International Journal of Clinical Pharmacy

, Volume 38, Issue 1, pp 127–134 | Cite as

Survey of pharmacists’ antibiotic dosing recommendations for sustained low-efficiency dialysis

  • Jian P. Mei
  • Azadeh Ali-Moghaddam
  • Bruce A. MuellerEmail author
Research Article


Background The use of hybrid renal replacement therapies like sustained low efficiency dialysis (SLED) is increasing in ICUs worldwide. However, pharmacokinetic studies designed to inform therapeutic antibiotic dosing in critically ill patients receiving SLED are limited. SLED operational characteristics vary across institutions. Pharmacists in institutions that utilize SLED are challenged to recommend therapeutic doses for antibiotics. Objective To characterize pharmacist-recommended antibiotic regimens for SLED. Methods An electronic survey was sent to pharmacist members of the American College of Clinical Pharmacy in the Nephrology or Critical Care Practice and Research Network. Dosing recommendations for a hypothetical critically ill septic patient were collected for cefepime, ceftaroline, daptomycin, levofloxacin, meropenem, and piperacillin/tazobactam. Main outcome measure Antibiotic regimens for the six antibiotics, their frequency, pharmacist’s experience with renal replacement therapies (RRT), post-graduate training, years of clinical experience, number of staffed beds in their hospital, and RRT employed in their ICUs. Results The survey was completed by 69 clinical pharmacists who had 8.5 ± 7.5 (mean ± SD) years of experience. All pharmacists had experience dosing medications for patients receiving RRT. The most frequently recommended regimen for each antibiotic was: cefepime 1000 mg every 24 h, ceftaroline 200 mg every 12 h, daptomycin 6 mg/kg every 24 h, levofloxacin 500 mg every 24 h, meropenem 1000 mg every 12 h, and piperacillin/tazobactam 2250 mg every 8 h. Up to nine distinct regimens were recommended for each antibiotic, and the total daily dose between these regimens ranged by as much as a 12-fold. Neither pharmacist’s experience with SLED, post-graduate training, nor years of clinical experience were significantly associated with particular dosing recommendations for the antibiotics. Conclusion Pharmacists working in institutions that utilize SLED make antibiotic dosing recommendations that vary 4–12-fold depending on the drug. Published research does not provide adequate guidance to optimally dose antibiotics in patients receiving SLED. More SLED pharmacokinetic trials, real-time serum concentration monitoring and advanced pharmacokinetic modeling techniques are necessary to ensure therapeutic dosing in patients receiving SLED.


Antibiotics Ceftaroline Critical care Daptomycin Cefepime Hemodialysis Levofloxacin Meropenem Pharmacokinetics Piperacillin SLED Tazobactam 



The authors sincerely thank all survey respondents for their time and valuable insight.


No funding was received for this study.

Conflicts of interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Supplementary material

11096_2015_214_MOESM1_ESM.docx (25 kb)
Supplementary material 1 (DOCX 24 kb)


