Importance of High Creatinine Clearance for Antibacterial Treatment in Sepsis

  • Jeffrey LipmanEmail author
  • Andrew Udy


Despite significant advances in organ support systems, and an improved understanding of the cellular and humoral mechanisms driving sepsis, there is still an unacceptably high in-hospital mortality rate associated with this syndrome. A key component to improving outcomes is the application of early antibacterial therapy, in sufficient dose and spectrum. This relies on an understanding of the relevant pharmacological properties of the chosen agent, in addition to the alterations in drug handling that are unique to the critically ill. In particular, the host response, in addition to the application of resuscitation fluids and vasoactive agents, can significantly alter renal drug elimination in this setting. A phenomenon termed augmented renal clearance, or ARC, is being increasingly recognised in subsets of critically ill patients. While plasma creatinine concentrations and other formulae estimating glomerular filtration lack sensitivity in identifying ARC, a measured creatinine clearance is a feasible and easily repeatable measure that can assist the clinician in identifying those at risk of sub-optimal drug exposure. Importantly, this should be routinely considered by the prescriber, in order to improve the chances of therapeutic success and reduce the opportunity for the selection of drug-resistant strains.


Intensive Care Unit Minimum Inhibitory Concentration Antibacterial Agent Therapeutic Drug Monitoring Renal Blood Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adam D, Zellner PR, Koeppe P et al (1989) Pharmacokinetics of ticarcillin/clavulanate in severely burned patients. J Antimicrob Chemother 24(Suppl B):121–129PubMedGoogle Scholar
  2. Adembri C, Fallani S, Cassetta MI et al (2008) Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion. Int J Antimicrob Agents 31:122–129PubMedGoogle Scholar
  3. Albanese J, Leone M, Garnier F et al (2004) Renal effects of norepinephrine in septic and nonseptic patients. Chest 126:534–539PubMedGoogle Scholar
  4. Andes D, van Ogtrop ML, Peng J et al (2002) In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob Agents Chemother 46:3484–3489PubMedGoogle Scholar
  5. Angus BJ, Smith MD, Suputtamongkol Y et al (2000) Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs. intermittent bolus injection in septicaemic melioidosis. Br J Clin Pharmacol 50:184–191PubMedGoogle Scholar
  6. Avant GR, Schenker S, Alford RH (1975) The effect of cirrhosis on the disposition and elimination of clindamycin. Am J Dig Dis 20:223–230PubMedGoogle Scholar
  7. Bagshaw SM, Uchino S, Bellomo R et al (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2:431–439PubMedGoogle Scholar
  8. Barbot A, Venisse N, Rayeh F et al (2003) Pharmacokinetics and pharmacodynamics of sequential intravenous and subcutaneous teicoplanin in critically ill patients without vasopressors. Intensive Care Med 29:1528–1534PubMedGoogle Scholar
  9. Baumann TJ, Staddon JE, Horst HM et al (1987) Minimum urine collection periods for accurate determination of creatinine clearance in critically ill patients. Clin Pharm 6:393–398PubMedGoogle Scholar
  10. Beckhouse MJ, Whyte IM, Byth PL et al (1988) Altered aminoglycoside pharmacokinetics in the critically ill. Anaesth Intensive Care 16:418–422PubMedGoogle Scholar
  11. Bellamy HM Jr, Bates BB, Reinarz JA (1966) Lincomycin metabolism in patients with hepatic insufficiency: effect of liver disease on lincomycin serum concentrations. Antimicrob Agents Chemother (Bethesda) 6:36–41Google Scholar
  12. Bellomo R, Wan L, May C (2008) Vasoactive drugs and acute kidney injury. Crit Care Med 36:S179–S186PubMedGoogle Scholar
  13. Benmalek F, Behforouz N, Benoist JF et al (1999) Renal effects of low-dose dopamine during vasopressor therapy for posttraumatic intracranial hypertension. Intensive Care Med 25:399–405PubMedGoogle Scholar
