open access

Vol 49, No 5 (2017)
Review articles
Published online: 2017-11-23
Submitted: 2017-10-01
Accepted: 2017-11-20
Get Citation

Applying pharmacokinetic/pharmacodynamic principles for optimizing antimicrobial therapy during continuous renal replacement therapy

Patrick M. Honore, Rita Jacobs, Elisabeth De Waele, Herbert D. Spapen
DOI: 10.5603/AIT.a2017.0071
·
Pubmed: 29171000
·
Anaesthesiol Intensive Ther 2017;49(5):412-418.

open access

Vol 49, No 5 (2017)
Review articles
Published online: 2017-11-23
Submitted: 2017-10-01
Accepted: 2017-11-20

Abstract

Continuous renal replacement therapy (CRRT) is progressively supplanting intermittent haemodialysis (IHD) in critically ill patients. Although CRRT indeed offers more appropriate haemodynamic, fluid, and metabolic stability, concern is rising about its impact on concomitant drugs and, in particular, antimicrobial treatment. Antimicrobial dose recommendations have been elaborated to avoid drug accumulation and toxicity in patients undergoing IHD. However, these dosing regimens have resulted in significant underdosing in patients undergoing CRRT, thereby increasing the risk of treatment failure and development of resistance. Applying pharmacokinetic/pharmacodynamic (PK/PD) principles may aid one to obtain more adequate antimicrobial therapy during CRRT. Much progress has been made in recent years resulting in relevant changes in particular antimicrobial therapies. In this review, we discuss antimicrobials that are frequently used in an intensive care setting. Drugs are divided according to their PK/PD characteristics and, wherever possible, dose recommendations during CRRT are provided. Of course, while therapeutic drug monitoring remains the best way to cope with PK/PD variability within a critically ill CRRT population, its bedside use is actually limited to some specific antibiotics.

Abstract

Continuous renal replacement therapy (CRRT) is progressively supplanting intermittent haemodialysis (IHD) in critically ill patients. Although CRRT indeed offers more appropriate haemodynamic, fluid, and metabolic stability, concern is rising about its impact on concomitant drugs and, in particular, antimicrobial treatment. Antimicrobial dose recommendations have been elaborated to avoid drug accumulation and toxicity in patients undergoing IHD. However, these dosing regimens have resulted in significant underdosing in patients undergoing CRRT, thereby increasing the risk of treatment failure and development of resistance. Applying pharmacokinetic/pharmacodynamic (PK/PD) principles may aid one to obtain more adequate antimicrobial therapy during CRRT. Much progress has been made in recent years resulting in relevant changes in particular antimicrobial therapies. In this review, we discuss antimicrobials that are frequently used in an intensive care setting. Drugs are divided according to their PK/PD characteristics and, wherever possible, dose recommendations during CRRT are provided. Of course, while therapeutic drug monitoring remains the best way to cope with PK/PD variability within a critically ill CRRT population, its bedside use is actually limited to some specific antibiotics.
Get Citation

Keywords

pharmacokinetics/pharmacodynamics; renal replacement therapy, continuous; antibiotics; antifungals

About this article
Title

Applying pharmacokinetic/pharmacodynamic principles for optimizing antimicrobial therapy during continuous renal replacement therapy

Journal

Anaesthesiology Intensive Therapy

Issue

Vol 49, No 5 (2017)

Pages

412-418

Published online

2017-11-23

DOI

10.5603/AIT.a2017.0071

Pubmed

29171000

Bibliographic record

Anaesthesiol Intensive Ther 2017;49(5):412-418.

Keywords

pharmacokinetics/pharmacodynamics
renal replacement therapy
continuous
antibiotics
antifungals

