[en] Co-trimoxazole is a frequently prescribed antibiotic worldwide. It is composed of both trimethoprim and sulfamethoxazol (Sfx) and is used in the treatment and prophylaxis of urinary tract and Pneumocystis jirovecii infections. The Sfx component appears to be nephrotoxic at high doses or doses inappropriately adjusted for glomerular filtration rate
(GFR). The trimethoprim component, even at recommended doses, inhibits tubular creatinine secretion, leading to a rapid but ultimately reversible increase in serum creatinine independent
of any changes in GFR. This translates into a falsely low estimated GFR when creatinine-based equations are used. This review focuses on evidence of the differential effects of trimethoprim and Sfx on serum creatinine concentrations and GFR and their relevance to clinical practice, with particular attention to kidney transplantation.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
DELANAYE, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Néphrologie
CAVALIER, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale
Masters PA, O'Bryan TA, Zurlo J, Miller DQ, Joshi N: Trimethoprim- sulfamethoxazole revisited. Arch Intern Med 2003; 163: 402-410. (Pubitemid 36241016)
Roth B, Falco EA, Hitchings GH, Bushby SR: 5-Benzyl-2,4- diaminopyrimidines as antibacterial agents. I. Synthesis and antibacterial activity in vitro. J Med Pharm Chem 1962; 91: 1103-1123.
Bach MC, Gold O, Finland M: Absorption and urinary execretion of trimethoprim, sulfamethoxazole, and trimethoprim-sulfamethoxazole: results with single doses in normal young adults and preliminary observations during therapy with trimethoprimsulfamethoxazole. J Infect Dis 1973; 128 (suppl):S584-S598.
Grose WE, Bodey GP, Loo TL: Clinical pharmacology of intravenously administered trimethoprim-sulfamethoxazole. Antimicrob Agents Chemother 1979; 15: 447-451. (Pubitemid 9206242)
Welling PG, Craig WA, Amidon GL, Kunin CM: Pharmacokinetics of trimethoprim and sulfamethoxazole in normal subjects and in patients with renal failure. J Infect Dis 1973; 128(suppl):556-566.
Van Scoy RE, Wilson WR: Antimicrobial agents in adult patients with renal insufficiency: initial dosage and general recommendations. Mayo Clin Proc 1987; 62: 1142-1145. (Pubitemid 18031823)
Hanley T: Septrim/bactrim-reported adverse reactions, October 14, 1968-April 14, 1969. Postgrad Med J 1969; 45(suppl):85.
Schofield CB, Masterton G, Moffett M, Mc-Gill MI: The treatment of gonorrhoea in women with sulphamethoxazole-trimethoprim. Postgrad Med J 1969; 45(suppl):81-86.
Kalowski S, Nanra RS, Mathew TH, Kincaid-Smith P: Deterioration in renal function in association with co-trimoxazole therapy. Lancet 1973;i:394-397.
Cryst C, Hammar SP: Acute granulomatous interstitial nephritis due to co-trimoxazole. Am J Nephrol 1988; 8: 483-488. (Pubitemid 19022764)
Smith EJ, Light JA, Filo RS, Yum MN: Interstitial nephritis caused by trimethoprimsulfamethoxazole in renal transplant recipients. JAMA 1980; 244: 360-361. (Pubitemid 10082308)
Garvey JP, Brown CM, Chotirmall SH, Dorman AM, Conlon PJ, Walshe JJ: Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome. Clin Nephrol 2009; 72: 331-336.
Pusey CD, Saltissi D, Bloodworth L, Rainford DJ, Christie JL: Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy. Q J Med 1983; 52: 194-211. (Pubitemid 14248294)
Lehr D: Clinical toxicity of sulfonamides. Ann NY Acad Sci 1957; 69: 417-447.
Tasker PR, MacGregor GA, de Wardener HE: Use of co-trimoxazole in chronic renal failure. Lancet 1975;i:1216-1218.
Horn B, Cottier P: Kreatininkonzentration im Serum vor und unter Behandlung mit Trimethoprim-Sulfamethoxazol (Bactrim). Schweiz Med Wochenschr 1974; 104: 1809-1812.
