| Revision as of 16:13, 25 April 2022 editSpidermario (talk | contribs)Extended confirmed users674 edits Add drug class← Previous edit | Latest revision as of 21:40, 19 October 2024 edit undo2601:642:c303:f370:845f:745f:fee:4663 (talk) Reclassified to Clostridioides in 2016. CE | ||
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| {{Short description|Antibiotic}}{{ |
{{Short description|Antibiotic}} | ||
| {{Distinguish|Thymidine monophosphate}} | |||
| {{Use dmy dates|date=March 2024}} | |||
| {{drugbox | |||
| {{cs1 config|name-list-style=vanc|display-authors=6}} | |||
| {{infobox drug | |||
| | Watchedfields = changed | | Watchedfields = changed | ||
| | verifiedrevid = 470615131 | | verifiedrevid = 470615131 | ||
| | drug_name = | |||
| ⚫ | | IUPAC_name = 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine | ||
| | image = Trimethoprim.svg | | image = Trimethoprim.svg | ||
| | width = 240 | | width = 240 | ||
| Line 12: | Line 13: | ||
| | alt2 = Ball-and-stick model of the trimethoprim molecule | | alt2 = Ball-and-stick model of the trimethoprim molecule | ||
| <!--Clinical data--> | <!-- Clinical data --> | ||
| | pronounce = {{IPAc-en|t|r|aɪ|ˈ|m|ɛ|θ|ə|p|r|ɪ|m}} | | pronounce = {{IPAc-en|t|r|aɪ|ˈ|m|ɛ|θ|ə|p|r|ɪ|m}} | ||
| | tradename =Proloprim, Monotrim, Triprim, others | | tradename = Proloprim, Monotrim, Triprim, others | ||
| | Drugs.com = {{drugs.com|monograph|trimethoprim}} | | Drugs.com = {{drugs.com|monograph|trimethoprim}} | ||
| ⚫ | | class = ]s | ||
| | MedlinePlus = a684025 | | MedlinePlus = a684025 | ||
| | |
| DailyMedID = Trimethoprim | ||
| | pregnancy_AU = B3 | | pregnancy_AU = B3 | ||
| ⚫ | | routes_of_administration = ] | ||
| | pregnancy_US = C | |||
| ⚫ | | class = ]s | ||
| ⚫ | | ATC_prefix = J01 | ||
| ⚫ | | ATC_suffix = EA01 | ||
| ⚫ | | ATC_supplemental = {{ATCvet|J51|EA01}} | ||
| | legal_AU = S4 | | legal_AU = S4 | ||
| | legal_CA = Rx-only | | legal_CA = Rx-only | ||
| | legal_UK = POM | | legal_UK = POM | ||
| | legal_US = Rx-only | | legal_US = Rx-only | ||
| ⚫ | | routes_of_administration = |
||
| <!--Pharmacokinetic data--> | <!-- Pharmacokinetic data --> | ||
| | bioavailability = 90–100% | | bioavailability = 90–100% | ||
| | protein_bound = 44% | | protein_bound = 44% | ||
| | metabolism = ] | | metabolism = ] | ||
| | elimination_half-life = 8–12 hours | | elimination_half-life = 8–12 hours | ||
| | excretion = |
| excretion = ] (50–60%), faeces (4%) | ||
| <!--Identifiers--> | <!-- Identifiers --> | ||
| | CAS_number_Ref = {{cascite|correct|??}} | | CAS_number_Ref = {{cascite|correct|??}} | ||
| | CAS_number = 738-70-5 | | CAS_number = 738-70-5 | ||
| ⚫ | | ATC_prefix = J01 | ||
| ⚫ | | ATC_suffix = EA01 | ||
| ⚫ | | ATC_supplemental = {{ATCvet|J51|EA01}} | ||
| | PubChem = 5578 | | PubChem = 5578 | ||
| | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | ||
| Line 55: | Line 56: | ||
| | PDB_ligand = TOP | | PDB_ligand = TOP | ||
| <!--Chemical data--> | <!-- Chemical data --> | ||
| ⚫ | | IUPAC_name = 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine | ||
| | C=14 | H=18 | N=4 | O=3 | | C=14 | H=18 | N=4 | O=3 | ||
| | smiles = Nc1nc(N)ncc1Cc(cc2OC)cc(OC)c2OC | | smiles = Nc1nc(N)ncc1Cc(cc2OC)cc(OC)c2OC | ||
| Line 64: | Line 66: | ||
| }} | }} | ||
| <!-- Definition and uses --> | <!-- Definition and uses --> | ||
| '''Trimethoprim''' ('''TMP''') is an ] used mainly in the treatment of ].<ref name=AHFS2015>{{cite web|title=Trimethoprim|url=https://www.drugs.com/monograph/trimethoprim.html|publisher=The American Society of Health-System Pharmacists|access-date= |
