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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A review of cephalosporin metabolism: a lesson to be learned for future chemotherapy.

The historical background information concerning the metabolism of cephalosporins and selected other antiinfectives was reviewed as a preface to discussion concerning desacetyl-cefotaxime (dCTX), a metabolite of cefotaxime (CTX) sodium. Cephalothin and cephapirin were metabolized at the 3-position to less active desacetyl forms. However, the parent drugs and their metabolites interact in a favorable manner resulting in dominant additive or synergist inhibition of susceptible bacterial pathogens. Similarly, CTX plus dCTX have been described as being synergist in their activity against greater than 70% of Enterobacteriaceae or staphylococci and greater than 80% of anaerobic bacteria. Antagonism was rare with only two species and of no clinical significance. More recently, reported studies showed enhanced activity of CTX/dCTX against pathogens producing meningitis compared to ceftriaxone and other contemporary therapeutic agents. The dCTX compound was classified as a drug with a potency superior to a "second-generation" cephalosporin and possessed greater beta-lactamase stability against some enzymes compared to CTX. These features may explain low reported rates of superinfections and adverse side-effects, including resistance arising on chemotherapy. Physicians are cautioned to take into account the potential favorable effects of drug metabolites on antimicrobial spectrum, potency and applied pharmacokinetics. In the case of CTX/dCTX, the laboratory results for CTX will always underestimate its value or potency because of the contribution of the metabolite.[1]


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