Peloquin C A
Infectious Disease Pharmacokinetics Laboratory (IDPL), National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Ann Pharmacother. 1993 Jul-Aug;27(7-8):928-37. doi: 10.1177/106002809302700722.
To update readers on the clinical management of infections secondary to Mycobacterium avium complex (MAC) in patients with AIDS. A general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease is provided. Several aspects of the treatment of the disease, including an historical perspective, current approaches, and future research opportunities, are described.
Current medical literature, including abstracts presented at international meetings, is reviewed. References were identified through MEDLINE, Current Contents, and published meeting abstracts.
Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of MAC are cited. Specific attention is given to the management of patients with MAC infection.
Information contributing to the discussion of the topics selected by the author is reviewed. Data supporting and disputing specific conclusions are presented.
Disseminated MAC infection is diagnosed antemortem in approximately 30 percent of patients with AIDS; postmortem rates of isolation exceed 50 percent. The incidence of MAC may increase as attempts at isolating the organism become more aggressive. The traditional approach to the isolation, susceptibility testing, and treatment of MAC has been derived from the management of Mycobacterium tuberculosis, with disappointing results. Newer radiometric in vitro methods of susceptibility testing appear to show more promise. Current mouse models of MAC are not true AIDS models; new CD4-deficient mouse models are being developed. Clinical mycobacteriologic and pharmacokinetic laboratory support have been underused, with treatment generally proceeding empirically. New agents that may contribute to the management of disseminated MAC infection include the macrolide derivatives clarithromycin and azithromycin. Research also continues with new rifamycins (including rifabutin) and fluoroquinolones (ciprofloxacin, sparfloxacin). Preliminary results suggest a central role for macrolides in the treatment of disseminated MAC; effective companion drugs are needed to prevent the rapid emergence of macrolide-resistant MAC.
Treatment results for disseminated MAC infection remain poor. Therapy may be improved by selecting drugs on the basis of susceptibility data for each isolate, rather than by using empiric regimens based on susceptibility trends. Significant antimycobacterial drug malabsorption has been documented, and may contribute to poor outcomes. More-potent agents are needed to improve the clinical outcome in AIDS patients with MAC.
向读者介绍艾滋病患者鸟分枝杆菌复合群(MAC)继发感染的临床管理。提供该病原体的概述、培养与药敏试验以及该疾病的临床表现。描述该疾病治疗的几个方面,包括历史观点、当前方法和未来研究机会。
查阅当前医学文献,包括在国际会议上发表的摘要。通过医学文献数据库(MEDLINE)、《现刊目次》和已发表的会议摘要确定参考文献。
引用关于MAC的流行病学、临床表现、培养与药敏试验以及治疗的数据。特别关注MAC感染患者的管理。
审查有助于作者所选主题讨论的信息。呈现支持和质疑特定结论的数据。
在约30%的艾滋病患者中生前诊断出播散性MAC感染;死后分离率超过50%。随着分离该病原体的尝试变得更加积极,MAC的发病率可能会增加。传统的MAC分离、药敏试验和治疗方法源自对结核分枝杆菌的管理,结果令人失望。更新的体外放射药敏试验方法似乎更有前景。当前的MAC小鼠模型并非真正的艾滋病模型;正在开发新的CD4缺陷小鼠模型。临床分枝杆菌学和药代动力学实验室支持未得到充分利用,治疗通常凭经验进行。可能有助于播散性MAC感染管理的新药包括大环内酯衍生物克拉霉素和阿奇霉素。对新型利福霉素(包括利福布汀)和氟喹诺酮类药物(环丙沙星、司帕沙星)的研究也在继续。初步结果表明大环内酯类药物在播散性MAC治疗中起核心作用;需要有效的辅助药物来防止耐大环内酯MAC的迅速出现。
播散性MAC感染的治疗效果仍然不佳。根据每个分离株的药敏数据选择药物,而非基于药敏趋势使用经验性方案,可能会改善治疗。已记录到显著的抗分枝杆菌药物吸收不良,这可能导致不良预后。需要更强效的药物来改善艾滋病合并MAC患者的临床结局。