Sulfamethoxazole. Medical search

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)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.Trimethoprim-Sulfamethoxazole Combination: This drug combination has proved to be an effective therapeutic agent with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.Dapsone: A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Drug Hypersensitivity: Immunologically mediated adverse reactions to medicinal substances used legally or illegally.Pneumonia, Pneumocystis: A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis.Trimethoprim Resistance: Nonsusceptibility of bacteria to the action of TRIMETHOPRIM.Sulfisoxazole: A short-acting sulfonamide antibacterial with activity against a wide range of gram- negative and gram-positive organisms.Drug Resistance, Bacterial: The ability of 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).Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Integrons: DNA elements that include the component genes and insertion site for a site-specific recombination system that enables them to capture mobile gene cassettes.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Pneumocystis jirovecii: A species of PNEUMOCYSTIS infecting humans and causing PNEUMOCYSTIS PNEUMONIA. It also occasionally causes extrapulmonary disease in immunocompromised patients. Its former name was Pneumocystis carinii f. sp. hominis.Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects.Tropheryma: A genus of gram-positive bacteria in the family Cellulomonadaceae.Urinary Tract Infections: Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA.Stenotrophomonas maltophilia: A species of STENOTROPHOMONAS, formerly called Xanthomonas maltophilia, which reduces nitrate. It is a cause of hospital-acquired ocular and lung infections, especially in those patients with cystic fibrosis and those who are immunosuppressed.Sulfadiazine: One of the short-acting SULFONAMIDES used in combination with PYRIMETHAMINE to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections.Sulfamethoxypyridazine: A sulfanilamide antibacterial agent.Dihydropteroate Synthase: An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15.4-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.Nocardia Infections: Infections with bacteria of the genus NOCARDIA.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).Whipple Disease: A chronic systemic infection by a gram-positive bacterium, Tropheryma whippelii, mainly affecting the SMALL INTESTINE but also the JOINTS; CARDIOVASCULAR SYSTEM; and the CENTRAL NERVOUS SYSTEM. The disease is characterized by fat deposits in the INTESTINAL MUCOSA and LYMPH NODES, malabsorption, DIARRHEA with fatty stools, MALNUTRITION, and ARTHRITIS.Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Escherichia coli Infections: Infections with bacteria of the species ESCHERICHIA COLI.Shigella sonnei: A lactose-fermenting bacterium causing dysentery.Nocardia: A genus of gram-positive, aerobic bacteria whose species are widely distributed and are abundant in soil. Some strains are pathogenic opportunists for humans and animals.Anti-Infective Agents, Urinary: Substances capable of killing agents causing urinary tract infections or of preventing them from spreading.Megaloblasts: Red blood cell precursors, corresponding to ERYTHROBLASTS, that are larger than normal, usually resulting from a FOLIC ACID DEFICIENCY or VITAMIN B 12 DEFICIENCY.Folic Acid Antagonists: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)Drug Eruptions: Adverse cutaneous reactions caused by ingestion, parenteral use, or local application of a drug. These may assume various morphologic patterns and produce various types of lesions.Pneumocystis: A genus of ascomycetous FUNGI, family Pneumocystidaceae, order Pneumocystidales. It includes various host-specific species causing PNEUMOCYSTIS PNEUMONIA in humans and other MAMMALS.Vibrio cholerae O1: Strains of VIBRIO CHOLERAE containing O ANTIGENS group 1. All are CHOLERA-causing strains (serotypes). There are two biovars (biotypes): cholerae and eltor (El Tor).Shigella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that ferments sugar without gas production. Its organisms are intestinal pathogens of man and other primates and cause bacillary dysentery (DYSENTERY, BACILLARY).Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.Hydroxylamines: Organic compounds that contain the (-NH2OH) radical.Salmonella enterica: A subgenus of Salmonella containing several medically important serotypes. The habitat for the majority of strains is warm-blooded animals.Enterobacteriaceae: A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock.Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Electrophoresis, Gel, Pulsed-Field: Gel electrophoresis in which the direction of the electric field is changed periodically. This technique is similar to other electrophoretic methods normally used to separate double-stranded DNA molecules ranging in size up to tens of thousands of base-pairs. However, by alternating the electric field direction one is able to separate DNA molecules up to several million base-pairs in length.Nalidixic Acid: A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA GYRASE.Tablets: Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is VIBRIO CHOLERAE. This condition can lead to severe dehydration in a matter of hours unless quickly treated.Sulfonamides: A group of compounds that contain the structure SO2NH2.Gram-Negative Bacterial Infections: Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)

Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: implications for differences in adverse drug reactions. (1/488)

Differences in the incidence of adverse drug reactions to trimethoprim-sulfamethoxazole and dapsone may result from differences in the formation, disposition, toxicity, and/or detoxification of their hydroxylamine metabolites. In this study, we examine whether differences in the biochemical processing of sulfamethoxazole hydroxylamine (SMX-NOH) and dapsone hydroxylamine (DDS-NOH) by erythrocytes [red blood cells (RBCs)] contribute to this differential incidence. The methemoglobin (MetHgb)-forming capacity of both metabolites was compared after a 60-min incubation with washed RBCs from four healthy human volunteers. DDS-NOH was significantly more potent (P =.004) but equally efficacious with SMX-NOH in its ability to form MetHgb. The elimination of potential differences in disposition by lysing RBCs did not change the MetHgb-forming potency of either hydroxylamine. At pharmacologically relevant concentrations, greater reduction to the parent amine occurred with DDS-NOH. Maintenance of MetHgb-forming potency was dependent on recycling with glutathione, but no difference in cycling efficiency was observed between DDS-NOH and SMX-NOH. In contrast, the pharmacodynamics of hydroxylamine-induced MetHgb formation were not changed by pretreatment with the glucose 6-phosphate dehydrogenase inhibitor epiandrosterone or by compounds that alter normal antioxidant enzyme activity. Methylene blue, which stimulates NADPH-dependent MetHgb reductase activity, decreased MetHgb levels but did not alter the differential potency of these hydroxylamines. DDS-NOH was also significantly more potent when incubated with purified human hemoglobin A0. Collectively, these data suggest that the inherently greater reactivity of DDS-NOH with hemoglobin, the greater conversion of DDS-NOH to its parent amine, and potential differences in disposition of hydroxylamine metabolites may contribute to the preferential development of dapsone-induced hemotoxicity and sulfamethoxazole-induced hypersensitivity reactions. (+info)

Renal stones and urinary infection: a study of antibiotic treatment. (2/488)

Twenty-two patients in whom renal calculi and urinary infection were closely associated were studied over two to five years. Four patients had previously had stones surgically removed, and five underwent pyelolithotomy during the course of the study. Urinary infection was treated with an appropriate antibacterial agent, and treatment was followed by long-term prophylaxis, usually with cotrimoxazole. A sterile urine was maintained for long periods in all these patients. In four patients, however, apparent stone growth occurred while the urine was sterile. On entering the study 21 of the 22 patients complained of symptoms. After treatment 19 of the 20 patients who were still attending were symptom-free. Six of the 22 patients entered the study with raised levels of serum creatinine; levels fell in four and remained raised in two. This antibacterial regimen, either alone or after surgery, will usually relieve symptoms and may prevent deterioration of renal function. (+info)

Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity. (3/488)

1. Bioactivation of sulphamethoxazole (SMX) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity. We have therefore examined the cellular metabolism, disposition and conjugation of SMX and its metabolites in vitro. 2. Flow cytometry revealed binding of N-hydroxy (SMX-NHOH) and nitroso (SMX-NO) metabolites of SMX, but not of SMX itself, to the surface of viable white blood cells. Cellular haptenation by SMX-NO was reduced by exogenous glutathione (GSH). 3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine (CYS), GSH, human peripheral blood cells and plasma, suggesting that this is an important and ubiquitous bioinactivation mechanism. 4. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer, and to a lesser extent, in cells and plasma. 5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability, with SMX having no effect. Lymphocytes were significantly (P<0.05) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils. 6. Partitioning of SMX-NHOH into red blood cells was significantly (P<0.05) lower than with the hydroxylamine of dapsone. 7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism. If an imbalance exists, haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur, and may result in drug hypersensitivity. (+info)

Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum. (4/488)

A multicenter study was conducted to assess the interlaboratory reproducibility of broth microdilution testing of the more common rapidly growing pathogenic mycobacteria. Ten isolates (four Mycobacterium fortuitum group, three Mycobacterium abscessus, and three Mycobacterium chelonae isolates) were tested against amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, sulfamethoxazole, and tobramycin (M. chelonae only) in four laboratories. At each site, isolates were tested three times on each of three separate days (nine testing events per isolate) with a common lot of microdilution trays. Agreement among MICs (i.e., mode +/- 1 twofold dilution) varied considerably for the different drug-isolate combinations and overall was best for cefoxitin (91.7 and 97.2% for one isolate each and 100% for all others), followed by doxycycline, amikacin, and ciprofloxacin. Agreement based on the interpretive category, using currently suggested breakpoints, also varied and overall was best for doxycycline (97.2% for one isolate and 100% for the rest), followed by ciprofloxacin and clarithromycin. Reproducibility among MICs and agreement by interpretive category was most variable for imipenem. Based on results reported from the individual sites, it appears that inexperience contributed significantly to the wide range of MICs of several drugs, especially clarithromycin, ciprofloxacin, and sulfamethoxazole. New interpretive guidelines are presented for the testing of M. fortuitum against clarithromycin; M. abscessus and M. chelonae against the aminoglycosides; and all three species against cefoxitin, doxycycline, and imipenem. (+info)

Pharmacokinetics and efficacy of trimethoprim-sulfamethoxazole in the treatment of gastroenteritis in children. (5/488)

In vitro studies indicates that the constitutents of the drug combination co-trimoxazole are synergistic against Salmonella and effective against shigella isolated from children ill with gastroenteritis. The drug is well absorbed in children with gastroenteritis due to a variety of causes and is distributed, excreted and metabolized in a manner similar to that seen in normal adult volunteers. The drug is tolerated well by children with gastroenteritis even in very high dosages. Despite its in vitro and pharmacokinetic advantages, co-trimoxazole was not any more efficient than any other durg or no therapy in the treatment of salmonella gastroenteritis; it seems to have a role, however, in the treatment of typhoid fever and may be life-saving in patients infected with ampicillin- and chloramphenical-resistant strains. It is also effective in the treatment of shigella gastroenteritis and is recommended where ampicillin-resistant strains are encountered. Its potential usefulenss for the treatment of other bacterial causes of gastroenteritis in children must be evaluated by further controlled therapeutic trials. (+info)

Cytotoxicity of sulfonamide reactive metabolites: apoptosis and selective toxicity of CD8(+) cells by the hydroxylamine of sulfamethoxazole. (6/488)

Treatment with sulfonamide antibiotics in HIV-infected patients is associated with a high incidence (> 40%) of adverse drug events, including severe hypersensitivity reactions. Sulfonamide reactive metabolites have been implicated in the pathogenesis of these adverse reactions. Sulfamethoxazole hydroxylamine (SMX-HA) induces lymphocyte toxicity and suppression of proliferation in vitro; the mechanism(s) of these immunomodulatory effects remain unknown. We investigated the cytotoxicity of SMX-HA via apoptosis on human peripheral blood mononuclear cells and purified cell subpopulations in vitro. CD19(+), CD4(+), and CD8(+) cells were isolated from human peripheral blood by positive selection of cell surface molecules by magnetic bead separation. SMX-HA induced significant CD8(+) cell death (67 +/- 7%) at 100 microM SMX-HA, with only minimal CD4(+) cell death (8 +/- 4%). No significant subpopulation toxicity was shown when incubated with parent drug (SMX). Flow cytometry measuring phosphatidylserine externalization 24 h after treatment with 100 microM and 400 microM SMX-HA revealed 14.1 +/- 0.7% and 25. 6 +/- 4.2% annexin-positive cells, respectively, compared to 3.7 +/- 1.2% in control PBMCs treated with 400 microM SMX. Internucleosomal DNA fragmentation was observed in quiescent and stimulated PBMCs 48 h after incubation with SMX-HA. Our data show that CD8(+) cells are highly susceptible to the toxic effects of SMX-HA through enhanced cell death by apoptosis. (+info)

