Chronic granulomatous disease: mode of action of sulfamethoxazole/trimethoprim.

Abstract

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.

• Authors: F K Gmünder, R A Seger
• Journal: Pediatric research (Pediatr Res) Vol. 15 Issue 12 Pg. 1533-7 (Dec 1981) ISSN: 0031-3998 [Print] United States
• PMID: 7322675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Trimethoprim
• Catalase
• Sulfamethoxazole

Topics

• Catalase (antagonists & inhibitors)
• Drug Therapy, Combination
• Granulocytes (drug effects, metabolism)
• Granulomatous Disease, Chronic (blood, drug therapy)
• Humans
• In Vitro Techniques
• Neutrophils (drug effects)
• Oxygen Consumption (drug effects)
• Staphylococcus aureus (drug effects)
• Sulfamethoxazole (pharmacology)
• Trimethoprim (pharmacology)