Trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole (TMP/SMX), also known as co-trimoxazole among other names, is an antibiotic used to treat a variety of bacterial infections.[2] It consists of one part trimethoprim to five parts sulfamethoxazole.[3] It is used for urinary tract infections, methicillin-resistant Staphylococcus aureus (MRSA) skin infections, travelers' diarrhea, respiratory tract infections, and cholera, among others.[2][3] It may be used both to treat and prevent pneumocystis pneumonia and toxoplasmosis in people with HIV/AIDS.[2] It can be given by mouth or intravenously.[2]

Trimethoprim/sulfamethoxazole
Trimethoprim (top) and sulfamethoxazole (bottom)
Combination of
SulfamethoxazoleSulfonamide antibiotic
TrimethoprimDihydrofolate reductase inhibitor
Clinical data
Trade namesBactrim, Cotrim, Septra, others
Other namesCo-trimoxazole (BAN UK)
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: C [1]
  • US: N (Not classified yet) [1]
    Routes of
    administration    		By mouth, intravenous[2]
    ATC code
    Legal status
    Legal status
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    ChEBI
    CompTox Dashboard (EPA)
      (verify)

    Common side effects include nausea, vomiting, rash, and diarrhea.[2] Severe allergic reactions and Clostridium difficile diarrhea may occasionally occur.[2] Its use in pregnancy is not recommended.[2][4] It appears to be safe for use during breastfeeding as long as the baby is healthy.[4] TMP/SMX generally results in bacterial death.[2] It works by blocking the making and use of folate by the microorganisms.[2]

    TMP/SMX was first sold in 1974.[5] It is on the World Health Organization's List of Essential Medicines.[6] It is available as a generic medication.[3][7] In 2017, it was the 121st most commonly prescribed medication in the United States, with more than six million prescriptions.[8][9]

    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.[10] 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.[11] It may be effective in a variety of upper and lower respiratory tract infections, kidney and urinary tract infections, gastrointestinal tract infections, skin and wound infections, sepsis, and other infections caused by sensitive organisms. Co-trimoxazole decreases the risk of recurrence of retinochoroiditis.[12] The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole more recently.[13]

    Susceptibility

    Organisms against which co-trimoxazole can be effective include:[14][15]

    The only notable nonsusceptible organisms are Pseudomonas aeruginosa, the mycoplasmae[15] and Francisella tularensis (the causative organism of tularaemia).[16][17]

    Pregnancy and breast feeding

    Its use during pregnancy is contraindicated, although it has been placed in Australian pregnancy category C and American pregnancy category D.[14] 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.[14] 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).[18][19] Animal studies have yielded similarly discouraging results.[20]

    It appears to be safe for use during breastfeeding as long as the baby is healthy.[4]

    Babies

    Its use in those less than 2 months of age is not recommended due to the risk of adverse side effects.[21]

    Adverse effects
    See also: List of side effects of trimethoprim/sulfamethoxazole

    Contraindications

    Contraindications include the following:[14][22]

    • 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 chronic kidney disease (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:[14][20][22][23][24][25]

    • ACE inhibitors like captopril, enalapril, lisinopril, perindopril, and ramipril due to the potential for additive hyperkalaemic effects[22]
    • 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 diuretics are at a heightened risk for developing thrombocytopaenia while on co-trimoxazole
    • Ciclosporin — 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 — 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.[26]
    • 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 elevated serum creatinine levels,[27] also urea, urinary glucose and urobilinogen tests.

    Overdose

    Likely signs of toxicity include:[20]

    • Nausea
    • Vomiting
    • Dizziness
    • Headache
    • Mental depression
    • Confusion
    • Thrombocytopenia
    • Uremia
    • Bone marrow depression
    • Loss of appetite
    • Colic
    • Drowsiness
    • Unconsciousness

    The recommended treatment for overdose includes:[20]

    • 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.[20]

    Pharmacology
    Tetrahydrofolate synthesis pathway

    The synergy between trimethoprim and sulfamethoxazole was first described in the late 1960s.[28][29][30] 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.[15]

    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.[15]

    Trimethoprim serves as a competitive inhibitor of dihydrofolate reductase (DHFR), hence inhibiting the de novo synthesis of tetrahydrofolate, the biologically active form of folate.[15]

    Tetrahydrofolate is crucial in the synthesis of purines, thymidine, and methionine which are needed for the production of DNA and proteins[31] during bacterial replication. Thus the net effect of each of these drugs is a bacteriostatic halt in replication. When combined, TMP and SMX are bactericidal.

