Enterobacteriaceae S  1(^) mg/L and R > 2 mg/L

(^)Tigecycline has decreased in vitro activity against Proteus, Providencia, and Morganella spp.

For anaerobic bacteria there is clinical evidence of efficacy in polymicrobial intra-abdominal infections, but no correlation between MIC values, PK/PD data and clinical outcome. Therefore, no breakpoint for susceptibility is given. It should be noted that the MIC distributions for organisms of the genera Bacteroides and Clostridium are wide and may include 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 vo