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Pharmacotherapy 1981Trimethoprim has recently been marketed as a single-entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was...
Trimethoprim has recently been marketed as a single-entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram-positive aerobic cocci and some gram-negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition. Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by E. coli, and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim-sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging.
Topics: Bacterial Infections; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Pregnancy; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections
PubMed: 6985448
DOI: 10.1002/j.1875-9114.1981.tb03548.x -
Medecine Et Maladies Infectieuses Jun 2017Already used in various countries, trimethoprim (TMP) was withdrawn from the French market in 1990, but should be soon available again. This article reviews the... (Review)
Review
Already used in various countries, trimethoprim (TMP) was withdrawn from the French market in 1990, but should be soon available again. This article reviews the experience of TMP use around the world and its current use in Europe. Label use and guidelines only recommend the use of TMP for the treatment of urinary tract infections (UTI). Compared with co-trimoxazole (Co-T), a combination of TMP and sulfamethoxazole (SMX), TMP has (a) a similar resistance rate among Escherichia coli strains (estimated between 10 and 20% in uncomplicated cystitis), (b) a similar clinical efficacy for cystitis prevention and treatment, (c) a lower toxicity (as severe toxicity adverse effects of Co-T come from its sulfonamide component), (d) limited data for the treatment of pyelonephritis and male UTIs, and (e) an important impact on the microbiota. TMP should thus be indicated in the third-line empirical treatment of acute uncomplicated cystitis (sparing fluoroquinolones and nitrofurantoin), in the prevention of recurrent acute cystitis when an antibiotic prophylaxis is required (possibly in first line), and in the treatment of documented acute cystitis at risk of complications. Updated data on the epidemiology of resistance to TMP per clinical pictures is now required. The bactericidal effect of TMP should also be confirmed on recent strains (although limited recent data suggests a bactericidia similar to that of Co-T) and its clinical efficacy should be evaluated in pyelonephritis and male UTI.
Topics: Anti-Bacterial Agents; Cystitis; Drug Resistance, Bacterial; Drug Utilization; Escherichia coli; Escherichia coli Infections; Fosfomycin; France; Humans; Practice Guidelines as Topic; Product Recalls and Withdrawals; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections
PubMed: 28043762
DOI: 10.1016/j.medmal.2016.12.001 -
The Medical Clinics of North America Jan 1982
Review
Topics: Bacteria; Bacterial Infections; Chemical Phenomena; Chemistry; Drug Combinations; Humans; Kinetics; Sulfamethoxazole; Trimethoprim
PubMed: 7038324
DOI: 10.1016/s0025-7125(16)31448-1 -
Mayo Clinic Proceedings Oct 1987The antimicrobial combination of trimethoprim and sulfamethoxazole is active in vitro against a variety of gram-positive and gram-negative bacteria. Clinically, it is...
The antimicrobial combination of trimethoprim and sulfamethoxazole is active in vitro against a variety of gram-positive and gram-negative bacteria. Clinically, it is useful for treatment and prophylaxis of various infections of the genitourinary tract and certain infections of the respiratory and gastrointestinal tracts. Trimethoprim-sulfamethoxazole by itself or in combination with other antimicrobial agents is indicated for most Nocardia asteroides infections. It is the antimicrobial agent of choice for Pneumocystis carinii pneumonia. The drug is relatively nontoxic in patients who do not have acquired immunodeficiency syndrome (AIDS), and it is available in oral and intravenous forms. The native compounds and the metabolites of trimethoprim and sulfamethoxazole are excreted primarily in the urine. When the creatinine clearance decreases to less than 30 ml/min, the dosage of trimethoprim-sulfamethoxazole should be adjusted.
Topics: Bacterial Infections; Drug Combinations; Drug Therapy, Combination; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 3498863
DOI: 10.1016/s0025-6196(12)65049-6 -
Annals of Internal Medicine Jun 1984Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration... (Review)
Review
Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration into tissues, including the cerebrospinal fluid. Clinical experience shows that trimethoprim-sulfamethoxazole may be beneficial in the treatment of gram-negative bacillary meningitis caused by organisms only moderately susceptible to third-generation cephalosporins (Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotic agents (Pseudomonas cepacia, Acinetobacter). The success of trimethoprim-sulfamethoxazole in the treatment of four patients with Staphylococcus aureus and two patients with Listeria monocytogenes meningitis shows that this drug may also be useful in treating infrequent types of gram-positive meningitis.
Topics: Adolescent; Adult; Animals; Bacteria; Child, Preschool; Drug Combinations; Enterobacteriaceae Infections; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Kinetics; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 6372565
DOI: 10.7326/0003-4819-100-6-881 -
Lancet (London, England) Mar 1980
Topics: Bacteria; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Sulfonamides; Trimethoprim; Urinary Tract Infections
PubMed: 6102239
DOI: No ID Found -
The Journal of Antibiotics Jan 2020The development of new mechanisms of resistance among pathogens, the occurrence and transmission of genes responsible for antibiotic insensitivity, as well as cancer... (Review)
Review
The development of new mechanisms of resistance among pathogens, the occurrence and transmission of genes responsible for antibiotic insensitivity, as well as cancer diseases have been a serious clinical problem around the world for over 50 years. Therefore, intense searching of new leading structures and active substances, which may be used as new drugs, especially against strain resistant to all available therapeutics, is very important. Dihydrofolate reductase (DHFR) has attracted a lot of attention as a molecular target for bacterial resistance over several decades, resulting in a number of useful agents. Trimethoprim (TMP), (2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine) is the well-known dihydrofolate reductase inhibitor and one of the standard antibiotics used in urinary tract infections (UTIs). This review highlights advances in design, synthesis, and biological evaluations in structural modifications of TMP as DHFR inhibitors. In addition, this report presents the differences in the active site of human and pathogen DHFR. Moreover, an excellent review of DHFR inhibition and their relevance to antimicrobial and parasitic chemotherapy was presented.
Topics: Anti-Bacterial Agents; Drug Design; Drug Development; Drug Discovery; Folic Acid Antagonists; Humans; Tetrahydrofolate Dehydrogenase; Trimethoprim
PubMed: 31578455
DOI: 10.1038/s41429-019-0240-6 -
Comprehensive Therapy May 1976
Review
Topics: Bacterial Infections; Drug Combinations; Drug Resistance, Microbial; Drug Synergism; Humans; Microbial Sensitivity Tests; Protein Binding; Sulfamethoxazole; Trimethoprim; Urinary Tract Infections
PubMed: 776520
DOI: No ID Found -
Drug Intelligence & Clinical Pharmacy May 1981The recent marketing of trimethoprim (TMP) as a single drug has resulted in interest in the use of this drug to treat common infections. The history and antibacterial... (Review)
Review
The recent marketing of trimethoprim (TMP) as a single drug has resulted in interest in the use of this drug to treat common infections. The history and antibacterial properties of TMP are reviewed. Indications for the clinical use of TMP are presented, and possible new uses for the drug are considered. The significance of adverse effects is discussed. The pharmacokinetic properties of TMP are reviewed with particular emphasis on the renal handling of the drug and its advantages over TMP/sulfonamide combinations in relation to renal function and toxicity.
Topics: Bacterial Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Kidney Diseases; Kinetics; Metabolic Clearance Rate; Tissue Distribution; Trimethoprim
PubMed: 7023899
DOI: 10.1177/106002808101500502 -
Indian Pediatrics Nov 1987
Topics: Adolescent; Bacterial Infections; Child; Drug Combinations; Drug Resistance, Microbial; Humans; Infant; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 3502468
DOI: No ID Found