    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.[15]

    Pharmacokinetics of co-trimoxazole[14][20]
    ComponentTmax (h)Vd (L)Protein bindingt1/2 (h)Excretion
    Sulfamethoxazole1-42066%8-10Renal
    Trimethoprim1-413042-45%10Renal

    Society and culture

    Approval
    Indications for co-trimoxazole
    Indication
    FDA-labelled indication?
    TGA-labelled indication?
    MHRA-labelled indication?    		 Literature support
    Acute infective exacerbation of COPDYesNoNoClinical trials are lacking.
    Prophylaxis in HIV-infected individualsNoNoNoEffective in one Ugandan study on morbidity, mortality, CD4-cell count, and viral load in HIV infection.[32]
    Otitis mediaPaediatric population onlyNoYesClinical trials have confirmed its efficacy in chronic active otitis media[33] and acute otitis media.[34]
    Travellers' diarrhoea, treatment & prophylaxisYesNoNoClinical trials have confirmed its efficacy as a treatment for travellers' diarrhoea.[35][36][37]
    Urinary tract infectionYesNoYesClinical trials have confirmed its efficacy in this indication.[15]
    Bacterial infections
    Acne vulgarisNoNoNoAt least one clinical trial supports its use in this indication.[38]
    ListeriaNoYesNoWell-designed clinical trials are lacking.
    MelioidosisNoYesNoClinical trials have confirmed its efficacy, with or without adjunctive doxycycline; although, co-trimoxazole alone seems preferable.[39][40][41]
    Pertussis (whooping cough)NoNoNoOne cochrane review supports its efficacy in preventing the spread of pertussis.[42]
    ShigellosisYesYesNoGenerally accepted treatment for shigellosis.[43] 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.[44]
    Staphylococcus aureus infectionsNoNoNoIn vitro and in vivo activity against both non-resistant and methicillin-resistant Staphylococcus aureus (MRSA) infections.[45][46][47][48][49][50][51]
    TuberculosisNoNoNoIn vitro and in vivo activity against both nonresistant and MDR strains of TB.[52][53][54]
    Whipple's diseaseNoNoNoCo-trimoxazole is the recommended standard treatment for whipple's disease in some treatment protocols.[55][56][57]
    Fungal and protozoal infections
    IsosporiasisNoNoNoClinical trials have confirmed its use in this indication.[58]
    MalariaNoNoNoClinical trials have confirmed its efficacy in both the treatment and prevention of malaria.[59]
    Pneumocystis jirovecii pneumoniaYesYesYesIts use as a prophylactic treatment is supported by one clinical trial involving children with acute lymphoblastic leukaemia.[60] Other than this and one other clinical trial into its efficacy as a treatment for pneumocystis pneumonia,[61] data on its use in both the treatment and prevention of pneumocystis pneumonia is significantly lacking.
    ToxoplasmosisYesPrevention onlyYesClinical trials have confirmed its prophylactic and therapeutic utility in cases of toxoplasmosis.[62][63][64][65][66][67]

    Route

    It can be given by mouth, as a tablet or suspension, or intravenously.[2][68]

    Trade names

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

    Co-trimoxazole (BAN) is manufactured and sold by many different companies. The following list of brand names is incomplete:

    • Bactrim, Bactrimel (manufactured by Roche and distributed in Europe)
    • Bactrom (Venezuela)
    • Bibactin (manufactured by PPM and distributed in Cambodia and some African countries)
    • Biseptol
    • Co-trimoxazole (Sandoz)
    • Cotrim
    • Deprim (AFT Pharmaceuticals)
    • Diseptyl (Israel)
    • Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia)
    • Infectrin, Bactrim (Brazil)
    • Novo-Trimel[69]
    • Primotren (Lek in Slovenia and other countries)
    • Polytrim
    • Resprim
    • Sanprima (manufactured by PT Sanbe Farma and distributed in Indonesia)
    • Septra (Aspen Pharmacare and formerly GlaxoSmithKline)
    • Septram (Panama)
    • Septran (GlaxoSmithKline)[70]
    • Septrin (Spain)[71]
    • Sulfatrim
    • Trisul
    • Vactrim (manufactured and distributed in Laos)

