- 同
- co-trimoxazole, TMP-SMZ, Bactrim, Cotrim, Septra, Sulfatrim
- 関
- Trimethoprim-sulfamethoxazole
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Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/28 02:18:41」(JST)
wiki en
|
Trimethoprim (top) and sulfamethoxazole (bottom)
|
|
| Combination of | |
|---|---|
| Trimethoprim | Dihydrofolate reductase inhibitor |
| Sulfamethoxazole | Sulfonamide antibiotic |
| Clinical data | |
| Trade names | Bactrim, Bactrimel, Biseptol, Co-trimoxazole, Cotrim, Resprim, Septrin, Septra, Sulfatrim, Trisul, Polytrim |
| AHFS/Drugs.com | monograph |
| Pregnancy category |
|
| Legal status |
|
| Routes of administration |
Oral, Intravenous[1] |
| Identifiers | |
| CAS Registry Number | 8064-90-2 |
| ATC code | J01EE01 |
| PubChem | CID: 358641 |
| DrugBank | DB00440 |
| ChemSpider | 318412 |
| ChEBI | CHEBI:3770 |
| Y (what is this?) (verify) | |
Trimethoprim/sulfamethoxazole (TMP/SMX) or co-trimoxazole (BAN) is an antibiotic used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazole. The drug has been marketed worldwide in generic preparations and under multiple brand names, including Septra (GlaxoSmithKline plc) and Bactrim (Hoffmann-La Roche). Co-trimoxazole is generally considered bactericidal, although its components are individually bacteriostatic.[2] It is an antifolate drug, and functions by inhibiting both de novo folate biosynthesis and metabolism.[3]
Common side effects of TMP/SMX include nausea, vomiting and diarrhoea.[4] Allergic reactions and Clostridium difficile diarrhea are also possible side effects.[4] Its use near the end of pregnancy is not recommended.[5] Some state it should not be used during breastfeeding while others say it is acceptable.[5][6]
It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[7]
Trimethoprim/sulfamethoxazole is often abbreviated as SXT, TMP-SMX, TMP-SMZ, or TMP-sulfa, although the abbreviating of drug names is not best practice in medicine.
Contents
- 1 Medical uses
- 1.1 Pregnancy and breast feeding
- 2 Adverse effects
- 2.1 Contraindications
- 2.2 Interactions
- 2.3 Overdose
- 3 Pharmacology
- 4 Trade names
- 5 Notes
- 6 References
Medical uses
Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed.[8] Because it has a higher incidence of adverse effects, including allergic responses, its use has been restricted in many countries to very specific circumstances where its improved efficacy has been demonstrated.[9] 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. The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole more recently.[10]
Organisms against which co-trimoxazole can be effective include:[3][11]
- Acinetobacter spp.
- Aeromonas hydrophila
- Alcaligenes xylosoxidans
- Bartonella henselae
- Bordetella pertussis (pertussis)
- Brucella spp.
- Burkholderia cepacia
- Burkholderia mallei (glanders)
- Burkholderia pseudomallei (melioidosis)
- Chlamydia trachomatis (chlamydia)
- Chryseobacterium meningosepticum
- Citrobacter spp.
- Enterobacter spp.
- Escherichia coli
- Haemophilus influenzae
- Hafnia alvei
- Kingella spp.
- Klebsiella granulomatis
- Klebsiella pneumoniae
- Legionella spp.
- Listeria monocytogenes (listeriosis)
- Moraxella catarrhalis
- Morganella morganii
- Mycobacterium tuberculosis (tuberculosis)
- Neisseria gonorrhoeae (gonorrhoea)
- Neisseria meningitidis (meningococcal disease)
- Nocardia spp.
- Plesiomonas shigelloides
- Pneumocystis jiroveci
- Proteus mirabilis
- Proteus vulgaris
- Providencia rettgeri
- Providencia stuartii
- Salmonella typhi (typhoid fever)
- Non-typhi Salmonella
- Serratia spp.
- Shigella spp.
