Trimethoprim/sulfamethoxazole, sold under the trade names Bactrim, Cotrim (a short form of the

British Approved Name A British Approved Name (BAN) is the official, non-proprietary, or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia (BP). The BAN is also the official name used in some countries around the world, because ...

, Co-trimoxazole) and Septra, among others, is a

fixed-dose combination A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

medication used to treat a variety of

bacterial infection Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are beneficial but others can cause infectious diseases. The number of t ...

s. It consists of one part

trimethoprim Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia ...

to five parts

sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Escherichia coli' ...

. It is used to treat

urinary tract infections A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (pye ...

methicillin-resistant Staphylococcus aureus Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

(MRSA) skin infections,

travelers' diarrhea Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, ...

, respiratory tract infections, and

cholera Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

, among others. It is used both to treat and prevent

pneumocystis pneumonia ''Pneumocystis'' pneumonia (PCP), also known as ''Pneumocystis jirovecii'' pneumonia (PJP), is a form of pneumonia that is caused by the yeast-like fungus '' Pneumocystis jirovecii''. ''Pneumocystis'' specimens are commonly found in the lungs o ...

and

toxoplasmosis Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or month ...

in people with

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

and other causes of immunosuppression. It can be given

orally The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

(swallowed by mouth) or

intravenous infusion Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

(slowly injected into a vein with an IV). Trimethoprim/sulfamethoxazole is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 143rd most commonly prescribed medication in the United States, with more than 3million prescriptions.

Medical uses

Trimethoprim/sulfamethoxazole generally kills bacteria, by blocking the microorganisms' ability to make and to use folate.

''Pneumocystis jirovecii'' pneumonia

Trimethoprim/sulfamethoxazole (TMP/SMX) is the medicine most commonly used to prevent ''Pneumocystis jirovecii'' pneumonia (PCP) People who get ''Pneumocystis'' pneumonia have a medical condition that weakens their

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

, like

, or take medicines (such as

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

and

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

s) that reduce the body's ability to fight

bacterial Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...

and

viral infections A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, ...

. People with HIV/AIDS are less likely to get ''Pneumocystis'' pneumonia as a result of

antiretroviral therapy The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of mul ...

(ART). However, ''Pneumocystis'' pneumonia is still a substantial public health problem. Most of what is scientifically known about ''Pneumocystis'' pneumonia and its treatment comes from studying people with HIV/AIDS.

Susceptibility

Organisms against which trimethoprim/sulfamethoxazole can be effective include: * ''

Acinetobacter ''Acinetobacter'' is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. ''Acinetobacter'' species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification. They are important ...

'' spp. * ''

Aeromonas ''Aeromonas'' is a genus of Gram-negative, Facultative anaerobic organism, facultative anaerobic, rod-shaped, bacteria that morphologically resemble members of the family Enterobacteriaceae. Most of the 14 described species have been associated w ...

'' spp. * ''

Alcaligenes ''Alcaligenes'' is a genus of Gram-negative, aerobic, rod-shaped bacteria in the order of Burkholderiales, family Alcaligenaceae. History The type species, ''A. faecalis'', was first isolated from stale beer by Johannes Petruschky in 1896. H ...

''/''

Achromobacter ''Achromobacter'' is a genus of bacteria, included in the family Alcaligenaceae in the order Burkholderiales. The cells are Gram-negative straight rods and are motile by using one to 20 peritrichous flagella. They are strictly aerobic and are fo ...

'' spp. * ''

Bartonella henselae ''Bartonella henselae'', formerly ''Rochalimæa henselae'', is a bacterium that is the causative agent of cat-scratch disease ( bartonellosis). It primarily infects red blood cells and endothelial cells and is transmitted to humans through scratch ...

'' * ''

Bordetella pertussis ''Bordetella pertussis'' is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus bacterium of the genus ''Bordetella'', and the causative agent of pertussis or whooping cough. Its virulence factors include pertussis toxin, adenyla ...

'' (

pertussis Whooping cough ( or ), also known as pertussis or the 100-day cough, is a highly contagious, vaccine-preventable bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, bu ...