  14. Blaser J, Stone BB, Groner MC et al (1987) Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance. Antimicrob Agents Chemother 31:1054–1060PubMedGoogle Scholar
  15. Bonapace CR, White RL, Friedrich LV et al (1999) Pharmacokinetics of cefepime in patients with thermal burn injury. Antimicrob Agents Chemother 43:2848–2854PubMedGoogle Scholar
  16. Bone RC, Balk RA, Cerra FB et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655PubMedGoogle Scholar
  17. Bosch JP, Saccaggi A, Lauer A et al (1983) Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate. Am J Med 75:943–950PubMedGoogle Scholar
  18. Boselli E, Breilh D, Saux MC et al (2006) Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia. Intensive Care Med 32:2059–2062PubMedGoogle Scholar
  19. Bratton SL, Chestnut RM, Ghajar J et al (2007a) Guidelines for the management of severe traumatic brain injury. I. Blood pressure and oxygenation. J Neurotrauma 24(Suppl 1):S7–S13PubMedGoogle Scholar
  20. Bratton SL, Chestnut RM, Ghajar J et al (2007b) Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds. J Neurotrauma 24(Suppl 1):S59–S64PubMedGoogle Scholar
  21. Bratton SL, Chestnut RM, Ghajar J et al (2007c) Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma 24(Suppl 1):S14–S20PubMedGoogle Scholar
  22. Brier ME, Stalker DJ, Aronoff GR et al (2003) Pharmacokinetics of linezolid in subjects with renal dysfunction. Antimicrob Agents Chemother 47:2775–2780PubMedGoogle Scholar
  23. Brink AJ, Richards GA, Cummins RR et al (2008) Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis. Int J Antimicrob Agents 32:455–458PubMedGoogle Scholar
  24. Brink AJ, Richards GA, Schillack V et al (2009) Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis. Int J Antimicrob Agents 33:432–436PubMedGoogle Scholar
  25. Brown R, Babcock R, Talbert J et al (1980) Renal function in critically ill postoperative patients: sequential assessment of creatinine osmolar and free water clearance. Crit Care Med 8:68–72PubMedGoogle Scholar
  26. Bubalo JS, Munar MY, Cherala G et al (2009) Daptomycin pharmacokinetics in adult oncology patients with neutropenic fever. Antimicrob Agents Chemother 53:428–434PubMedGoogle Scholar
  27. Buijk SE, Mouton JW, Gyssens IC et al (2002) Experience with a once-daily dosing program of aminoglycosides in critically ill patients. Intensive Care Med 28:936–942PubMedGoogle Scholar
  28. Burkhardt O, Kumar V, Katterwe D et al (2007) Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: pharmacokinetics with special consideration of free-drug concentration. J Antimicrob Chemother 59:277–284PubMedGoogle Scholar
  29. Bustamante CI, Drusano GL, Tatem BA et al (1984) Postantibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother 26:678–682PubMedGoogle Scholar
  30. Calandra T, Cohen J (2005) The International Sepsis Forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 33:1538–1548PubMedGoogle Scholar
  31. Castellino P, Giordano C, Perna A et al (1988) Effects of plasma amino acid and hormone levels on renal hemodynamics in humans. Am J Physiol 255:F444–F449PubMedGoogle Scholar
  32. Chambers HE, Sande MA (1996) Goodman and Gillman’s The pharmacological basis of therapeutics. McGraw Hill, New YorkGoogle Scholar
  33. Cherry RA, Eachempati SR, Hydo L et al (2002) Accuracy of short-duration creatinine clearance determinations in predicting 24-hour creatinine clearance in critically ill and injured patients. J Trauma 53:267–271PubMedGoogle Scholar
  34. Claus B, Colpaert K, Hoste EA et al (2010) Increased glomerular filtration in the critically ill patient receiving anti-infective treatment. Crit Care 14(Suppl 1):P509Google Scholar
  35. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedGoogle Scholar
  36. Conil JM, Georges B, Mimoz O et al (2006a) Influence of renal function on trough serum concentrations of piperacillin in intensive care unit patients. Intensive Care Med 32:2063–2066PubMedGoogle Scholar
