Antimicrobial Research Laboratory, New Chemistry Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bengaluru 560064 , Karnataka , India.
J Med Chem. 2019 Apr 11;62(7):3184-3205. doi: 10.1021/acs.jmedchem.8b01093. Epub 2018 Nov 21.
Vancomycin, a natural glycopeptide antibiotic, was used as the antibiotic of last resort for the treatment of multidrug-resistant Gram-positive bacterial infections. However, almost 30 years after its use, resistance to vancomycin was first reported in 1986 in France. This became a major health concern, and alternative treatment strategies were urgently needed. New classes of molecules, including semisynthetic antibacterial compounds and newer generations of the previously used antibiotics, were developed. Semisynthetic derivatives of vancomycin with enhanced binding affinity, membrane disruption ability, and lipid binding properties have exhibited promising results against both Gram-positive and Gram-negative bacteria. Various successful approaches developed to overcome the acquired resistance in Gram-positive bacteria, intrinsic resistance in Gram-negative bacteria, and other forms of noninherited resistance to vancomycin have been discussed in this Perspective.
万古霉素是一种天然糖肽类抗生素，曾被用作治疗多重耐药革兰阳性菌感染的最后手段。然而，在其使用近 30 年后，1986 年法国首次报道了万古霉素耐药。这成为一个主要的健康问题，迫切需要替代的治疗策略。新的分子类别，包括半合成抗菌化合物和以前使用的抗生素的新一代，已经被开发出来。万古霉素的半合成衍生物具有增强的结合亲和力、膜破坏能力和脂质结合特性，对革兰阳性菌和革兰阴性菌都表现出了有前景的效果。本文从各个方面讨论了克服革兰阳性菌获得性耐药、革兰阴性菌固有耐药以及万古霉素非遗传性耐药的各种成功方法。
