Prabhakaran K, Harris E B, Randhawa B, Adams L B, Williams D L, Hastings R C
Laboratory Research Branch, GWL Hansen's Disease Center, Louisiana State University, Baton Rouge 70894-2059.
Microbios. 1993;76(309):251-61.
Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectively. Now multidrug-resistant tuberculosis is spreading in many countries, especially with the emergence of AIDS. Multidrug treatment is being promoted at present to eradicate leprosy. Since M. leprae may also become multidrug-resistant, new approaches have to be adopted for controlling mycobacterial diseases. Mycobacteria usually synthesize beta-lactamase and are insensitive to beta-lactam antibiotics. M. tuberculosis contains a constitutive beta-lactamase; de-repression of beta-lactamase has been reported in M. leprae. Three different beta-lactam/beta-lactamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam) were used to suppress the growth of several strains of mycobacteria (including M. tuberculosis H37Rv) in vitro. Ampicillin/sulbactam is a potent bactericidal agent against M. leprae multiplying in mouse foot pads. In the present work, ampicillin/sulbactam showed higher activity than the other drug combinations. The beta-lactam/beta-lactamase inhibitors are likely to be effective as rational therapeutic agents against mycobacterial infections.
结核分枝杆菌和麻风分枝杆菌分别对用于治疗结核病和麻风病的药物产生耐药性。如今，耐多药结核病正在许多国家蔓延，尤其是随着艾滋病的出现。目前正在推广联合用药治疗以根除麻风病。由于麻风分枝杆菌也可能产生耐多药性，因此必须采用新的方法来控制分枝杆菌病。分枝杆菌通常合成β-内酰胺酶，并且对β-内酰胺类抗生素不敏感。结核分枝杆菌含有一种组成型β-内酰胺酶；在麻风分枝杆菌中已报道有β-内酰胺酶的去阻遏现象。三种不同的β-内酰胺/β-内酰胺酶抑制剂组合（氨苄西林/舒巴坦、阿莫西林/克拉维酸和哌拉西林/他唑巴坦）用于在体外抑制几种分枝杆菌菌株（包括结核分枝杆菌H37Rv）的生长。氨苄西林/舒巴坦是一种对在小鼠脚垫中繁殖的麻风分枝杆菌有效的杀菌剂。在本研究中，氨苄西林/舒巴坦显示出比其他药物组合更高的活性。β-内酰胺/β-内酰胺酶抑制剂作为抗分枝杆菌感染的合理治疗药物可能是有效的。