  37. Conil JM, Georges B, Breden A et al (2006b) Increased amikacin dosage requirements in burn patients receiving a once-daily regimen. Int J Antimicrob Agents 28:226–230PubMedGoogle Scholar
  38. Conil JM, Georges B, Lavit M et al (2007a) A population pharmacokinetic approach to ceftazidime use in burn patients: influence of glomerular filtration, gender and mechanical ventilation. Br J Clin Pharmacol 64:27–35PubMedGoogle Scholar
  39. Conil JM, Georges B, Fourcade O et al (2007b) Intermittent administration of ceftazidime to burns patients: influence of glomerular filtration. Int J Clin Pharmacol Ther 45:133–142PubMedGoogle Scholar
  40. Conil JM, Georges B, Fourcade O et al (2007c) Assessment of renal function in clinical practice at the bedside of burn patients. Br J Clin Pharmacol 63:583–594PubMedGoogle Scholar
  41. Conil JM, Georges B, Lavit M et al (2007d) Pharmacokinetics of ceftazidime and cefepime in burn patients: the importance of age and creatinine clearance. Int J Clin Pharmacol Ther 45:529–538PubMedGoogle Scholar
  42. Conil JM, Georges B, de Lussy A et al (2008) Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches. Int J Antimicrob Agents 32:505–510PubMedGoogle Scholar
  43. Craig W (1984) Pharmacokinetic and experimental data on beta-lactam antibiotics in the treatment of patients. Eur J Clin Microbiol 3:575–578PubMedGoogle Scholar
  44. Craig WA (1998) Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 26:1–10; quiz 11–12PubMedGoogle Scholar
  45. Craig WA (2001) Does the dose matter? Clin Infect Dis 33(Suppl 3):S233–S237PubMedGoogle Scholar
  46. Craig WA (2003) Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am 17:479–501PubMedGoogle Scholar
  47. Cruciani M, Gatti G, Lazzarini L et al (1996) Penetration of vancomycin into human lung tissue. J Antimicrob Chemother 38:865–869PubMedGoogle Scholar
  48. Dailly E, Kergueris MF, Pannier M et al (2003) Population pharmacokinetics of imipenem in burn patients. Fundam Clin Pharmacol 17:645–650PubMedGoogle Scholar
  49. Dailly E, Le Floch R, Deslandes G et al (2008) Influence of glomerular filtration rate on the clearance of vancomycin administered by continuous infusion in burn patients. Int J Antimicrob Agents 31:537–539PubMedGoogle Scholar
  50. Day NP, Phu NH, Mai NT et al (2000) Effects of dopamine and epinephrine infusions on renal hemodynamics in severe malaria and severe sepsis. Crit Care Med 28:1353–1362PubMedGoogle Scholar
  51. Del Favero A, Patoia L, Rosina R et al (1991) Pharmacokinetics and tolerability of teicoplanin in healthy volunteers after single increasing doses. Antimicrob Agents Chemother 35:2551–2557PubMedGoogle Scholar
  52. del Mar Fernandez de Gatta Garcia M, Revilla N, Calvo MV et al (2007) Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients. Intensive Care Med 33:279–285PubMedGoogle Scholar
  53. Dellinger RP, Levy MM, Carlet JM et al (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36:296–327PubMedGoogle Scholar
  54. Desjars P, Pinaud M, Bugnon D et al (1989) Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med 17:426–429PubMedGoogle Scholar
  55. Di Giantomasso D, May CN, Bellomo R (2002) Norepinephrine and vital organ blood flow. Intensive Care Med 28:1804–1809PubMedGoogle Scholar
  56. Di Giantomasso D, May CN, Bellomo R (2003a) Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis. Intensive Care Med 29:1774–1781PubMedGoogle Scholar
  57. Di Giantomasso D, May CN, Bellomo R (2003b) Vital organ blood flow during hyperdynamic sepsis. Chest 124:1053–1059PubMedGoogle Scholar
  58. Di Giantomasso D, Bellomo R, May CN (2005) The haemodynamic and metabolic effects of epinephrine in experimental hyperdynamic septic shock. Intensive Care Med 31:454–462PubMedGoogle Scholar
  59. Di Giantomasso D, Morimatsu H, Bellomo R et al (2006) Effect of low-dose vasopressin infusion on vital organ blood flow in the conscious normal and septic sheep. Anaesth Intensive Care 34:427–433PubMedGoogle Scholar
