Old dogs that learn new tricks: Modified antimicrobial agents that escape pre-existing resistance mechanisms

Increasing numbers of resistant bacteria and decreasing numbers of efficient antimicrobial agents demand for the development of new highly potent antimicrobial agents. The two main directions for the development of new antimicrobial agents are either the development of completely novel antimicrobial agents, or the modification of already existing antimicrobial molecules. The second direction proved to be a more successful and cost-efficient way of generating new antimicrobial agents. For this, chemical modifications have been included which render the antimicrobial agents insensitive to prevalent bacterial resistance mechanisms. However, detailed knowledge of the resistance mechanisms is indispensable. Molecular analysis of resistance mechanisms provides the required data to identify critical target structures. Furthermore, modification of antimicrobial agents makes it possible to escape known resistance mechanisms. In this report, two examples for such successful developments, one from human medicine (telithromycin) and the other from veterinary medicine (florfenicol), are presented.