Sulfamethoxazole Trimethoprim (Cotrimoxazole) ================================================= **PD Dialyzability**: Likely Pharmacokinetic Parameters [1]_ [2]_ -------------------------------------- =========================================================================== ============================= ===================== \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\ Sulfamethoxazole (SMX) Trimethoprim (TMP) =========================================================================== ============================= ===================== Molecular Weight (Da) 253.28 290.32 Plasma Protein Binding (%) 50 30 - 70 Volume of Distribution (L/Kg) 0.28 1.0-2.2 Hepatic Metabolism |pk1| |pk2| Excreted Unchanged (%) 70 60 - 80 Half-Life; Normal Renal Function (hours) 10 20 - 50 Half-Life; ESRD (hours) 9 - 13 20 - 49 =========================================================================== ============================= ===================== CAPD Dosing: [3]_ [4]_ [5]_ [6]_ ----------------------------------- * 2.5 - 5mg TMP Q24H or 1.0g SMX Q24H CCPD Dosing: ---------------- * No literature identified. Extrapolate dosing from CAPD dosing recommendations. Indication Specific PD Dosing: --------------------------------- * Exit-Site and Tunnel Infections: SMX/TMP 400/80mg PO daily [6]_ * Peritonitis: SMX/TMP 800/160mg PO BID [6]_ * Catheter-related infections: SMX/TMP 800/160mg PO BID [7]_ Literature Summary: ---------------------- +--------+----------+--------------+------------+-------------------+ | Title | Patient | Intervention | Outcome | Note | +========+==========+==============+============+===================+ | |L1| | * |L2| | * |L3| | * |L4| | * |L5| | | [8]_ | * |L6| | * |L7| | * |L8| | * |L9| | | | * |L10| | | | | | | * |L11| | | | | +--------+----------+--------------+------------+-------------------+ | |L12| | * |L2| | * |L13| | * |L14| | * |L5| | | [9]_ | * |L15| | | | | | | * |L16| | | | | | | * |L17| | | | | +--------+----------+--------------+------------+-------------------+ | |L18| | * |L2| | * |L19| | * |L20| | * |L5| | | [10]_ | * |L21| | | * |L22| | | | | * |L23| | | | | | | * |L24| | | | | +--------+----------+--------------+------------+-------------------+ | |L25| | * |L2| | * |L26| | * |L27| | * |L28| | | [11]_ | * |L29| | * |L30| | * |L31| | | | | * |L32| | | | | | | * |L33| | | | | +--------+----------+--------------+------------+-------------------+ | |L34| | * |L2| | * |L35| | * |L36| | * |L5| | | [12]_ | * |L37| | * |L38| | * |L39| | | +--------+----------+--------------+------------+-------------------+ References ------------ .. [1] Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 Jan 1;34(suppl_1):D668–72. .. [2] American Pharmacist Association. Drug information handbook: a comprehensive resource for all clinicians and healthcare professionals [Internet]. Hudson, Ohio: American Pharmacist association; 2012 [cited 2018 Jan 24]. Available from: http://online.lexi.com.login.ezproxy.library.ualberta.ca/lco/action/home?siteid=1 .. [3] Gilbert B, Robbins P, Livornese LL. Use of Antibacterial Agents in Renal Failure. Med Clin North Am. 2011;95(2):677–702. .. [4] Aronoff GR. Drug prescribing in renal failure: dosing guidelines for adults and children. 5th ed. Philadelphia, PA: American College of Physicians; 2007. .. [5] Adjusting oral antibiotics to estimated creatinine clearance [Internet]. [cited 2018 Jan 24]. Available from: http://www.vhpharmsci.com/VHFormulary/Tools/ADJUSTING%20ORAL%20ANTIBIOTICS.pdf .. [6] Li PK-T, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, Gupta A, et al. Peritoneal Dialysis-Related Infections Recommendations: 2010 Update. Perit Dial Int. 2010;30(4):393–423. .. [7] Szeto C-C, Li PK-T, Johnson DW, Bernardini J, Dong J, Figueiredo AE, et al. ISPD Catheter-Related Infection Recommendations: 2017 Update. Perit Dial Int. 2017 Mar 1;37(2):141–54. .. [8] Morris AJ, Henderson GK, Bremner DA, Collins JF. Relapsing peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis due to Corynebacterium aquaticum. J Infect. 