BACKGROUND Trimethoprim [2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine] is an antifolate drug. It selectively inhibits the bacterial dihydrofolate reductase (DHFR) enzyme. RESULTS In the crystal structures of trimethoprim (TMP)-hydrogen phthalate (1) and trimethoprim-hydrogen adipate (2), one of the N atoms of the pyrimidine ring is protonated and it interacts with the deprotonated carb...

Members of the genus Neisseria are relatively nonsusceptible to trimethoprim, an inhibitor of dihydrofolate reductase. For example, the minimal inhibitory concentration (MIC) of trimethoprim for N. gonorrhoeae ranges from 2 to 70 mug/ml, whereas the MIC for Escherichia coli is 0.2 mug/ml or less. In an effort to understand this difference, dihydrofolate reductase was partially purified from fiv...

Out of 210 isolates of Haemophilus influenzae obtained from the sputum of 63 patients with chronic respiratory infections 109 (52%) were resistant to trimethoprim-sulphamethoxazole by the disc test. The minimal inhibitory concentrations of trimethoprim for 17 out of 18 strains recorded as resistant were 10 mug/ml or higher. Resistant strains were isolated from time to time from 32 (82%) out of ...

Co-trimoxazole is a combination antibiotic made up of trimethoprim and sulphamethoxazole that is first line treatment for Pneumocystis jirovecii pneumonia (PJP). Hyperkalaemia is a relatively common side effect of the trimethoprim component of co-trimoxazole but it is not well recognised by clinicians. The mechanism of action causing hyperkalaemia due to trimethoprim is similar to the potassium...

Treatment with either pentamidine isethionate or trimethoprim-sulfamethoxazole significantly reduces the mortality of Pneumocystis carinii pneumonia. It is not known whether a combination might act in an additive, synergistic, or antagonistic manner. We studied the interaction of these two agents in the steroid-conditioned rat model of pneumocystosis. Of animals receiving pentamidine alone, 48%...

OBJECTIVES Iclaprim is a novel 2,4-diaminopyrimidine that exhibits potent, rapid bactericidal activity against major Gram-positive pathogens, including methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus, and is currently in clinical development for the treatment of complicated skin and skin structure infections. An understanding of the known mechanism of resistanc...

Various sulfonamides and trimethoprim were given orally twice a day to healthy volunteers. The drug concentrations in serum and tissue fluid from skin blisters were determined concomitantly. Maximal serum concentrations were obtained after 1 to 3 h. Absorption of sulfacarbamide and sulfadimidine was more rapid than for sulfadiazine, sulfamethoxazole, and trimethoprim. The penetration to blister...