Authors

Patrick M. Honore
Rita Jacobs
Elisabeth De Waele
Herbert D. Spapen

References (63)
  1. Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014; 42(8): 1749–1755.
  2. Seyler L, Cotton F, Taccone FS, et al. Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Crit Care. 2011; 15(3): R137.
  3. Honore PM, Jacobs R, Hendrickx I, et al. Prevention and treatment of sepsis-induced acute kidney injury: an update. Ann Intensive Care. 2015; 5(1): 51.
  4. Leypoldt JK, Jaber BL, Lysaght MJ, et al. Kinetics and dosing predictions for daily haemofiltration. Nephrol Dial Transplant. 2003; 18(4): 769–776.
  5. Jeffrey RF, Khan AA, Prabhu P, et al. A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system. Artif Organs. 1994; 18(6): 425–428.
  6. Roberts DM. The relevance of drug clearance to antibiotic dosing in critically ill patients. Curr Pharm Biotechnol. 2011; 12(12): 2002–2014.
  7. Roberts DM, Liu X, Roberts JA, et al. RENAL Replacement Therapy Study Investigators. A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics. Crit Care. 2015; 19: 84.
  8. Van Herendael B, Jeurissen A, Tulkens PM, et al. Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin? Ann Intensive Care. 2012; 2(1): 22.
  9. Honore PM, Jacobs R, Joannes-Boyau O, et al. Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review. ASAIO J. 2013; 59(2): 99–106.
  10. Roger C, Cotta M, Muller L, et al. Impact of renal replacement modalities on the clearance of piperacillin-tazobactam administered via continuous infusion in critically ill patients. International Journal of Antimicrobial Agents. 2017; 50(2): 227–231.
  11. Boselli E, Breilh D, Rimmelé T, et al. Alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to patients with ventilator-associated pneumonia. Crit Care Med. 2008; 36(5): 1500–1506.
  12. Yang H, Zhang C, Zhou Q, et al. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. PLoS One. 2015; 10(1): e0116769.
  13. Isla A, Gascón AR, Maynar J, et al. In vitro AN69 and polysulphone membrane permeability to ceftazidime and in vivo pharmacokinetics during continuous renal replacement therapies. Chemotherapy. 2007; 53(3): 194–201.
  14. Mariat C, Venet C, Jehl F, et al. Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation. Crit Care. 2006; 10(1): R26.
  15. Isla A, Rodríguez-Gascón A, Trocóniz IF, et al. Population pharmacokinetics of meropenem in critically ill patients undergoing continuous renal replacement therapy. Clin Pharmacokinet. 2008; 47(3): 173–180.
  16. Bilgrami I, Roberts JA, Wallis SC, et al. Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration. Antimicrob Agents Chemother. 2010; 54(7): 2974–2978.
  17. Jaruratanasirikul S, Sriwiriyajan S. Stability of meropenem in normal saline solution after storage at room temperature. Southeast Asian J Trop Med Public Health. 2003; 34(3): 627–629.
  18. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009; 66(1): 82–98.
  19. Neely MN, Youn G, Jones B, et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 2014; 58(1): 309–316.
  20. Prybylski JP. A Strategy for Dosing Vancomycin to Therapeutic Targets Using Only Trough Concentrations. Clin Pharmacokinet. 2017; 56(3): 263–272.
  21. Lodise TP, Lomaestro B, Graves J, et al. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. 2008; 52(4): 1330–1336.
  22. Waineo MF, Kuhn TC, Brown DL. The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion. J Clin Pharm Ther. 2015; 40(3): 259–265.
  23. Hao JJ, Chen H, Zhou JX. Continuous versus intermittent infusion of vancomycin in adult patients: A systematic review and meta-analysis. Int J Antimicrob Agents. 2016; 47(1): 28–35.
  24. Spapen HD, Janssen van Doorn K, Diltoer M, et al. Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. Ann Intensive Care. 2011; 1(1): 26.
  25. Lacave G, Caille V, Bruneel F, et al. Incidence and risk factors of acute kidney injury associated with continuous intravenous high-dose vancomycin in critically ill patients: A retrospective cohort study. Medicine (Baltimore). 2017; 96(7): e6023.
  26. Lin H, Bukovskaya Y, De Moya M, et al. Vancomycin continuous infusion versus intermittent infusion during continuous venovenous hemofiltration: slow and steady may win the race. Ann Intensive Care. 2015; 5: 10.
  27. Beumier M, Roberts JA, Kabtouri H, et al. A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy. J Antimicrob Chemother. 2013; 68(12): 2859–2865.
  28. MacGowan AP. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother. 2003; 51 Suppl 2: ii17–ii25.
  29. Villa G, Di Maggio P, De Gaudio AR, et al. Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review. Crit Care. 2016; 20(1): 374.
  30. Villa G, Zaragoza JJ, Sharma A, et al. Cytokine removal with high cut-off membrane: review of literature. Blood Purif. 2014; 38(3-4): 167–173.
  31. Adembri C, Fallani S, Cassetta MI, et al. Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion. Int J Antimicrob Agents. 2008; 31(2): 122–129.
  32. De Pascale G, Fortuna S, Tumbarello M, et al. Linezolid plasma and intrapulmonary concentrations in critically ill obese patients with ventilator-associated pneumonia: intermittent vs continuous administration. Intensive Care Med. 2015; 41(1): 103–110.
  33. Klepser ME, Wolfe EJ, Jones RN, et al. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997; 41(6): 1392–1395.
  34. Shrikhande S, Friess H, Issenegger C, et al. Fluconazole penetration into the pancreas. Antimicrob Agents Chemother. 2000; 44(9): 2569–2571.