'''Trimethoprim''' ('''TMP''') is an ] used mainly in the treatment of ].<ref name=AHFS2015>{{cite web|title=Trimethoprim|url=https://www.drugs.com/monograph/trimethoprim.html|publisher=The American Society of Health-System Pharmacists|access-date=1 August 2015|url-status=live|archive-url=https://web.archive.org/web/20150924014936/http://www.drugs.com/monograph/trimethoprim.html|archive-date=24 September 2015}}</ref> Other uses include for ] and ].<ref name=AHFS2015/> With ] or ] it may be used for ] in people with ].<ref name=AHFS2015/><ref>{{cite journal | vauthors = Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE | title = Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America | journal = Clinical Infectious Diseases | volume = 58 | issue = 9 | pages = 1308–1311 | date = May 2014 | pmid = 24585567 | pmc = 3982842 | doi = 10.1093/cid/ciu094 }}</ref> It is taken ] (swallowed by mouth).<ref name=AHFS2015/> | ||
| <!-- Side effects --> | <!-- Side effects --> | ||
| Common side effects include nausea, changes in taste, and rash.<ref name=AHFS2015/> Rarely it may result in blood problems such as not enough ] or ].<ref name=AHFS2015/> Trimethoprim may cause sun sensitivity.<ref name=AHFS2015/> There is evidence of potential harm during |
Common side effects include nausea, changes in taste, and rash.<ref name=AHFS2015/> Rarely it may result in blood problems such as not enough ] or ].<ref name=AHFS2015/> Trimethoprim may cause sun sensitivity.<ref name=AHFS2015/> There is evidence of potential ] in some animals but not humans.<ref name=TGA2014>{{cite web|title=Prescribing medicines in pregnancy database|url=http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw|work=Australian Government|access-date=22 April 2014|date=3 March 2014|url-status=live|archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw|archive-date=8 April 2014}}</ref> It works by blocking ] metabolism via ] in some bacteria, preventing creation of bacterial ] and ] and leading to bacterial cell death.<ref name=AHFS2015/> | ||
| <!-- History, society and culture --> | <!-- History, society and culture --> | ||
| Trimethoprim was first used in 1962.<ref name=Huo2001>{{cite journal| |
Trimethoprim was first used in 1962.<ref name=Huo2001>{{cite journal | vauthors = Huovinen P | title = Resistance to trimethoprim-sulfamethoxazole | journal = Clinical Infectious Diseases | volume = 32 | issue = 11 | pages = 1608–1614 | date = June 2001 | pmid = 11340533 | doi = 10.1086/320532 | doi-access = free }}</ref> It is on the ].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is available as a generic medication.<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=113}}</ref> | ||
| ==Medical uses== | ==Medical uses== | ||
| It is primarily used in the treatment of ], although it may be used against any susceptible ].<ref name="AMH">{{cite book | |
It is primarily used in the treatment of ], although it may be used against any susceptible ].<ref name="AMH">{{cite book | veditors = Rossi S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref> It may also be used to treat and prevent '']'' pneumonia.<ref name = AMH/> It is generally not recommended for the treatment of ] such as ] (the leading cause of antibiotic-induced diarrhea).<ref name = AMH/> Trimethoprim has been used in trials to treat ].<ref name="Pradhan">{{cite journal | vauthors = Pradhan E, Bhandari S, Gilbert RE, Stanford M | title = Antibiotics versus no treatment for toxoplasma retinochoroiditis | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 5 | pages = CD002218 | date = May 2016 | pmid = 27198629 | pmc = 7100541 | doi = 10.1002/14651858.CD002218.pub2 }}</ref> | ||
| Resistance to trimethoprim is increasing, but it is still a first |
Resistance to trimethoprim is increasing, but it is still a first-line antibiotic in many countries.<ref>{{cite web |url=https://www.nice.org.uk/advice/ktt10/chapter/evidence-context |title=Three-day courses of antibiotics for uncomplicated urinary tract infection | Guidance and guidelines | NICE |date=15 January 2015 |access-date=30 December 2015 |url-status=live |archive-url=https://web.archive.org/web/20151208004951/http://www.nice.org.uk/advice/ktt10/chapter/Evidence-context |archive-date=8 December 2015 }}</ref> | ||
