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In vitro bactericidal activity of daptomycin versus vancomycin Cmax concentrations in the presence of human albumin physiological concentrations against vancomycin-susceptible but tolerant methicillin-resistant Staphylococcus aureus

Abstract number: P1988

Torrico M., Aguilar L., Gonzalez N., Gimenez M.J., Cafini F., Alou L., Sevillano D., Cleeland R., Prieto J.

Objective: To study the antibacterial activity (log10 reduction) and time to obtain bactericidal activity (time to obtain geqslant R: gt-or-equal, slanted3 log10 – 99.9% – initial inocula reduction, T99.9%) in the presence of physiological concentrations of human albumin by concentrations similar to Cmax obtained in serum with 6 mg/kg od daptomycin and 1g bid vancomycin regimens, against vancomycin-susceptible but tolerant methicillin-resistant Staphylococcus aureus (MRSA).

Methods: Killing curves were performed with final inocula of approx. 107 cfu/ml, and a final concentration of 98.6 mg/l daptomycin or 65.7 mg/l vancomycin, using as media Mueller-Hinton broth (Cmax-MH) and MH broth with 4 g/dl human albumin (Cmax-HAlb). In the case of daptomycin, media were supplemented with Ca2+ (by adding 100 mg/l of Ca2+ in media containing albumin and 50 mg/l in media without albumin) in order to obtain a physiological free Ca2+ concentration.

Results: MIC/MBC (mg/l) of daptomycin and vancomycin, T99.9% (h) and log10 initial inocula reduction at 12 h/24 h are shown in the Tables.

Conclusions: Daptomycin Cmax exhibited rapid (leqslant R: less-than-or-eq, slant3 h) bactericidal activity while vancomycin did not achieve bactericidal activity along 24 h against vancomycin-susceptible but tolerant MRSA. The presence of human albumin physiological concentrations slightly delayed T99.9% for daptomycin.

 Daptomycin
MIC/MBC1/1
Strain 1
1/2
Strain 2
2/2
Strain 3
2/4
Strain 4
 T99.9%12 h/24 hT99.9%12 h/24 hT99.9%12 h/24 hT99.9%12 h/24 h
Cmax-MH25.8/5.916.0/6.016.0/6.026.0/6.0
Cmax-HAlb35.5/5.626.0/6.026.0/6.035.2/5.9
 Vancomycin
MIC/MBC0.5/16
Strain 1
1/32
Strain 2
2/32
Strain 3
1/32
Strain 4
 T99.9%12 h/24 hT99.9%12 h/24 hT99.9%12 h/24 hT99.9%12 h/24 h
Cmax-MH>240.1/0.4>240.1/1.3>240.1/1.0>240.1/1.5
Cmax-HAlb>240.1/0.9>240.3/1.8>240.2/1.3>240.2/1.1

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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