    Cost

    Trimethoprim/sulfamethoxazole is relatively inexpensive as of 2019.[7] In the United States, it is about US$0.40 per dose.[2]

    gollark: Hmm. Is solar responsible for any deaths?
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    gollark: What of GTech™ sentient mathematical objects™?
    gollark: It does not. Nuclear waste is tiny and buried in sensible underground locations.
    gollark: (and the accidents were all preventable)

    References
    1. "Sulfamethoxazole / trimethoprim Use During Pregnancy". Drugs.com. 8 March 2019. Retrieved 15 April 2020.
    2. "Co-trimoxazole". The American Society of Health-System Pharmacists. Archived from the original on 2015-09-06. Retrieved Aug 1, 2015.
    3. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 105. ISBN 9781284057560.
    4. "Sulfamethoxazole / trimethoprim Pregnancy and Breastfeeding Warnings". Archived from the original on 6 September 2015. Retrieved 31 August 2015. An extensive systematic review of sulfonamide usage near term and during breastfeeding found no side effects in infants; the authors concluded that use of this combination drug during breastfeeding presents no risk of neonatal kernicterus... LactMed: Use is considered acceptable when breastfeeding healthy, full-term infants after the newborn period
    5. Oxford Handbook of Infectious Diseases and Microbiology. OUP Oxford. 2009. p. 56. ISBN 9780191039621. Archived from the original on 2015-11-24.
    6. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    7. Brown, Di; Edwards, Helen; Buckley, Thomas; Aitken, Robyn L. (2019). Lewis's Medical-Surgical Nursing EBook: Assessment and Management of Clinical Problems. Elsevier Health Sciences. p. 1173. ISBN 978-0-7295-8708-2.
    8. "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
    9. "Sulfamethoxazole; Trimethoprim - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
    10. 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. doi:10.1080/1120009X.1993.11741097. PMID 8195839.
    11. "Co-trimoxazole use restricted". Drug Ther Bull. 33 (12): 92–3. December 1995. doi:10.1136/dtb.1995.331292. PMID 8777892.
    12. Pradhan E, Bhandari S, Gilbert RE, Stanford M (2016). "Antibiotics versus no treatment for toxoplasma retinochoroiditis" (PDF). Cochrane Database Syst Rev. 5 (5). CD002218. doi:10.1002/14651858.CD002218.pub2. PMID 27198629.
    13. 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.
    14. "Bactrim, Bactrim DS (trimethoprim/sulfamethoxazole) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 16 January 2014. Retrieved 13 January 2014.
    15. 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.
    16. "TULAREMIA" (PDF). Infectious Disease Epidemiology Section. Louisiana Office of Public Health. 17 July 2011. Archived (PDF) from the original on 23 February 2014. Retrieved 12 February 2014.
    17. Harik, NS (1 July 2013). "Tularemia: Epidemiology, Diagnosis, and Treatment" (PDF). Pediatric Annals. 42 (7): 288–292. doi:10.3928/00904481-20130619-13. PMID 23805970. Archived (PDF) from the original on 22 February 2014.
    18. Yang, J; Xie, RH; Krewski, D; Wang, YJ; Walker, M; Wen, SW (May 2011). "Exposure to trimethoprim/sulfamethoxazole but not other FDA category C and D anti-infectives is associated with increased risks of preterm birth and low birth weight". International Journal of Infectious Diseases. 15 (5): e336–e341. doi:10.1016/j.ijid.2011.01.007. PMID 21345707.