  60. Dolton M, Xu H, Cheong E et al (2010) Vancomycin pharmacokinetics in patients with severe burn injuries. Burns 36(4):469–76, Epub 2009 Oct 28PubMedGoogle Scholar
  61. Drusano GL (2003) Prevention of resistance: a goal for dose selection for antimicrobial agents. Clin Infect Dis 36:S42–S50PubMedGoogle Scholar
  62. Dunser MW, Ruokonen E, Pettila V et al (2009) Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care 13:R181PubMedGoogle Scholar
  63. Fernandez de Gatta MM, Fruns I, Hernandez JM et al (1993) Vancomycin pharmacokinetics and dosage requirements in hematologic malignancies. Clin Pharm 12:515–520PubMedGoogle Scholar
  64. Finfer S, Bellomo R, Lipman J et al (2004) Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units. Intensive Care Med 30:589–596PubMedGoogle Scholar
  65. Finfer S, Bellomo R, McEvoy S et al (2006) Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study. BMJ 333:1044PubMedGoogle Scholar
  66. Forrest A, Nix DE, Ballow CH et al (1993) Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 37:1073–1081PubMedGoogle Scholar
  67. Fuster-Lluch O, Geronimo-Pardo M, Peyro-Garcia R et al (2008) Glomerular hyperfiltration and albuminuria in critically ill patients. Anaesth Intensive Care 36:674–680PubMedGoogle Scholar
  68. Garrelts JC, Jost G, Kowalsky SF et al (1996) Ciprofloxacin pharmacokinetics in burn patients. Antimicrob Agents Chemother 40:1153–1156PubMedGoogle Scholar
  69. Gentry-Nielsen MJ, Olsen KM, Preheim LC (2002) Pharmacodynamic activity and efficacy of linezolid in a rat model of pneumococcal pneumonia. Antimicrob Agents Chemother 46:1345–1351PubMedGoogle Scholar
  70. Georges B, Conil JM, Cougot P et al (2005) Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen. Int J Clin Pharmacol Ther 43:360–369PubMedGoogle Scholar
  71. Goldstein A (1949) The interactions of drugs and plasma proteins. J Pharmacol Exp Ther 95(Pt. 2):102–165PubMedGoogle Scholar
  72. Gomez CM, Cordingly JJ, Palazzo MG (1999) Altered pharmacokinetics of ceftazidime in critically ill patients. Antimicrob Agents Chemother 43:1798–1802PubMedGoogle Scholar
  73. Gous A, Lipman J, Scribante J et al (2005) Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis. Int J Antimicrob Agents 26:50–55PubMedGoogle Scholar
  74. Graninger W, Zeitlinger M (2004) Clinical applications of levofloxacin for severe infections. Chemotherapy 50(Suppl 1):16–21PubMedGoogle Scholar
  75. Gwilt PR, Smith RB (1986) Protein binding and pharmacokinetics of lincomycin following intravenous administration of high doses. J Clin Pharmacol 26:87–90PubMedGoogle Scholar
  76. Hanes SD, Wood GC, Herring V et al (2000) Intermittent and continuous ceftazidime infusion for critically ill trauma patients. Am J Surg 179:436–440PubMedGoogle Scholar
  77. Herrera-Gutierrez ME, Seller-Perez G, Banderas-Bravo E et al (2007) Replacement of 24-h creatinine clearance by 2-h creatinine clearance in intensive care unit patients: a single-center study. Intensive Care Med 33:1900–1906PubMedGoogle Scholar
  78. Higa GM, Murray WE (1987) Alterations in aminoglycoside pharmacokinetics in patients with cancer. Clin Pharm 6:963–966PubMedGoogle Scholar
  79. Hoffken G, Lode H, Prinzing C et al (1985) Pharmacokinetics of ciprofloxacin after oral and parenteral administration. Antimicrob Agents Chemother 27:375–379PubMedGoogle Scholar
  80. Holmes CL, Walley KR, Chittock DR et al (2001) The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 27:1416–1421PubMedGoogle Scholar
  81. Hoste EA, Damen J, Vanholder RC et al (2005) Assessment of renal function in recently admitted critically ill patients with normal serum creatinine. Nephrol Dial Transplant 20:747–753PubMedGoogle Scholar
  82. Ibrahim EH, Sherman G, Ward S et al (2000) The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 118:146–155PubMedGoogle Scholar
  83. Ikawa K, Morikawa N, Ikeda K et al (2008) Pharmacokinetic-pharmacodynamic target attainment analysis of biapenem in adult patients: a dosing strategy. Chemotherapy 54:386–394PubMedGoogle Scholar