) * ''

Brucella ''Brucella'' is a genus of Gram-negative bacterium, bacteria, named after David Bruce (microbiologist), David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 μm), non-Bacterial capsule, encapsulated, non-motile, facultatively ...

'' spp. * ''

Burkholderia cepacia ''Burkholderia cepacia'' complex (BCC) is a species complex consisting of ''Burkholderia cepacia'' and at least 20 different biochemically similar species of Gram-negative bacteria. They are catalase-producing and lactose-nonfermenting. Membe ...

'' * ''

Burkholderia mallei ''Burkholderia mallei'' is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus '' Burkholderia'' causing glanders; the Latin name of this disease (''malleus'') gave its name to the species causing it. It is closely ...

'' (

glanders Glanders is a contagious, zoonotic infectious disease caused by the bacterium '' Burkholderia mallei'', which primarily occurs in horses, mules, and donkeys, but can also be contracted by dogs and cats, pigs, goats, and humans. The term ''glan ...

) * ''

Burkholderia pseudomallei ''Burkholderia pseudomallei'' (also known as ''Pseudomonas pseudomallei'') is a Gram-negative, bipolar, aerobic, motile rod-shaped bacterium. It is a soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in ...

'' (

melioidosis Melioidosis is an infectious disease caused by a gram-negative bacterium called ''Burkholderia pseudomallei''. Most people exposed to ''B. pseudomallei'' experience no symptoms, but complications can range from fever and skin changes to pneumon ...

) * ''

Chlamydia Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

'' spp. * '' Chryseobacterium meningosepticum'' * ''

Citrobacter ''Citrobacter'' is a genus of Gram-negative, aerobic, rod-shaped coliform bacteria of the Enterobacteriaceae family. ''Citrobacter'' spp. cause opportunistic infections (including urinary tract infections, gastroenteritis, and bacteremia). ...

'' spp. * ''

Enterobacter ''Enterobacter'' is a genus of common Gram-negative, Facultative anaerobic organism, facultatively anaerobic, bacillus (shape), rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. Cultures are found in soil, water, sewage, ...

'' spp. * ''

Enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are Gram-positive cocci that often occur in pairs ( diplococci) or short chains, and are difficult to distinguish from streptococci on physical ch ...

'' spp. * ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' * ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

spp.'' * '' Hafnia alvei'' * ''

Kingella ''Kingella'' is a genus of bacteria of the family Neisseriaceae. It belongs to the HACEK group of fastidious Gram-negative bacteria that tend to cause endocarditis. ''Kingella kingae'' is its type species. Species As of 2021, five species belo ...

'' spp. * ''

Klebsiella granulomatis ''Klebsiella granulomatis'' is a Gram-negative, rod-shaped bacterium of the genus ''Klebsiella'' known to cause the sexually transmitted infection granuloma inguinale (or donovanosis). It was formerly called ''Calymmatobacterium granulomatis''. ...

'' * ''

Klebsiella pneumoniae ''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar. Although found in the normal flora of the mo ...

'' * ''

Legionella ''Legionella'' is a genus of gram-negative bacteria, gram-negative bacteria that can be seen using a silver stain or grown in a special media that contains cysteine, an amino acid. It is known to cause legionellosis (all illnesses caused by ''Legi ...

'' spp. * ''

Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the ho ...

'' (

listeriosis Listeriosis is a bacterial infection most commonly caused by '' Listeria monocytogenes'', although '' L. ivanovii'' and '' L. grayi'' have been reported in certain cases. Listeriosis can cause severe illness, including severe sepsis, me ...

) * ''

Moraxella catarrhalis ''Moraxella catarrhalis'' is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the in ...

'' * ''

Morganella morganii ''Morganella morganii'' is a species of Gram-negative bacterium, bacteria.eMedicineMorganella infections/ref> It has a commensalism, commensal relationship within the intestinal tracts of humans, mammals, and reptiles as normal flora. Although '' ...

'' * ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'' (

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

) * ''

Neisseria gonorrhoeae ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular) or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria first isolated by Albert Ludwig Sigesmund Neisser, Albert Neisser in 1879. An obligate human pathog ...

'' (

gonorrhoea Gonorrhoea or gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium ''Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Gonorrhea is spread through sexual c ...

) * ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as the meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to a ...

'' (

meningococcal disease Meningococcal disease is a serious infection caused by ''Neisseria meningitidis'', also known as meningococcus, a gram negative diplococcus. Meningococcal disease includes meningitis, meningococcal septicemia, or a combination of both, which c ...

) * ''

Nocardia ''Nocardia'' is a genus of weakly staining Gram-positive, catalase, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (appearing similar to fungi, but being truly bacteria). It contains a total of 8 ...

'' spp. * ''

Plesiomonas shigelloides ''Plesiomonas shigelloides'' is a species of bacteria and the only member of its genus. It is a Gram-negative, rod-shaped bacterium which has been isolated from freshwater, freshwater fish, shellfish, cattle, goats, swine, cats, dogs, monkeys, ...

'' * ''

Pneumocystis jirovecii ''Pneumocystis jirovecii'' (previously ''P. carinii'') 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. P ...

'' * ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively Anaerobic organism, anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus (bacterium), Proteus'' infections in human ...

'' * ''

Proteus vulgaris ''Proteus vulgaris'' is a rod-shaped, nitrate-reducing, indole-positive and catalase-positive, hydrogen sulfide-producing, Gram-negative bacterium that inhabits the intestinal tracts of humans and animals. It can be found in soil, water, and ...

'' * ''

Providencia rettgeri ''Providencia rettgeri'' (commonly ''P. rettgeri''), is a Gram negative bacterium that is commonly found in both water and land environments. ''P. rettgeri'' is in the genus Providencia (bacterium), Providencia, along with ''Providencia stuartii ...

'' * ''

Providencia stuartii ''Providencia stuartii'' (commonly ''P. stuartii''), is a Gram negative bacillus that is commonly found in soil, water, and sewage. ''P. stuartii'' is the most common of the 5 species found in the genus Providencia (bacterium), Providencia, with ...

'' * ''

Salmonella typhi ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of ''Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includin ...

'' (

typhoid fever Typhoid fever, also known simply as typhoid, is a disease caused by '' Salmonella enterica'' serotype Typhi bacteria, also called ''Salmonella'' Typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often th ...

) * Non-typhi (

food poisoning Foodborne illness (also known as foodborne disease and food poisoning) is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions (the agents of mad cow disease), and toxins such ...

) ''

Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...

'' * ''

Serratia ''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. They are typically 1–5 μm in length, do not produce spores, and can be found in water, soil, plants, and animals. Some mem ...

'' spp. * ''

Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...

'' spp. * ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

'' * ''

Staphylococcus epidermidis ''Staphylococcus epidermidis'' is a Gram-positive bacterium, and one of over 40 species belonging to the genus ''Staphylococcus''. It is part of the human flora, normal human microbiota, typically the skin flora, skin microbiota, and less commonl ...

'' * ''

Staphylococcus saprophyticus ''Staphylococcus saprophyticus'' is a Gram-positive coccus belonging to the genus ''Staphylococcus''. ''S. saprophyticus'' is a common cause of community-acquired urinary tract infections. History ''Staphylococcus saprophyticus'' was not recogni ...

'' * ''

Stenotrophomonas maltophilia '' Stenotrophomonas maltophilia'' is an aerobic, nonfermentative, Gram-negative bacterium. It is an uncommon bacterium and human infection is difficult to treat. Initially classified as ''Bacterium bookeri'', then renamed ''Pseudomonas maltoph ...

'' * ''

Streptococcus agalactiae ''Streptococcus agalactiae'' (also known as group B streptococcus or GBS) is a gram-positive coccus (round bacterium) with a tendency to form chains (as reflected by the genus name ''Streptococcus''). It is a beta-hemolytic, catalase-negative, an ...

'' * ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, hemolysis (microbiology), alpha-hemolytic member of the genus ''Streptococcus''. ''S. pneumoniae'' cells are usually found in pairs (diplococci) and do not f ...

'' * ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' * ''

Streptococcus viridans The viridans streptococci are a large group of commensal streptococcal Gram-positive bacteria species that are α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), although ...