1986;13:151–156. .. [9] Hansen W, Dratwa MAX, Tielemans C, Wens R, Collart F, Yourassowsky E. Pseudomonas paucimobilis Peritonitis in Patients Treated by Peritoneal Dialysis. J Clin Microbiol. 1984;20(6):1225–1226. .. [10] Pepersack F, Haene MD, Toussaint C. Campylobacter jejuni Peritonitis Complicating Continuous Ambulatory Peritoneal Dialysis. J Clin Microbiol. 1982;16(4):739–741. .. [11] Churchill DN, Taylor DW, Vas SI, Singer J, Beecroft ML, Wu G, et al. Peritonitis in Continuous Ambulatory Peritoneal Dialysis (CAPD) Patients: A Randomized Clinical Trial of Cotrimoxazole Prophylaxis. Perit Dial Int. 1988;8:125–128. .. [12] Singlas E, Colin JN, Rottembourg J, Meessen JP, Martin AD, Legrain M, et al. Pharmacokinetics of Sulfamethoxazole- Trimethoprim Combination During Chronic Peritoneal Dialysis : Effect of Peritonitis. Eur J CLin Pharmacol. 1982;21:409–415. .. |pk1| replace:: Minor hepatic metabolism by the liver to produce inactive metabolite .. |pk2| replace:: Minor hepatic metabolism .. |L1| replace:: Relapsing peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis due to Corynebacterium aquaticum. .. |L2| replace:: CAPD .. |L3| replace:: SMX/TMP 100/20 mg/L IP .. |L4| replace:: Initial clinical improvement noted .. |L5| replace:: No ADR reported .. |L6| replace:: 33 year old male .. |L7| replace:: Then SMX/TMP 200/40 mg IP .. |L8| replace:: Patient experienced disease recurrence resulting in switch of antibiotic .. |L9| replace:: Patient initially failed to respond to IV vancomycin, PO doxycycline and IP cefamandole .. |L10| replace:: Presenting with cloudy dialysate .. |L11| replace:: Diagnosed with peritonitis due to *Corynebacterium aquaticum* .. |L12| replace:: Pseudomonas paucimobilis peritonitis in patients treated by peritoneal dialysis. .. |L13| replace:: SMX/TMP 80/16 mg/L IP x 2 weeks .. |L14| replace:: Clinical improvement .. |L15| replace:: 74 year old female .. |L16| replace:: Presenting with diffuse abdominal pain, vomiting and cloudy peritoneal effluent .. |L17| replace:: Diagnosed with peritonitis due to *Pseudomonas paucimonbilis* .. |L18| replace:: Campylobacter jejuni peritonitis complicating continuous ambulatory peritoneal dialysis. .. |L19| replace:: SMX/TMP 80/16mg/L IP .. |L20| replace:: No clinical improvement observed .. |L21| replace:: 50 year old male with a history of peritonitis .. |L22| replace:: Patient switched to IP gentamicin and erythromycin therapy .. |L23| replace:: Presenting with diarrhea, low-grade fever, abdominal discomfort, and cloudy peritoneal effluent .. |L24| replace:: Diagnosed with peritonitis due to *Campylobacter jejuni* .. |L25| replace:: Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: A randomized clinical trial of cotrimoxazole prophylaxis. .. |L26| replace:: 56 given SMX/TMP 800/160mg PO daily .. |L27| replace:: Time to peritonitis .. |L28| replace:: SMX/TMP prophylaxis did not prevent CAPD peritonitis .. |L29| replace:: 105 patients .. |L30| replace:: 49 patients given Placebo .. |L31| replace:: Side effects causing discontinuation resulted in 30% of patients treated with SMX/TMP .. |L32| replace:: 18-80 years old .. |L33| replace:: Patients had previous history of peritonitis .. |L34| replace:: Pharmacokinetics of sulfamethoxazole - trimethoprim combination during chronic peritoneal dialysis: Effect of peritonitis. .. |L35| replace:: SMX/TMP 20/4mg/kg PO .. |L36| replace:: Peak serum SMX concentration .. |L37| replace:: 18 patients, 15 otherwise healthy and 3 with peritonitis .. |L38| replace:: SMX/TMP 80/16mg/L IP .. |L39| replace:: Peak TMP concentration