Briefly describe two different strategies used to develop antibiotics. Explain a limitation for each one of these strategies. Document Preview: PERSPECTIVESto combat successive waves of...

PERSPECTIVES to combat successive waves of resistant OPINION — ANTI-INFECTIVES pathogens. Analogously, zithromax and biaxin are second-generation variants of the natural product erythromycin. Third-gener- Where will new antibiotics come from? ation macrolides, the 3-ketolides, have now been approved in Europe and are under review in the United States for clinical Christopher Walsh approval. In turn, the best-selling fluoro- quinolones are second-generation mole- There is a constant need for new antibacterial organisms become widespread. The number cules, and newer, third-generation versions, drugs owing to the inevitable development of of new antibiotics that are needed to treat such as gatifloxacin, have been introduced in resistance that follows the introduction of the same bacterial infection also increases recent years. Other antibacterial drugs, such antibiotics to the clinic. When a new class of reciprocally. For example, in the 1940s, as tetracyclines and isoniazid, still have useful antibiotic is introduced, it is effective at first, staphylococcal infections were treated with roles in therapy but they are not the focus of but will eventually select for survival of the first-generation penicillins. Within a year, this perspective. small fraction of bacterial populations that resistance had appeared in Staphylococcus have an intrinsic or acquired resistance aureus, and a decade later, ß-lactam resistance Innovation gap mechanism. Pathogens that are resistant to had spurred the development and introduc- Although the history of antibiotic develop- multiple drugs emerge around the globe, so tion of methicillin. Methicillin-resistant ment demonstrates the remarkably successful how robust are antibiotic discovery S. aureus (MRSA) became so prevalent that, mining of NATURAL PRODUCT SCAFFOLDS by gen- processes? in 1986, vancomycin became a front-line erations of medicinal chemists to meet the antibiotic to treat MRSA infections. Since challenges of resistance...