Co-trimoxazole (abbreviated SXT) is a bacteriostatic 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, as listed in the British Pharmacopoeia, which has been widely adopted as an official monograph name around the world (except for the United States). Co-trimoxazole is marketed by GlaxoSmithKline under the trade name Septrin®, by Hoffmann-La Roche as Bactrim®; and by many other generic pharmaceutical manufacturers under a variety of names. Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacteria protein production, interfering with bacteria DNA production interfering with bacteria cellular metabolism Bacteriostatic antibiotics inhibit growth and repoduction of the bacteria, though do not kill it, while bactericidal antibiotics kill bacteria. ... An antibiotic is a drug that kills or slows the growth of bacteria. ... Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections (cystitis). ... Sulfamethoxazole is a sulfonamide antibiotic. ... GlaxoSmithKline (GSK) plc is a pharmaceutical, biologicals and healthcare company. ... Hoffmann-La Roche, Ltd. ... A generic drug is a drug which is bioequivalent to a brand name drug with respect to pharmacokinetic and pharmacodynamic properties, but is normally sold for a lower price. ...

Synergistic action

Co-trimoxazole exhibits a synergistic antibacterial effect when compared to each of its components administered singly. This is because trimethoprim and sulfamethoxazole inhibit successive steps in the folate synthesis pathway (see diagram below). Synergy or synergism, most often refers to the phenomenon of two or more discrete influences or agents acting in common to create an effect which is greater than the sum of the effects each is able to create independently. ... Folic acid (the anion form is called folate) is a B-complex vitamin (once called vitamin M) that is important in preventing neural tube defects (NTDs) in the developing human fetus. ...

Tetrahydrofolate synthesis pathway

Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate reductase. Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and are competitive inhibitors of the enzyme; inhibiting the production of dihydropteroic acid. Image File history File links tetrahydrofolate synthesis pathway File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... Sulfonamides, also known as sulfa drugs, are synthetic antimicrobial agents derived from sulfonic acid. ... Para-Aminobenzoic acid (PABA) is a chemical used in sunscreen that is an essential nutrient for some bacteria. ... In biochemistry one distinguishes two ways in which a molecule may block the action of an enzymes: competitive and noncompetitive inhibition. ...

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 nucleosides thymidine and uridine. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) 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. Folic acid (the anion form is called folate) is a B-complex vitamin (once called vitamin M) that is important in preventing neural tube defects (NTDs) in the developing human fetus. ... In law, the expression trial de novo literally means new trial. It is most often used in certain legal systems that provide for one form of trial, then another if a party remains unsatisfied with the decision. ... Nucleosides are glycosylamines made by attaching a nucleobase to a ribose ring. ... Deoxythymidine is a molecule (known as a nucleoside) that is formed when thymine is attached to a deoxyribose ring (also known as a deoxyribofuranose) via a β-N1-glycosidic bond. ... Uridine is a molecule (known as a nucleoside) that is formed when uracil is attached to a ribose ring (also known as a ribofuranose) via a β-N1-glycosidic bond. ... DNA replication - Wikipedia /**/ @import /w/skins-1. ... Transcription is the process through which a DNA sequence is enzymatically copied by an RNA polymerase to produce a complementary RNA. In the case of protein-encoding DNA, transcription is the beginning of the process that ultimately leads to the translation of the genetic code (via the mRNA intermediate) into...

Clinical indications

Co-trimoxazole is more effective than either of its components individually in treating bacterial infections. It may be effective in a variety of upper and lower respiratory tract infections, renal and urinary tract infections, gastrointestinal tract infections, skin and wound infections, septicaemias and other infections caused by sensitive organisms. In humans the respiratory tract is the part of the anatomy that has to do with the process of respiration or breathing. ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... A urinary tract infection is an infection of the urinary tract. ... The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and expels the remaining waste. ... Sepsis (in Greek Σήψις) is a serious medical condition caused by a severe systemic infection leading to a systemic inflammatory response. ...

Specific indications for its use include: (Rossi, 2004)

• treatment and prophylaxis of pneumonia caused by Pneumocystis jiroveci (P. carinii)
• infections caused by Listeria monocytogenes, Nocardia spp., Stenotrophomonas maltophilia (Zanthomonas maltophilia)
• melioidosis
• shigellosis
• traveller's diarrhoea
• prophylaxis of cerebral toxoplasmosis in HIV patients
• Whipple's disease

Binomial name Pneumocystis jiroveci Pneumocystis jiroveci, also known by its former name Pneumocystis carinii, is a fungus (earlier classified as a protozoa) that causes pneumocystis carinii pneumonia (PCP). ... Binomial name Listeria monocytogenes Listeria monocytogenes is a Gram-positive bacterium, in the division Firmicutes, named for Joseph Lister. ... Melioidosis, also known as pseudoglanders and Whitmores disease (after Capt Alfred Whitmore) is an uncommon infectious disease caused by a Gram-negative bacterium, Burkholderia pseudomallei, found in soil and water. ... Diarrhoea is the correct way to spell the word Diarrhoea. ... -1... Whipples disease is a rare disease caused by the bacteria Thropheryma whipplei. ...

Safety

There has been some concern about its use, however, since it has been associated with rare but serious adverse effects including Stevens-Johnson syndrome, myelosuppression and agranulocytosis; especially in the elderly. (Joint Formulary Committee, 2004) Stevens-Johnson syndrome (SJS) is a severe and potentially life-threatening (15% of cases) disease, it is a hypersensitivity complex affecting the skin and the mucous membranes, a severe expression of erythema multiforme (EM) (and so SJS is also called erythema multiforme major). ... Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. ...

In some countries, co-trimoxazole has been withdrawn due to these toxic effects.

Thus the current British Committee on Safety of Medicines (CSM) guidelines recommend limiting its use to:

• Pneumocystis jiroveci (P. carinii) pneumonia
• Toxoplasmosis and nocardiosis
• acute exacerbations of chronic bronchitis and infections of the urinary tract where there is good rationale for use
• acute otitis media in children where there is good rationale

Binomial name Pneumocystis jiroveci Pneumocystis jiroveci, also known by its former name Pneumocystis carinii, is a fungus (earlier classified as a protozoa) that causes pneumocystis carinii pneumonia (PCP). ... Otitis media (also known as glue ear) is an inflammation of the middle ear, usually associated with a buildup of fluid and frequently causes an earache. ...

References

• Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
• Joint Formulary Committee (2004). British National Formulary 47 ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. ISBN 0-85369-854-9.