Co-trimoxazole
Encyclopedia
Trimethoprim/sulfamethoxazole or co-trimoxazole (abbreviated SXT, TMP-SMX, TMP-SMZ or TMP-sulfa) is a sulfonamide
antibiotic
combination of trimethoprim
and sulfamethoxazole
, in the ratio
of 1 to 5, used in the treatment of a variety of bacterial infections.
The name co-trimoxazole is the British Approved Name
, and has been marketed worldwide under many trade name
s including Septra (GSK
), Bactrim (Roche
), and various generic
preparations. Sources differ as to whether co-trimoxazole usually is a bactericide or a bacteriostatic agent
.
infections, renal and urinary tract infections, gastrointestinal tract
infections, skin and wound infections, septicaemias and other infections caused by sensitive organisms. The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole in various settings more recently.
The current British
Committee on Safety of Medicines (CSM) guidelines recommend limiting its use to:
Specific indications for its use include:
itself, but it is often prescribed to immunocompromised patients as Pneumocystis jirovecii
pneumonia
prophylaxis.
, agranulocytosis
, and severe liver damage (cholestatic hepatosis, hepatitis, liver necrosis, and fulminant liver failure). Due to displacement of bilirubin from albumin, there is an increased risk of kernicterus
in the fetus during the last six weeks of pregnancy. Also, renal impairment up to acute renal failure and anuria have been reported. These side effects are seen especially in the elderly and may be fatal. (Joint Formulary Committee, 2004). Both folic acid
and folinic acid
were found equally effective in reducing the adverse effects of TMP-SMX, so unless new evidence is found for folinic acid that shows it is more effective than the cheaper folic acid, the latter will continue to be the preferred treatment method.
Trimethoprim/sulfamethoxazole may have the following adverse reactions:
The synergy
between trimethoprim and sulfamethoxazole was first described in a series of in vitro
and in vivo
experiments published in the late 1960s. Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately; the reason is because they inhibit successive steps in the folate
synthesis pathway (see diagram below).
It is unclear whether this synergy occurs at doses used in humans, because, at the concentrations seen in blood and tissues, the ratio of trimethoprim to sulfamethoxazole is 1:20, which is less than the 1:5 ratio needed in vitro for synergy to occur.
Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate synthetase
. Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and, thus, are competitive inhibitors of the enzyme, inhibiting the production of dihydropteroic acid.
Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase
, inhibiting synthesis of tetrahydrofolic acid.
Folic acid
is an essential precursor in the de novo
synthesis of the DNA nucleoside
s thymidine
and uridine
. Bacteria are unable to take up folic acid from the environment (i.e., the infection host) and, thus, are dependent on their own de novo synthesis - inhibition of the enzyme starves the bacteria of two bases necessary for DNA replication
and transcription
.
names are listed here, but this list is not complete.
Sulfonamide (medicine)
Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
combination of trimethoprim
Trimethoprim
Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections.It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors...
and sulfamethoxazole
Sulfamethoxazole
Sulfamethoxazole is a sulfonamide bacteriostatic antibiotic.It is most often used as part of a synergistic combination with trimethoprim in a 5:1 ratio in co-trimoxazole , also known under trade names such as Bactrim, Septrin, or Septra; in Eastern Europe it is marketed as Biseptol...
, in the ratio
Ratio
In mathematics, a ratio is a relationship between two numbers of the same kind , usually expressed as "a to b" or a:b, sometimes expressed arithmetically as a dimensionless quotient of the two which explicitly indicates how many times the first number contains the second In mathematics, a ratio is...
of 1 to 5, used in the treatment of a variety of bacterial infections.
The name co-trimoxazole is the British Approved Name
British Approved Name
A British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...
, and has been marketed worldwide under many trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
s including Septra (GSK
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
), Bactrim (Roche
Hoffmann-La Roche
F. Hoffmann-La Roche Ltd. is a Swiss global health-care company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange....
