ne (1.5 %) vs comparators (0.5 %) were observed.
AST and ALT abnormalities in Tygacil-treated patients were reported more frequently in the post therapy period than in those in comparator-treated patients, which occurred more often on therapy.
In all Phase 3 and 4 (cSSSI and cIAI) studies, death occurred in 2.4 % (54/2216) of patients receiving tigecycline and 1.7% (37/2206) of patients receiving comparator drugs.
Paediatric population
data were available from a multiple dose PK study (see section 5.2). No new or unexpected safety concerns were observed with tigecycline in this study.
4.9 Overdose
No specific information is available on the treatment of overdosage. Intravenous administration of tigecycline at a single dose of 300 mg over 60 minutes in healthy volunteers resulted in an increased incidence of nausea and vomiting. Tigecycline is not removed in significant quantities by haemodialysis.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, Tetracyclines, ATC code: J01AA12.
Mode of action
Tigecycline, a glycylcycline antibiotic, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains.
In general, tigecycline is considered bacteriostatic. At 4 times the minimum inhibitory concentration (MIC), a 2-log reduction in colony counts was observed with tigecycline against Enterococcus spp., Staphylococcus aureus, and Escherichia coli.
Mechanism of resistance
Tigecycline is able to overcome the two major tetracycline resistance mechanisms, ribosomal protection and efflux. Cross-resistance between tigecycline and minocycline-resistant isolates among the Enterobacteriaceae due to multi-drug resistance (MDR) efflux pumps has been shown. There is no target-based cross-resistance between tigecycline and most classes of antibiotics.
Tigecycline is vulnerable to chromosomally-encoded multidrug efflux pumps of Proteeae and Pseudomonas aeruginosa. Pathogens of the family Proteeae (Proteus spp., Providencia spp., and Morganella spp.) are generally less susceptible to tigecycline than other members of the Enterobacteriaceae. Decreased susceptibility in both groups has been attributed to the overexpression of the non-specific AcrAB multi-drug efflux pump. Decreased susceptibility in Acinetobacter baumannii has been attributed to the overexpression of the AdeABC efflux pump.
Breakpoints
Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:
Staphylococcus spp. S 0.5 mg/L and R > 0.5 mg/L
Streptococcus spp. other than S. pneumoniae S 0.25 mg/L and R > 0.5 mg/L
Enterococcus spp. S 0.25 mg/L and R > 0.5 mg/L
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 i |
