RT Journal Article
T1 In vitro effect of physiological concentrations of human albumin on the antibacterial activity of tigecycline
A1 Alou Cervera, Luis
A1 Gimenez, María José
A1 Cafini, Fabio
A1 Aguilar, Lorenzo
A1 Sevillano Fernández, David
A1 González Hidalgo, Natalia
A1 Torrico, Martha
A1 Prieto Prieto, José
A1 Garcia-Rey, César
A1 Garcia-Escribano, Nuria
AB Objectives: To determine C(max) 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 10(7) cfu/mL) were performed with 0.88 mg/L final concentrations (serum C(max) after a 100 mg 1 h infusion) in Mueller-Hinton broth supplemented with Ca(2+) and Mg(2+) (MH) and in MH with 4 g/dL human albumin. Controls were curves in MH with concentrations similar to the free fraction (fC(max) = 0.17 mg/L) calculated using protein binding. Activity was measured as log(10) initial inoculum reduction (log(10) initial inoculum-log(10) 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 beta-lactamase (0.12/0.25); and Acinetobacter baumannii (0.25/1).Results: At 24 h the fC(max) produced mean decreases of < or =0.1 cfu/mL for all strains, in contrast to the bactericidal activity (mean >3 log(10) reduction) provided by C(max) concentrations in the presence or absence of albumin for E. coli and E. faecium, and an activity nearly bactericidal for S. aureus (mean approximately 2.8 log(10) reduction). In the case of the A. baumannii isolate the C(max) in the presence or absence of albumin produced a mean reduction of 2.56 log(10) 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.
PB Oxford University Press
SN 0305-7453
YR 2009
FD 2009-10-16
LK https://hdl.handle.net/20.500.14352/107083
UL https://hdl.handle.net/20.500.14352/107083
LA eng
NO Alou L, Giménez MJ, Cafini F, Aguilar L, Sevillano D, González N, Torrico M, Prieto J, García-Rey C, García-Escribano N. In vitro effect of physiological concentrations of human albumin on the antibacterial activity of tigecycline. J Antimicrob Chemother. 2009 Dec;64(6):1230-3.
NO Wyeth Farma S.A.
DS Docta Complutense
RD 9 abr 2025