Safir M Courtney, Bhavnani Sujata M, Slover Christine M, Ambrose Paul G, Rubino Christopher M
Institute for Clinical Pharmacodynamics, Inc., Schenectady, NY 12305, USA.
Antibiotics (Basel). 2020 Jul 15;9(7):412. doi: 10.3390/antibiotics9070412.
It is often said that the marketplace for new antibiotics is broken. This notion is supported by the observation that many recently-approved antibiotics to treat drug-resistant bacteria have failed commercially in a spectacular fashion. Today, companies with peak market-cap values in excess of USD 500 million to 1 billion prior to product launch regularly sell for pennies on the dollar a few years after market introduction. It is possible, however, that the market is not as broken as we perceive. That is, in the collective mind of the clinician, recently-approved antibiotics may be too-poorly differentiated to justify their broad use and inordinate cost relative to those already existing. Perhaps we in the antibacterial drug development field must change our way of thinking if we are to survive and thrive. Rather than reflexively developing new β-lactam-β-lactamase inhibitor combinations for every new enzyme that evades our current inhibitors, we should focus discovery and development efforts on agents that revolutionize how we potentiate antibiotics. To this end, there has been renewed interest in phage therapies, virulence inhibitors, bacterial growth rate modulators, monoclonal antibodies, and other approaches to augment antibiotic effects. Herein, we suggest that the unmet medical need is less about adding poorly-differentiated antibiotics to our armamentarium and more about the need for innovation in how we augment antibiotic regimen effects.
人们常说，新型抗生素市场已经失灵。这一观点得到了以下观察结果的支持：许多最近获批用于治疗耐药菌的抗生素在商业上遭遇了惨败。如今，那些在产品推出前市值峰值超过5亿美元至10亿美元的公司，在进入市场几年后，其股价往往只剩几美分。然而，市场可能并不像我们认为的那样失灵。也就是说，在临床医生的普遍观念中，与现有抗生素相比，最近获批的抗生素可能没有足够的差异优势来证明其广泛使用的合理性以及过高的成本。如果我们想要生存和发展，抗菌药物研发领域的我们或许必须改变思维方式。与其盲目地为每一种能逃避现有抑制剂的新酶开发新的β-内酰胺-β-内酰胺酶抑制剂组合，我们应该将发现和开发工作集中在那些能彻底改变我们增强抗生素效力方式的药物上。为此，人们对噬菌体疗法、毒力抑制剂、细菌生长速率调节剂、单克隆抗体以及其他增强抗生素效果的方法重新产生了兴趣。在此，我们认为未满足的医疗需求不在于往我们的药物库中添加缺乏差异优势的抗生素，而更多在于我们如何增强抗生素治疗效果方面需要创新。