| ===Spectrum of susceptibility=== | ===Spectrum of susceptibility=== | ||
| Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim.<ref name="dailymed.nlm.nih.gov">{{Cite web| |
Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim.<ref name="dailymed.nlm.nih.gov">{{Cite web| work = DailyMed | title = TRIMETHOPRIM- trimethoprim tablet|url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4e9183f-d0eb-4ba7-9204-760b1fd62010| publisher = U.S. National Library of Medicine |access-date = 4 November 2015|url-status = live|archive-url = https://web.archive.org/web/20150930162821/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4e9183f-d0eb-4ba7-9204-760b1fd62010|archive-date = 30 September 2015}}</ref><ref>{{Cite web| work = DailyMed | title = PRIMSOL- trimethoprim hydrochloride solution|url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a06ea7d8-a884-4b62-a87f-c36d824f2aa4| publisher = U.S. National Library of Medicine |access-date = 4 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151117024132/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a06ea7d8-a884-4b62-a87f-c36d824f2aa4|archive-date = 17 November 2015}}</ref> | ||
| * '']'' | * '']'' | ||
| * '']'' | * '']'' | ||
| Line 96: | Line 98: | ||
| * Rashes | * Rashes | ||
| * Sun sensitivity | * Sun sensitivity | ||
| * Itchiness<ref name=":1">{{Cite web|title = PROLOPRIM® (trimethoprim)100-mg and 200-mg Scored Tablets|url = http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=3220| |
* Itchiness<ref name=":1">{{Cite web| work = DailyMed | title = PROLOPRIM® (trimethoprim)100-mg and 200-mg Scored Tablets|url = http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=3220| publisher = U.S. National Library of Medicine |access-date = 4 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151117015344/http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=3220|archive-date = 17 November 2015}}</ref><ref>{{Cite book|title = American Hospital Formulary Service- Drug Information 2002.| vauthors = Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J |publisher = Williams and Wilkins|location = Baltimore, MD|pages = 236}}</ref> | ||
| === Rare === | === Rare === | ||
| * Can cause ] (low levels of ]) by lowering ] levels; this may also cause ].<ref name=":2">{{Cite book|title = Drug Information for the Health Care Professional |
* Can cause ] (low levels of ]) by lowering ] levels; this may also cause ].<ref name=":2">{{Cite book|title = Drug Information for the Health Care Professional | edition = 22nd | volume = 1 |last = MICROMEDEX Thomson Health Care. USPDI | publisher = Thomson Health Care |location = Greenwood Village, CO. | date = 2002 | page = 2849 }}</ref> | ||
| * Trimethoprim antagonizes the ] <!-- (ENaC) --> in the ], thus acting like ]. This can cause increased potassium levels in the body (]).<ref>{{ |
* Trimethoprim antagonizes the ] <!-- (ENaC) --> in the ], thus acting like ]. This can cause increased potassium levels in the body (]).<ref>{{cite journal | vauthors = Choi MJ, Fernandez PC, Patnaik A, Coupaye-Gerard B, D'Andrea D, Szerlip H, Kleyman TR | title = Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS | journal = The New England Journal of Medicine | volume = 328 | issue = 10 | pages = 703–706 | date = March 1993 | pmid = 8433730 | doi = 10.1056/NEJM199303113281006 | doi-access = free }}</ref> | ||
| * Can compete with ] for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.<ref>{{ |