  35. Hughes CE, Bennett RL, Tuna IC, et al. Activities of fluconazole (UK 49,858) and ketoconazole against ketoconazole-susceptible and -resistant Candida albicans. Antimicrob Agents Chemother. 1988; 32(2): 209–212.
  36. Pappas PG, Kauffman CA, Andes DR, et al. Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 62(4): 409–417.
  37. Muhl E, Martens T, Iven H, et al. Influence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmacokinetics of fluconazole. Eur J Clin Pharmacol. 2000; 56(9-10): 671–678.
  38. Kishino S, Koshinami Y, Hosoi T, et al. Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration. Ther Drug Monit. 2001; 23(1): 4–8.
  39. Pittrow L, Penk A. Dosage adjustment of fluconazole during continuous renal replacement therapy (CAVH, CVVH, CAVHD, CVVHD). Mycoses. 1999; 42(1-2): 17–19.
  40. Yagasaki K, Gando S, Matsuda N, et al. Pharmacokinetics and the most suitable dosing regimen of fluconazole in critically ill patients receiving continuous hemodiafiltration. Intensive Care Med. 2003; 29(10): 1844–1848.
  41. Bouman CSC, van Kan HJM, Koopmans RP, et al. Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing. Intensive Care Med. 2006; 32(12): 2013–2019.
  42. Honoré PM, Jacobs R, Spapen HD. Use of Antifungal Drugs during Continuous Hemofiltration Therapies. Annual Update in Intensive Care and Emergency Medicine 2012. 2012: 337–344.
  43. Pea F, Viale P, Pavan F, et al. Pharmacokinetic considerations for antimicrobial therapy in patients receiving renal replacement therapy. Clin Pharmacokinet. 2007; 46(12): 997–1038.
  44. Taccone FS, de Backer D, Laterre PF, et al. Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy. Int J Antimicrob Agents. 2011; 37(6): 531–535.
  45. de Montmollin E, Bouadma L, Gault N, et al. Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen. Intensive Care Med. 2014; 40(7): 998–1005.
  46. Brasseur A, Hites M, Roisin S, et al. A high-dose aminoglycoside regimen combined with renal replacement therapy for the treatment of MDR pathogens: a proof-of-concept study. J Antimicrob Chemother. 2016; 71(5): 1386–1394.
  47. Tang W, Cho Y, Hawley CM, et al. The role of monitoring gentamicin levels in patients with gram-negative peritoneal dialysis-associated peritonitis. Perit Dial Int. 2014; 34(2): 219–226.
  48. Roger C, Nucci B, Molinari N, et al. Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations. Int J Antimicrob Agents. 2015; 46(1): 21–27.
  49. Allou N, Charifou Y, Augustin P, et al. A study to evaluate the first dose of gentamicin needed to achieve a peak plasma concentration of 30 mg/l in patients hospitalized for severe sepsis. Eur J Clin Microbiol Infect Dis. 2016; 35(7): 1187–1193.
  50. Somogyi A, Kong C, Sabto J, et al. Disposition and removal of metronidazole in patients undergoing haemodialysis. Eur J Clin Pharmacol. 1983; 25(5): 683–687.
  51. Hobbiss JH, Carr ND, Schofield PF. Are we using the correct dose of metronidazole in colorectal surgery? J R Soc Med. 1988; 81(2): 95–96.
  52. Grégoire N, Aranzana-Climent V, Magréault S, et al. Clinical Pharmacokinetics and Pharmacodynamics of Colistin. Clin Pharmacokinet. 2017; 56(12): 1441–1460.
  53. Bergen PJ, Landersdorfer CB, Zhang J, et al. Pharmacokinetics and pharmacodynamics of 'old' polymyxins: what is new? Diagn Microbiol Infect Dis. 2012; 74(3): 213–223.
  54. Honore PM, Jacobs R, Lochy S, et al. Acute respiratory muscle weakness and apnea in a critically ill patient induced by colistin neurotoxicity: key potential role of hemoadsorption elimination during continuous venovenous hemofiltration. Int J Nephrol Renovasc Dis. 2013; 6: 107–111.
  55. Karaiskos I, Friberg LE, Galani L, et al. Challenge for higher colistin dosage in critically ill patients receiving continuous venovenous haemodiafiltration. Int J Antimicrob Agents. 2016; 48(3): 337–341.
  56. Verdoodt A, Honore PM, Jacobs R, et al. High-dose colistin combined with continuous veno-venous haemofiltration for treatment of multidrug-resistant Gram-negative infection in critically ill patients. Abstract accepted for the 30th Annual Congress of the European Society of Intensive Care Medicine Vienna, Austria - September 23-27. 2017.
  57. Honore PM, Jacobs R, Joannes-Boyau O, et al. Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review. ASAIO J. 2013; 59(2): 99–106.
  58. van Zanten ARH, Polderman KH, van Geijlswijk IM, et al. Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort study. J Crit Care. 2008; 23(3): 422–430.
  59. Burgess DS. Use of pharmacokinetics and pharmacodynamics to optimize antimicrobial treatment of Pseudomonas aeruginosa infections. Clin Infect Dis. 2005; 40 Suppl 2: S99–104.
  60. Malone RS, Fish DN, Abraham E, et al. Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother. 2001; 45(10): 2949–2954.
  61. Shotwell MS, Madonia PN, Connor MJ, et al. Ciprofloxacin pharmacokinetics in critically ill patients receiving concomitant continuous venovenous hemodialysis. Am J Kidney Dis. 2015; 66(1): 173–175.
  62. Utrup TR, Mueller EW, Healy DP, et al. High-dose ciprofloxacin for serious gram-negative infection in an obese, critically ill patient receiving continuous venovenous hemodiafiltration. Ann Pharmacother. 2010; 44(10): 1660–1664.
  63. Davies SP, Azadian BS, Kox WJ, et al. Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis. Nephrol Dial Transplant. 1992; 7(8): 848–854.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

VM Media sp. z o.o. VM Group sp.k., Grupa Via Medica, Świętokrzyska 73 St., 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl