Trimethoprim Alone: Clinical Uses

  • D. W. Barry
  • K. H. Pattishall
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 64)


Trimethoprim (TMP) is an effective and potent antibacterial agent. Although academics and practitioners alike have been intrigued by the consistent enhancement of TMP’s activity by sulfamethoxazole and have more recently been fascinated by its synergism with other sulfonamides as well as agents as disparate as polymyxin and rifampin, it would be unfortunate if this intellectual attraction were to prevent a critical examination of the potential use of TMP alone in certain infections. In this chapter, the accumulated clinical data on the use of TMP as a single entity will be reviewed so that the comparative safety and efficacy of this drug may be defined. We will also analyze those clinical situations in which its synergistic activity with sulfamethoxazole is required to cure the infection and those in which it is not. In addition, by examination of available in vitro, epidemiologic, and human experimental data, the risk and clinical relevance of the potential emergence of TMP-resistant organisms may be determined.


Urinary Tract Infection Recurrent Urinary Tract Infection Gastrointestinal Upset Fecal Flora Uncomplicated Urinary Tract Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adatto K, Doebele KG, Galland L, Granowetter L (1979) Behavioral factors and urinary tract infection. JAMA 241: 2525–2526PubMedCrossRefGoogle Scholar
  2. Arnauld R, Soutoul JH, Gallier J, Borderon JC, Borderon E (1972) A study of the passage of trimethoprim into the maternal milk. Ouest Med 25: 959–964Google Scholar
  3. Arvilommi H, Vuori M, Salmi A (1976) Sulfamethoxazole-trimethoprim: effect on antibody response in man. Chemotherapy 22: 37–42PubMedCrossRefGoogle Scholar
  4. Bach MC, Gold O, Finland M (1973) Absorption and urinary excretion of trimethoprim, sulfamethoxazole, and trimethoprim-sulfamethoxazole: Results with single doses in normal young adults and preliminary observations during therapy with trimethoprimsulfamethoxazole. J Infect Dis 128:S584–S598CrossRefGoogle Scholar
  5. Beck H, Pechere JC (1970) A combination of trimethoprim with sulfamethoxazole: pharmacodynamic activity in old men. In: Umezawa H (ed) Progress in antimicrobial and anticancer chemotherapy. Proc 6 th Int Congr Chemother. Baltimore University Park Press, Baltimore, pp 663–667Google Scholar
  6. Bendall MJ, Grüneberg RN (1979) An outbreak of infection caused by trimethoprim-resistant coliform bacilli in a geriatric unit. Age Ageing 8: 231–236PubMedCrossRefGoogle Scholar
  7. Black M, Rabin L, Schatz N (1980) Nitrofurantoin-induced chronic active hepatitis. Ann Intern Med 92: 62–64PubMedGoogle Scholar
  8. Brooks D, Maudar A (1972) Pathogenesis of the urethral syndrome in women and its diagnosis in general practice. Lancet 2: 893–898PubMedCrossRefGoogle Scholar
  9. Brumfitt W, Pursell R (1972) Double-blind trial to compare ampicillin, cephalexin, cotrimoxazole, and trimethoprim in treatment of urinary infection. Br Med J 2: 673–676PubMedCrossRefGoogle Scholar
  10. Brun C, Raaschou F, Eriksen KR (1965) Simultaneous bacteriologic studies of renal biopsies and urine. In: Kass EH (ed) Progress in pyelonephritis. Davis, Philadelphia, pp 461–467Google Scholar
  11. Burchall JJ, Hitchings GH (1965) Inhibitor binding analysis of dihydrofolate reductases from various species. Mol Pharmacol 1: 126–136PubMedGoogle Scholar