), and various generic
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
preparations. Sources differ as to whether co-trimoxazole usually is a bactericide or a bacteriostatic agent
Bacteriostatic agent
A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily harming them otherwise. Depending on their application, bacteriostatic antibiotics, disinfectants, antiseptics and preservatives can be...
.
Clinical indications
Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed. Along with its associated greater incidence of adverse effects including allergic responses (see below), its widespread use has been restricted in many countries to very specific circumstances where its improved efficacy is demonstrated. It may be effective in a variety of upper and lower respiratory tractRespiratory tract
In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
infections, renal and urinary tract infections, gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
infections, skin and wound infections, septicaemias and other infections caused by sensitive organisms. The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole in various settings more recently.
The current British
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
Committee on Safety of Medicines (CSM) guidelines recommend limiting its use to:
- Pneumocystis pneumoniaPneumocystis pneumoniaPneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...
- Toxoplasmosis and nocardiosisNocardiosisNocardiosis is an infectious disease affecting either the lungs or the whole body . It is due to infection by bacterium of the genus Nocardia, most commonly Nocardia asteroides or Nocardia brasiliensis.It is most common in men, especially those with a compromised immune system...
- Acute exacerbations of chronic bronchitisBronchitisAcute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
and infections of the urinary tract where there is good rationale for use - Acute otitis mediaOtitis mediaOtitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...
in children where there is good rationale
Specific indications for its use include:
HIV
Being an antibiotic, co-trimoxazole does not have any activity against HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
itself, but it is often prescribed to immunocompromised patients as Pneumocystis jirovecii
Pneumocystis jirovecii
Pneumocystis jirovecii is a yeast-like fungus of the genus Pneumocystis. The causative organism of Pneumocystis pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. Prior to its discovery as a human-specific pathogen, P. jirovecii was known as P...
pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
prophylaxis.
Bacterial
- Infections caused by Listeria monocytogenes, Nocardia spp., StenotrophomonasStenotrophomonasStenotrophomonas is a genus of Gram-negative bacteria. With species ranging from common soil organisms to opportunistic human pathogens , the molecular taxonomy of the genus is still somewhat unclear....
maltophilia (Zanthomonas maltophilia) - Staphylococcus saprophyticusStaphylococcus saprophyticusStaphylococcus saprophyticus is a coagulase-negative species of Staphylococcus bacteria. S. saprophyticus is often implicated in urinary tract infections. S. saprophyticus is resistant to the antibiotic novobiocin, a characteristic that is used in laboratory identification to distinguish it from S...
infections presenting as urinary tract infectionUrinary tract infectionA urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
or cystitisCystitisCystitis is a term that refers to urinary bladder inflammation that results from any one of a number of distinct syndromes. It is most commonly caused by a bacterial infection in which case it is referred to as a urinary tract infection.-Signs and symptoms:... - Susceptible strains of Escherichia coliEscherichia coliEscherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
- MelioidosisMelioidosisMelioidosis is an infectious disease caused by a Gram-negative bacterium, Burkholderia pseudomallei, found in soil and water. It is of public health importance in endemic areas, particularly in Thailand and northern Australia. It exists in acute and chronic forms. Symptoms may include pain in...
- ShigellosisShigellosisShigellosis, also known as bacillary dysentery or Marlow Syndrome, in its most severe manifestation, is a foodborne illness caused by infection by bacteria of the genus Shigella. Shigellosis rarely occurs in animals other than humans and other primates like monkeys and chimpanzees...
- Whipple's diseaseWhipple's diseaseWhipple's disease is a rare, systemic infectious disease caused by the bacterium Tropheryma whipplei. First described by George Hoyt Whipple in 1907 and commonly considered a gastrointestinal disorder, Whipple's disease primarily causes malabsorption but may affect any part of the body including...