  1. 1.
    Center for Disease Control. Hospitalization discharge diagnoses for kidney disease—United States. 2008;1980–2005(57):309–12.Google Scholar
  2. 2.
    Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010;38:261–75.CrossRefPubMedGoogle Scholar
  4. 4.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.CrossRefPubMedGoogle Scholar
  5. 5.
    Lewis SJ, Mueller BA. Antibiotic dosing in patients with acute kidney injury: “enough but not too much”. J Intensive Care Med. 2014. doi: 10.1177/0885066614555490.PubMedGoogle Scholar
  6. 6.
    Scoville BA, Mueller BA. Medication dosing in critically ill patients with acute kidney injury treated with renal replacement therapy. Am J Kidney Dis. 2013;61:490–500.CrossRefPubMedGoogle Scholar
  7. 7.
    Marshall MR, Golper TA, Shaver MJ, Alam MG, Chatoth DK. Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy. Kidney Int. 2001;60:777–85.CrossRefPubMedGoogle Scholar
  8. 8.
    Baldwin I, Bellomo R, Naka T, Koch B, Fealy N. A pilot randomized controlled comparison of extended daily dialysis with filtration and continuous veno-venous hemofiltration: fluid removal and hemodynamics. Int J Artif Organs. 2007;30:1083–9.PubMedGoogle Scholar
  9. 9.
    Ahmed Z, Gilibert S, Krevolin L. Cost analysis of continuous renal replacement and extended hemodialysis. Dial Transplant. 2009;38:500–3.CrossRefGoogle Scholar
  10. 10.
    Berbece AN, Richardson RM. Sustained low-efficiency dialysis in the ICU: cost, anticoagulation, and solute removal. Kidney Int. 2006;70:963–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Overberger P, Pesacreta M, Palevsky PM. VA/NIH Acute Renal Failure Trial Network. Management of renal replacement therapy in acute kidney injury: a survey of practitioner prescribing practices. Clin J Am Soc Nephrol. 2007;2:623–30.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lorenzen JM, Broll M, Kaever V, Burhenne H, Hafer C, Clajus C, et al. Pharmacokinetics of ampicillin/sulbactam in critically ill patients with acute kidney injury undergoing extended dialysis. Clin J Am Soc Nephrol. 2012;7:385–90.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kielstein JT, Lorenzen J, Kaever V, Burhenne H, Broll M, Hafer C, et al. Risk of underdosing of ampicillin/sulbactam in patients with acute kidney injury undergoing extended daily dialysis—a single case. Nephrol Dial Transplant. 2009;24:2283–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Strunk AK, Schmidt JJ, Baroke E, Bode-Boger SM, Martens-Lobenhoffer J, Welte T, et al. Single- and multiple-dose pharmacokinetics and total removal of colistin in a patient with acute kidney injury undergoing extended daily dialysis. J Antimicrob Chemother. 2014;69:2008–10.CrossRefPubMedGoogle Scholar
  15. 15.
    Burkhardt O, Joukhadar C, Traunmuller F, Hadem J, Welte T, Kielstein JT. Elimination of daptomycin in a patient with acute renal failure undergoing extended daily dialysis. J Antimicrob Chemother. 2008;61:224–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Kielstein JT, Eugbers C, Bode-Boeger SM, Martens-Lobenhoffer J, Haller H, Joukhadar C, et al. Dosing of daptomycin in intensive care unit patients with acute kidney injury undergoing extended dialysis—a pharmacokinetic study. Nephrol Dial Transplant. 2010;25:1537–41.CrossRefPubMedGoogle Scholar
  17. 17.
    Burkhardt O, Hafer C, Langhoff A, Kaever V, Kumar V, Welte T, et al. Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis. Nephrol Dial Transplant. 2009;24:267–71.CrossRefPubMedGoogle Scholar
  18. 18.
    Roberts JA, Field J, Visser A, Whitbread R, Tallot M, Lipman J, et al. Using population pharmacokinetics to determine gentamicin dosing during extended daily diafiltration in critically ill patients with acute kidney injury. Antimicrob Agents Chemother. 2010;54:3635–40.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Deshpande P, Chen J, Gofran A, Murea M, Golestaneh L. Meropenem removal in critically ill patients undergoing sustained low-efficiency dialysis (SLED). Nephrol Dial Transplant. 2010;25:2632–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Kielstein JT, Czock D, Schopke T, Hafer C, Bode-Boger SM, Kuse E, et al. Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis. Crit Care Med. 2006;34:51–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Czock D, Husig-Linde C, Langhoff A, Schopke T, Hafer C, de Groot K, et al. Pharmacokinetics of moxifloxacin and levofloxacin in intensive care unit patients who have acute renal failure and undergo extended daily dialysis. Clin J Am Soc Nephrol. 2006;1:1263–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Fiaccadori E, Maggiore U, Rotelli C, Giacosa R, Parenti E, Picetti E, et al. Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure. Crit Care Med. 2004;32:2437–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Cremaschi E, Maggiore U, Maccari C, Cademartiri C, Andreoli R, Fiaccadori E. Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED). Minerva Anestesiol. 2010;76:961–4.PubMedGoogle Scholar