  84. Ishikawa M, Nishioka M, Hanaki N et al (2006) Postoperative metabolic and circulatory responses in patients that express SIRS after major digestive surgery. Hepatogastroenterology 53:228–233PubMedGoogle Scholar
  85. Joukhadar C, Klein N, Mayer BX et al (2002) Plasma and tissue pharmacokinetics of cefpirome in patients with sepsis. Crit Care Med 30:1478–1482PubMedGoogle Scholar
  86. Joynt GM, Lipman J, Gomersall CD et al (2001) The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients. J Antimicrob Chemother 47:421–429PubMedGoogle Scholar
  87. Kashuba AD, Nafziger AN, Drusano GL et al (1999) Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. Antimicrob Agents Chemother 43:623–629PubMedGoogle Scholar
  88. Kim KE, Onesti G, Ramirez O et al (1969) Creatinine clearance in renal disease. A reappraisal. Br Med J 4:11–14PubMedGoogle Scholar
  89. Kim KE, Onesti G, Swartz C (1972) Creatinine clearance and glomerular filtration rate. Br Med J 1:379–380PubMedGoogle Scholar
  90. Kitzes-Cohen R, Farin D, Piva G et al (2002) Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients. Int J Antimicrob Agents 19:105–110PubMedGoogle Scholar
  91. Knudsen JD, Fuursted K, Raber S et al (2000) Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection. Antimicrob Agents Chemother 44:1247–1254PubMedGoogle Scholar
  92. Kohl BA, Deutschman CS (2006) The inflammatory response to surgery and trauma. Curr Opin Crit Care 12:325–332PubMedGoogle Scholar
  93. Kollef MH, Sherman G, Ward S et al (1999) Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115:462–474PubMedGoogle Scholar
  94. Kumar A, Roberts D, Wood KE et al (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596PubMedGoogle Scholar
  95. Lamoth F, Buclin T, Csajka C et al (2009) Reassessment of recommended imipenem doses in febrile neutropenic patients with hematological malignancies. Antimicrob Agents Chemother 53:785–787PubMedGoogle Scholar
  96. Langenberg C, Wan L, Egi M et al (2006) Renal blood flow in experimental septic acute renal failure. Kidney Int 69:1996–2002PubMedGoogle Scholar
  97. Larsson AJ, Walker KJ, Raddatz JK et al (1996) The concentration-independent effect of monoexponential and biexponential decay in vancomycin concentrations on the killing of Staphylococcus aureus under aerobic and anaerobic conditions. J Antimicrob Chemother 38:589–597PubMedGoogle Scholar
  98. Latenser BA (2009) Critical care of the burn patient: the first 48 hours. Crit Care Med 37:2819–2826PubMedGoogle Scholar
  99. Levey AS, Bosch JP, Lewis JB et al (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470PubMedGoogle Scholar
  100. Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29:530–538PubMedGoogle Scholar
  101. Li C, Kuti JL, Nightingale CH et al (2005) Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection. J Antimicrob Chemother 56:388–395PubMedGoogle Scholar
  102. Lin J, Knight EL, Hogan ML et al (2003) A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol 14:2573–2580PubMedGoogle Scholar
  103. Lipman J, Scribante J, Gous AG et al (1998) Pharmacokinetic profiles of high-dose intravenous ciprofloxacin in severe sepsis. The Baragwanath Ciprofloxacin Study Group. Antimicrob Agents Chemother 42:2235–2239PubMedGoogle Scholar
  104. Lipman J, Gomersall CD, Gin T et al (1999a) Continuous infusion ceftazidime in intensive care: a randomized controlled trial. J Antimicrob Chemother 43:309–311PubMedGoogle Scholar
  105. Lipman J, Wallis SC, Rickard C (1999b) Low plasma cefepime levels in critically ill septic patients: pharmacokinetic modeling indicates improved troughs with revised dosing. Antimicrob Agents Chemother 43:2559–2561PubMedGoogle Scholar
  106. Lipman J, Wallis SC, Rickard CM et al (2001) Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing. Intensive Care Med 27:363–370PubMedGoogle Scholar
  107. Lipman J, Wallis SC, Boots RJ (2003) Cefepime versus cefpirome: the importance of creatinine clearance. Anesth Analg 97:1149–1154; table of contentsPubMedGoogle Scholar