- Traveler's diarrheaTraveler's diarrheaTraveler's diarrhea , is the most common illness affecting travelers. An estimated 10 million people—20% to 50% of international travelers—develop it annually. TD is defined as three or more unformed stools in 24 hours passed by a traveler, commonly accompanied by abdominal cramps, nausea, and...
- Acne vulgarisAcne vulgarisAcne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...
Protozoan
- IsosporiasisIsosporiasisIsosporiasis is a human intestinal disease caused by the parasite Isospora belli. It is found worldwide, especially in tropical and subtropical areas. Infection often occurs in immuno-compromised individuals, notably AIDS patients, and outbreaks have been reported in institutionalized groups in the...
- prophylaxis of cerebral toxoplasmosisToxoplasmosisToxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
in HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
patients - Cyclospora cayetanensisCyclospora cayetanensisCyclospora cayetanensis is a protozoan that causes disease in humans, and perhaps other primates. It has been linked in the United States from fecally-contaminated imported raspberries and was virtually unknown before about 1990, but has been on the rise since...
Fungal
- Treatment and prophylaxis of pneumonia caused by Pneumocystis jirovecii (formerly identified as P. carinii and commonly seen in immunocompromised patients including those suffering from cancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
or HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
/AIDSAIDSAcquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
)
Side effects
There has been some concern about its use, however, since it has been associated with both frequent mild allergic reactions and serious adverse effects, including Stevens–Johnson syndrome, myelosuppression, mydriasisMydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
, agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
, and severe liver damage (cholestatic hepatosis, hepatitis, liver necrosis, and fulminant liver failure). Due to displacement of bilirubin from albumin, there is an increased risk of kernicterus
Kernicterus
Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin, which circulates...
in the fetus during the last six weeks of pregnancy. Also, renal impairment up to acute renal failure and anuria have been reported. These side effects are seen especially in the elderly and may be fatal. (Joint Formulary Committee, 2004). Both folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
and folinic acid
Folinic acid
Folinic acid or leucovorin , generally administered as calcium or sodium folinate , is an adjuvant used in cancer chemotherapy involving the drug methotrexate. It is also used in synergistic combination with the chemotherapy agent 5-fluorouracil.Levofolinic acid and its salts are the enantiopure...
were found equally effective in reducing the adverse effects of TMP-SMX, so unless new evidence is found for folinic acid that shows it is more effective than the cheaper folic acid, the latter will continue to be the preferred treatment method.
Trimethoprim/sulfamethoxazole may have the following adverse reactions:
- Allergic – Stevens–Johnson syndrome, toxic epidermal necrolysis, anaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
, allergic myocarditisMyocarditisMyocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
, erythema multiformeErythema multiformeErythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
, exfoliative dermatitisErythrodermaErythroderma is an inflammatory skin disease with erythema and scaling that affects nearly the entire cutaneous surface....
, angiodema, drug fever, chills, Henoch–Schönlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
and rash. In addition, periarteritis nodosa and systemic lupus erythematosis have been reported. - Endocrine – The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.
- Gastrointestinal – Hepatitis, including cholestatic jaundice and hepatic necrosis, elevation of serum transaminase and bilirubin, pseudo-membranous enterocolitisEnterocolitisEnterocolitis is an inflammation of the colon and small intestine. However, most conditions are categorized as one or the other of the following:* Enteritis is the inflammation of the small intestine...
, pancreatitisPancreatitisPancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
, stomatitisStomatitisStomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth...
, glossitisGlossitisGlossitis is inflammation of the tongue. It causes the tongue to swell and change color. Finger-like projections on the surface of the tongue may be lost, causing the tongue to appear smooth....
, nausea, emesis, abdominal pain, diarrhea, anorexia. - Genitourinary – Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguriaOliguriaOliguria is the low output of urine, It is clinically classified as an output below 300-500ml/day. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome, multiple organ dysfunction syndrome, urinary...
and anuriaAnuriaAnuria means nonpassage of urine, in practice is defined as passage of less than 50 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage renal...
