Recent derivatives from smaller classes of fermentation-derived antibacterials

Introduction: New antibiotics, without cross-resistance to existing agents, are needed to treat infections caused by increasingly resistant pathogens and to improve the safety and efficacy of older agents. Renewed investigations of several older but smaller or underexploited classes of fermentation-derived antibiotics have generated active new derivatives and analogs that resulted from medicinal chemistry programs and/or manipulations of the biosynthetic pathways of producing microbes. Several of these programs have now produced clinical candidates undergoing preclinical studies or early clinical trials. Areas covered: This review surveys the recent patent and journal literature for relevant new antibacterial derivatives from about 2007 until the present. Expert opinion: Following the regulatory approvals of daptomycin and retapamulin for human use, these renewed investigations of underdeveloped fermentation-derived classes have demonstrated the further potential to discover new clinical candidates. However, many other classes of natural product antibiotics still remain underinvestigated and are thus available for renewed examinations. This strategy is one means for finding new antibiotics to add to the physician's armamentarium for treating resistant pathogens.