    19. Santos, F; Sheehy, O; Perreault, S; Ferreira, E; Berard, A (October 2011). "Exposure to anti-infective drugs during pregnancy and the risk of small-for-gestational-age newborns: a case–control study". BJOG. 118 (11): 1374–1382. doi:10.1111/j.1471-0528.2011.03041.x. PMID 21749628.
    20. "BACTRIM®" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 18 September 2012. Retrieved 13 January 2014.
    21. "Drugs & Medications". www.webmd.com. Retrieved 2019-04-19.
    22. "Co-Trimoxazole Tablets 80/400mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Actavis UK Ltd. 17 October 2012. Archived from the original on 13 January 2014. Retrieved 13 January 2014.
    23. "BACTRIM DS (sulfamethoxazole and trimethoprim) tablet BACTRIM (sulfamethoxazole and trimethoprim) tablet [AR Scientific, Inc.]". DailyMed. AR Scientific, Inc. June 2013. Archived from the original on 14 January 2014. Retrieved 13 January 2014.
    24. Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
    25. Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
    26. Juvet T, Gourineni V, Ravi S, Zarich S. Life-threatening hyperkalemia: a potentially lethal drug combination. Connecticut Medicine [serial online]. September 2013;77(8):491-493. Available from: MEDLINE Complete, Ipswich, MA.
    27. Gentry CA, Nguyen AT. An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. Ann Pharmacother. 2013;47(12):1618-1626. doi:10.1177/1060028013509973
    28. Bushby SR, Hitchings GH (1968). "Trimethoprim, a sulphonamide potentiator". Br J Pharmacol. 33 (1): 72–90. doi:10.1111/j.1476-5381.1968.tb00475.x. PMC 1570262. PMID 5301731.
    29. Böhni E (1969). "Vergleichende bakteriologische untersuchungen mit der Kombination Trimethoprim/Sulfamethoxazole in vitro und in vivo". Chemotherapy. 14 (Suppl): Suppl:1–21. doi:10.1159/000220651. PMID 4908562.
    30. Böhni E (1969). "Chemotherapeutic activity of the combination of trimethoprim and sulfamethoxazole in infections of mice". Postgrad Med J. 45 (Suppl): Suppl:18–21. PMID 4902845.
    31. Pubchem. "Tetrahydrofolic acid". pubchem.ncbi.nlm.nih.gov. Retrieved 2018-02-26.
    32. Mermin, J; Lule, J; Ekwaru, JP; Malamba, S; Downing, R; Ransom, R; Kaharuza, F; Culver, D; Kizito, F; Bunnell, R; Kigozi, A; Nakanjako, D; Wafula, W; Quick, R (October 2004). "Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda". The Lancet. 364 (9443): 1428–1434. doi:10.1016/S0140-6736(04)17225-5. PMID 15488218.
    33. van der Veen, EL; Rovers, MM; Albers, FW; Sanders, EA; Schilder, AG (May 2007). "Effectiveness of trimethoprim/sulfamethoxazole for children with chronic active otitis media: a randomized, placebo-controlled trial" (PDF). Pediatrics. 119 (5): 897–904. doi:10.1542/peds.2006-2787. hdl:1874/25986. PMID 17473089.
    34. Leiberman, A; Leibovitz, E; Piglansky, L; Raiz, S; Press, J; Yagupsky, P; Dagan, R (March 2001). "Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media". Pediatric Infectious Disease Journal. 20 (3): 260–264. doi:10.1097/00006454-200103000-00009. PMID 11303827.
    35. Ericsson CD, Johnson PC, Dupont HL, Morgan DR, Bitsura JA, de la Cabada FJ (February 1987). "Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial". Annals of Internal Medicine. 106 (2): 216–220. doi:10.7326/0003-4819-106-2-216. PMID 3541724.
    36. Ericsson, CD; DuPont, HL; Mathewson, JJ; West, MS; Johnson, PC; Bitsura, JA (January 1990). "Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide". Journal of the American Medical Association. 263 (2): 257–261. doi:10.1001/jama.1990.03440020091039. PMID 2403603.
