Inderlied C B, Kolonoski P T, Wu M, Young L S
Department of Pathology, University of Southern California, Children's Hospital, Los Angeles 90027.
Antimicrob Agents Chemother. 1989 Feb;33(2):176-80. doi: 10.1128/AAC.33.2.176.
The Mycobacterium avium complex (MAC) is a common cause of disseminated infection in patients with acquired immunodeficiency syndrome and is increasingly seen as a cause of infection in other immunocompromised patients. Traditional antimycobacterial therapy often is ineffective, and there is a clear need for antibiotics with proven activity against the MAC. Three agents, amikacin, ciprofloxacin, and imipenem, were tested in vitro for activity against MAC strain 101. Amikacin was bacteriostatic, with an MIC of 4.8 micrograms/ml, which is significantly lower than the concentration in serum obtained with standard dosing. Imipenem and ciprofloxacin had little or no activity alone (MICs, greater than 16 and 4.7 micrograms/ml, respectively), but when they were combined with amikacin there was bactericidal activity. Each agent was tested individually and in combination by using the beige mouse model of disseminated MAC infection. There was no mortality in a group of animals infected with MAC 101 and treated with amikacin alone; also, there was a significant decrease in the infection of the blood, liver, and spleen. There was no apparent improvement in therapeutic effectiveness when amikacin was combined with the other agents. Neither ciprofloxacin nor imipenem was active as a single agent, which was consistent with the in vitro activities of these agents. Amikacin in combination with traditional antimycobacterial agents warrants further study as potential therapy for disseminated MAC infections.
鸟分枝杆菌复合体(MAC)是获得性免疫缺陷综合征患者播散性感染的常见病因,并且越来越多地被视为其他免疫功能低下患者的感染病因。传统的抗分枝杆菌疗法通常无效,因此显然需要有已证实对MAC有活性的抗生素。对阿米卡星、环丙沙星和亚胺培南这三种药物进行了体外测试,以检测它们对MAC菌株101的活性。阿米卡星具有抑菌作用,MIC为4.8微克/毫升,显著低于标准给药后血清中的浓度。亚胺培南和环丙沙星单独使用时几乎没有活性(MIC分别大于16和4.7微克/毫升),但与阿米卡星联合使用时有杀菌活性。通过使用播散性MAC感染的米色小鼠模型对每种药物单独及联合使用进行了测试。感染MAC 101并单独用阿米卡星治疗的一组动物没有死亡;此外,血液、肝脏和脾脏中的感染也显著减少。当阿米卡星与其他药物联合使用时,治疗效果没有明显改善。环丙沙星和亚胺培南作为单一药物均无活性,这与这些药物的体外活性一致。阿米卡星与传统抗分枝杆菌药物联合使用作为播散性MAC感染的潜在治疗方法值得进一步研究。