'' * ''

Toxoplasma gondii ''Toxoplasma gondii'' () is a species of parasitic alveolate that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but members of the cat family (felidae) are the only known d ...

'' (

) * '' Tropheryma whippelii'' (

Whipple's disease Whipple'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 as a gastrointestinal disorder, Whipple's disease primarily causes ...

) * ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaerobe and Vibrio, comma-shaped bacteria. The bacteria naturally live in Brackish water, brackish or saltwater where they att ...

'' (

) * ''

Yersinia enterocolitica ''Yersinia enterocolitica'' is a Gram-negative, rod-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29 ° C (72–84 °F), but it becomes nonmotile at normal human body temperature. ''Y. enterocolitica ...

'' * ''

Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly ''Pasteurella pestis'') is a Gram-negative bacteria, gram-negative, non-motile bacteria, non-motile, coccobacillus Bacteria, bacterium without Endospore, spores. It is related to pathogens ''Yer ...

'' (

bubonic plague Bubonic plague is one of three types of Plague (disease), plague caused by the Bacteria, bacterium ''Yersinia pestis''. One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and ...

) * ''

Yersinia pseudotuberculosis ''Yersinia pseudotuberculosis'' is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by ''Y. pseudotuber ...

'' The only notable nonsusceptible organisms are ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'', the

mycoplasma ''Mycoplasma'' is a genus of bacteria that, like the other members of the class ''Mollicutes'', lack a cell wall, and its peptidoglycan, around their cell membrane. The absence of peptidoglycan makes them naturally resistant to antibiotics ...

e and ''

Francisella tularensis ''Francisella tularensis'' is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. It is nonspore-forming, nonmotile, and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. It i ...

'' (the causative organism of

tularaemia Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium ''Francisella tularensis''. Symptoms may include fever, skin ulcers, and lymphadenopathy, enlarged lymph nodes. Occasionally, a form that results in pneumonia ...

Pregnancy and breast feeding

Its use during pregnancy is contraindicated, although it has been placed in Australian pregnancy category C. Its use during the first trimester (during

organogenesis Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal org ...

) and 12 weeks prior to pregnancy has been associated with an increased risk of congenital malformations, especially malformations associated with maternal folic acid deficiency (which is most likely related to the mechanism of action of co-trimoxazole) such as

neural tube defects Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embry ...

such as

spina bifida Spina bifida (SB; ; Latin for 'split spine') is a birth defect in which there is incomplete closing of the vertebral column, spine and the meninges, membranes around the spinal cord during embryonic development, early development in pregnancy. T ...

, cardiovascular malformations (e.g.

Ebstein's anomaly Ebstein's anomaly is a congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced downwards towards the apex of the right ventricle of the heart. Ebstein's anomaly has great anatomical heterogeneity tha ...

), urinary tract defects, oral clefts, and club foot in epidemiological studies. Its use later on during pregnancy also increases the risk of preterm labour (odds ratio: 1.51) and low birth weight (odds ratio: 1.67). Animal studies have yielded similarly discouraging results. It appears to be safe for use during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

as long as the baby is healthy.

Babies

Its use in those less than 2 months of age is not recommended due to the risk of adverse side effects.

Adverse effects

Common side effects include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

, rash, and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. Severe

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

s and ''Clostridioides difficile'' infection may occasionally occur. Its use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is not recommended. It appears to be safe for use during

as long as the baby is healthy.

Contraindications

Contraindications include the following: * Known hypersensitivity to trimethoprim, sulphonamides or any other ingredients in the formulations * Pregnancy * Severe liver failure, marked liver parenchymal damage, or jaundice. * Serious haematological disorders and

porphyria Porphyria ( or ) is a group of disorders in which substances called porphyrins build up in the body, adversely affecting the skin or nervous system. The types that affect the nervous system are also known as Porphyria#Acute porphyrias, acute p ...

(due to the sulfonamide component of the preparation). * Severe

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

(CrCl <15 ml/min) where repeated measurements of the plasma concentration cannot be performed

Interactions

Its use is advised against in people being concomitantly treated with: *

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

s like

captopril Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...

enalapril Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosem ...

lisinopril Lisinopril is a medication belonging to the drug class of angiotensin-converting enzyme (ACE) inhibitors and is used to treat hypertension (high blood pressure), heart failure, and heart attacks. For high blood pressure it is usually a first- ...

perindopril Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease. As a long-acting ACE inhibitor, perindopril works by inhibiting production of the vasoconstriction hormone, angiotensin, there ...

