Höger P H, Seger R A, Schaad U B, Hitzig W H
Pediatr Res. 1985 Jan;19(1):38-44. doi: 10.1203/00006450-198501000-00011.
In chronic granulomatous disease (CGD) polymorphonuclear leukocytes (PMN) are unable to kill phagocytized catalase-positive bacteria. Therefore, patients with CGD are prone to infections and dependent on antimicrobial agents able to penetrate PMN membranes and to act intracellularly. Owing to their good lipid solubility, trimethoprim/sulfamethoxazole and rifampicin passively diffuse the membrane. In contrast, fosfomycin is transported actively into the cell. In normal PMN, it reaches cellular-to-extracellular ratios of 1.83 after 15 min, in CGD-PMN 2.18 after 30 min. At concentrations between 16 and 200 mg/liter, fosfomycin was able to kill staphylococci surviving within CGD-PMN, thus compensating for the bactericidal deficiency in CGD. A combination of low concentrations of fosfomycin (8 mg/liter) plus rifampicin (0.06 mg/liter) was more effective at the intracellular level than either agent alone. Apart from a stimulation of PMN-chemiluminescence of yet unknown significance, the agent did not interfere with other neutrophil functions. Clinical investigations are indicated to study whether fosfomycin can be added to the small number of antibiotics useful in CGD.
在慢性肉芽肿病（CGD）中，多形核白细胞（PMN）无法杀死吞噬的过氧化氢酶阳性细菌。因此，CGD患者易于感染，且依赖于能够穿透PMN细胞膜并在细胞内发挥作用的抗菌药物。由于甲氧苄啶/磺胺甲恶唑和利福平具有良好的脂溶性，它们可被动扩散通过细胞膜。相比之下，磷霉素是被主动转运到细胞内的。在正常PMN中，15分钟后其细胞内与细胞外的比例达到1.83，在CGD-PMN中30分钟后达到2.18。在浓度为16至200毫克/升之间时，磷霉素能够杀死CGD-PMN内存活的葡萄球菌，从而弥补CGD中的杀菌缺陷。低浓度的磷霉素（8毫克/升）加利福平（0.06毫克/升）的组合在细胞内水平上比单独使用任何一种药物都更有效。除了对PMN化学发光有尚未明确意义的刺激作用外，该药物不干扰其他中性粒细胞功能。需要进行临床研究以探讨磷霉素是否可以添加到少数对CGD有用的抗生素中。
