国内外抗耐药复方抗生素研发的现状及开发策略

细菌耐药导致β-内酰胺类抗生素临床使用严重受限,β-内酰胺酶抑制剂与该类抗生素合用有效解决了这一难题。近年来,欧美在新复方抗生素研发方面发展迅速,尤其是近两年FDA先后快速批准了两个新的β-内酰胺类抗生素/β-内酰胺酶抑制剂复方抗生素,分别为ceftolozane/三唑巴坦(商品名:zerbaxa)和头孢他啶/阿维巴坦(商品名:avycaz),很大程度的缓解了目前耐药菌无药可用的局面。我国药企基于已有的β-内酰胺类抗生素和β-内酰胺酶抑制剂进行较多探索研究,目前已有多家药企在复方抗生素的开发中投入了大量研究。本文阐述了国内外复方抗生素研发情况、政策法规对研发内容的要求、政府对抗耐药菌抗生素研发的鼓励政策,分析国内复方抗生素研发的不足并提出开发建议,为国内合理开发该类抗生素提供参考。

The current state and R&D strategies of antibiotics combinations against drug-resistant bacteria in China and aboard

Antibiotic resistance led to the clinical use of β-lactam antibiotics (BL) severely limited, whereas β-lactamase inhibitors (BLI) perfectly resolved this problem in combination with BL. In recent years, the novel antibiotic compounds have been developed rapidly in Europe and the United states. FDA has recently approved two BL/BLI combinations ceftolozane-tazobactam (trade name: zerbaxa) and ceftazidime-avibactam (trade name: avycaz), respectively], which alleviate the incurable state of drug-resistant bacteria to a large extent. Based on the existing BL and BLI, Chinese pharmaceutical manufactures also have done many researches in the development of BL/BLI combinations. In this paper, we described the progress of the development of antibiotic compounds in China and abroad, the requirements of the regulations on the research and development of drugs, the government's policies for encouraging the development of antibiotics against drug-resistant bacteria, and then analyzed the shortcomings and proposed several suggestions for the R&D of antibiotic compounds, in order to provide references for reasonable development of BL/BLI combination in