Caterson RJ, Collett PV, Hood VL, Duggin GG, Horvath JS, Johnson JR, Sampson J, Tiller DJ: Trimethoprim/sulfamethoxazole and renal function in transplant patients. Clin Pharmacol Ther 1978; 23: 553-557. (Pubitemid 8347678)
Berglund F, Killander J, Pompeius R: Effect of trimethoprim- sulfamethoxazole on the renal excretion of creatinine in man. J Urol 1975; 114: 802-808.
Bye A: Letter: drug interference with creatinine assay. Clin Chem 1976; 22: 283-284.
Kastrup J, Petersen P, Bartram R, Hansen JM: The effect of trimethoprim on serum creatinine. Br J Urol 1985; 57: 265-268. (Pubitemid 15061011)
Berg KJ, Gjellestad A, Nordby G, Rootwelt K, Djoseland O, Fauchald P, Mehl A, Narverud J, Talseth T: Renal effects of trimethoprim in ciclosporin-and azathioprine-treated kidney-allografted patients. Nephron 1989; 53: 218-222. (Pubitemid 19237480)
Maki DG, Fox BC, Kuntz J, Sollinger HW, Belzer FO: A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation. Side effects of trimethoprim- sulfamethoxazole, interaction with cyclosporine. J Lab Clin Med 1992; 119: 11-24.
Odlind B, Hartvig P, Fjellstrom KE, Lindstrom B, Bengtsson S: Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods. Eur J Clin Pharmacol 1984; 26: 393-397. (Pubitemid 14139499)
Howards SS: Letter: effect of trimethoprim sulfamethoxazole on the renal excretion of creatinine in man. J Urol 1976; 116: 134.
Trollfors B, Wahl M, Alestig K: Co-trimoxazole, creatinine and renal function. J Infect 1980; 2: 221-226. (Pubitemid 10014891)
Kainer G, Rosenberg AR: Effect of co-trimoxazole on the glomerular filtration rate of healthy adults. Chemotherapy 1981; 27: 229-232. (Pubitemid 11047701)
Ringden O, Myrenfors P, Klintmalm G, Tyden G, Ost L: Nephrotoxicity by co-trimoxazole and cyclosporin in transplanted patients. Lancet 1984;i:1016-1017. (Pubitemid 14148915)
Thompson JF, Chalmers DH, Hunnisett AG, Wood RF, Morris PJ: Nephrotoxicity of trimethoprim and cotrimoxazole in renal allograft recipients treated with cyclosporine. Transplantation 1983; 36: 204-206. (Pubitemid 13036034)
Nyberg G, Gabel H, Althoff P, Bjork S, Herlitz H, Brynger H: Adverse effect of trimethoprim on kidney function in renal transplant patients. Lancet 1984;i:394-395. (Pubitemid 14183300)
Maillard N, Mehdi M, Thibaudin L, Berthoux F, Alamartine E, Mariat C: Creatinine-based GFR predicting equations in renal transplantation: reassessing the tubular secretion effect. Nephrol Dial Transplant 2010; 25: 3076-3082.
