Mechanisms of resistance to trimethoprim, the sulfonamides, and trimethoprim-sulfamethoxazole. 1982

R L Then

A variety of different mechanisms are known to be responsible for either natural or acquired resistance to trimethoprim, the sulfonamides, or trimethoprim-sulfonamide combinations. Some mechanisms of obvious clinical importance have been studied intensively. Among these are unique bypass mechanisms such as the synthesis of drug-resistant, plasmid-coded dihydrofolate reductase or dihydropteroate synthetase; such mechanisms so far have not been encountered in studies of resistance to other drugs. This article focuses on several mechanisms of resistance that have rarely been discussed in the past, including metabolic alteration of trimethoprim or the sulfonamides and hyperproduction of p-aminobenzoic acid, and on the simultaneous presence of more than one mechanism. The role of these mechanisms in the resistance of clinical isolates requires further investigation.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010129 4-Aminobenzoic Acid An aminobenzoic acid isomer that combines with pteridine and GLUTAMIC ACID to form FOLIC ACID. The fact that 4-aminobenzoic acid absorbs light throughout the UVB range has also resulted in its use as an ingredient in SUNSCREENS. PABA,p-Aminobenzoic Acid,para-Aminobenzoic Acid,4-Aminobenzoic Acid, Potassium Salt,Aminobenzoic Acid (USP),Epit Vit,Epitelplast,Hachemina,Magnesium para-Aminobenzoate,Pabasan,Paraminan,Paraminol,Potaba,Potassium 4-Aminobenzoate,Potassium Aminobenzoate,4 Aminobenzoic Acid,4 Aminobenzoic Acid, Potassium Salt,4-Aminobenzoate, Potassium,Aminobenzoate, Potassium,Potassium 4 Aminobenzoate,p Aminobenzoic Acid,para Aminobenzoic Acid,para-Aminobenzoate, Magnesium
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D001419 Bacteria One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive. Eubacteria
D013420 Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p208) Sulfamethylisoxazole,Gantanol,Sulfisomezole,Sulphamethoxazole
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D013941 Thymine One of four constituent bases of DNA. 5-Methyluracil,5 Methyluracil
D014295 Trimethoprim A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported. Proloprim,Trimpex

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