  12. Burman LG (1980) Resistance to trimethoprim. Lancet 1: 1409PubMedCrossRefGoogle Scholar
  13. Bushby SRM (1969) Combined antibacterial action in vitro of trimethoprim and sulfonamides. Postgrad Med J 45: S10–S18Google Scholar
  14. Bushby SRM (1973) Trimethoprim-sulfamethoxazole: in vitro microbiological aspects. J Infect Dis 128: S442–S462CrossRefGoogle Scholar
  15. Bushby SRM, Hitchings GH (1968) Trimethoprim, a sulphonamide potentiator. Br J Pharmacol Chemother 33: 72–90PubMedGoogle Scholar
  16. Chow AW, Taylor PR, Yoshikawa TT, Gruze LB (1979) A nosocomial outbreak of infections due to multiply-resistant Proteus mirabilis: role of intestinal colonization as a major reservoir. J Infect Dis 139: 621–627PubMedCrossRefGoogle Scholar
  17. Cox CE, Montgomery WG (1969) Combined trimethoprim-sulfisoxazole therapy of urinary infections. Postgrad Med J 45: 65–71PubMedCrossRefGoogle Scholar
  18. Craig WA, Kunin CM (1973) Distribution of trimethoprim-sulfamethoxazole in tissues of rhesus monkeys. J Infect Dis 128: S575–S579CrossRefGoogle Scholar
  19. Dabhoiwala NF, Bye A, Claridge M (1976) A study of concentrations of trimethoprim-sulfamethoxazole in the human prostate gland. Br J Urol 48: 77–81PubMedCrossRefGoogle Scholar
  20. Darrell JH, Garrod LP, Waterworth PM (1968) Trimethoprim: laboratory and clinical studies. J Clin Pathol 21: 202–209PubMedCrossRefGoogle Scholar
  21. Dubach UC, Forgo I, Bückert A (1973) Absence of a hypoglycemic effect of Bactrim in healthy subjects. Klin Wochenschr 51: 1028–1029PubMedCrossRefGoogle Scholar
  22. Eatman FB, Maggio AC, Pocelinko R et al. (1977) Blood and salivary concentrations of sulfamethoxazole and trimethoprim in man. J Pharmacokinet Biopharm 5: 615–624PubMedCrossRefGoogle Scholar
  23. Fairley KF, Carson NE, Gutch RC et al. (1971) Site of infection in acute urinary tract infection in general practice. Lancet 2: 615–618PubMedCrossRefGoogle Scholar
  24. Fang LST, Tolokoff-Rubin NE, Rubin RH (1978) Efficacy of single-dose and conventional amoxicillin therapy in urinary tract infection localized by the antibody-coated bacteria technic. N Engl J Med 298: 413–416PubMedCrossRefGoogle Scholar
  25. Fowle ASE (1973) Aspects of the pharmacokinetics behaviour of trimethoprim and sulphamethoxazole. In: Bernstein LS, Salter AJ (eds) Trimethoprim/sulphamethoxazole in bacterial infections — a Wellcome Foundation Symposium. Churchill Livingston, Edinburgh London, pp 63–72Google Scholar
  26. Fowler JE, Stamey TS (1977) Studies of introital colonization in women with recurrent urinary infections: the role of bacterial adherence. J Urol 117: 472–476PubMedGoogle Scholar
  27. Fries N, Keuth U, Braun JS (1975) Studies of cerebrospinal fluid diffusion of trimethoprim in infants and children. Fortsch Med 93: 1178–1183Google Scholar
  28. Frisch JM (1963) Clinical experience with adverse reactions to trimethoprim-sulfamethoxazole. J Infect Dis 128:S 607-S 611CrossRefGoogle Scholar
  29. Gallagher DJA, Montgomerie JZ, North JDK (1965) Acute infections of the urinary tract and the urethral syndrome in general practice. Br Med J 1: 622–626PubMedCrossRefGoogle Scholar
  30. Gleckman RA (1973) A cooperative controlled study of the use of trimethoprim-sulfamethoxazole in chronic urinary tract infections. J Infect Dis 128:S647–S651CrossRefGoogle Scholar
  31. Gnarpe H, Fridberg J (1976) The penetration of trimethoprim into seminal fluid and serum. Scand J Infect Dis 8: S50–S52Google Scholar
  32. Greene BM, Thomas FE Jr, Alford RH (1975) Trimethoprim-sulfamethoxazole and brain abcess. Ann Intern Med 82: 812–813PubMedGoogle Scholar
  33. Grüneberg RN, Bendell MJ (1979) Hospital outbreak of trimethoprim resistance in pathogenic coliform bacteria. Br Med J 2: 7–9PubMedCrossRefGoogle Scholar
  34. Grüneberg RN, Leakey A, Bendall MJ, Smellie JM (1975) Bowel flora in urinary tract infection: effect of chemotherapy with special reference to cotrimoxazole. Kidney Int 8: S122–S129Google Scholar
  35. Guerrant RL, Wood SJ, Krongard L, Reid RA, Hodge RH (1981) Resistance among fecal flora of patients taking sulfamethoxazole-trimethoprim or trimethoprim alone. Antimicrob Agents Chemother 19: 33–38PubMedGoogle Scholar
  36. Gurwith M, Troug K (1980) Comparison of prophylactic trimethoprim/sulfamethoxazole and trimethoprim alone in compromised hosts. In: Nelson JD, Grassi C (eds) Current chemotherapy and infectious disease. Proc 11th Int Congr Chemother and 19th Intersci Conf Antimicrob Agents Chemother. The American Society for Microbiology, Washington, DC, pp 1446–1447Google Scholar
  37. Hansen I, Lykkegaard Nielsen M, Nielsen JB (1975) A new method for homogenization of bone exemplified by measurement of trimethoprim in human bone tissue. Acta Pharmacol Toxicol (Copenh) 37: 33–42CrossRefGoogle Scholar
  38. Helle M (1975) Trimethoprim in the long-term treatment of children’s urinary tract infections (in Finnish). Lääkeuutiset 4: 125–127Google Scholar
  39. Hjortshoj A, Elsborg L, Jensen E (1978) Folate status during long-term therapy with trimethoprim and sulphadiazine. Chemotherapy 24: 327–331PubMedCrossRefGoogle Scholar
  40. Hoigné R, Müller U, Schneider HR (1970) A comparison of chemotherapy in patients with urinary tract infections using trimethoprim alone and in combination with sulfamethoxazole (Gantanol). In: Umezawa H (ed) Progress in antimicrobial and anticancer chemotherapy. Proc 6th Int Congr Chemother. University of Tokyo Press, Tokyo, pp 971–974Google Scholar
  41. Hoppe-Seyler G, Schollmeyer P, Grandpierre B, Junkers K (1974) Behavior of trimethoprim and sulphamethoxazole in anuria in hemodialysis and peritoneal dialysis. Verh Dtsch Ges Inn Med 80: 672–676PubMedGoogle Scholar
  42. Hoppu K, Partanen S, Koskela E (1980) Trimethoprim poisoning. Lancet 1: 778PubMedCrossRefGoogle Scholar
  43. Hughes WT, Kuhn S, Chaudhary S et al. (1977) Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. N Eng J Med 297: 1419–1426CrossRefGoogle Scholar
  44. Huovinen P, Toivanen P (1980) Trimethoprim resistance in Finland after five years’ use of plain trimethoprim. Br Med J 280: 72–74PubMedCrossRefGoogle Scholar
  45. Iravani A, Richard GA, Baer H (1981) Treatment of uncomplicated urinary tract infections with trimethoprim versus sulfisoxazole with special reference to antibody-coated bacteria and fecal flora. Antimicrob Agents Chemother 19: 842–850PubMedGoogle Scholar
  46. Iravani A, Richard GA, Baer H (1982) Once-a-day trimethoprim versus nitrofurantoin in treatment of acute urinary tract infections in young women, with special reference to periurethral, vaginal, and rectal flora. Rev Inf Dis 4: 378–387CrossRefGoogle Scholar
  47. Iwarson S, Lidin-Janson G (1979) Long-term, low-dose trimethoprim prophylaxis in patients with recurrent urinary tract infections. J Antimicrob Chemother 5: 316–318PubMedCrossRefGoogle Scholar
  48. Jones SR, Smith JW, Sanford JP (1974) Localization of urinary tract infections by detection of antibody-coated bacteria in urine sediment. N Engl J Med 290: 591–593PubMedCrossRefGoogle Scholar
  49. Jordan GW, Krajden SF, Hoeprich PD, Wong GA, Peirce TH, Rausch DC (1975) Trimethoprim-sulfamethoxazole in chronic bronchitis. CMA J 112: 91S–95SGoogle Scholar
  50. Kahn SB, Fein SA, Brodksy I (1968) Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 9: 550–560PubMedGoogle Scholar
  51. Kasanen A, Kaarsalo E, Hiltunen R, Soini V (1974) Comparison of long-term, low-dosage nitrofurantoin, methenamine hippurate, trimethoprim, and trimethoprim-sulfamethoxazole on the control of recurrent urinary tract infection. Ann Clin Res 6: 285–289PubMedGoogle Scholar
  52. Kasanen A, Anttila M, Kahela P et al. (1978) Trimethoprim, pharmacology, antimicrobial activity and clinical use in urinary tract infections. Ann Clin Res 10: 1–39PubMedGoogle Scholar
  53. Kass EH (1956) Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 69: 56PubMedGoogle Scholar
  54. Kass EH (1960) The role of asymptomatic bacteriuria in the pathogenesis of pyelonephritis. In: Quinn EL, Kass EH (eds) Biology of pyelonephritis. Little Brown, Boston, pp 399–418Google Scholar
  55. Koch UJ, Schumann KP, Kuchler R, Kewitz H (1973) Efficacy of trimethoprim, sulfamethoxazole and the combination of both in acute urinary tract infection. Chemotherapy 19: 314–321PubMedCrossRefGoogle Scholar
  56. Koutts J, Van der Weyden MB, Cooper M (1973) Effect of trimethoprim on folate metabolism in human bone marrow. Aust NZ J Med 3: 245–250CrossRefGoogle Scholar
  57. Kunin CM, Craig WA, Uehling DT (1978) Trimethoprim therapy for urinary tract infection. JAMA 239: 2588–2590PubMedCrossRefGoogle Scholar
  58. Lacey RW, Lord VL, Gunasekera HKW, Leiberman PJ, Luxton DEA (1980) Comparison of trimethoprim alone with trimethoprim/sulfamethoxazole in the treatment of respiratory and urinary infections with particular reference to selection of trimethoprim resistance. Lancet 1: 1270–1273PubMedCrossRefGoogle Scholar
  59. Lykkegaard-Nielsen M, Hansen L (1972) Trimethoprim in human prostatic tissue and prostatic fluid. Scand J Urol Nephrol 6: 244–248CrossRefGoogle Scholar
  60. Mabeck CE, Vejlsgaard R (1979) Treatment of urinary tract infections with sulfonamide and/or trimethoprim. Infection 7: S414–S415PubMedCrossRefGoogle Scholar
  61. Männistö PT (1976) Comparison of oxolinic acid, trimethoprim, and trimethoprim-sulfamethoxazole in the treatment of long-term control of urinary tract infection. Curr Ther Res 20: 645–654PubMedGoogle Scholar
  62. Martin DC, Arnold JD (1968) Treatment of acute falciparum malaria with sulfalene and trimethoprim. JAMA 203: 476–480PubMedCrossRefGoogle Scholar
  63. McNaughton RD, Riben P, Light B et al. (1980) Comparison of trimethoprim and trimethoprim/sulfamethoxazole prophylaxis in neutropenic patients: elimination of potential pathogens and emergence of resistance. In: Nelson JD, Grassi C (eds) Current chemotherapy and infectious disease. Proc 11th Int Congr Chemother and 19th Intersci Conf Antimicrob Agents Chemother. The American Society for Microbiology, Washington, DC, pp 1444–1446Google Scholar
  64. Messing EM, Stamey TA (1978) Interstitial cystitis: early diagnosis, pathology and treatment. Urology 12: 381–392PubMedCrossRefGoogle Scholar
  65. Mond NC, Percival A, Williams JD, Brumfitt W (1965) Presentation, diagnosis, and treatment of urinary tract infections in general practice. Lancet 1: 514–516PubMedCrossRefGoogle Scholar
  66. Mundt KA, Polk BF (1979) Identification of site of urinary tract infections by antibody-coated bacteria assay. Lancet 1: 1172–1175CrossRefGoogle Scholar
  67. O’Brien TF, Ross DG, Guzman MA, Medeiros AA, Hedges RW, Botstein D (1980) Dissemination of an antibiotic resistance plasmid in hospital patient flora. Antimicrob Agents Chemother 17: 537–543PubMedGoogle Scholar
  68. Oosterlinck W, Defoort R, Renders G (1975) The concentration of sulfamethoxazole and trimethoprim in human prostate gland. Br J Urol 47: 301–304PubMedCrossRefGoogle Scholar
  69. Pancoast SJ, Hyams DM, Neu HC (1980) Effect of trimethoprim and trimethophrim/sulfamethoxazole on development of drug-resistant vaginal and fecal floras. Antimicrob Agents Chemother 17: 263–268PubMedGoogle Scholar
  70. Pohjanpelto PE, Sarmelo TJ, Raines T (1974) Penetration of trimethoprim and sulfamethoxazole into the aqueous humour. Br J Ophthalmol 58: 606–608PubMedCrossRefGoogle Scholar
  71. Reid DW, Caillé G, Kaufman NR (1975) Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately, and in combination. Can Med Assoc J 112:S67–S72Google Scholar
  72. Rieder J (1973) Excretion of sulfamethoxazole and trimethoprim into human bile. J Infect Dis 128: S574CrossRefGoogle Scholar
  73. Rieder J, Schwartz DE, Femex M et al. (1974) Pharmacokinetics of the antibacterial combination sulfamethoxazole plus trimethoprim in patients with normal or impaired kidney function. Antibiot Chemother 18: 148–198PubMedGoogle Scholar
  74. Rubin RH, Fang LS, Jones SR et al. (1980) Single-dose amoxicillin therapy for urinary tract infection. JAMA 244: 561–564PubMedCrossRefGoogle Scholar
  75. Sabel KG, Brandberg A (1975) Treatment of meningitis and septicemia in infancy with a sulfamethoxazole/trimethoprim combination. Acta Paediatr Scand 64: 25–32PubMedCrossRefGoogle Scholar
  76. Salmon JD, Fowle AS, Bye A (1975) Concentrations of trimethoprim and sulfamethoxazole in the aqueous humour and plasma from regimens of co-trimoxazole in man. J Antimicrob Chemother 1: 205–211PubMedCrossRefGoogle Scholar
  77. Sander J, Fellner H, Kalstad S et al. (1980) Treatment of urinary tract infections in outpatients: double-blind comparison between trimethoprim and nitrofurantoin. In: Nelson JD, Grassi C (eds) Current chemotherapy and infectious disease. Proc 11 th Int Congr Chemother and 19 th Intersci Conf Antimicrob Agents Chemother. The American Society for Microbiology, Washington, DC, pp 1299–1300Google Scholar
  78. Schnaars P, Escher J (1969) Results of treating acute and chronic infections of the urinary tract with Bactrim or its individual components sulfamethoxazole and trimethoprim. Praxis 58: 1279–1283PubMedGoogle Scholar
  79. Schneider M, Schwarzenberg L, Cattam A, Schlumberger JR, Amiel JL, Mathé G (1965) Treatment of a number of proteus infections with trimethoprim. Presse Med 73: 893–894PubMedGoogle Scholar
  80. Schwartz DE, Ziegler WH (1969) Assay and pharmacokinetics of trimethoprim in man and animals. Postgrad Med J 45: S32–S37CrossRefGoogle Scholar
  81. Seneca H, Zinsser HH, Uson A (1974) Chronic urinary tract infections. NY State J Med 74: 494–498Google Scholar
  82. Sharp JR, Ishak KG, Zimmerman HJ (1980) Chronic active hepatitis and severe hepatic necrosis associated with nitrofurantoin. Ann Intern Med 92: 14–19PubMedGoogle Scholar
  83. Sharpstone P (1969) The renal handling of trimethoprim and sulphamethoxazole in man. Postgrad Med J 45: S38–S42Google Scholar
  84. Sietzen W, Knothe H (1978) Effect of trimethoprim, trimethoprim/sulfamethoxazole and sulfamethoxazole on the occurrence of drug-resistant Enterobacteriaceae in the human bowel flora. In: Siegenthaler W, Luethy R (eds) Current chemotherapy. Proc 10th Int Congr Chemother. The American Society for Microbiology, Washington, DC, pp 660–662Google Scholar
  85. Sourander LB, Werner GE (1967) Efficacy and tolerance of sulfonamide-trimethoprim combinations in geriatric patients with bacteriuria. Proc 5th Int Congr Chemother. Wiener Medizinische Academie, Vienna, pp 199Google Scholar
  86. Sourander L, Saarimaa H, Arvilommi H (1972) Treatment of sulfonimide-resistant urinary tract infections with a combination of sulfonimide and trimethoprim. Acta Med Scand 191: 1–3PubMedGoogle Scholar
  87. Stamey TA, Govan DE, Palmer JM (1965) The localization and treatment of urinary tract infections: the role of bactericidal urine levels as opposed to serum levels. Medicine 44: 1–36PubMedCrossRefGoogle Scholar
  88. Stamey TA, Condy M (1975) The diffusion and concentration of trimethoprim in human vaginal fluid. J Infect Dis 131: 261–266PubMedCrossRefGoogle Scholar
  89. Stamey TA (1978) Urinary tract infections in women. In: Harrison JH, Gittes RF, Perlmutter AD, Stamey TA, Walsh PC (eds) Campbell’s urology, 4th edn. Saunders, Philadelphia, pp 451–479Google Scholar
  90. Stamm WE, Counts GW, Wagner KF, Martin D, Gregory D, McKevitt M, Turck M, Holmes KK (1980) Antimicrobial prophylaxis of recurrent urinary tract infections. Ann Intern Med 92: 770–775PubMedGoogle Scholar
  91. Steinberg SE, Campbell CL, Rabinovitch PS, Hillman RS (1980) The effect of trimethoprim/sulfamethoxazole on Friend erythroleukemia cells. Blood 55: 501–504PubMedGoogle Scholar
  92. Svedhem A, Iwarson S (1979) Cerebrospinal fluid concentrations of trimethoprim during oral and parenteral treatment. J Antimicrob Chemother 5: 717–720PubMedCrossRefGoogle Scholar
  93. Thomas FE, Jackson RT, Melly A, Alford RH (1977) Sequential hospitalwide outbreaks of resistant Serratia and Klebsiella infection. Arch Intern Med 137: 581–584PubMedCrossRefGoogle Scholar
  94. Thomas V, Shelokov A, Forland M (1974) Antibody-coated bacteria in the urine and the site of urinary tract infection. N Engl J Med 290: 588–590PubMedCrossRefGoogle Scholar
  95. Towner KJ, Pearson NJ, Cattell WR, O’Grady FO (1979) Trimethoprim R plasmids isolated during long-term treatment of urinary tract infection with co-trimoxazole. J Antimicrob Chemother 5: 45–52PubMedCrossRefGoogle Scholar
  96. Van der Waaij D, Berghuis JM, Lekkarkerk JEC (1972) Colonization resistance of the digestive tract of mice during systemic antibiotic treatment. J Hyg (Camb) 70: 605–610CrossRefGoogle Scholar
  97. Vosti KL (1975) Recurrent urinary tract infections: prevention by prophylactic antibiotics after sexual intercourse. JAMA 231: 934–940PubMedCrossRefGoogle Scholar
  98. Welling PG, Craig WA, Amidon GL, Kunin CM (1973) Pharmacokinetics of trimethoprim and sulfamethoxazole in normal subjects and in patients with renal failure. J Infect Dis 128: S556–S566CrossRefGoogle Scholar
  99. Ylikorkala O, Sjöstedt E, Järvinen R, Raines T (1973) Trimethoprim-sulfonamide combination administered orally and intravaginally in the first trimester of pregnancy: its absorption into serum and transfer to amniotic fluid. Acta Obstet Gynecol Scand 52: 229–234PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • D. W. Barry
  • K. H. Pattishall

There are no affiliations available

Personalised recommendations