Is hydroxylamine-induced cytotoxicity a valid marker for hypersensitivity reactions to sulfamethoxazole in human immunodeficiency virus-infected individuals? (7/488)

Hypersensitivity (HS) reactions to sulfonamides and sulfones continue to limit their use in human immunodeficiency virus (HIV)-infected individuals. In vitro cytotoxicity of hydroxylamine metabolites toward peripheral blood mononuclear cells (PBMCs) has been proposed as a marker for these HS reactions. To test the validity of this in vitro system, we determined the selective susceptibility of PBMCs from HIV-infected patients to the cytotoxic effects of hydroxylamine metabolites of sulfamethoxazole (SMX) and dapsone (DDS). Concentration-cytotoxic response data were collected using PBMCs from 12 sulfa-HS (10 SMX-HS and 2 SMX/DDS-HS) and 10 sulfa-tolerant HIV-infected individuals. Although sulfamethoxazole hydroxylamine (SMX-NOH) and dapsone hydroxylamine (DDS-NOH) both caused concentration-dependent increases in cell death, DDS-NOH was significantly more potent in each subject (P <.0001). A comparison of a variety of mean data for sulfa-HS and -tolerant patient populations failed to demonstrate the increased susceptibility of PBMCs from HS patients, noted by others, to either SMX-NOH or DDS-NOH. Moreover, any trend toward an increased susceptibility of PBMCs from HS patients was eliminated when adjusted for control cell death. PBMCs from sulfa-HS patients showed significantly greater susceptibility to the stress of short term in vitro incubation (P <. 02). Mean (S.D.) vehicle control cell death values were 24.1% (7.6%) for HS patients and 17.1% (4.4%) for tolerant patients. No significant correlation was observed between hydroxylamine-induced or control cell death and any of the recorded clinical parameters. Although several potential reasons are proposed to explain the disparity with past investigations, the data suggest that in vitro cytotoxicity is not a valid marker for HS reactions in HIV-infected individuals using currently accepted experimental procedures. (+info)

Cerebral toxoplasmosis - a late complication of allogeneic haematopoietic stem cell transplantation. (8/488)

Toxoplasma gondii infection reactivation predominantly occurs among patients after allogeneic haematopoietic stem cell transplantation. Mostly, reactivation occurs during first 3 months after transplant, especially when risk factors are present. We report a case of late cerebral toxoplasmosis reactivation, which was probably triggered by a brief course of corticosteroids, administered for chronic graft-versus-host disease (cGVHD). In the presence of risk factors, such as cGVHD, prophylactic treatment for toxoplasmosis should be reinstituted; Trimethoprim-sulfamethoxasole most probably prevented earlier reactivation of toxoplasmosis in our patient. (+info)

Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: implications for differences in adverse drug reactions. (1/488)

Renal stones and urinary infection: a study of antibiotic treatment. (2/488)

Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity. (3/488)

Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum. (4/488)

Pharmacokinetics and efficacy of trimethoprim-sulfamethoxazole in the treatment of gastroenteritis in children. (5/488)

Cytotoxicity of sulfonamide reactive metabolites: apoptosis and selective toxicity of CD8(+) cells by the hydroxylamine of sulfamethoxazole. (6/488)

Is hydroxylamine-induced cytotoxicity a valid marker for hypersensitivity reactions to sulfamethoxazole in human immunodeficiency virus-infected individuals? (7/488)

Cerebral toxoplasmosis - a late complication of allogeneic haematopoietic stem cell transplantation. (8/488)

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