  108. Llopis-Salvia P, Jimenez-Torres NV (2006) Population pharmacokinetic parameters of vancomycin in critically ill patients. J Clin Pharm Ther 31:447–454PubMedGoogle Scholar
  109. Lodise TP Jr, Lomaestro B, Drusano GL (2007) Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis 44:357–363PubMedGoogle Scholar
  110. Loirat P, Rohan J, Baillet A et al (1978) Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin. N Engl J Med 299:915–919PubMedGoogle Scholar
  111. Lorente L, Lorenzo L, Martin MM et al (2006) Meropenem by continuous versus intermittent infusion in ventilator-associated pneumonia due to gram-negative bacilli. Ann Pharmacother 40:219–223PubMedGoogle Scholar
  112. Lorente L, Jimenez A, Palmero S et al (2007) Comparison of clinical cure rates in adults with ventilator-associated pneumonia treated with intravenous ceftazidime administered by continuous or intermittent infusion: a retrospective, nonrandomized, open-label, historical chart review. Clin Ther 29:2433–2439PubMedGoogle Scholar
  113. Lorente L, Jimenez A, Martin MM et al (2009) Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents 33:464–468PubMedGoogle Scholar
  114. Lortholary O, Tod M, Rizzo N et al (1996) Population pharmacokinetic study of teicoplanin in severely neutropenic patients. Antimicrob Agents Chemother 40:1242–1247PubMedGoogle Scholar
  115. Lortholary O, Lefort A, Tod M et al (2008) Pharmacodynamics and pharmacokinetics of antibacterial drugs in the management of febrile neutropenia. Lancet Infect Dis 8:612–620PubMedGoogle Scholar
  116. Lovering AM, Vickery CJ, Watkin DS et al (1995) The pharmacokinetics of meropenem in surgical patients with moderate or severe infections. J Antimicrob Chemother 36:165–172PubMedGoogle Scholar
  117. Lowdin E, Odenholt I, Cars O (1998) In vitro studies of pharmacodynamic properties of vancomycin against Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother 42:2739–2744PubMedGoogle Scholar
  118. Lugo G, Castaneda-Hernandez G (1997) Relationship between hemodynamic and vital support measures and pharmacokinetic variability of amikacin in critically ill patients with sepsis. Crit Care Med 25:806–811PubMedGoogle Scholar
  119. MacGowan AP (1998) Pharmacodynamics, pharmacokinetics, and therapeutic drug monitoring of glycopeptides. Ther Drug Monit 20:473–477PubMedGoogle Scholar
  120. MacGowan AP (2003) Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother 51(Suppl 2):ii17–ii25PubMedGoogle Scholar
  121. Marik PE, Lipman J, Kobilski S et al (1991a) A prospective randomized study comparing once- versus twice-daily amikacin dosing in critically ill adult and paediatric patients. J Antimicrob Chemother 28:753–764PubMedGoogle Scholar
  122. Marik PE, Havlik I, Monteagudo FS et al (1991b) The pharmacokinetic of amikacin in critically ill adult and paediatric patients: comparison of once- versus twice-daily dosing regimens. J Antimicrob Chemother 27(Suppl C):81–89PubMedGoogle Scholar
  123. Marin C, Eon B, Saux P et al (1990) Renal effects of norepinephrine used to treat septic shock patients. Crit Care Med 18:282–285PubMedGoogle Scholar
  124. Martin JH, Fay MF, Ungerer JP (2009) eGFR–use beyond the evidence. Med J Aust 190:197–199PubMedGoogle Scholar
  125. Martin JH, Fay MF, Udy A et al (2010) Pitfalls of using estimations of glomerular filtration in an intensive care population. Intern Med J. doi: 10.1111/j.1445-5994.2010.02160.x
  126. McKinnon PS, Paladino JA, Schentag JJ (2008) Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T  >  MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections. Int J Antimicrob Agents 31:345–351PubMedGoogle Scholar
  127. McNabb JJ, Nightingale CH, Quintiliani R et al (2001) Cost-effectiveness of ceftazidime by continuous infusion versus intermittent infusion for nosocomial pneumonia. Pharmacotherapy 21:549–555PubMedGoogle Scholar