- Staphylococcus aureus
- Staphylococcus epidermidis
- Staphylococcus saprophyticus
- Stenotrophomonas maltophilia
- Streptococcus agalactiae
- Streptococcus faecalis
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Streptococcus viridans
- Toxoplasma gondii (toxoplasmosis)
- Tropheryma whippelii (Whipple's disease)
- Vibrio cholerae (cholera)
- Yersinia enterocolitica
- Yersinia pestis (bubonic plague)
- Yersinia pseudotuberculosis
The only notable nonsusceptible organisms are the mycoplasmae[11] and Francisella tularensis (the causative organism of tularaemia).[12][13]
Pregnancy and breast feeding
Its use during pregnancy is contraindicated, although it has been placed in Australian and American pregnancy category C.[3] Despite this, its use during the first trimester (during organogenesis) 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 such as spina bifida, cardiovascular malformations (e.g. Ebstein's anomaly), urinary tract defects, oral clefts, and club foot in epidemiological studies.[3] 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).[14][15] Animal studies have yielded similarly discouraging results.[16] It is also excreted in breast milk and hence nursing during treatment with co-trimoxazole is generally advised against.[3]
| Indication | FDA-labelled indication? |
TGA-labelled indication? |
MHRA-labelled indication? |
Literature support |
|---|---|---|---|---|
| Acute infective exacerbation of chronic bronchitis | Yes | No | No | Clinical trials are lacking. |
| Prophylaxis in HIV-infected individuals | No | No | No | Effective in one Ugandan study on morbidity, mortality, CD4-cell count, and viral load in HIV infection.[17] |
| Otitis media | Paediatric population only | No | Yes | Clinical trials have confirmed its efficacy in chronic active otitis media[18] and acute otitis media.[19] |
| Travellers' diarrhoea, treatment & prophylaxis | Yes | No | No | Clinical trials have confirmed its efficacy as a treatment for travellers' diarrhoea.[20][21][22] |
| Urinary tract infection | Yes | No | Yes | Clinical trials have confirmed its efficacy in this indication.[11] |
| Bacterial infections | ||||
| Acne vulgaris | No | No | No | At least one clinical trial supports its use in this indication.[23] |
| Listeria | No | Yes | No | Well-designed clinical trials are lacking. |
| Melioidosis | No | Yes | No | Clinical trials have confirmed its efficacy, with or without adjunctive doxycycline; although, co-trimoxazole alone seems preferable.[24][25][26] |
| Pertussis (whooping cough) | No | No | No | One cochrane review supports its efficacy in preventing the spread of pertussis.[27] |
| Shigellosis | Yes | Yes | No | Generally accepted treatment for shigellosis.[28] A recent Cochrane review found that while it is an effective treatment for shigellosis it also produces more significant adverse effects than other antibiotic drugs.[29] |
| Staphylococcus aureus infections | No | No | No | In vitro and in vivo activity against both non-resistant and methicillin-resistant Staphylococcus aureus (MRSA) infections.[30][31][32][33][34][35][36] |
| Tuberculosis | No | No | No | In vitro and in vivo activity against both nonresistant and MDR strains of TB.[37][38][39] |
| Whipple's disease | No | No | No | Co-trimoxazole is the recommended standard treatment for whipple's disease in some treatment protocols.[40][41][42] |
| Fungal and protozoal infections | ||||
| Isosporiasis | No | No | No | Clinical trials have confirmed its use in this indication.[43] |
| Malaria | No | No | No | Clinical trials have confirmed its efficacy in both the treatment and prevention of malaria.[44] |
| Pneumocystis jirovecii pneumonia | Yes | Yes | Yes | Its use as a prophylactic treatment is supported by one clinical trial involving children with acute lymphoblastic leukaemia.[45] Other than this and one other clinical trial into its efficacy as a treatment for pneumocystis pneumonia,[46] data on its use in both the treatment and prevention of pneumocystis pneumonia is significantly lacking. |
| Toxoplasmosis | Yes | Prevention only | Yes | Clinical trials have confirmed its prophylactic and therapeutic utility in cases of toxoplasmosis.[47][48][49][50][51][52] |
| Other indications | ||||
| Granulomatosis with polyangiitis (formerly Wegener's) | No | No | No | Two clinical trials have supported its efficacy in this indication.[53][54] |
Adverse effects
See also: List of side effects of trimethoprim/sulfamethoxazole
Contraindications
Contraindications include the following:[3][55]
- Known hypersensitivity to trimethoprim, sulphonamides or any other ingredients in the formulations
- Pregnancy – especially in the period prior to birth
- Severe hepatic failure, marked liver parenchymal damage or jaundice.
- Serious haematological disorders and porphyria (due to the sulfonamide component of the preparation).
- Severe renal insufficiency (CrCl <15 ml/min) where repeated measurements of the plasma concentration cannot be performed
- Co-trimoxazole should not be given to neonates during the first 6 weeks, except for the treatment/prophylaxis of pneumocytosis jiroveci (P. carinii) in infants of four weeks of age or greater.