* Can compete with ] for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.<ref>{{cite journal | vauthors = Naderer O, Nafziger AN, Bertino JS | title = Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions | journal = Antimicrobial Agents and Chemotherapy | volume = 41 | issue = 11 | pages = 2466–2470 | date = November 1997 | pmid = 9371351 | pmc = 164146 | doi = 10.1128/AAC.41.11.2466 }}</ref> | ||
| * Use in ] infections may lead to an increase in expression of ].<ref>{{cite journal | vauthors = Kimmitt PT, Harwood CR, Barer MR | title = Toxin |
* Use in ] infections may lead to an increase in expression of ].<ref>{{cite journal | vauthors = Kimmitt PT, Harwood CR, Barer MR | title = Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response | journal = Emerging Infectious Diseases | volume = 6 | issue = 5 | pages = 458–465 | year = 2000 | pmid = 10998375 | pmc = 2627954 | doi = 10.3201/eid0605.000503 }}</ref> | ||
| === Contraindications === | === Contraindications === | ||
| * Known ] to trimethoprim | * Known ] to trimethoprim | ||
| * History of ] due to folate deficiency<ref name=":0">{{Cite web| |
* History of ] due to folate deficiency<ref name=":0">{{Cite web| work = DailyMed | title = PRIMSOL- trimethoprim hydrochloride solution|url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a06ea7d8-a884-4b62-a87f-c36d824f2aa4| publisher = U.S. National Library of Medicine |access-date = 4 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151117024132/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a06ea7d8-a884-4b62-a87f-c36d824f2aa4|archive-date = 17 November 2015}}</ref><!-- supports all --> | ||
| It may be involved in a reaction similar to ] when alcohol is consumed after it is used, in particular when used in combination with ].<ref>{{cite journal | vauthors = Edwards DL, Fink PC, Van Dyke PO | title = Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole | journal = Clinical Pharmacy | volume = 5 | issue = 12 | pages = 999–1000 | date = December 1986 | pmid = 3492326 | url = http://cat.inist.fr/?aModele=afficheN&cpsidt=8287529 | url-status = live | archive-url = https://web.archive.org/web/20090124113327/http://cat.inist.fr/?aModele=afficheN&cpsidt=8287529 | archive-date = 24 January 2009 }}</ref><ref>{{cite journal | vauthors = Heelon MW, White M | title = Disulfiram-cotrimoxazole reaction | journal = Pharmacotherapy | volume = 18 | issue = 4 | pages = 869–870 | year = 1998 | pmid = 9692665 | doi = 10.1002/j.1875-9114.1998.tb03913.x | url = http://cat.inist.fr/?aModele=afficheN&cpsidt=2340043 | url-status = live | s2cid = 23968977 | archive-url = https://web.archive.org/web/20090124113456/http://cat.inist.fr/?aModele=afficheN&cpsidt=2340043 | archive-date = 24 January 2009 }}</ref> | |||
| === Pregnancy === | === Pregnancy === | ||
| Based on the studies that show that trimethoprim crosses the ] and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first ] of pregnancy.<ref name="Sivojelezova 1085–1086">{{ |
Based on the studies that show that trimethoprim crosses the ] and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first ] of pregnancy.<ref name="Sivojelezova 1085–1086">{{cite journal | vauthors = Sivojelezova A, Einarson A, Shuhaiber S, Koren G | title = Trimethoprim-sulfonamide combination therapy in early pregnancy | journal = Canadian Family Physician | volume = 49 | pages = 1085–1086 | date = September 2003 | pmid = 14526858 | pmc = 2214286 }}</ref> | ||
| The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A |
The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A 2013 study found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.<ref>{{cite journal | vauthors = Andersen JT, Petersen M, Jimenez-Solem E, Broedbaek K, Andersen EW, Andersen NL, Afzal S, Torp-Pedersen C, Keiding N, Poulsen HE | title = Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study | journal = Epidemiology and Infection | volume = 141 | issue = 8 | pages = 1749–1755 | date = August 2013 | pmid = 23010291 | pmc = 9151599 | doi = 10.1017/S0950268812002178 | s2cid = 19917493 }}</ref> | ||