  128. Meagher AK, Ambrose PG, Grasela TH et al (2005a) Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent. Diagn Microbiol Infect Dis 52:165–171PubMedGoogle Scholar
  129. Meagher AK, Ambrose PG, Grasela TH et al (2005b) The pharmacokinetic and pharmacodynamic profile of tigecycline. Clin Infect Dis 41(Suppl 5):S333–S340PubMedGoogle Scholar
  130. Mimoz O, Rolland D, Adoun M et al (2006) Steady-state trough serum and epithelial lining fluid concentrations of teicoplanin 12 mg/kg per day in patients with ventilator-associated pneumonia. Intensive Care Med 32:775–779PubMedGoogle Scholar
  131. Mohr JF 3rd, Ostrosky-Zeichner L, Wainright DJ et al (2008) Pharmacokinetic evaluation of single-dose intravenous daptomycin in patients with thermal burn injury. Antimicrob Agents Chemother 52:1891–1893PubMedGoogle Scholar
  132. Moise-Broder PA, Forrest A, Birmingham MC et al (2004) Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet 43:925–942PubMedGoogle Scholar
  133. Moore RD, Lietman PS, Smith CR (1987) Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 155:93–99PubMedGoogle Scholar
  134. Mouton JW, den Hollander JG (1994) Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model. Antimicrob Agents Chemother 38:931–936PubMedGoogle Scholar
  135. Mouton JW, Vinks AA (2005) Pharmacokinetic/pharmacodynamic modelling of antibacterials in vitro and in vivo using bacterial growth and kill kinetics: the minimum inhibitory concentration versus stationary concentration. Clin Pharmacokinet 44:201–210PubMedGoogle Scholar
  136. Mouton JW, Vinks AA, Punt NC (1997) Pharmacokinetic-pharmacodynamic modeling of activity of ceftazidime during continuous and intermittent infusion. Antimicrob Agents Chemother 41:733–738PubMedGoogle Scholar
  137. Mueller SC, Henkel KO, Neumann J et al (1999) Perioperative antibiotic prophylaxis in maxillofacial surgery: penetration of clindamycin into various tissues. J Craniomaxillofac Surg 27:172–176PubMedGoogle Scholar
  138. Muralidharan G, Micalizzi M, Speth J et al (2005) Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob Agents Chemother 49:220–229PubMedGoogle Scholar
  139. Nakashima M, Uematsu T, Kosuge K et al (1995) Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans. Antimicrob Agents Chemother 39:2635–2640PubMedGoogle Scholar
  140. Nicolau DP (2003) Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling. J Infect Chemother 9:292–296PubMedGoogle Scholar
  141. Nicolau DP, McNabb J, Lacy MK et al (2001) Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia. Int J Antimicrob Agents 17:497–504PubMedGoogle Scholar
  142. Nix DE, Spivey JM, Norman A et al (1992) Dose-ranging pharmacokinetic study of ciprofloxacin after 200-, 300-, and 400-mg intravenous doses. Ann Pharmacother 26:8–10PubMedGoogle Scholar
  143. Noel G, Strauss R, Shah A et al (2008) Poster K-486. Ceftobiprole versus Ceftazidime combined with Linezolid for Treatment of Patients with Noscomial Pneumonia. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy & 46th Infectious Diseases Society of America Joint Scientific Meeting, October 25-28, Washington, USAGoogle Scholar
  144. Nuytinck HK, Offermans XJ, Kubat K et al (1988) Whole-body inflammation in trauma patients. An autopsy study. Arch Surg 123:1519–1524PubMedGoogle Scholar
  145. Nyhlen A, Ljungberg B, Nilsson-Ehle I (2001) Pharmacokinetics of ceftazidime in febrile neutropenic patients. Scand J Infect Dis 33:222–226PubMedGoogle Scholar
  146. Olsen KM, Rudis MI, Rebuck JA et al (2004) Effect of once-daily dosing vs. multiple daily dosing of tobramycin on enzyme markers of nephrotoxicity. Crit Care Med 32:1678–1682PubMedGoogle Scholar
  147. Orlando R, Floreani M, Padrini R et al (1998) Determination of inulin clearance by bolus intravenous injection in healthy subjects and ascitic patients: equivalence of systemic and renal clearances as glomerular filtration markers. Br J Clin Pharmacol 46:605–609PubMedGoogle Scholar
  148. Ott L, McClain CJ, Gillespie M et al (1994) Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma 11:447–472PubMedGoogle Scholar