Interactions
Its use is advised against in patients being concomitantly treated with:[3][16][55][56][57][58]
- ACE inhibitors like captopril, enalapril, lisinopril, perindopril, and ramipril due to the potential for additive hyperkalaemic effects[55]
- Prilocaine — additive risk of methaemoglobinaemia
- Antiarrhythmics like amiodarone (increased risk of ventricular arrhythmias) and dofetilide (increased risk of QT interval prolongation)
- Antibacterials like dapsone (increases plasma levels of both drugs), methenamine (increased risk of crystalluria) and rifampicin (as it may lead to an increased plasma level of rifampicin and lower plasma levels of trimethoprim)
- Anticoagulants like warfarin and acenocoumarol — anticoagulant effects of either drug is potentiated by this combination
- Sulfonylureas — effects enhanced
- Phenytoin, half-life of phenytoin is increased
- Antifolates like pyrimethamine, proguanil and methotrexate 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, more specifically, lamivudine (increased plasma concentrations of lamivudine), zalcitabine (increased plasma concentrations of zalcitabine) and zidovudine (increased risk of haematological reactions)
- Procainamide and/or amantadine may have their plasma concentrations increased bilaterally or unilaterally.
- Clozapine and other antipsychotics — increased risk of haematological side effects
- Nucleoside analogue antineoplastics like azathioprine and mercaptopurine — increased risk of haematological toxicity
- Digoxin — increase in digoxin levels in a proportion of elderly patients
- Diuretics — elderly patients receiving thiazide antidiuretics are at a heightened risk for developing thrombocytopaenia while on co-trimoxazole
- Ciclosporin — patients that 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.
- Potassium aminobenzoate — effects of sulfonamides (like sulfamethoxazole) inhibited.
- Laboratory tests; trimethoprim and sulfonamides have been reported to interfere with diagnostic tests, including serum-methotrexate and serum-plasma creatinine levels, also urea, urinary glucose and urobilinogen tests.
Overdose
Likely signs of toxicity include:[16]
- Nausea
- Vomiting
- Dizziness
- Headache
- Mental depression
- Confusion
- Bone marrow depression
- Loss of appetite
- Colic
- Drowsiness
- Unconsciousness
The recommended treatment for overdose includes:[16]
- Administration of activated charcoal
- Stomach pumping
- General supportive measures
- Haemodialysis, which is moderately effective in clearing co-trimoxazole from the plasma.
- Calcium folinate 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.[16]
Pharmacology
Tetrahydrofolate synthesis pathway
The synergy between trimethoprim and sulfamethoxazole was first described in the late 1960s.[59][60][61] 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.[11]
Sulfamethoxazole, a sulfonamide, induces its therapeutic effects by interfering with the de novo (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.[11]
Trimethoprim serves as a competitive inhibitor of dihydrofolate reductase (DHFR), hence inhibiting the de novo synthesis of tetrahydrofolate, the biologically active form of folate.[11]
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.[11]
| Component | Tmax (hrs) | Vd (L) | Protein binding | t1/2 (hrs) | Excretion |
|---|---|---|---|---|---|
| Sulfamethoxazole | 1-4 | 20 | 66% | 8-10 | Renal |
| Trimethoprim | 1-4 | 130 | 42-45% | 10 | Renal |
Trade names
Co-trimoxazole is manufactured and sold by many different companies. The following list of brand names is incomplete:
- Bactrim, Bactrimel (Roche)
- Bactrom (Venezuela)
- Bibactin (manufactured by PPM and distributed in Cambodia and some African countries)
- Biseptol
- Co-trimoxazole (Sandoz)
- Cotrim
- Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia)
- Infectrin (Brazil)
- Primotren (Lek in Slovenia and other countries)
- Sanprima (manufactured by PT Sanbe Farma and distributed in Indonesia)
- Septra (Aspen Pharmacare and formerly GlaxoSmithKline)
- Septram (Panama)
- Sulfatrim
- Trisul
- Vactrim (manufactured and distributed in Laos)
Notes
References
- ^ "Trimethoprim/Sulfamethoxazole". Retrieved 21 June 2013.
- ^ "Co-trimoxazole". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. 23 September 2011. Retrieved 7 January 2014.
- ^ a b c d e f g h "Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 13 January 2014.
- ^ a b "Septra DS". WebMD. Retrieved 28 March 2015.
- ^ a b "Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole) dosing, indications, interactions, adverse effects and more". WebMD. Retrieved 28 March 2015.
- ^ "Co-trimoxazole". The American Society of Health-System Pharmacists. Retrieved Mar 2015.
- ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ Brumfitt, W; Hamilton-Miller, JM (December 1993). "Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines". Journal of Chemotherapy 5 (6): 465–9. PMID 8195839.
- ^ "Co-trimoxazole use restricted". Drug Ther Bull 33 (12): 92–3. December 1995. doi:10.1136/dtb.1995.331292. PMID 8777892.