, and crystalluriaCrystalluriaCrystalluria refers to crystals found in the urine when performing a urine test. Crystalluria is considered as one of the side effects of sulphonamides.-Clinical significance:It can be an indication of urolithiasis.It can be associated with cysteinuria....
. - Hematologic – AgranulocytosisAgranulocytosisGranulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
, aplastic anemiaAplastic anemiaAplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. The condition, per its name, involves both aplasia and anemia...
, thrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, leukopeniaLeukopeniaLeukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
, neutropeniaNeutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, hemolytic anemia, megaloblastic anemia, hypoprothrominemia, methemoglobinemiaMethemoglobinemiaMethemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is an oxidized form of hemoglobin that has an increased affinity for oxygen, resulting in a reduced ability to release oxygen to tissues. The oxygen–hemoglobin...
, eosinophiliaEosinophiliaEosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
. - Metabolic – HyperkalemiaHyperkalemiaHyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
, hyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
. - Musculoskeletal – ArthralgiaArthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and myalgiaMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
. - Neurologic – Aseptic meningitisAseptic meningitisAseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
, convulsions, peripheral neuritis, ataxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, vertigo, tinnitus, headache. - Psychiatric – Hallucinations, depression, apathy, nervousness.
- Respiratory System – Cough, shortness of breath, and pulmonary infiltrates.
- Miscellaneous – Weakness, fatigue, insomnia.
Mechanism of action
Synergy
Synergy may be defined as two or more things functioning together to produce a result not independently obtainable.The term synergy comes from the Greek word from , , meaning "working together".-Definitions and usages:...
between trimethoprim and sulfamethoxazole was first described in a series of in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
and in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
experiments published in the late 1960s. Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately; the reason is because they inhibit successive steps in the folate
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
synthesis pathway (see diagram below).
It is unclear whether this synergy occurs at doses used in humans, because, at the concentrations seen in blood and tissues, the ratio of trimethoprim to sulfamethoxazole is 1:20, which is less than the 1:5 ratio needed in vitro for synergy to occur.
Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate synthetase
Dihydropteroate synthetase
Dihydropteroate synthetase is an enzyme classified under . It produces dihydropteroate in bacteria, but it is not expressed in most eukaryotes including humans...
. Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and, thus, are competitive inhibitors of the enzyme, inhibiting the production of dihydropteroic acid.
Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase
Dihydrofolate reductase
- Function :Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids...
, inhibiting synthesis of tetrahydrofolic acid.
Folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
is an essential precursor in the de novo
De novo synthesis
De novo synthesis refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to their being recycled after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as...
synthesis of the DNA nucleoside
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
s thymidine
Thymidine
Thymidine is a chemical compound, more precisely a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine in double-stranded DNA...
and uridine
Uridine
Uridine is a molecule that is formed when uracil is attached to a ribose ring via a β-N1-glycosidic bond.If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine....
. Bacteria are unable to take up folic acid from the environment (i.e., the infection host) and, thus, are dependent on their own de novo synthesis - inhibition of the enzyme starves the bacteria of two bases necessary for DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
and transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
.
Trade names
Co-trimoxazole is manufactured and sold by many different companies. Some of the brandBrand
The American Marketing Association defines a brand as a "Name, term, design, symbol, or any other feature that identifies one seller's good or service as distinct from those of other sellers."...
names are listed here, but this list is not complete.
- Bactrim, Bactrimel (Roche)
- Co-trimoxazole (SandozSandozFounded in 2003, Sandoz presently is the generic drug subsidiary of Novartis, a multinational pharmaceutical company. The company develops, manufactures and markets generic drugs as well as pharmaceutical and biotechnological active ingredients....
) - Cotrim
- Septrin, Septra (GlaxoSmithKlineGlaxoSmithKlineGlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
and formerly Burroughs Wellcome) - Sulfatrim
- Biseptol
- Trisul