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 Minor hepatic metabolism by the liver to produce inactive metabolite Minor hepatic metabolism
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
Relapsing peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis due to Corynebacterium aquaticum. [8]
  • CAPD
  • 33 year old male
  • Presenting with cloudy dialysate
  • Diagnosed with peritonitis due to Corynebacterium aquaticum
  • SMX/TMP 100/20 mg/L IP
  • Then SMX/TMP 200/40 mg IP
  • Initial clinical improvement noted
  • Patient experienced disease recurrence resulting in switch of antibiotic
  • No ADR reported
  • Patient initially failed to respond to IV vancomycin, PO doxycycline and IP cefamandole
Pseudomonas paucimobilis peritonitis in patients treated by peritoneal dialysis. [9]
  • CAPD
  • 74 year old female
  • Presenting with diffuse abdominal pain, vomiting and cloudy peritoneal effluent
  • Diagnosed with peritonitis due to Pseudomonas paucimonbilis
  • SMX/TMP 80/16 mg/L IP x 2 weeks
  • Clinical improvement
  • No ADR reported
Campylobacter jejuni peritonitis complicating continuous ambulatory peritoneal dialysis. [10]
  • CAPD
  • 50 year old male with a history of peritonitis
  • Presenting with diarrhea, low-grade fever, abdominal discomfort, and cloudy peritoneal effluent
  • Diagnosed with peritonitis due to Campylobacter jejuni
  • SMX/TMP 80/16mg/L IP
  • No clinical improvement observed
  • Patient switched to IP gentamicin and erythromycin therapy
  • No ADR reported
Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: A randomized clinical trial of cotrimoxazole prophylaxis. [11]
  • CAPD
  • 105 patients
  • 18-80 years old
  • Patients had previous history of peritonitis
  • 56 given SMX/TMP 800/160mg PO daily
  • 49 patients given Placebo
  • Time to peritonitis
  • Side effects causing discontinuation resulted in 30% of patients treated with SMX/TMP
  • SMX/TMP prophylaxis did not prevent CAPD peritonitis
Pharmacokinetics of sulfamethoxazole - trimethoprim combination during chronic peritoneal dialysis: Effect of peritonitis. [12]
  • CAPD
  • 18 patients, 15 otherwise healthy and 3 with peritonitis
  • SMX/TMP 20/4mg/kg PO
  • SMX/TMP 80/16mg/L IP
  • Peak serum SMX concentration
  • Peak TMP concentration
  • No ADR reported

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](1, 2, 3) 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.