Trimethoprim-Sulfamethoxazole Revisited
Philip A. Masters, MD; Thomas A. O’Bryan, MD; John Zurlo, MD; Debra Q. Miller, MD; Nirmal Joshi, MD Duringthepast3decades,thecombinationoftrimethoprimandsulfamethoxazole
has occupied a central role in the treatment of various commonly encountered in-fections and has also been particularly useful for several specific clinical conditions.
However, changing resistance patterns and the introduction of newer broad- spectrum antibiotics have led to the need to carefully redefine the appropriate use of this agent inclinical practice. While trimethoprim-sulfamethoxazole’s traditional role as empirical therapy forseveral infections has been modified by increasing resistance, it remains a highly useful alternativeto the new generation of expanded-spectrum agents if resistance patterns and other clinical vari-ables are carefully considered. It also seems to have an increasing role as a cost-effective pathogen-directed therapy with the potential to decrease or delay development of resistance to newer anti-biotics used for empirical treatment. In addition, trimethoprim-sulfamethoxazole continues to bethe drug of choice for several clinical indications.
folic acid and a necessary cofactor in the syn- spectrum of in vitro antimicrobial suscep- thesis of thymidine, purines, and bacterial tibility and an improved toxicity profile DNA (Figure). Sulfamethoxazole, a sul-
fonamide drug, is a structural analogue of threat of development of resistant organ- isms from selection pressure and the high thesis of the intermediary dihydrofolic acid cost of these drugs raise significant con- from its precursors. Trimethoprim is a struc- tural analogue of the pteridine portion of di- hydrofolic acid that competitively inhibits therapeutically equivalent in clinical prac- quently, the production of tetrahydrofolic tice. With a renewed interest in appropri- acid from dihydrofolic acid. This sequen- ate antibiotic use for common infections1 tial blockade of 2 enzymes in one pathway results in an effective bactericidal action.
conscious health care, this article exam- sulfamethoxazole to redefine its therapeu- tic role in relation to newer antimicrobial agents in the face of resistance trends and late synthesis pathway produces in vitrosynergism,2-4 and it was postulated that MECHANISM OF ACTION
such synergy would occur in vivo. It wasalso hoped that the use of 2 agents in a zole resulted from the recognition that bac- teria are obligate folic acid synthesizers, ergy has been questioned by studies5,6 of uri- nary tract infections (UTIs) and respira- tory tract infections in which trimethoprim inhibit bacterial synthesis of tetrahydrofo- alone seems to be as efficacious as the com- lic acid, the physiologically active form of bination product. In addition, emerging sul-fonamide resistance and the finding that theactivity of the trimethoprim component is From the Divisions of General Internal Medicine (Drs Masters, O’Bryan, Miller, andJoshi) and Infectious Diseases (Dr Zurlo), The Pennsylvania State University College the antibiotic7 call into question the pro- (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
and the ability of the combinationproduct to potentially decrease the de- velopment of resistance may be im-portant factors in determining the PHARMACOLOGICAL
preparations are manufactured in a1:5 fixed ratio of trimethoprim to Folate synthesis pathway and sites of action of trimethoprim and sulfamethoxazole.
sulfamethoxazole that results in peakserum concentrations of both drugs t h e d o s a g e o f t r i m e t h o p r i m - DRUG INTERACTIONS
nal fluid, prostatic fluid, and bile.
in Table 1.
methoxazole is primarily metabo-lized in the liver, with approximately TOXICITY AND
munocompetent patients (Table 2).
(REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
Table 1. Major Drug Interactions With Trimethoprim-Sulfamethoxazole
sociation with the drug at lower dosesused to treat routine infections, even Medication
Mechanism (Responsible Component)
Increases the free serum methotrexate fraction Increases the elimination half-life, increasing Increases the elimination half-life, increasing sulfonylureas, particularly in high doses, withincreased insulin output and, rarely, Decreases renal tubular secretion of procainamide and its active metabolite, N-acetylprocainamide, Hematological
Induces metabolism of contraceptive agents, leading to decreased effectiveness (unclear) Although trimethoprim inhibits di-hydrofolate reductase in bacteria, itis estimated that an approximately50 000 times increased concentra- Table 2. Adverse Effects With Trimethoprim-Sulfamethoxazole
in Immunocompetent Patients
hibit the human form of this en-zyme.43 Consequently, despite the Reaction
Estimated Frequency of Occurrence
3%-4% (severe or life-threatening reactions rare) May cause a mild (∼10%) elevation of the serum creatinine level at standard doses withoutdecreasing the glomerular filtration rate May lead to hyperkalemia at high doses and at standard doses in patients with existing renal failure or concurrent use of other medications known to increase the serum potassium level Rare, but occasionally severe; comparable to other Uncommon; delirium and psychosis reported cal disorders, including multipleforms of anemia, granulocytopenia,agranulocytosis, and thrombocyto-penia. These reactions have also Dermatological
t r i m e t h o p r i m - s u l f a m e t h o x a - Adverse Reactions in Human
Immunodeficiency Virus
(HIV)–Infected Patients
and treatment of Pneumocystis cari- (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
number of resistant E coli isolates Urinary Tract Infections
ceae, including Escherichia coli, Kleb- siella pneumoniae, and Proteus mi- tient factors favorable to the use of tri- rabilis, accounting for its widespread prim resistance in E coli isolates ANTIMICROBIAL ACTIVITY
Respiratory Tract Infections
Staphylococcus aureus and 7 genera of Enterobacteriaceae, including E coli, of H influenzae.79 It has also been a laxis of recurrent otitis media.86,87 Un- (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
trimethoprim-sulfamethoxazole.Strep- tococcus pyogenes is variably suscep- Clinical Use
in HIV-Infected Patients
resistance among Salmonella isolates Treatment of Active Infections. Be-
penicillin-resistant strains of S pneu- cally variable than with Shigella spe- dence of infections due to Salmonella typhi has been stable since the mid H influenzae in the United States, steadily.95 Multidrug-resistant S typhi ternative in ␤-lactam–allergicpatients the treatment of enterotoxigenic E coli in the interior of Mexico,96 but parts of the world.97 Yersinia entero- colitica,98 Vibrio cholerae,99 and Aeromonas hydrophila100 are bacte- bidity or in those 60 years or older.
role. Mutations in the P carinii dihy- Skin-Associated Infections
Many isolates of S aureus and Staphy- lococcus epidermidis remain suscep- protozoal parasites Isospora and Cy- GI Tract Infections
Salmonella and Shigella species and enterotoxigenic E coli were widely (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
Prophylaxis. Trimethoprim-sulfa-
negative bacilli and for Listeria mono- for selected indications in carefully as- zole is frequently used to treat No- mary prophylaxis for Toxoplasma gon- cardia infections,130 and is effica- dii in HIV-infected patients). It con- CONCLUSIONS
Other Uses
(Table 3) with a well-defined ad-
organ transplantation.121,122 It is alsocommonly used prophylactically inafebrile neutropenic individuals, al- Table 3. Comparative Cost of Trimethoprim-Sulfamethoxazole
vs Selected Antibiotics
though the effectiveness of this prac-tice has been questioned.123 It is no Antibiotic†
Adult Dosing
Cost, $‡
longer considered an acceptable em-pirical treatment for febrile pa- m u n o c o m p r o m i s e d p a t i e n t s .
Stenotrophomonas (Xanthomonas) maltophilia is typically resistant to organisms, including Burkholderia(Pseudomonas) cepacia, Acinetobac- *Data from Red Book Updates.134†Generic drugs were used for comparison, if available.
ter, and Alcaligenes, are frequently ‡Given for a 10-day course of therapy, based on the average wholesale price plus a $4 dispensing fee.
(REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
8. Howe R, Spencer R. Cotrimoxazole: rationale for 31. McCue JD, Zandt JR. Acute psychoses associ- re-examining its indications for use. Drug Saf. ated with the use of ciprofloxacin and trimeth- oprim-sulfamethoxazole. Am J Med. 1991;90: 9. Brumfitt W, Pursell R. Trimethoprim-sulfa- methoxazole in the treatment of bacteriuria in 32. Brumfitt W, Pursell R. Double-blind trial to com- women. J Infect Dis. 1973;128(suppl):657- pare ampicillin, cephalexin, co-trimoxazole and trimethoprim in treatment of urinary infections.
10. Smilack JD. Trimethoprim-sulfamethoxazole.
Mayo Clin Proc. 1999;74:730-734.
33. Frisch JM. Clinical experience with adverse re- actions to trimethoprim-sulfamethoxazole. J In- sulfamethoxazole in the United States. Ann In- fect Dis. 1973;128(suppl):S607-S611.
34. Gleckman R, Alvarez S, Joubert DW. Drug therapy 12. O’Reilly R, Motley C. Racemic warfarin and tri- reviews: trimethoprim-sulfamethoxazole. Am methoprim-sulfamethoxazole interaction in hu- J Hosp Pharm. 1979;36:893-906.
mans. Ann Intern Med. 1979;91:34-36.
35. Boye NP, Gaustad P. Double-blind comparative 13. O’Reilly R. Stereoselective interaction of trimeth- study of ofloxacin and trimethoprim-sulfamethoxa- oprim-sulfamethoxazole with the separated enan- zole in the treatment of patients with acute exac- S [X] maltophilia and other nonfer- tiomorphs of racemic warfarin in man. N Engl erbations of chronic bronchitis and chronic ob- structive lung disease. Infection. 1991;19(suppl Isospora, Cyclospora, Nocardia, and 14. van Meerten E, Verweij J, Schellens J. Antineo- plastic agents: drug interactions of clinical sig- 36. Grubbs NC, Schultz HJ, Henry NK, Ilstrup DM, nificance. Drug Saf. 1995;12:168-182.
Muller SM, Wilson WR. Ciprofloxacin versus tri- 15. Tett S, Triggs E. Use of methotrexate in older pa- methoprim-sulfamethoxazole: treatment of com- tients: a risk-benefit assessment. Drugs Aging. munity-acquired urinary tract infections in a pro- spective, controlled, double-blind comparison.
16. Hansen JM, Kampmann JP, Siersbaek-Nielsen Mayo Clin Proc. 1992;67:1163-1168.
K, et al. The effect of different sulfonamides on 37. Heck J, Staneck JL, Cohen MB, et al. Preven- phenytoin metabolism in man. Acta Med Scand tion of travelers’ diarrhea: ciprofloxacin versus trimethoprim/sulfamethoxazole in adult volun- 17. Brumfitt W, Hamilton-Miller J. Limitations of and teers working in Latin America and the Carib- indications for the use of co-trimoxazole. J Che- bean. J Travel Med. 1994;1:136-142.
38. Roujeau J, Kelly J, Naldi L, et al. Medication use 18. Johnson JF, Dobmeier ME. Symptomatic hypo- and the risk of Stevens-Johnson syndrome or Accepted for publication June 13, 2002. glycemia secondary to a glipizide-trimethoprim/ toxic epidermal necrolysis. N Engl J Med. 1995; sulfamethoxazole drug interaction. DICP. 1990; prints: Philip A. Masters, MD, Divi- 39. Egan CA, Grant WJ, Morris SE, Saffle JR, Zone 19. Chan J, Cockram C, Critchley J. Drug-induced sion of General Internal Medicine, JJ. Plasmapheresis as an adjunct treatment in disorders of glucose metabolism: mechanisms toxic epidermal necrolysis. J Am Acad Derma- and management. Drug Saf. 1996;15:135-157.
College of Medicine, 500 University 20. Kosoglou T, Rocci M, Vlasses P. Trimethoprim 40. Berglund F, Killander J, Pompeius R. Effect of alters the disposition of procainamide and N- trimethoprim-sulfamethoxazole on the renal ex- acetylprocainamide. Clin Pharmacol Ther. 1988; cretion of creatinine in man. J Urol. 1975;114: 21. Abramowicz M, ed. Oral contraceptives. Med Lett 41. Bye A. Drug interference with creatinine assay. 22. Lawson D, Jick H. Adverse reactions to co- 42. Shouval D, Ligumsky M, Ben-Ishay D. Effect of trimoxazole in hospitalized medical patients. Am co-trimoxazole on normal creatinine clearance.
1. Gonzales R, Bartlett JG, Besser RE, et al. Prin- ciples of appropriate antibiotic use for treat- 23. Lawson D, MacDonald S. Antibacterial therapy 43. Burchall JJ, Hitchings GH. Inhibitor binding analy- ment of acute respiratory tract infections in adults: in general medical wards. Postgrad Med J. 1977; sis of dihydrofolate reductases from various spe- background, specific aims, and methods. Ann In- cies. Mol Pharmacol. 1965;1:126-136.
24. Jick H. Adverse reactions to trimethoprim- 44. Kovacs JA, Hiemenz JW, Macher AM, et al. Pneu- 2. Bushby SRM, Hitchings GH. Trimethoprim, a sul- sulfamethoxazole in hospitalized patients. Rev mocystis carinii pneumonia: a comparison be- phonamide potentiator. Br J Pharmacol. 1968; tween patients with the acquired immunodefi- 25. Ducharme M, Smythe M, Strohs G. Drug- 3. Bushby SRM. Trimethoprim-sulfamethoxazole: induced alterations in serum creatinine concen- immunodeficiencies. Ann Intern Med. 1984;100: in vitro microbiological aspects. J Infect Dis. trations. Ann Pharmacother. 1993;27:622-633.
26. Choi MJ, Fernandez PC, Patnaik A, et al. Brief re- 45. Sattler FR, Cowan R, Nielsen DM, Ruskin J. Tri- 4. Darrell JH, Garrod LP, Waterworth PM. Trimeth- port: trimethoprim-induced hyperkalemia in a pa- oprim: laboratory and clinical studies. J Clin tient with AIDS. N Engl J Med. 1993;328:703- pentamidine for treatment of Pneumocystis ca- rinii pneumonia in the acquired immunodefi- 5. Brumfitt W, Hamilton-Miller JM, Havard CW, 27. Velazquez H, Perazella M, Wright F, Ellison D. Re- ciency syndrome: a prospective, noncrossover Tansley H. Trimethoprim alone compared to co- nal mechanism of trimethoprim-induced hyper- study. Ann Intern Med. 1988;109:280-287.
trimoxazole in lower respiratory infections: phar- kalemia. Ann Intern Med. 1993;119:296-301.
46. Klein NC, Duncanson FP, Lenox TH, et al. Tri- macokinetics and clinical effectiveness. Scand 28. Marinella M. Trimethoprim-induced hyperkale- methoprim-sulfamethoxazole versus pentami- J Infect Dis. 1985;17:99-105.
mia: an analysis of reported cases. Gerontol- dine for Pneumocystis carinii pneumonia in AIDS 6. Lacey RW, Lord VL, Gunasekera HK, Leiber- patients: results of a large prospective random- man PJ, Luxton DE. Comparison of trimetho- 29. Jick H, Derby L. A large population-based fol- ized treatment trial. AIDS. 1992;6:301-305.
prim alone with trimethoprim-sulphamethoxa- low-up study of trimethoprim-sulphamethoxa- 47. Medina I, Mills J, Leoung G, et al. Oral therapy zole in the treatment of respiratory and urinary zole, trimethoprim, and cephalexin for uncom- for Pneumocystis carinii pneumonia in the ac- infections with particular reference to selection mon serious drug toxicity. Pharmacotherapy. of trimethoprim resistance. Lancet. 1980;1:1270- trolled trial of trimethoprim-sulfamethoxazole ver- 30. Ambramowicz M, ed. Drugs that may cause psy- sus trimethoprim-dapsone. N Engl J Med. 1990; 7. Rubin R, Swartz M. Trimethoprim-sulfamethoxa- chiatric symptoms. Med Lett Drugs Ther. 2000; zole. N Engl J Med. 1980;303:426-432.
48. Jung AC, Paauw DS. Management of adverse re- (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
actions to trimethoprim-sulfamethoxazole in hu- tance in the AIDS era. J Infect Dis. 1999;180: 82. Hughes DT. Single-blind comparative trial of tri- man immunodeficiency virus–infected pa- methoprim-sulphamethoxazole and ampicillin in tients. Arch Intern Med. 1994;154:2402-2406.
66. Lepelletier D, Caroff N, Reynaud A, Richet H.
the treatment of exacerbations of chronic bron- 49. Hughes WT, LaFon SW, Scott JD, Masur H. Ad- Escherichia coli: epidemiology and analysis of verse events associated with trimethoprim- risk factors for infections caused by resistant 83. Pines A, Greenfield JS, Raafat H, Rahman M, Sid- sulfamethoxazole and atovaquone during the strains. Clin Infect Dis. 1999;29:548-552.
diqui AM. Preliminary experience with trimeth- treatment of AIDS-related Pneumocystis carinii 67. Steinke DT, Seaton RA, Phillips G, MacDonald oprim and sulphamethoxazole in the treatment pneumonia. J Infect Dis. 1995;171:1295-1301.
TM, Davey PG. Factors associated with trimeth- of purulent chronic bronchitis. Postgrad Med J. 50. Porteous DM, Berger TG. Severe cutaneous drug oprim-resistant bacteria isolated from urine reactions (Stevens-Johnson syndrome and toxic samples. J Antimicrob Chemother. 1999;43:841- 84. Anderson G, Williams L, Pardoe T, Peel ET. Co- epidermal necrolysis) in human immunodefi- trimoxazole versus cefaclor in acute on chronic ciency virus infection. Arch Dermatol. 1991;127: 68. Wright SW, Wrenn KD, Haynes ML. Trimetho- bronchitis. J Antimicrob Chemother. 1981;8: prim-sulfamethoxazole resistance among uri- 51. Greenberg S, Reiser IW, Chou SY. Hyperkale- nary coliform isolates. J Gen Intern Med. 1999; 85. Hughes DT. The use of combinations of trimeth- mia with high-dose trimethoprim-sulfamethoxa- oprim and sulphonamides in the treatment of zole therapy. Am J Kidney Dis. 1993;22:603- 69. Zhanel GG, Karlowsky JA, Harding GKM, et al, chest infections. J Antimicrob Chemother. 1983; for the Canadian Urinary Isolate Study Group. A 52. Aboulafia DM. Tremors associated with trimeth- Canadian national surveillance study of urinary 86. Gaskins JD, Holt RJ, Kyong CU, Weart CW, Ward oprim-sulfamethoxazole therapy in a patient with tract isolates from outpatients: comparison of the J. Chemoprophylaxis of recurrent otitis media us- AIDS: case report and review. Clin Infect Dis. activities of trimethoprim-sulfamethoxazole, am- ing trimethoprim/sulfamethoxazole. Drug Intell picillin, mecillinam, nitrofurantoin, and cipro- 53. Jurado R, Carpenter SL, Rimland D. Case re- floxacin. Antimicrob Agents Chemother. 2000; 87. Principi N, Marchisio P, Massironi E, Grasso RM, Filiberti G. Prophylaxis of recurrent acute otitis induced meningitis in patients with HIV infec- 70. Sahm DF, Thornsberry C, Mayfield DC, Jones ME, media and middle-ear effusion: comparison of tion. Am J Med Sci. 1996;312:27-29.
