Gram-positive organisms are responsible for some of the most serious of human infections. Resistance to front-line antimicrobial agents can complicate otherwise curative therapy. These organisms possess multiple drug resistance mechanisms, with drug efflux being a significant contributing factor. Efflux proteins belonging to all five transporter families are involved, and frequently can transport multiple structurally unrelated compounds resulting in a multidrug resistance (MDR) phenotype. In addition to clinically relevant antimicrobial agents, MDR efflux proteins can transport environmental biocides and disinfectants which may allow persistence in the healthcare environment and subsequent acquisition by patients or staff. Intensive research on MDR efflux proteins and the regulation of expression of their genes is ongoing, providing some insight into the mechanisms of multidrug recognition and transport. Inhibitors of many of these proteins have been identified, including drugs currently being used for other indications. Structural modifications guided by structure–activity studies have resulted in the identification of potent compounds. However, lack of broad-spectrum pump inhibition combined with potential toxicity has hampered progress. Further work is required to gain a detailed understanding of the multidrug recognition process, followed by application of this knowledge in the design of safer and more highly potent inhibitors.

革兰氏阳性生物是某些最严重的人类感染的原因。对一线抗微生物药物的耐药性可能会使治疗方法复杂化。这些生物具有多种耐药机制，药物外排是重要的促成因素。属于所有五个转运蛋白家族的外排蛋白都参与其中，并且经常可以转运多种结构上不相关的化合物，从而导致多药耐药性（MDR）表型。除临床相关的抗菌剂外，MDR外排蛋白还可以转运环境杀生物剂和消毒剂，从而可以在医疗环境中持久存在，并随后被患者或工作人员所使用。正在进行关于MDR外排蛋白及其基因表达调控的深入研究，提供了对多种药物识别和转运机制的一些见解。已经鉴定出许多这些蛋白的抑制剂，包括目前用于其他适应症的药物。通过结构活性研究指导的结构修饰已鉴定出有效的化合物。然而，缺乏广谱泵抑制作用与潜在毒性相结合已经阻碍了进展。需要进一步的工作来获得对多药识别过程的详细理解，然后在设计更安全，更有效的抑制剂时应用这些知识。通过结构活性研究指导的结构修饰已鉴定出有效的化合物。然而，缺乏广谱泵抑制作用与潜在毒性相结合，阻碍了其进展。需要进一步的工作来获得对多药识别过程的详细理解，然后在设计更安全，更有效的抑制剂时应用这些知识。通过结构活性研究指导的结构修饰已鉴定出有效的化合物。然而，缺乏广谱泵抑制作用与潜在毒性相结合，阻碍了其进展。需要进一步的工作来获得对多药识别过程的详细理解，然后在设计更安全，更有效的抑制剂时应用这些知识。