    37. Rendi-Wagner, P; Kollaritsch, H (March 2002). "Drug Prophylaxis for Travelers' Diarrhea" (PDF). Clinical Infectious Diseases. 34 (5): 628–633. doi:10.1086/338640. PMID 11803509. Archived (PDF) from the original on 2016-06-16.
    38. Nordin, K; Hallander, H; Fredriksson, T; Rylander, C; et al. (1978). "A clinical and bacteriological evaluation of the effect of sulphamethoxazole-trimethoprim in acne vulgaris, resistant to prior therapy with tetracyclines". Dermatologica. 157 (4): 245–53. doi:10.1159/000250840. PMID 150980.
    39. Chetchotisakd, P; Chaowagul, W; Mootsikapun, P; Budhsarawong, D; Thinkamrop, B (January 2001). "Maintenance therapy of melioidosis with ciprofloxacin plus azithromycin compared with cotrimoxazole plus doxycycline" (PDF). The American Journal of Tropical Medicine and Hygiene. 64 (1–2): 24–27. doi:10.4269/ajtmh.2001.64.24. PMID 11425157.
    40. Chusri S, Hortiwakul T, Charoenmak B, Silpapojakul K (November 2012). "Outcomes of patients with melioidosis treated with cotrimoxazole alone for eradication therapy". The American Journal of Tropical Medicine and Hygiene. 87 (5): 927–932. doi:10.4269/ajtmh.2012.12-0136. PMC 3516270. PMID 23033403.
    41. Chetchotisakd, P; Chierakul, W; Chaowagul, W; Anunnatsiri, S; Phimda, K; Mootsikapun, P; Chaisuksant, S; Pilaikul, J; Thinkhamrop, B; Phiphitaporn, S; Susaengrat, W; Toondee, C; Wongrattanacheewin, S; Wuthiekanun, V; Chantratita, N; Thaipadungpanit, J; Day, NP; Limmathurotsakul, D; Peacock, SJ (November 2013). "Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial". The Lancet. 383 (9919): 807–14. doi:10.1016/S0140-6736(13)61951-0. PMC 3939931. PMID 24284287.
    42. Altunaiji, S.; Kukuruzovic, R.; Curtis, N.; Massie, J. (2007-07-18). "Antibiotics for whooping cough (pertussis)". The Cochrane Database of Systematic Reviews (3): CD004404. doi:10.1002/14651858.CD004404.pub3. ISSN 1469-493X. PMID 17636756.
    43. Sureshbabu, J; Venugopalan, P; Abuhammour, W (25 June 2012). Fennelly, G; Windle, ML; Lutwick, LI; Tolan Jr, RW; Steele, RW (eds.). "Shigella Infection Medication". Medscape Reference. WebMD. Archived from the original on 8 January 2014. Retrieved 8 January 2014.
    44. Christopher, PR; David, KV; John, SM; Sankarapandian, V (August 2010). "Antibiotic therapy for Shigella dysentery (Review)" (PDF). The Cochrane Database of Systematic Reviews (8): CD006784. doi:10.1002/14651858.CD006784.pub4. PMC 6532574. PMID 20687081. Archived from the original (PDF) on 2014-01-08.
    45. Grim, SA; Rapp, RP; Martin, CA; Evans, ME (February 2005). "Trimethoprim-Sulfamethoxazole as a Viable Treatment Option for Infections Caused by Methicillin-Resistant Staphylococcus aureus". Pharmacotherapy. 25 (2): 253–264. doi:10.1592/phco.25.2.253.56956. PMID 15767239.
    46. Cenizal, MJ; Skiest, D; Luber, S; Bedimo, R; Davis, P; Fox, P; Delaney, K; Hardy, RD (July 2007). "Prospective Randomized Trial of Empiric Therapy with Trimethoprim-Sulfamethoxazole or Doxycycline for Outpatient Skin and Soft Tissue Infections in an Area of High Prevalence of Methicillin-Resistant Staphylococcus aureus". Antimicrobial Agents and Chemotherapy. 51 (7): 2628–2630. doi:10.1128/AAC.00206-07. PMC 1913240. PMID 17502411.
    47. LaPlante, KL; Leonard, SN; Andes, DR; Craig, WA; Rybak, MJ (April 2008). "Activities of Clindamycin, Daptomycin, Doxycycline, Linezolid, Trimethoprim-Sulfamethoxazole, and Vancomycin against Community-Associated Methicillin-Resistant Staphylococcus aureus with Inducible Clindamycin Resistance in Murine Thigh Infection and In Vitro Pharmacodynamic Models". Antimicrobial Agents and Chemotherapy. 52 (6): 2156–2162. doi:10.1128/AAC.01046-07. PMC 2415789. PMID 18411321.
    48. Pappas, G; Athanasoulia, AP; Matthaiou, DK; Falagas, ME (April 2009). "Trimethoprim-sulfamethoxazole for methicillin-resistant Staphylococcus aureus: a forgotten alternative?". Journal of Chemotherapy. 21 (2): 115–126. doi:10.1179/joc.2009.21.2.115. ISSN 1973-9478. PMID 19423463.
    49. Goldberg, E; Paul, M; Talker, O; Samra, Z; Raskin, M; Hazzan, R; Leibovici, L; Bishara, J (May 2010). "Co-trimoxazole versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteraemia: A retrospective cohort study" (PDF). Journal of Antimicrobial Chemotherapy. 65 (8): 1779–1783. doi:10.1093/jac/dkq179. PMID 20507860. Archived (PDF) from the original on 2014-08-01.
    50. Cadena, J; Nair, S; Henao-Martinez, AF; Jorgensen, JH; Patterson, JE; Sreeramoju, PV (December 2011). "Dose of Trimethoprim-Sulfamethoxazole To Treat Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus". Antimicrobial Agents and Chemotherapy. 55 (12): 5430–5432. doi:10.1128/AAC.00706-11. PMC 3232808. PMID 21930870.
    51. Avery, LM; Steed, ME; Woodruff, AE; Hasan, M; Rybak, MJ (November 2012). "Daptomycin-Nonsusceptible Vancomycin-Intermediate Staphylococcus aureus Vertebral Osteomyelitis Cases Complicated by Bacteremia Treated with High-Dose Daptomycin and Trimethoprim-Sulfamethoxazole". Antimicrobial Agents and Chemotherapy. 56 (11): 5990–5993. doi:10.1128/AAC.01046-12. PMC 3486608. PMID 22869580.
    52. Forgacs, P; Wengenack, NL; Hall, L; Zimmerman, SK; Silverman, ML; Roberts, GD (November 2009). "Tuberculosis and trimethoprim-sulfamethoxazole". Antimicrobial Agents and Chemotherapy. 53 (11): 4789–4793. doi:10.1128/AAC.01658-08. PMC 2772331. PMID 19564358.
    53. Vilchèze, C; Jacobs, WR Jr (October 2012). "The combination of sulfamethoxazole, trimethoprim, and isoniazid or rifampin is bactericidal and prevents the emergence of drug resistance in Mycobacterium tuberculosis" (PDF). Antimicrobial Agents and Chemotherapy. 56 (10): 5142–5148. doi:10.1128/AAC.00832-12. PMC 3457372. PMID 22825115.
    54. Alsaad, N; van Altena, R; Pranger, AD; van Soolingen, D; de Lange, WC; van der Werf, TS; Kosterink, JG; Alffenaar, JW (August 2013). "Evaluation of co-trimoxazole in the treatment of multidrug-resistant tuberculosis". The European Respiratory Journal. 42 (2): 504–512. doi:10.1183/09031936.00114812. PMID 23100498.
    55. Fenollar, F; Raoult, D (January 2001). "Whipple's Disease". Clinical and Vaccine Immunology. 8 (1): 1–8. doi:10.1128/CDLI.8.1.1-8.2001. PMC 96003. PMID 11139188.
    56. Ojeda, E; Cosme, A; Lapaza, J; Torrado, J; Arruabarrena, I; Alzate, L (February 2010). "Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001". Rev Esp Enferm Dig. 102 (2): 108–123. doi:10.4321/s1130-01082010000200006. PMID 20361847.
    57. Puéchal X (November 2013). "Whipple's disease" (PDF). Postgraduate Medical Journal. 89 (1057): 659–665. doi:10.1136/postgradmedj-2012-202684rep. PMID 24129033.
    58. Lagrange-Xélot, M; Porcher, R; Sarfati, C; de Castro, N; Carel, O; Magnier, JD; Delcey, V; Molina, JM (February 2008). "Isosporiasis in patients with HIV infection in the highly active antiretroviral therapy era in France". HIV Medicine. 9 (2): 126–30. doi:10.1111/j.1468-1293.2007.00530.x. PMID 18257775.