| ==Mechanism of action== | ==Mechanism of action== | ||
| ] | ] | ||
| Trimethoprim binds to ] and inhibits the reduction of ] (DHF) to ] (THF).<ref name = drugs82/> THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.<ref name = drugs82/> Trimethoprim's |
Trimethoprim binds to ] and inhibits the reduction of ] (DHF) to ] (THF).<ref name = drugs82/> THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.<ref name = drugs82/> Trimethoprim's inhibitory activity for bacterial dihydrofolate reductase is sixty thousand times greater than for human dihydrofolate reductase.<ref>{{cite journal | vauthors = Burchall JJ | title = Mechanism of action of trimethoprim-sulfamethoxazole. II | journal = The Journal of Infectious Diseases | volume = 128 | pages = Suppl: 437-Suppl: 441 | date = November 1973 | pmid = 4585969 | doi = 10.1093/infdis/128.Supplement_3.S437 | ref = TMP1 | jstor = 30105875 }}</ref> ] inhibits ], an enzyme involved further upstream in the same pathway.<ref name = drugs82/> ] are commonly used in combination due to possible synergistic effects, and reduced development of resistance.<ref name = drugs82>{{cite journal | vauthors = Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS | title = Trimethoprim: a review of its antibacterial activity, pharmacokinetics and therapeutic use in urinary tract infections | journal = Drugs | volume = 23 | issue = 6 | pages = 405–430 | date = June 1982 | pmid = 7049657 | doi = 10.2165/00003495-198223060-00001 | s2cid = 21806926 }}</ref> This benefit has been questioned.<ref name=Brumfitt1993>{{cite journal | vauthors = Brumfitt W, Hamilton-Miller JM | title = Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines | journal = Journal of Chemotherapy | volume = 5 | issue = 6 | pages = 465–469 | date = December 1993 | pmid = 8195839 | doi = 10.1080/1120009X.1993.11741097 }}</ref> | ||
| ] synthesis pathway|thumb|none|upright=1.25]] | ] synthesis pathway|thumb|none|upright=1.25]] | ||
| Line 122: | Line 127: | ||
| Its name is derived from ''trimeth''yl''o''xy-]. | Its name is derived from ''trimeth''yl''o''xy-]. | ||
| ==See also== | |||
| * ] | |||
| * ] | |||
| {{Clear right}} | {{Clear right}} | ||
| == References == | == References == | ||
| {{reflist}} | {{reflist}} | ||
| ==External links== | |||
| * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/trimethoprim | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Trimethoprim }} | |||
| {{Sulfonamides and trimethoprim}} | {{Sulfonamides and trimethoprim}} | ||
| ⚫ | {{Portal bar | Medicine}} | ||
| ⚫ | {{ |
||
| ] | ] | ||
Latest revision as of 21:40, 19 October 2024
Antibiotic Not to be confused with Thymidine monophosphate.Pharmaceutical compound
 | |
 | |
| Clinical data | |
|---|---|
| Pronunciation | /traɪˈmɛθəprɪm/ |
| Trade names | Proloprim, Monotrim, Triprim, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a684025 |
| License data |
|
| Pregnancy category |
|
| Routes of administration | By mouth |
| Drug class | Diaminopyrimidines |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 90–100% |
| Protein binding | 44% |
| Metabolism | Liver |
| Elimination half-life | 8–12 hours |
| Excretion | Kidney (50–60%), faeces (4%) |
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| PDB ligand | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.010.915  |
| Chemical and physical data | |
| Formula | C14H18N4O3 |
| Molar mass | 290.323 g·mol |
| 3D model (JSmol) | |
SMILES
| |
InChI
| |
| (verify) | |
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 in people with HIV/AIDS. It is taken orally (swallowed by mouth).
