Gmünder F K, Seger R A
Pediatr Res. 1981 Dec;15(12):1533-7. doi: 10.1203/00006450-198112000-00017.
Four possible modes of action for the clinically observed effectiveness of sulfamethoxazole/trimethoprim in chronic granulomatous disease were evaluated: (1) inhibition of bacterial catalase, (2) improvement of granulocyte oxygen metabolism, (3) synergism of the antibiotic with nonoxygen-dependent granulocyte killing mechanisms, and (4) a purely antibiotic effect based on uptake and concentration of the antibiotic by and within granulocytes. While the first three mechanisms were excluded, the fourth mechanism is highly probable; sulfamethoxazole was found to reach granulocyte associated concentrations 1.7-fold and trimethoprim 4.1-fold of extracellular levels. Penicillin G, a known nonpenetrating antibiotic, reached 0.3-fold, and tetracycline, a known penetrating agent, 7.1-fold the extracellular level. These findings indicate that sulfamethoxazole/trimethoprim is an antibiotic combination uniquely suited for the long-term prophylaxis of infections in patients with defects of intracellular phagocyte killing.
对临床观察到的磺胺甲恶唑/甲氧苄啶治疗慢性肉芽肿病有效性的四种可能作用方式进行了评估：（1）抑制细菌过氧化氢酶，（2）改善粒细胞氧代谢，（3）抗生素与非氧依赖性粒细胞杀伤机制的协同作用，以及（4）基于抗生素被粒细胞摄取和在粒细胞内聚集的纯粹抗生素效应。虽然前三种机制被排除，但第四种机制很有可能；发现磺胺甲恶唑在粒细胞内的浓度达到细胞外水平的1.7倍，甲氧苄啶为4.1倍。已知的非穿透性抗生素青霉素G达到细胞外水平的0.3倍，已知的穿透性药物四环素达到细胞外水平的7.1倍。这些发现表明，磺胺甲恶唑/甲氧苄啶是一种特别适合长期预防细胞内吞噬细胞杀伤缺陷患者感染的抗生素组合。