    59. Manyando, C; Njunju, EM; D'Alessandro, U; Van Geertruyden, JP (2013). "Safety and Efficacy of Co-Trimoxazole for Treatment and Prevention of Plasmodium falciparum Malaria: A Systematic Review". PLoS ONE. 8 (2): e56916. Bibcode:2013PLoSO...856916M. doi:10.1371/journal.pone.0056916. PMC 3579948. PMID 23451110.
    60. Agrawal, AK; Chang, PP; Feusner, J (January 2011). "Twice weekly Pneumocystis jiroveci pneumonia prophylaxis with trimethoprim-sulfamethoxazole in pediatric patients with acute lymphoblastic leukemia". Journal of Pediatric Hematology/Oncology. 33 (1): e1–4. doi:10.1097/MPH.0b013e3181fd6fca. PMID 21102354.
    61. Safrin, S; Finkelstein, DM; Feinberg, J; Frame, P; Simpson, G; Wu, A; Cheung, T; Soeiro, R; Hojczyk, P; Black, JR (May 1996). "Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group". Annals of Internal Medicine. 124 (9): 792–802. doi:10.7326/0003-4819-124-9-199605010-00003. PMID 8610948.
    62. Canessa, A; Del Bono, V; De Leo, P; Piersantelli, N; Terragna, A (February 1992). "Cotrimoxazole therapy of Toxoplasma gondii encephalitis in AIDS patients". European Journal of Clinical Microbiology and Infectious Diseases. 11 (2): 125–130. doi:10.1007/BF01967063. PMID 1396726.
    63. Torre, D; Casari, S; Speranza, F; Donisi, A; Gregis, G; Poggio, A; Ranieri, S; Orani, A; Angarano, G; Chiodo, F; Fiori, G; Carosi, G (June 1998). "Randomized Trial of Trimethoprim-Sulfamethoxazole versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients with AIDS". Antimicrobial Agents and Chemotherapy. 42 (6): 1346–1349. doi:10.1128/AAC.42.6.1346. PMC 105601. PMID 9624473.
    64. Muñoz, P; Arencibia, J; Rodríguez, C; Rivera, M; Palomo, J; Yañez, J; Bouza, E (April 2003). "Trimethoprim-Sulfamethoxazole as Toxoplasmosis Prophylaxis for Heart Transplant Recipients" (PDF). Clinical Infectious Diseases. 36 (7): 932–933. doi:10.1086/368209. PMID 12652396.
    65. Béraud, G; Pierre-François, S; Foltzer, A; Abel, S; Liautaud, B; Smadja, D; Cabié, A (April 2009). "Cotrimoxazole for treatment of cerebral toxoplasmosis: an observational cohort study during 1994-2006" (PDF). The American Journal of Tropical Medicine and Hygiene. 80 (4): 583–587. doi:10.4269/ajtmh.2009.80.583. PMID 19346380.
    66. Alavi, SM; Alavi, L (September 2010). "Treatment of toxoplasmic lymphadenitis with co-trimoxazole: double-blind, randomized clinical trial". International Journal of Infectious Diseases. 14 (Supplement 3): e67–e69. doi:10.1016/j.ijid.2009.11.015. PMID 20194044.
    67. Patil, HV; Patil, VC; Rajmane, V; Raje, V (January 2011). "Successful treatment of cerebral toxoplasmosis with cotrimoxazole". Indian Journal of Sexually Transmitted Diseases. 32 (1): 44–46. doi:10.4103/0253-7184.81255. PMC 3139289. PMID 21799577.
    68. "Sulfamethoxazole and Trimethoprim". Drugs.com. Aug 31, 2019. Retrieved 2019-11-21.
    69. "Novo-Trimel Advanced Patient Information - Drugs.com". Drugs.com. Drugs.com. Retrieved 1 February 2018.
    70. "Septran/Sepman Double Strength - Co-Trimoxazole Oral Formulations" (PDF). GlaxoSmithKline. 2017-08-13. Archived (PDF) from the original on 2018-06-01. Retrieved 2018-06-01.
    71. "SEPTRIN FORTE Comp. 800/160 mg - Datos generales". Archived from the original on 2015-06-16. Retrieved 2015-08-17.
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