, and

ramipril Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 y ...

due to the potential for additive hyperkalaemic effects *

Prilocaine Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical ...

— additive risk of methaemoglobinaemia *

Antiarrhythmics Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia. M ...

amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxys ...

(increased risk of ventricular arrhythmias) and

dofetilide Dofetilide is a class III antiarrhythmic agents, antiarrhythmic agent. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 microgram, μg of dofetilide. It is not a ...

(increased risk of QT interval prolongation) * Antibacterials like

dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...

(increases plasma levels of both drugs), methenamine (increased risk of crystalluria) and

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...

(as it may lead to an increased plasma level of rifampicin and lower plasma levels of trimethoprim) * Anticoagulants like

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

and

acenocoumarol Acenocoumarol is an anticoagulant that functions as a vitamin K antagonist (like warfarin). It is a derivative of coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be descri ...

— anticoagulant effects of either drug is potentiated by this combination *

Sulfonylureas Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, ...

— effects enhanced *

Phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...

, half-life of phenytoin is increased *

Antifolates Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, ...

pyrimethamine Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...

proguanil Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resist ...

and

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

increase the risk of associated side effects like bone marrow toxicity, folic acid supplementation should be considered. A significant risk of megaloblastic anaemia exists with doses of pyrimethamine in excess of 25 mg/wk. *

Antivirals Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...

, more specifically,

lamivudine Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typi ...

(increased plasma concentrations of lamivudine),

zalcitabine Zalcitabine (2′-3′-di deoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Dru ...

(increased plasma concentrations of zalcitabine) and

zidovudine Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mothe ...

(increased risk of haematological reactions) *

Procainamide Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is a sodium channel blocker of cardiomyocytes; thus it is classified by the Vaughan Williams classification system as class Ia. ...

and/or

amantadine Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because ...

may have their plasma concentrations increased bilaterally or unilaterally. *

Clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

and other antipsychotics — increased risk of haematological side effects *

Nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...

analogue antineoplastics like

azathioprine Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus er ...

and

mercaptopurine Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's d ...

— increased risk of haematological toxicity *

Digoxin Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

— increase in digoxin levels in a proportion of elderly patients *

Diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

— elderly patients receiving thiazide diuretics are at a heightened risk for developing

thrombocytopaenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coa ...

while on co-trimoxazole *

Ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...

— patients who have received a kidney transplant and are receiving co-trimoxazole and ciclosporin concomitantly are at an increased risk of having a reversible deterioration in their kidney function. *

Spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

— concurrent use can increase the likelihood of hyperkalemia, especially in the elderly. The trimethoprim portion acts to prevent potassium excretion in the distal tubule of the nephron. * Potassium aminobenzoate — effects of sulfonamides (like

Sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Escherichia coli' ...

) inhibited. * Laboratory tests — trimethoprim and sulfonamides have been reported to interfere with diagnostic tests, including serum-methotrexate and elevated serum

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an impor ...

levels, also urea, urinary glucose and urobilinogen tests.

Overdose

Likely signs of toxicity include: * Nausea * Vomiting * Dizziness * Headache * Mental depression * Confusion * Thrombocytopenia *

Uremia Uremia is the condition of having high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which ...

* Bone marrow depression * Loss of appetite * Colic * Drowsiness * Unconsciousness The recommended treatment for overdose includes: * Administration of activated charcoal * Stomach pumping * General supportive measures * Haemodialysis, which is moderately effective in clearing co-trimoxazole from the plasma. *

Calcium folinate Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to t ...

treatment in cases of blood dyscrasias * Forcing oral fluids Alkalinisation of the urine may reduce the toxicity of sulfamethoxazole, but it may increase the toxic effects of trimethoprim.