Common side effects include nausea, changes in taste, and rash. Rarely it may result in blood problems such as not enough platelets or white blood cells. Trimethoprim may cause sun sensitivity. There is evidence of potential harm during pregnancy in some animals but not humans. It works by blocking folate metabolism via dihydrofolate reductase in some bacteria, preventing creation of bacterial DNA and RNA and leading to bacterial cell death.
Trimethoprim was first used in 1962. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.
Medical uses
It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species. It may also be used to treat and prevent Pneumocystis jirovecii pneumonia. It is generally not recommended for the treatment of anaerobic infections such as Clostridioides difficile colitis (the leading cause of antibiotic-induced diarrhea). Trimethoprim has been used in trials to treat retinitis.
Resistance to trimethoprim is increasing, but it is still a first-line antibiotic in many countries.
Spectrum of susceptibility
Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim.
- Escherichia coli
- Proteus mirabilis
- Klebsiella pneumoniae
- Enterobacter species
- Coagulase-negative Staphylococcus species, including S. saprophyticus
- Streptococcus pneumoniae
- Haemophilus influenzae
Side effects
Common
- Nauseas
- Change in taste
- Vomiting
- Diarrhea
- Rashes
- Sun sensitivity
- Itchiness
Rare
- Can cause thrombocytopenia (low levels of platelets) by lowering folic acid levels; this may also cause megaloblastic anemia.
- Trimethoprim antagonizes the epithelial sodium channel in the distal tubule, thus acting like amiloride. This can cause increased potassium levels in the body (hyperkalemia).
- Can compete with creatinine for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.
- Use in EHEC infections may lead to an increase in expression of Shiga toxin.
Contraindications
- Known hypersensitivity to trimethoprim
- History of megaloblastic anemia due to folate deficiency
It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.
Pregnancy
Based on the studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.
The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A 2013 study found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.
Mechanism of action
Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis. Trimethoprim's inhibitory activity for bacterial dihydrofolate reductase is sixty thousand times greater than for human dihydrofolate reductase. Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway. Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance. This benefit has been questioned.
History
Trimethoprim was first used in 1962. In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland.
Its name is derived from trimethyloxy-pyrimidine.
References
- ^ "Trimethoprim". The American Society of Health-System Pharmacists. Archived from the original on 24 September 2015. Retrieved 1 August 2015.
- Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE (May 2014). "Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America". Clinical Infectious Diseases. 58 (9): 1308–1311. doi:10.1093/cid/ciu094. PMC 3982842. PMID 24585567.
- "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Archived from the original on 8 April 2014. Retrieved 22 April 2014.
- ^ Huovinen P (June 2001). "Resistance to trimethoprim-sulfamethoxazole". Clinical Infectious Diseases. 32 (11): 1608–1614. doi:10.1086/320532. PMID 11340533.
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| Quinolones (inhibit bacterial topoisomerase and/or DNA gyrase, thereby inhibiting DNA replication) |
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| Anaerobic DNA inhibitors |
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