Tigecycline Approved by EMEA, 2006

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TigecyclineApproved by EMEA, 2006
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• Glycylcycline (relative minocycline)
• Intravenous only
• licenced for complicated skin and skin structure
  infections (CSSSI) and complicated
  intra-abdominal infection (IAI)
• dosage for complicated SSSI and IAI 100mg
  followed by 50mg 12 hourly

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EUCAST view

• clinically useful activity against staphylococci,
  ß-haemolytic streptococci, enterococci, E. coli,
  Klebsiella spp, and several other
  Enterobacteriaceae.
• promising but unproven activity against
  Acinetobacter and several anaerobes which have
  not received breakpoints.
• EUCAST does not consider tigecycline active
  against Pseudomonas aeruginosa and some species
  of Enterobacteriacae (Proteus, Morganella and
  Providencia) which have not received breakpoints.

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Tigecycline activity

• www.eucast.org

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Tigecycline pharmacokinetics
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Monte Carlo simulations and Pk/Pd breakpoints
Data from human studies in complicated skin and skin structure infections, and complicated intra-abdominal infection, on the AUC/MIC breakpoint are imprecise. However, the use of these targets in Monte Carlo simulations suggest a Pk/Pd breakpoint for S. aureus of ?0.25 mg/L and E. coli of ?0.5 mg/L.
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8. Clinical breakpoints 8. Clinical breakpoints
Non-species-related breakpoints 0.25 / 0.5 mg/L based on the pK/pD-data available. Pk/Pd data are difficult to assess. Relationships for tetracyclines are not well understood but AUC/MIC is probably relevant. There is a large difference between simple animal experiments and complex human infections. Mixed organisms are common in human infections and surgical intervention has a significant effect on outcome than the antimicrobial agents in cIAI.
Species-related breakpoints Enterobacteriaceae with the exclusion of Proteus, Morganella and Providencia. Staphylococcus spp. Enterococcus spp. (provided EMEA decides to include Enterococcus faecalis or E.faecalis and E.faecium among appropriate targets). Streptococcus spp except S.pneumoniae. Gram-negative anaerobes as part of mixed intraabdominal infections but without MIC-breakpoints due to a lack of correlation between clinical results and MIC-values.
Species without breakpoints Pseudomonas spp. Enterococcus spp. (if EMEA decides not to include Enterococcus faecalis or E.faecalis and E.faecium among appropriate targets) S. pneumoniae. H. influenzae M. catarrhalis. N. gonorrhoeae N. meningitidis Gram-negative anaerobes (see above)
Clinical qualifications Breakpoints apply only to CSSSI and CIAI
Additional comment None
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