Grosset J, Ji B
Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Drugs. 1997;54 Suppl 2:23-7; discussion 28-9. doi: 10.2165/00003495-199700542-00006.
The prevalence of clarithromycin-resistant mutants in untreated bacterial populations of Mycobacterium avium-intracellulare complex (MAC) has been demonstrated to be between 10(-7) and 10(-8) colony-forming units (CFUs) in the beige mouse model. Selection of these mutants occurred during clarithromycin monotherapy if treatment was initiated when the bacterial population size reached approximately 10(8) CFUs per spleen. Likewise, selection of clarithromycin-resistant MAC was induced in AIDS patients during therapy with clarithromycin alone or in combination with drugs that were ineffective for the treatment or prevention of MAC infection. Because the emergence of clarithromycin resistance during preventive therapy was observed exclusively in AIDS patients with CD4+ cell counts < or = 25 cells/microliter, clarithromycin monotherapy can be recommended for the prevention of MAC infection in AIDS patients with CD4+ cell counts of > or = 50 cells/microliter. However, a clarithromycin-containing combination regimen is recommended for patients with CD4+ cell counts < 50 cells/microliter. Since preliminary animal experiments and clinical trials indicate that amikacin, ethambutol or rifabutin in combination with clarithromycin may prevent, or at least delay, the selection of clarithromycin-resistant mutants, further preventive trials are urgently needed to confirm these observations.
在米色小鼠模型中，鸟分枝杆菌胞内菌复合群（MAC）未经治疗的细菌群体中克拉霉素耐药突变体的流行率已被证明在10^(-7)至10^(-8)菌落形成单位（CFU）之间。如果在细菌群体大小达到约每脾脏10^8 CFU时开始治疗，这些突变体的选择会在克拉霉素单药治疗期间发生。同样，在单独使用克拉霉素或与对MAC感染治疗或预防无效的药物联合治疗的艾滋病患者中，也会诱导出克拉霉素耐药的MAC。由于仅在CD4+细胞计数≤25个/微升的艾滋病患者预防性治疗期间观察到克拉霉素耐药性的出现，因此对于CD4+细胞计数≥50个/微升的艾滋病患者，可推荐使用克拉霉素单药预防MAC感染。然而，对于CD4+细胞计数<50个/微升的患者，推荐使用含克拉霉素的联合治疗方案。由于初步动物实验和临床试验表明，阿米卡星、乙胺丁醇或利福布汀与克拉霉素联合使用可能预防或至少延迟克拉霉素耐药突变体的选择，因此迫切需要进一步的预防性试验来证实这些观察结果。
