In vitro effect of physiological concentrations of human albumin on the antibacterial activity of tigecycline

• Published in: Journal of antimicrobial chemotherapy 2009-12, Vol.64 (6), p.1230-1233
• Main Authors: Alou, Luis, Giménez, María-José, Cafini, Fabio, Aguilar, Lorenzo, Sevillano, David, González, Natalia, Torrico, Martha, Prieto, José, García-Rey, César, García-Escribano, Nuria
• Format: Article
• Language: English
• Subjects: Acinetobacter; Acinetobacter baumannii - drug effects; Albumins - pharmacology; Anti-Bacterial Agents - antagonists & inhibitors; Anti-Bacterial Agents - pharmacology; Antibiotics; Binding sites; Colony Count, Microbial; Culture Media - chemistry; Drug dosages; E. coli; enterococci; Enterococcus faecium - drug effects; Glycoproteins - metabolism; Humans; killing curves; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Microbial Viability - drug effects; Minocycline - analogs & derivatives; Minocycline - antagonists & inhibitors; Minocycline - pharmacology; MRSA; Protein Binding; Proteins; Serum Albumin - metabolism; Serum Albumin, Human; Staphylococcus infections
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkp371

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 × 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.