- ^ Falagas ME, Grammatikos AP, Michalopoulos A (October 2008). "Potential of old-generation antibiotics to address current need for new antibiotics". Expert Rev Anti Infect Ther 6 (5): 593–600. doi:10.1586/14787210.6.5.593. PMID 18847400.
- ^ a b c d e f g Wormser, GP; Keusch, GT; Heel, RC (December 1982). "Co-trimoxazole (trimethoprim-sulfamethoxazole): an updated review of its antibacterial activity and clinical efficacy". Drugs 24 (6): 459–518. doi:10.2165/00003495-198224060-00002. PMID 6759092.
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UpToDate Contents
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- 1. トリメトプリムスルファメトキサゾール：概要 trimethoprim sulfamethoxazole an overview
- 2. フルオロキノロン類、ドキシサイクリン、およびトリメトプリムスルファメトキサゾールに対する肺炎レンサ球菌の耐性 resistance of streptococcus pneumoniae to the fluoroquinolones doxycycline and trimethoprim sulfamethoxazole
- 3. 黄色ブドウ球菌の皮膚・軟部組織感染症の疑い：新生児の評価とマネージメント suspected staphylococcus aureus skin and soft tissue infections evaluation and management in neonates
- 4. HIVに感染していない患者のニューモシスチス肺炎の治療と予防 treatment and prevention of pneumocystis pneumonia in hiv uninfected patients
- 5. 頭蓋内硬膜外膿瘍 intracranial epidural abscess
English Journal
- Concurrent Plasmodium infection, anemia and their correlates among newly diagnosed people living with HIV/AIDS in Northern Ethiopia.
- Beyene HB1, Tadesse M2, Disassa H3, Beyene MB4.
- Acta tropica.Acta Trop.2017 May;169:8-13. doi: 10.1016/j.actatropica.2017.01.007. Epub 2017 Jan 21.
- PMID 28119046
- Rectal microbiota among HIV-uninfected, untreated HIV, and treated HIV-infected in Nigeria.
- Nowak RG1, Bentzen SM, Ravel J, Crowell TA, Dauda W, Ma B, Liu H, Blattner WA, Baral SD, Charurat ME; TRUSTRV368 Study Group.
- AIDS (London, England).AIDS.2017 Mar 27;31(6):857-862. doi: 10.1097/QAD.0000000000001409.
- PMID 28118207
- Severe co-trimoxazole-induced hypoglycaemia in a patient with microscopic polyangiitis.
- Conley TE1, Mohiuddin A2, Naz N3.
- BMJ case reports.BMJ Case Rep.2017 Mar 16;2017. pii: bcr2016218976. doi: 10.1136/bcr-2016-218976.
- PMID 28302661
Japanese Journal
- (27)日本人全身性エリテマトーデス患者におけるST合剤の副作用とN-acetyltransferase 2遺伝子多型の関係
- 副島 誠
- 東京女子医科大学雑誌 78(2/3), 161-162, 2008-03
- NAID 110007524637
- Susceptibility of Enterococcus faecalis biofilm to antibiotics and calcium hydroxide
- Chai Wen L.,Hamimah Hassan,Cheng Soo C.,Sallam Atiya A.,Abdullah Mariam
- Journal of Oral Science 49(2), 161-166, 2007
- … (ATCC 29212) biofilm was exposed to ampicillin, co-trimoxazole, erythr omycin, oxytetracycline, vancomycin, vancomycin followed by gentamicin, Ca(OH)<Sub>2</Sub>, and phosphate-buffered saline (control). … 0.05) detected significant differences among the test agents, except in the ampicillin group versus the co-trimoxazole group. …
- NAID 130000072689
Related Links
- Co-trimoxazoleとは？goo Wikipedia (ウィキペディア) 。出典：Wikipedia（ウィキペディア）フリー百科事典。 Co-trimoxazoleとは - goo Wikipedia (ウィキペディア) gooトップ サイトマップ スタートページに設定 RSS ヘルプ メニューへスキップ ...
- 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 ...
Related Pictures
★リンクテーブル★
| リンク元 | 「ST合剤」「septra」 |
| 関連記事 | 「CO」「cod」「Co」「c」 |
「ST合剤」
- 英
- ST mixture
- 同
- スルファメトキサゾール・トリメトプリム合剤 sulfamethoxazole and trimethoprim mixture、スルファメトキサゾール・トリメトプリム SMX-TMP
- コトリモキサゾール co-trimoxazole
- 関
- サルファ合剤、サルファ剤
特徴
構造
作用機序
薬理作用
抗菌スペクトル
動態
適応
注意
禁忌
副作用
「septra」
- 関
- Trimethoprim-sulfarnethoxazole co-trimoxazole, TMP-SMZ, Bactrim, Cotrim
「CO」
「cod」