Karlowsky JA. Multidrug-resistant urinary tract amoxicillin with sulfamethoxazole and trimeth- 54. Singer SJ, Racoosin JA, Viraraghavan R. Rhab- isolates of Escherichia coli: prevalence and pa- oprim. AJDC. 1989;143:1414-1418 [published domyolysis in human immunodeficiency virus– tient demographics in the United States in 2000.
correction appears in AJDC. 1990;144:1180].
Antimicrob Agents Chemother. 2001;45:1402- 88. Niederman MS, Bass JB Jr, Campbell GD, et al, sulfamethoxazole. Clin Infect Dis. 1998;26:233- for the American Thoracic Society and the Medi- 71. Huovinen P. Increases in rates of resistance to cal Section of the American Lung Association.
55. Shafer RW, Seitzman PA, Tapper ML. Success- trimethoprim. Clin Infect Dis. 1997;24(suppl): Guidelines for the initial management of adults ful prophylaxis of Pneumocystis carinii pneu- with community-acquired pneumonia: diagno- monia with trimethoprim-sulfamethoxazole in 72. Manges AR, Johnson JR, Foxman B, O’Bryan TT, sis, assessment of severity, and initial antimi- AIDS patients with previous allergic reactions.
Fullerton KE, Riley LW. Widespread distribu- crobial therapy. Am Rev Respir Dis. 1993;148: J Acquir Immune Defic Syndr. 1989;2:389- tion of urinary tract infections caused by a mul- tidrug-resistant Escherichia coli clonal group.
89. Hoban DJ, Doern GV, Fluit AC, Roussel- 56. Gluckstein D, Ruskin J. Rapid oral desensitiza- N Engl J Med. 2001;345:1007-1013.
Delvallez M, Jones RN. Worldwide prevalence of tion to trimethoprim-sulfamethoxazole (TMP- 73. Gupta K, Hooten TM, Stamm WE. Increasing an- antimicrobial resistance in Streptococcus pneu- SMZ): use in prophylaxis for Pneumocystis ca- timicrobial resistance and the management of un- moniae, Haemophilus influenzae, and Mo- rinii pneumonia in patients with AIDS who were complicated community-acquired urinary tract raxella catarrhalis in the SENTRY Antimicrobial previously intolerant to TMP-SMZ. Clin Infect Dis. infections. Ann Intern Med. 2001;135:41-50.
Surveillance Program, 1997-1999. Clin Infect Dis. 74. Warren JW, Abrutyn E, Hebel JR, Johnson JR, 57. Gompels MM, Simpson N, Snow M, Spickett G, Schaeffer AJ, Stamm WE, for the Infectious Dis- 90. Sinus and Allergy Health Partnership. Antimi- Ong E. Desensitization to co-trimoxazole (tri- eases Society of America. Guidelines for anti- crobial treatment guidelines for acute bacterial microbial treatment of uncomplicated acute bac- rhinosinusitis. Otolaryngol Head Neck Surg. 2000; infected patients: is patch testing a useful pre- terial cystitis and acute pyelonephritis in women.
dictor of reaction? J Infect. 1999;38:111-115.
Clin Infect Dis. 1999;29:745-758.
