the Pharmacodynamic Activity of Simulated Total versus Free-Drug Serum Concentrations of Cefditoren (400 Milligrams) versus Amoxicillin-Clavulanic Acid (2,000/125 Milligrams) against Haemophilus influenzae Strains Exhibiting an N526K Mutation in the ftsI Gene
Antimicrob. Agents Chemother., October 1, 2007; 51(10): 3699 - 3706.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.