nclude values in excess of 2 mg/L tigecycline.
There is limited evidence of the clinical efficacy of tigecycline against enterococci. However, polymicrobial intra-abdominal infections have shown to respond to treatment with tigecycline in clinical trials.
Susceptibility
The preva lence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local preva lence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Pathogen
Commonly Susceptible Species
Gram-positive Aerobes
Enterococcus spp.
Staphylococcus aureus*
Staphylococcus epidermidis
Staphylococcus haemolyticus
Streptococcus agalactiae*
Streptococcus anginosus group* (includes S. anginosus, S. intermedius and S. constellatus)
Streptococcus pyogenes*
Viridans group streptococci
Gram-negative Aerobes
Citrobacter freundii*
Citrobacter koseri
Escherichia coli*
Klebsiella oxytoca*
Anaerobes
Clostridium perfringens†
Peptostreptococcus spp.†
Prevotella spp.
Species for which acquired resistance may be a problem
Gram-negative Aerobes
Acinetobacter baumannii
Burkholderia cepacia
Enterobacter aerogenes
Enterobacter cloacae*
Klebsiella pneumoniae*
Morganella morganii
Proteus spp.
Providencia spp.
Serratia marcescens
Stenotrophomonas maltophilia
Anaerobes
Bacteroides fragilis group†
Inherently resistant organisms
Gram-negative Aerobes
Pseudomonas aeruginosa
*denotes species against which it is considered that activity has been satisfactorily demonstrated in clinical studies.
see section 5.1, Breakpoints above.
5.2 Pharmacokinetic properties
Absorption
Tigecycline is administered intravenously and therefore has 100 % bioavailability.
Distribution
The in vitro plasma protein binding of tigecycline ranges from approximately 71 % to 89 % at concentrations observed in clinical studies (0.1 to 1.0 μg/ml). Animal and human pharmacokinetic studies have demonstrated that tigecycline readily distributes to tissues.
In rats receiving single or multiple doses of 14C-tigecycline, radioactivity was well distributed to most tissues, with the highest overall exposure observed in bone marrow, salivary glands, thyroid gland, spleen, and kidney. In humans, the steady-state volume of distribution of tigecycline averaged 500 to 700 L (7 to 9 L/kg), indicating that tigecycline is extensively distributed beyond the plasma volume and concentrates into tissues.
No data are available on whether tigecycline can cross the blood-brain barrier in humans.
In clinical pharmacology studies using the therapeutic dosage regimen of 100 mg followed by 50 mg q12h, serum tigecycline steady-state Cmax was 866±233 ng/ml for 30-minute infusions and 634±97 ng/ml for 60-minute infusions. The steady-state AUC0-12h was 2349±850 ng•h/ml.
Biotransformation
On average, it is estimated that less than 20 % of tigecycline is metabolised before excretion. In healthy male volunteers, following the administration of 14C-tigecycline, unchanged tigecycline was the primary 14C-labelled material recovered in urine and faeces, but a glucuronide, an N-acetyl metabolite and a tigecycline epimer were al |