91. Niederman MS, Mandell LA, Anzueto A, et al, for 58. Bach MC, Finland M, Gold O, Wilcox C. Suscep- 75. Lipsky BA. Prostatitis and urinary tract infec- the American Thoracic Society. Guidelines for the tibility of recently isolated pathogenic bacteria tion in men: what’s new; what’s true? Am J Med. to trimethoprim and sulfamethoxazole sepa- acquired pneumonia: diagnosis, assessment of rately and combined. J Infect Dis. 1973;128 76. Marchant C, Shurin PA. Antibacterial therapy for severity, antimicrobial therapy, and prevention.
acute otitis media: a critical analysis. Rev Infect Am J Respir Crit Care Med. 2001;163:1730- 59. Huovinen P. Resistance to trimethoprim- sulfamethoxazole. Clin Infect Dis. 2001;32:1608- 77. Blumer JL, Bertino JS Jr, Husak MP. Compari- 92. Bartlett JG, Dowell SF, Mandell LA, File TM, son of cefaclor and trimethoprim-sulfamethoxa- Musher DM, Fine MJ. Practice guidelines for the 60. Huovinen P, Sundstro¨m L, Swedeberg G, Sko¨ld zole in the treatment of acute otitis media. Pe- O. Trimethoprim and sulfonamide resistance. An- diatr Infect Dis. 1984;3:25-29.
nia in adults. Clin Infect Dis. 2000;31:347-382.
timicrob Agents Chemother. 1995;39:279-289.
78. Feldman W, Sutcliffe T, Dulberg C. Twice-daily an- 93. Ansdell VE, Ericsson CD. Prevention and em- 61. Stamm WE, Hooten TM. Management of uri- tibiotics in the treatment of acute otitis media: tri- piric treatment of traveler’s diarrhea. Med Clin nary tract infections in adults. N Engl J Med. 1993; methoprim-sulfamethoxazole versus amoxicillin- clavulanate. CMAJ. 1990;142:924-925.
94. Murray BE. Resistance of Shigella, Salmonella, 62. Goldstein FW, Papadopoulou B, Acar JF. The 79. Schwartz RH, Rodriguez WJ, Khan WN, Mann and other selected enteric pathogens to antimi- changing pattern of trimethoprim resistance in crobial agents. Rev Infect Dis. 1986;8(suppl): Paris, with a review of worldwide experience. Rev sulfamethoxazole in the treatment of otitis me- dia caused by ampicillin-resistant strains of Hae- 95. Ackers M-L, Puhr ND, Tauxe RV, Mintz ED. Labo- 63. Gruneberg RN. Changes in urinary pathogens and mophilus influenzae. Rev Infect Dis. 1982;4:514- ratory-based surveillance of Salmonella sero- their antibiotic sensitivities, 1971-1992. J Anti- type Typhi infections in the United States: anti- microb Chemother. 1994;33(suppl A):1-8.
80. Williams JW, Holleman DR, Samsa GP, Simel DL.
microbial resistance on the rise. JAMA. 2000; 64. Gupta K, Scholes D, Stamm WE. Increasing Randomized controlled trial of 3 vs 10 days of prevalence of antimicrobial resistance among trimethoprim/sulfamethoxazole for acute max- 96. Bandres JC, Mathewson JJ, Ericsson CD, Du- uropathogens causing acute uncomplicated cys- illary sinusitis. JAMA. 1995;273:1015-1021.
pont HL. Trimethoprim/sulfamethoxazole re- titis in women. JAMA. 1999;281:736-738.
81. Renmarker K. A comparative trial of co- mains active against enterotoxigenic Escheri- 65. Martin JN, Rose DA, Hadley WK, Perdreau- trimoxazole and doxycycline in the treatment of chia coli and Shigella species in Guadalajara, Remington F, Lam PK, Gerberding JL. Emer- acute exacerbations of chronic bronchitis. Scand Mexico. Am J Med Sci. 1992;303:289-291.
gence of trimethoprim-sulfamethoxazole resis- 97. Hoge CW, Gambel JM, Srijan A, Pitarangsi C, Ech- (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.
everria P. Trends in antibiotic resistance among cystis species, Blastocystis hominis, and Cyclo- persons with AIDS. J Acquir Immune Defic Syndr. diarrheal pathogens isolated in Thailand over 15 spora. In: Mandell GL, Bennett JE, Dolin R, eds.
years. Clin Infect Dis. 1998;26:341-345.
Principles and Practice of Infectious Diseases. 5th 121. Fishman JA. Prevention of infection caused by 98. Gutman LT, Wilfert CM, Quan T. Susceptibility ed. Philadelphia, Pa: Churchill Livingstone Inc; Pneumocystis carinii in transplant patients. Clin of Yersinia enterocolitica to trimethoprim- Infect Dis. 2001;33:1397-1405.
sulfamethoxazole. J Infect Dis. 1973;128(suppl): 110. Bartlett JG. Medical Management of HIV Infec- 122. Guidelines for preventing opportunistic infec- tion. Baltimore, Md: Johns Hopkins University; tions among hematopoietic stem cell trans- 99. Pastore G, Rizzo G, Fera G, Schiraldi O. Trimeth- plant recipients. MMWR Recomm Rep. 2000; oprim-sulphamethoxazole in the treatment of 111. Canessa A, Del Bono V, De Leo P, Piersantelli cholera: comparison with tetracycline and chlor- N, Terragna A. Cotrimoxazole therapy of Toxo- 123. Kerr KG. The prophylaxis of bacterial infections amphenicol. Chemotherapy. 1977;23:121-128.
plasma gondii encephalitis in AIDS patients. Eur in neutropenic patients. J Antimicrob Che- 100. Kuijper EJ, Peeters MF, Schoenmakers BS, Zanen J Clin Microbiol Infect Dis. 1992;11:125-130.
HC. Antimicrobial susceptibility of sixty human 112. Torre D, Speranza F, Martegani R, Zeroli C, Banfi 124. Hughes WT, Armstrong D, Bodey GP, et al, for fecal isolates of Aeromonas species. Eur J Clin M, Airoldi M. A retrospective study of treatment the Infectious Diseases Society of America. 2002 Microbiol Infect Dis. 1989;8:248-250.
of cerebral toxoplasmosis in AIDS patients with Guidelines for the use of antimicrobial agents in 101. DuPont HL, Ericsson CD. Prevention and treat- trimethoprim-sulphamethoxazole. J Infect. 1998; neutropenic patients with cancer. Clin Infect Dis. ment of traveler’s diarrhea. N Engl J Med. 1993; 113. US Public Health Service (USPHS) and Infec- 125. Fass RJ, Barnishan J, Solomon MC, Ayers LW. In 102. Diekema DJ, Pfaller MA, Schmitz FJ, et al, and tious Diseases Society of America (IDSA). 1999 vitro activities of quinolones, ␤-lactams, tobra- the SENTRY Participants Group. Survey of in- USPHS/IDSA guidelines for the prevention of op- mycin, and trimethoprim-sulfamethoxazole against fections due to Staphylococcus species: fre- portunistic infections in persons infected with hu- nonfermentative gram-negative bacilli. Antimi- quency of occurrence and antimicrobial suscep- man immunodeficiency virus. MMWR Re- crob Agents Chemother. 1996;40:1412-1418.
tibility of isolates collected in the United States, comm Rep. 1999;48(RR-10):1-59, 61-66.
126. Gales AC, Jones RN, Forward KR, Lin˜ares J, Canada, Latin America, Europe, and the west- 114. Stein DS, Stevens RC, Terry D, et al. Use of low- Sader HS, Verhoef J. Emerging importance of ern Pacific region for the SENTRY Antimicro- dose trimethoprim-sulfamethoxazole thrice multi-drug resistant Acinetobacter species and bial Surveillance Program, 1997-1999. Clin In- weekly for primary and secondary prophylaxis Stenotrophomonas maltophilia as pathogens in fect Dis. 2001;32(suppl):S114-S132.
of Pneumocystis carinii pneumonia in human im- seriously ill patients: geographic patterns, epi- 103. Hoskins TW, Bernstein LS. Trimethoprim/ munodeficiency virus–infected patients. Antimi- demiological features, and trends in the SENTRY sulphadiazine compared with penicillin V in the crob Agents Chemother. 1991;35:1705-1709.
Antimicrobial Surveillance Program (1997-1999).
treatment of streptococcal throat infections. J An- 115. Hardy WD, Feinberg J, Finkelstein DM, et al. A Clin Infect Dis. 2001;32(suppl):S104-S113.
timicrob Chemother. 1981;8:495-496.
controlled trial of trimethoprim-sulfamethoxa- 127. Winslow DL, Pankey GA. In vitro activities of tri- 104. Hughes WT, Feldman S, Chaudhary SC, Ossi MJ, zole or aerosolized pentamidine for secondary methoprim and sulfamethoxazole against Liste- Cox F, Sanyal SK. Comparison of pentamidine prophylaxis of Pneumocystis carinii pneumo- ria monocytogenes. Antimicrob Agents Che- isethionate and trimethoprim-sulfamethoxa- nia in patients with the acquired immunodefi- zole in the treatment of Pneumocystis carinii ciency syndrome: AIDS Clinical Trials Group pro- 128. Spitzer PG, Hammer SM, Karchmer AW. Treat- pneumonia. J Pediatr. 1978;92:285-291.
tocol 021. N Engl J Med. 1992;327:1842-1848.
ment of Listeria monocytogenes infection with 105. Ruf B, Rohde I, Pohle HD. Efficacy of clindamycin/ 116. Ioannidis JPA, Cappelleri JC, Skolnik PR, Lau J, trimethoprim-sulfamethoxazole: case report and primaquine versus trimethoprim/sulfamethoxa- Sacks HS. A meta-analysis of the relative effi- review of the literature. Rev Infect Dis. 1986;8: zole in primary treatment of Pneumocystis ca- cacy and toxicity of Pneumocystis carinii pro- rinii pneumonia. Eur J Clin Microbiol Infect Dis. phylactic regimens. Arch Intern Med. 1996;156: 129. Meyer RD, Liu S. Determination of the effect of antimicrobics in combination against Listeria 106. Safrin S, Finkelstein DM, Feinberg J, et al, for the 117. Carr A, Tindall B, Brew BJ, et al. Low-dose tri- monocytogenes. Diagn Microbiol Infect Dis. ACTG 108 Study Group. Comparison of three methoprim-sulfamethoxazole prophylaxis for regimens for treatment of mild to moderate Pneu- toxoplasmic encephalitis in patients with AIDS.
130. Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22: mocystis carinii pneumonia in patients with AIDS: Ann Intern Med. 1992;117:106-111.
a double-blind, randomized, trial of oral trimeth- 118. Anglaret X, Chene G, Attia A, et al. Early chemo- 131. Feurle GE, Marth T. An evaluation of antimicro- oprim-sulfamethoxazole, dapsone-trimetho- prophylaxis with trimethoprim-sulphamethoxa- bial treatment for Whipple’s disease: tetracy- prim, and clindamycin-primaquine. Ann Intern zole for HIV-1 infected adults in Abidjan, Cote cline versus trimethoprim-sulfamethoxazole. Dig d’Ivoire: a randomised trial. Lancet. 1999;353: 107. Toma E, Thorne A, Singer J, et al, for the CTN- 132. Durand DV, Lecomte C, Cathe´bras P, Rousset 119. Wiktor SZ, Sassan-Morokro M, Grant AD, et al.
H, Godeau P, and the SNFMI Research Group on quine vs trimethoprim-sulfamethoxazole therapy Efficacy of trimethoprim-sulphamethoxazole pro- Whipple Disease. Whipple disease: clinical re- for mild and moderately severe Pneumocystis phylaxis to decrease morbidity and mortality in view of 52 cases. Medicine (Baltimore). 1997; carinii pneumonia in patients with AIDS: a mul- HIV-1–infected patients with tuberculosis in Abid- ticenter, double-blind, randomized trial (CTN jan, Cote d’Ivoire: a randomised controlled trial.
133. Stegeman CA, Tervaert JW, de Jong PE, Kallen- 004). Clin Infect Dis. 1998;27:524-530.
berg CGM. Trimethoprim-sulfamethoxazole (co- 108. Kazanjian P, Locke AB, Hossler PA, et al. Pneu- 120. Buskin SE, Newcomer LM, Koutsky LA, Hooton trimoxazole) for the prevention of relapses of We- mocystis carinii mutations associated with sulfa TM, Spach DH, Hopkins SG. Effect of trimetho- gener’s granulomatosis. N Engl J Med. 1996; and sulfone prophylaxis failures in AIDS pa- prim-sulfamethoxazole as Pneumocystis cari- tients. AIDS. 1998;12:873-878.
nii pneumonia prophylaxis on bacterial illness, 134. Red Book Updates. Montvale, NJ: Medical Eco- 109. Keystone JS, Kozarsky P. Isospora belli, Sarco- Pneumocystis carinii pneumonia, and death in (REPRINTED) ARCH INTERN MED/ VOL 163, FEB 24, 2003 2003 American Medical Association. All rights reserved.


Hormone i

Wirkstoffliste - Sympathikus 9.10.2013 Catecholamine ß2-Sympathomimetika α -Mimetika Indirekte Sympathomimetika Nicht-selektive ß-Adrenozeptorantagonisten (ß-Blocker) Wirkstoffliste - Parasympathikus Direkte Parasympathomimetika Parasympatholytika (Muskarinrezeptorantagonisten) Acetylcholinesterasehemmstoffe Physostigmin Wirkstoffliste - Antipark


Le but est d’éviter de produire des techniciens de la médecine. Ce dernier doit développer une cosmogonie (= vision du monde) générale. Étude critique des sciences destinée à déterminer leurs origines logiques, leur valeur, leur portée pour la pensée et pour l’homme. Étude des sciences, approche philosophique et critique de la pertinence des connaissances, des recherches, des

Copyright © 2010-2014 Internet pdf articles