Background/Aims: There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing. Methods: Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters. Results: TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against Pneumocystis jirovecii. Conclusions: CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT.

1.
Sattler FR, Cowan R, Nielsen DM, Ruskin J: Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study. Ann Intern Med 1988;109:280-287.
2.
Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents: Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America, 2013. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (accessed May 22, 2014).
3.
Brooke JS: Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 2012;25:2-41.
4.
Garazi M, Singer C, Tai J, Ginocchio CC: Bloodstream infections caused by Stenotrophomonas maltophilia: a seven-year review. J Hosp Infect 2012;81:114-118.
5.
Mehta RL, Pascual MT, Soroko S, Savage BR, Himmelfarb J, Ikizler TA, Paganini EP, Chertow GM; Program to Improve Care in Acute Renal Disease: Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int 2004;66:1613-1621.
6.
Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294:813-818.
7.
Aronoff GR, Bennett WM, Berns JS, et al: Drug Prescribing in Renal Failure, ed 5. Philadelphia, PA, USA, American College of Physicians, 2007.
8.
Lexicomp: Lexicomp Online. Philadelphia, PA, Wolters Kluwer Health, 2014. http://online.lexi.com/ (accessed May 22, 2014).
9.
Micromedex Healthcare Series: DRUGDEX System. Greenwood Village, CO, Truven Health Analytics, 2014. http://ww.thomsonhc.com/ (accessed May 22, 2014).
10.
Sicor Pharmaceuticals Inc: Sulfamethoxazole and trimethoprim injection USP, prescribing information. Irvine, CA, 2008.
11.
Amini H, Ahmadiani A: Rapid and simultaneous determination of sulfamethoxazole and trimethoprim in human plasma by high-performance liquid chromatography. J Pharm Biomed Anal 2007;43:1146-1150.
12.
Kaplan SA, Weinfeld RE, Abruzzo CW, McFaden K, Jack ML, Weissman L: Pharmacokinetic profile of trimethoprim-sulfamethoxazole in man. J Infect Dis 1973;128(suppl):547-555.
13.
Hess MM, Boucher BA, Laizure SC, Stevens RC, Sanders PL, Janning SW, Croce MA, Fabian TC: Trimethoprim-sulfamethoxazole pharmacokinetics in trauma patients. Pharmacotherapy 1993;13:602-606.
14.
Chin TW, Vandenbroucke A, Fong IW: Pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients. Antimicrob Agents Chemother 1995;39:28-33.
15.
Varoquaux O, Lajoie D, Gobert C, Cordonnier P, Ducreuzet C, Pays M, Advenier C: Pharmacokinetics of the trimethoprim-sulphamethoxazole combination in the elderly. Br J Clin Pharmacol 1985;20:575-581.
16.
Stevens RC, Laizure SC, Williams CL, Stein DS: Pharmacokinetics and adverse effects of 20-mg/kg/day trimethoprim and 100-mg/kg/day sulfamethoxazole in healthy adult subjects. Antimicrob Agents Chemother 1991;35:1884-1890.
17.
Stevens RC, Laizure SC, Sanders PL, Stein DS: Multiple-dose pharmacokinetics of 12 milligrams of trimethoprim and 60 milligrams of sulfamethoxazole per kilogram of body weight per day in healthy volunteers. Antimicrob Agents Chemother 1993;37:448-452.
18.
Patel RB, Welling PG: Clinical pharmacokinetics of co-trimoxazole (trimethoprim-sulphamethoxazole). Clin Pharmacokinet 1980;5:405-423.
19.
Curkovic I, Luthi B, Franzen D, Ceschi A, Rudiger A, Corti N: Trimethoprim/Sulfamethoxazole pharmacokinetics in two patients undergoing continuous venovenous hemodiafiltration. Ann Pharmacother 2010;44:1669-1672.
20.
Lau WK, Young LS: Trimethoprim-sulfamethoxazole treatment of Pneumocystis carinii pneumonia in adults. N Engl J Med 1976;295:716-718.
21.
Hughes WT, Feldman S, Chaudhary SC, Ossi MJ, Cox F, Sanyal SK: Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J Pediatr 1978;92:285-291.
22.
Winston DJ, Lau WK, Gale RP, Young LS: Trimethoprim-sulfamethoxazole for the treatment of Pneumocystis carinii pneumonia. Ann Intern Med 1980;92:762-769.
23.
Trissel LA: Handbook of Injectable Drugs, ed 17. Bethesda, MD, American Society of Health-System Pharmacists, 2013.
24.
Kronfol NO, Lau AH, Barakat MM: Aminoglycoside binding to polyacrylonitrile hemofilter membranes during continuous hemofiltration. ASAIO Trans 1987;33:300-303.
25.
Choi G, Gomersall CD, Lipman J, Wong A, Joynt GM, Leung P, Ramsay SJ, Ho OM: The effect of adsorption, filter material and point of dilution on antibiotic elimination by haemofiltration an in vitro study of levofloxacin. Int J Antimicrob Agents 2004;24:468-472.
26.
Lam PKN, Tian Q, Ip M, Gomersall CD: In vitro adsorption of gentamicin and netilmicin by polyacrylonitrile and polyamide hemofiltration filters. Antimicrob Agents Chemother 2010;54:963-965.
27.
Krishnamurthy RB, Upton RN, Fajumi AO, Lai S, Charlton CS, Ousley RM, Martinez AM, McConnell H, O'Connor SN, Ong J, Macintyre PE, Chapman MJ, Ludbrook GL: Pharmacokinetics of oxycodone after subcutaneous administration in a critically ill population compared with a healthy cohort. Anaesth Intensive Care 2012;40:269-274.
28.
Kees MG, Schaeftlein A, Haeberle HA, Kees F, Kloft C, Heininger A: Population pharmacokinetics and pharmacodynamic evaluation of intravenous and enteral moxifloxacin in surgical intensive care unit patients. J Antimicrob Chemother 2013;68:1331-1337.
29.
Mahmoudi L, Mohammadpour AH, Ahmadi A, Niknam R, Mojtahedzadeh M: Influence of sepsis on higher daily dose of amikacin pharmacokinetics in critically ill patients. Eur Rev Med Pharmacol Sci 2013;17:285-291.
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