Azidamfenicol

A 19 year old man developed an acute contact dermatitis of the anogenital region after the application of an antimycotic cream containing clotrimazole and azida col. Patch testing revealed sensitization to both active ingredients.

The in vitro antimicrobial activity of the antieczematic Bay f 4797 was studied. This combination drug contains the three active components acidamfenicol, clotrimazole and dexamethasone (prospective trade name: Baycuten). Various bacterial and fungal species of importance in dermatology served as test organisms. All the bacterial strains examined were found to be moderately susceptible to acidamfenicol; clotrimazole showed good inhibitory values agaisnt all the fungal species and the gram-positive bacterial strains. Additionally it was checked whether a synergistic or antagonistic interaction occurs with respect to the antimicrobial activity. An interference which could lead to impairment of the therapeutic activity was not observed.

Antimicrobial resistance represents a major threat to human health and knowledge of the underlying mechanisms is therefore vital. Here, we report the discovery and characterization of oxidoreductases that inactivate the broad-spectrum antibiotic chloramphenicol via dual oxidation of the C3-hydroxyl group. Accordingly, chloramphenicol oxidation either depends on standalone glucose-methanol-choline (GMC)-type flavoenzymes, or on additional aldehyde dehydrogenases that boost overall turnover. These enzymes also enable the inactivation of the chloramphenicol analogues thiamphenicol and azidamfenicol, but not of the C3-fluorinated florfenicol. Notably, distinct isofunctional enzymes can be found in Gram-positive (e. g., Streptomyces sp.) and Gram-negative (e. g., Sphingobium sp.) bacteria, which presumably evolved their selectivity for chloramphenicol independently based on phylogenetic analyses. Mechanistic and structural studies provide further insights into the catalytic mechanisms of these biotechnologically interesting enzymes, which, in sum, are both a curse and a blessing by contributing to the spread of antibiotic resistance as well as to the bioremediation of chloramphenicol.