Urakami Y, Kimura N, Okuda M, Inui K: Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney. Pharm Res 2004; 21: 976-981. (Pubitemid 38870147)
Cacini W, Myre SA: Uptake of trimethoprim by renal cortex. Biochem Pharmacol 1985; 34: 3483-3488. (Pubitemid 16252525)
Lee J, Hollyer R, Rodelas R, Preuss HG: The influence of trimethoprim, sulfamethoxazole, and creatinine on renal organic anion and cation transport in rat kidney tissue. Toxicol Appl Pharmacol 1981; 58: 184-193. (Pubitemid 11117283)
Shemesh O, Golbetz H, Kriss JP, Myers BD: Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28: 830-838. (Pubitemid 16156326)
Dijkmans BA, van Hooff JP, de Wolff FA, Mattie H: The effect of co-trimoxazole on serum creatinine. Br J Clin Pharmacol 1981; 12: 701-703. (Pubitemid 11027987)
Myre SA, McCann J, First MR, Cluxton RJ Jr: Effect of trimethoprim on serum creatinine in healthy and chronic renal failure volunteers. Ther Drug Monit 1987; 9: 161-165. (Pubitemid 17078115)
Naderer O, Nafziger AN, Bertino JS Jr: Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions. Antimicrob Agents Chemother 1997; 41: 2466-2470. (Pubitemid 27467558)
Roy MT, First MR, Myre SA, Cacini W: Effect of co-trimoxazole and sulfamethoxazole on serum creatinine in normal subjects. Ther Drug Monit 1982; 4: 77-79. (Pubitemid 12141014)
Sandberg T, Trollfors B: Effect of trimethoprim on serum creatinine in patients with acute cystitis. J Antimicrob Chemother 1986; 17: 123-124. (Pubitemid 16186340)
Odutola TA, Cameron JS, Sacks S: Effect of co-trimoxazole on plasma creatinine concentrations in renal transplant recipients. Nephrol Dial Transplant 1994; 9: 1845.
Cantaluppi A, Graziani G, Ponticelli C, Grasso S, Meinardi G, Piaia F, Tamassia V: Pharmacokinetic study of the new sulfamethopyrazine-trimethoprim combination (kelfiprim) in renal insufficiency. Eur J Clin Pharmacol 1984; 27: 345-348. (Pubitemid 15201356)
Berglund F: Urinary excretion patterns for substances with simultaneous secretion and reabsorption by active transport. Acta Physiol Scand 1961; 52: 276-290.
Ducharme MP, Smythe M, Strohs G: Druginduced alterations in serum creatinine concentrations. Ann Pharmacother 1993; 27: 622-633. (Pubitemid 23144228)
Smith GW, Cohen SB: Hyperkalaemia and non-oliguric renal failure associated with trimethoprim. BMJ 1994; 308: 454. (Pubitemid 24084190)
KDIGO clinical practice guideline for the care of kidney transplant recipients: Am J Transplant 2009; 9(suppl 3):S1-S155.
Delanaye P, Cohen EP: Formula-based estimates of the GFR: equations variable and uncertain. Nephron Clin Pract 2008; 110:c48-c53.
Xie D, Joffe MM, Brunelli SM, Beck G, Chertow GM, Fink JC, Greene T, Hsu CY, Kusek JW, Landis R, Lash J, Levey AS, O'Conner A, Ojo A, Rahman M, Townsend RR, Wang H, Feldman HI: A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease. Clin J Am Soc Nephrol 2008; 3: 1332-1338.
Mariat C, Maillard N, Phayphet M, Thibaudin L, Laporte S, Alamartine E, Berthoux F: Estimated glomerular filtration rate as an end point in kidney transplant trial: where do we stand? Nephrol Dial Transplant 2008; 23: 33-38. (Pubitemid 351767426)
White CA, Huang D, Akbari A, Garland J, Knoll GA: Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review. Am J Kidney Dis 2008; 51: 1005-1015. (Pubitemid 351697570)
Poge U, Gerhardt T, Stoffel-Wagner B, Palmedo H, Klehr HU, Sauerbruch T, Woitas RP: Beta-trace protein-based equations for calculation of GFR in renal transplant recipients. Am J Transplant 2008; 8: 608-615. (Pubitemid 351287548)
White CA, Akbari A, Doucette S, Fergusson D, Knoll GA: Estimating glomerular filtration rate in kidney transplantation: is the new chronic kidney disease epidemiology collaboration equation any better? Clin Chem 2010; 56: 474-477.
White C, Akbari A, Hussain N, Dinh L, Filler G, Lepage N, Knoll GA: Chronic kidney disease stage in renal transplantation classification using cystatin C and creatininebased equations. Nephrol Dial Transplant 2007; 22: 3013-3020. (Pubitemid 350093435)
Seronie-Vivien S, Delanaye P, Pieroni L, Mariat C, Froissart M, Cristol JP: Cystatin C: current position and future prospects. Clin Chem Lab Med 2008; 46: 1664-1686.