Pharmacology

The

synergy Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...

between trimethoprim and sulfamethoxazole was first described in the late 1960s. Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately, because they inhibit successive steps in the folate synthesis pathway. They are given in a one-to-five ratio in their tablet formulations so that when they enter the body their concentration in the blood and tissues is roughly one-to-twenty — the exact ratio required for a peak synergistic effect between the two. Sulfamethoxazole, a

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

, induces its therapeutic effects by interfering with the ''

de novo De novo (Latin, , used in English to mean 'from the beginning', 'anew') may refer to: Science and computers * ''De novo'' mutation, a new germline mutation not inherited from either parent * ''De novo'' protein design, the creation of a protei ...

'' (that is, from within the cell) synthesis of folate inside microbial organisms such as protozoa, fungi and bacteria. It does this by competing with ''p''-aminobenzoic acid (PABA) in the biosynthesis of dihydrofolate. Trimethoprim serves as a competitive inhibitor of

dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in one-carbon transfer chemistry. ...

(DHFR), hence inhibiting the ''de novo'' synthesis of tetrahydrofolate, the biologically active form of folate. Tetrahydrofolate is crucial in the synthesis of

purine Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted puri ...

thymidine Thymidine (nucleoside#List of nucleosides and corresponding nucleobases, symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine nucleoside, deoxynucleoside. Deoxythymidine is the DNA nuc ...

, and

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

which are needed for the production of DNA and proteins during bacterial replication. The effects of trimethoprim causes a backlog of dihydrofolate (DHF) and this backlog can work against the inhibitory effect the drug has on tetrahydrofolate biosynthesis. This is where the sulfamethoxazole comes in; its role is in depleting the excess DHF by preventing it from being synthesised in the first place. Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed.

Society and culture

Legal status

Brand names

Trimethoprim/sulfamethoxazole may be abbreviated as SXT, SMZ-TMP, TMP-SMX, TMP-SMZ, or TMP-sulfa. The generic

(BAN) Co-trimoxazole is used for trimethoprim/sulfamethoxazole manufactured and sold by many different companies. The following list of brand names is incomplete: * Bactrim, Bactrimel (manufactured by

Roche F. Hoffmann-La Roche AG, commonly known as Roche (), is a Switzerland, Swiss multinational corporation, multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, ...

and distributed in Europe) * Bactrom (Venezuela) * Bibactin (manufactured by PPM and distributed in Cambodia and some African countries) * Biseptol * Sumetrolim * Co-trimoxazole (used as generic UK name) * Cotrim * Deprim (

AFT Pharmaceuticals This list of ship directions provides succinct definitions for terms applying to spatial orientation in a marine environment or location on a vessel, such as ''fore'', ''aft'', ''astern'', ''aboard'', or ''topside''. Terms * Abaft (prepositi ...

) * Diseptyl (Israel) * Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia) * Infectrin, Bactrim (Brazil) * Novo-Trimel * Primadex (manufactured by Dexa Medica and distributed in Indonesia) * Primotren ( Lek in

Slovenia Slovenia, officially the Republic of Slovenia, is a country in Central Europe. It borders Italy to the west, Austria to the north, Hungary to the northeast, Croatia to the south and southeast, and a short (46.6 km) coastline within the Adriati ...

and other countries) * Resprim * Sanprima (manufactured by Sanbe Farma and distributed in Indonesia) * Septra (

Aspen Pharmacare Aspen Pharmacare Holdings Limited is a public multinational pharmaceutical company headquartered in uMhlanga, South Africa. Founded in 1997, it listed on the Johannesburg Stock Exchange (JSE) in 1998, and purchased South African Druggists in ...

and formerly

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

) * Septram (Panama) * Septran (GlaxoSmithKline) * Septrin (Spain) * Sulfatrim * Teva-Trimel * Trisul * Vactrim (manufactured and distributed in Laos)

Economics

Trimethoprim/sulfamethoxazole is relatively inexpensive as of 2019.

References

{{DEFAULTSORT:Trimethoprim Sulfamethoxazole Acetaldehyde dehydrogenase inhibitors Combination antibiotics Drugs developed by Pfizer Drugs developed by GSK plc Drugs developed by Novartis Drugs developed by Hoffmann-La Roche World Health Organization essential medicines Wikipedia medicine articles ready to translate