JAC Advance Access originally published online on October 16, 2009
Journal of Antimicrobial Chemotherapy 2009 64(6):1230-1233; doi:10.1093/jac/dkp371
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Original research |
In vitro effect of physiological concentrations of human albumin on the antibacterial activity of tigecycline
1 Microbiology Department, School of Medicine, Universidad Complutense, Avda Complutense s/n, 28040 Madrid, Spain 2 Medical Department, Wyeth Farma S.A., Ctra N-I, km. 23 Desvío Algete Km.1, San Sebastián de los Reyes, 28700 Madrid, Spain
Received 16 June 2009; returned 12 August 2009; revised 9 September 2009; accepted 22 September 2009
* Corresponding author. Tel: +34-91-3941505; Fax: +34-91-3941511; E-mail: laguilar{at}med.ucm.es
Objectives: To determine Cmax tigecycline activity in the presence/absence of physiological concentrations of human albumin with free fraction concentrations as controls.
Methods: Killing curves (final inoculum: 1.0–5.0 x 107 cfu/mL) were performed with 0.88 mg/L final concentrations (serum Cmax after a 100 mg 1 h infusion) in Mueller–Hinton broth supplemented with Ca2+ and Mg2+ (MH) and in MH with 4 g/dL human albumin. Controls were curves in MH with concentrations similar to the free fraction (fCmax = 0.17 mg/L) calculated using protein binding. Activity was measured as log10 initial inoculum reduction (log10 initial inoculum–log10 at 12 h/24 h). Target strains (tigecycline MIC/MBC; mg/L) were: methicillin-resistant Staphylococcus aureus heteroresistant to vancomycin (0.12/0.25); Enterococcus faecium (0.12/0.25); Escherichia coli producing extended-spectrum β-lactamase (0.12/0.25); and Acinetobacter baumannii (0.25/1).
Results: At 24 h the fCmax produced mean decreases of 
0.1 cfu/mL for all strains, in contrast to the bactericidal activity (mean >3 log10 reduction) provided by Cmax concentrations in the presence or absence of albumin for E. coli and E. faecium, and an activity nearly bactericidal for S. aureus (mean 
2.8 log10 reduction). In the case of the A. baumannii isolate the Cmax in the presence or absence of albumin produced a mean reduction of 2.56 log10 cfu/mL at 12 h (time of one dosing interval), with a bacteriostatic profile when considering 24 h colony counts (similar counts at 0 and 24 h).
Conclusions: Correcting the total concentration for the reported literature binding values is unreliable since tigecycline antibacterial activity was greater than that suggested by the free fraction of the drug.
Keywords: protein binding , killing curves , MRSA , enterococci , Acinetobacter , E. coli