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Drug Investigation

, Volume 3, Issue 5, pp 299–307 | Cite as

Cefetamet: Its In Vitro Activity and Interaction with β-Lactamases and Penicillin-Binding Proteins

  • Wolfgang Cullmann
  • Rudolf L. Then
Review Article

Summary

Cefetamet pivoxil (pivoxyl) is an orally active cephalosporin in advanced clinical development sharing a 2-aminothiazolyl- and a methoxyimino-moiety as side chains, in common with other third generation cephalosporins. Consequently, cefetamet is highly active against various Gram-positive and Gram-negative pathogens such as β-haemolytic streptococci [serogroup A: median minimum concentration inhibiting 90% of pathogens (MIC90) 0.06 mg/L; serogroup B: median MIC90 1 mg/L], Streptococcus pneumoniae, Haemophilus influenzae β-lactamase positive (median MIC90 0.25 mg/L), Enterobacteriaceae [Escherichia coli, Klebsiella spp., most Enterobacter spp., Proteus and Providencia spp., Salmonella spp., Shigella spp. and Yersinia enterocolitica (median MIC90 ≤ 2 mg/L)]. Cefetamet is inactive against Staphylococcus spp., Pseudomonas aeruginosa, and most members of Bacteroides and Clostridia spp.

Cefetamet is not affected by most plasmid-mediated β-lactamases, such as the TEM-1/-2, OX A 1–3 and SHV enzymes. Moreover, it exhibits greater stability against the recently evolved ‘extended-spectrum’ β-lactamases than many other third generation cephalosporins; however, it is inactive against TEM-3 (synonym CTX-l)-producing isolates, although fully active against the ‘new’ SHV-enzyme-producing isolates. There was complete cross-resistance between Cefetamet and the third generation cephalosporins in cephalosporinase-(Richmond’s and Sykes class I classification) overproducing enterobacteria. On the contrary, Cefetamet was more stable against the class III P. vulgaris enzyme than most other oxyimino-cephalosporins. Cefetamet exhibited high affinity for the penicillin-binding proteins (PBPs) 3 [concentration required to decrease binding of 14C-benzylpenicillin by 50% (IC50): 2.5 mg/L] and PBP la (IC50: 4.2 mg/L) of E. coli W3110 and for the PBPs 3 (IC50: 1.3 mg/L) and PBP la (IC50: 0.3 mg/L) of E. cloacae 908 S, but had very low affinity for S. aureus PBPs (IC50 ≥ 50 mg/L), thus explaining its lack of clinically relevant activity against staphylococci.

Keywords

Cephalosporin Drug Invest Clavulanic Acid Cefaclor Generation Cephalosporin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Wolfgang Cullmann
    • 1
  • Rudolf L. Then
    • 1
  1. 1.Pharma Division/Preclinical ResearchF. Hoffmann-La Roche LtdBasleSwitzerland

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