{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T01:15:56Z","timestamp":1793927756469,"version":"4.8.0"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,24]],"date-time":"2012-01-24T00:00:00Z","timestamp":1327363200000},"content-version":"vor","delay-in-days":11157,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[1981,7,8]]},"abstract":"<jats:p>Trimethoprim has recently been marketed as a single\u2010entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram\u2010positive aerobic cocci and some gram\u2010negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition.<\/jats:p>\n                  <jats:p>\n                    Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by\n                    <jats:italic>E. coli<\/jats:italic>\n                    , and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim\u2010sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging. (Pharmacotherapy 1981;1:14\u201320)\n                  <\/jats:p>","DOI":"10.1002\/j.1875-9114.1981.tb03548.x","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T12:50:26Z","timestamp":1450270226000},"page":"14-19","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":155,"title":["Trimethoprim: Mechanisms of Action, Antimicrobial Activity, Bacterial Resistance, Pharmacokinetics, Adverse Reactions, and Therapeutic Indications"],"prefix":"10.1002","volume":"1","author":[{"given":"Richard","family":"Gleckman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Blagg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Joubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,24]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1968.tb00475.x"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.21.2.202"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S442"},{"key":"e_1_2_1_5_2","first-page":"5","article-title":"Trimethoprim\u2010sulfamethoxazole: a reappraisal","volume":"112","author":"O'Grady F.","year":"1975","journal-title":"Can Med Assoc J"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S433"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S437"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S498"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S508"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/5.Supplement_B.61"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S502"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.25.6.531"},{"key":"e_1_2_1_13_2","first-page":"571","article-title":"Bacterial resistance to trimethoprim (editorial)","volume":"2","year":"1980","journal-title":"Br Med J"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)92171-2"},{"key":"e_1_2_1_15_2","first-page":"834","article-title":"Thymine\u2010requiring bacteria associated with co\u2010trimoxazole therapy","volume":"1","author":"Maskell R","year":"1975","journal-title":"Lancet"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.27.7.565"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)90855-8"},{"issue":"3","key":"e_1_2_1_18_2","first-page":"283","article-title":"Trimethoprim","volume":"23","author":"Brumfitt W","year":"1980","journal-title":"Br J Hosp Med"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000221918"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.17.2.263"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-92-6-770"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)92331-6"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000237834"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.280.6213.517"},{"key":"e_1_2_1_25_2","first-page":"1409","article-title":"Resistance to trimethoprim (letter)","volume":"1","author":"Brumfitt W","year":"1980","journal-title":"Lancet"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.280.6220.1054-f"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.280.6207.72"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.29.4.292"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.31.9.850"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6181.7"},{"key":"e_1_2_1_31_2","first-page":"926","article-title":"Trimethoprim\u2010resistant conforms (letter)","volume":"2","author":"Brumfitt W","year":"1977","journal-title":"Lancet"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)92456-X"},{"key":"e_1_2_1_33_2","first-page":"32","article-title":"Assay and pharmacokinetics of trimethoprim in man and animals","volume":"45","author":"Schwartz DE","year":"1969","journal-title":"Postgrad Med J"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S547"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600590318"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S556"},{"key":"e_1_2_1_37_2","first-page":"217","volume-title":"Antibiotics and chemotherapy","author":"Hansen I","year":"1978"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01639009"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-91-3-420"},{"key":"e_1_2_1_40_2","first-page":"47","article-title":"The penetration of sulfadiazine, sulfamethoxazole, and trimethoprim into the prostate gland, epididymis, and testis in man","volume":"25","author":"Seppamen J.","year":"1980","journal-title":"Ann Clin Res"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S584"},{"key":"e_1_2_1_42_2","first-page":"893","article-title":"Trimethoprim\u2010sulfamethoxazole","volume":"36","author":"Gleckman R","year":"1979","journal-title":"Am J Hosp Pharm"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S580"},{"key":"e_1_2_1_44_2","first-page":"1915","article-title":"Trimethoprim\u2010sulfamethoxazole","volume":"78","author":"Wormser G.","year":"1978","journal-title":"NY State J Med"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S567"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/5.Supplement_B.159"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/131.3.261"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S574"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365597209132095"},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1975.tb03970.x"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1976.tb02748.x"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/5.6.717"},{"key":"e_1_2_1_53_2","first-page":"67","article-title":"Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately and in combination","volume":"112","author":"Reid D","year":"1975","journal-title":"Can Med Assoc J"},{"key":"e_1_2_1_54_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016347309158319"},{"key":"e_1_2_1_55_2","first-page":"687","volume-title":"Proceedings of the Eighth Congress of Chemotherapy","author":"Miller R","year":"1973"},{"key":"e_1_2_1_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/5.Supplement_B.97"},{"key":"e_1_2_1_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01639017"},{"key":"e_1_2_1_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)91282-9"},{"key":"e_1_2_1_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)67149-0"},{"key":"e_1_2_1_60_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/clinchem\/22.2.283","article-title":"Drug interference with creatinine assay","volume":"22","author":"Bye A.","year":"1976","journal-title":"Clin Chem"},{"key":"e_1_2_1_61_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5815.673"},{"key":"e_1_2_1_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_3.S647"},{"key":"e_1_2_1_63_2","doi-asserted-by":"publisher","DOI":"10.1159\/000221470"},{"key":"e_1_2_1_64_2","first-page":"645","article-title":"Comparison of oxolonic acid, trimethoprim, and trimethoprim\u2010sulfamethoxazole in the treatment and long\u2010term control of urinary tract infection","volume":"20","author":"Mannisoto PT.","year":"1976","journal-title":"Curr Ther Res"},{"key":"e_1_2_1_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01639025"},{"key":"e_1_2_1_66_2","first-page":"202","article-title":"Trimethoprim in the treatment of acute urinary tract infection","volume":"25","author":"Kasanen A","year":"1979","journal-title":"Curr Ther Res"},{"key":"e_1_2_1_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)91732-8"},{"key":"e_1_2_1_68_2","first-page":"71","article-title":"The treatment of bacteriuria in pregnant women with sulfamethoxazole and trimethoprim","volume":"45","author":"Williams JD","year":"1969","journal-title":"Postgrad Med"},{"key":"e_1_2_1_69_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.239.24.2588"},{"key":"e_1_2_1_70_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/030006057900700204","article-title":"Controlled clinical trial of a rifampicin\u2010trimethoprim combination (Rifaprim) and cotrimoxazole in patients with chronic urinary tract infections","volume":"7","author":"Adachi T","year":"1979","journal-title":"J Int Med Res"},{"key":"e_1_2_1_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.19.4.513"},{"key":"e_1_2_1_72_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.282.6261.364"},{"key":"e_1_2_1_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(81)90190-4"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fj.1875-9114.1981.tb03548.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fj.1875-9114.1981.tb03548.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/j.1875-9114.1981.tb03548.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T16:28:48Z","timestamp":1761064128000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/j.1875-9114.1981.tb03548.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1981,7,8]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1981,7,8]]}},"alternative-id":["10.1002\/j.1875-9114.1981.tb03548.x"],"URL":"https:\/\/doi.org\/10.1002\/j.1875-9114.1981.tb03548.x","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[1981,7,8]]},"assertion":[{"value":"2012-01-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}