  24. 24.
    Swoboda S, Ober MC, Lichtenstern C, Saleh S, Schwenger V, Sonntag HG, et al. Pharmacokinetics of linezolid in septic patients with and without extended dialysis. Eur J Clin Pharmacol. 2010;66:291–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Clajus C, Kuhn-Velten WN, Schmidt JJ, Lorenzen JM, Pietsch D, Beutel G, et al. Cotrimoxazole plasma levels, dialyzer clearance and total removal by extended dialysis in a patient with acute kidney injury: risk of under-dosing using current dosing recommendations. BMC Pharmacol Toxicol. 2013;14:19.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ahern JW, Lai C, Rebuck JA, Possidente CJ, Weidner M. Experience with vancomycin in patients receiving slow low-efficiency dialysis. Hosp Pharm. 2004;39:138–43.Google Scholar
  27. 27.
    Golestaneh L, Gofran A, Mokrzycki MH, Chen JL. Removal of vancomycin in sustained low-efficiency dialysis (SLED): a need for better surveillance and dosing. Clin Nephrol. 2009;72:286–91.CrossRefPubMedGoogle Scholar
  28. 28.
    Petejova N, Martinek A, Zahalkova J, Duricova J, Brozmanova H, Urbanek K, et al. Vancomycin removal during low-flux and high-flux extended daily hemodialysis in critically ill septic patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012;156:342–7.PubMedGoogle Scholar
  29. 29.
    Bogard KN, Peterson NT, Plumb TJ, Erwin MW, Fuller PD, Olsen KM. Antibiotic dosing during sustained low-efficiency dialysis: special considerations in adult critically ill patients. Crit Care Med. 2011;39:560–70.CrossRefPubMedGoogle Scholar
  30. 30.
    Mueller BA, Scoville BA. Adding to the armamentarium: antibiotic dosing in extended dialysis. Clin J Am Soc Nephrol. 2012;7:373–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Erstad BL, Haas CE, O’Keeffe T, Hokula CA, Parrinello K, Theodorou AA. Interdisciplinary patient care in the intensive care unit: focus on the pharmacist. Pharmacotherapy. 2011;31:128–37.CrossRefPubMedGoogle Scholar
  32. 32.
    Jurado LV, Steelman JD. The role of the pharmacist in the intensive care unit. Crit Care Nurs Q. 2013;36:407–14.CrossRefPubMedGoogle Scholar
  33. 33.
    Jiang SP, Zhu ZY, Wu XL, Lu XY, Zhang XG, Wu BH. Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study. Ther Clin Risk Manag. 2014;10:405–12.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7–20.CrossRefPubMedGoogle Scholar
  35. 35.
    Lewis SJ, Mueller BA. Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent. Semin Dial. 2014;27(5):441–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Harris LE, Reaves AB, Krauss AG, Griner J, Hudson JQ. Evaluation of antibiotic prescribing patterns in patients receiving sustained low-efficiency dialysis: opportunities for pharmacists. Int J Pharm Pract. 2013;21(1):55–61.CrossRefPubMedGoogle Scholar
  37. 37.
    Martinez MN, Papich MG, Drusano GL. Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob Agents Chemother. 2012;56:2795–805.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Package Insert. Cubicin. Lexington (MA): Cubist Pharmaceuticals; 2015. NDC 67919-011-01.Google Scholar
  39. 39.
    Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29:562–77.CrossRefPubMedGoogle Scholar
  40. 40.
    Carlier M, Taccone FS, Beumier M, Seyler L, Cotton F, Jacobs F, et al. Population pharmacokinetics and dosing simulations of cefepime in septic shock patients receiving continuous renal replacement therapy. Int J Antimicrob Agents. 2015; 46(4):413–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Nehus EJ, Mouksassi S, Vinks AA, Goldstein S. Meropenem in children receiving continuous renal replacement therapy: clinical trial simulations using realistic covariates. J Clin Pharmacol. 2014;54:1421–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Gharibian KN, Lewis SJ, Mueller BA. Cefepime dosing in modeled critically Ill patients receiving SHIFT hemofiltration or hemodialysis renal replacement therapies. San Diego: American Society of Nephrology Kidney Week; 2015.Google Scholar
  43. 43.
    Gharibian KN, Lewis SJ, Mueller BA. Identification of Optimal ceftazidime dosing regimens in modeled critically Ill patients receiving SHIFT renal replacement therapy. San Diego: American Society of Nephrology Kidney Week; 2015.Google Scholar
  44. 44.
    Roberts JA, Mehta RL, Lipman J. Sustained low efficiency dialysis allows rational renal replacement therapy, but does it allow rational drug dosing? Crit Care Med. 2011;39:602–3.CrossRefPubMedGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015

Authors and Affiliations

  • Jian P. Mei
    • 1
  • Azadeh Ali-Moghaddam
    • 1
  • Bruce A. Mueller
    • 1
    Email author
  1. 1.Department of Clinical PharmacyUniversity of Michigan College of PharmacyAnn ArborUSA

Personalised recommendations