  149. Pankuch GA, Jacobs MR, Appelbaum PC (2003) Postantibiotic effects of daptomycin against 14 staphylococcal and pneumococcal clinical isolates. Antimicrob Agents Chemother 47:3012–3014PubMedGoogle Scholar
  150. Parikh CR, Devarajan P (2008) New biomarkers of acute kidney injury. Crit Care Med 36:S159–S165PubMedGoogle Scholar
  151. Parrillo JE (1993) Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477PubMedGoogle Scholar
  152. Parrillo JE, Parker MM, Natanson C et al (1990) Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 113:227–242PubMedGoogle Scholar
  153. Pea F, Porreca L, Baraldo M et al (2000) High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures. J Antimicrob Chemother 45:329–335PubMedGoogle Scholar
  154. Pea F, Di Qual E, Cusenza A et al (2003a) Pharmacokinetics and pharmacodynamics of intravenous levofloxacin in patients with early-onset ventilator-associated pneumonia. Clin Pharmacokinet 42:589–598PubMedGoogle Scholar
  155. Pea F, Brollo L, Viale P et al (2003b) Teicoplanin therapeutic drug monitoring in critically ill patients: a retrospective study emphasizing the importance of a loading dose. J Antimicrob Chemother 51:971–975PubMedGoogle Scholar
  156. Pea F, Viale P, Candoni A et al (2004) Teicoplanin in patients with acute leukaemia and febrile neutropenia: a special population benefiting from higher dosages. Clin Pharmacokinet 43:405–415PubMedGoogle Scholar
  157. Pea F, Furlanut M, Negri C et al (2009) Prospectively validated dosing nomograms for maximizing the pharmacodynamics of vancomycin administered by continuous infusion in the critically ill patients: the Optivanco study. Antimicrob Agents Chemother 53(5):1863–7, Epub 2009 Feb 17PubMedGoogle Scholar
  158. Petersen PJ, Jacobus NV, Weiss WJ et al (1999) In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob Agents Chemother 43:738–744PubMedGoogle Scholar
  159. Piscitelli SC, Danziger LH, Rodvold KA (1992) Clarithromycin and azithromycin: new macrolide antibiotics. Clin Pharm 11:137–152PubMedGoogle Scholar
  160. Poggio ED, Nef PC, Wang X et al (2005a) Performance of the Cockcroft-Gault and modification of diet in renal disease equations in estimating GFR in ill hospitalized patients. Am J Kidney Dis 46:242–252PubMedGoogle Scholar
  161. Poggio ED, Wang X, Greene T et al (2005b) Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol 16:459–466PubMedGoogle Scholar
  162. Preston SL, Drusano GL, Berman AL et al (1998) Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials. JAMA 279:125–129PubMedGoogle Scholar
  163. Prins JM, Buller HR, Kuijper EJ et al (1993) Once versus thrice daily gentamicin in patients with serious infections. Lancet 341:335–339PubMedGoogle Scholar
  164. Rea RS, Capitano B, Bies R et al (2008) Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit 30:674–681PubMedGoogle Scholar
  165. Rebuck JA, Fish DN, Abraham E (2002) Pharmacokinetics of intravenous and oral levofloxacin in critically ill adults in a medical intensive care unit. Pharmacotherapy 22:1216–1225PubMedGoogle Scholar
  166. Redl-Wenzl EM, Armbruster C, Edelmann G et al (1993) The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med 19:151–154PubMedGoogle Scholar
  167. Rello J, Sole-Violan J, Sa-Borges M et al (2005) Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides. Crit Care Med 33:1983–1987PubMedGoogle Scholar
  168. Rice TW, Bernard GR (2005) Therapeutic intervention and targets for sepsis. Annu Rev Med 56:225–248PubMedGoogle Scholar
  169. Rivers E, Nguyen B, Havstad S et al (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedGoogle Scholar
  170. Roberts JA, Lipman J (2006) Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis. Clin Pharmacokinet 45:755–773PubMedGoogle Scholar
  171. Roberts JA, Lipman J (2007) Optimizing use of beta-lactam antibiotics in the critically ill. Semin Respir Crit Care Med 28:579–585PubMedGoogle Scholar
  172. Roberts JA, Paratz J, Paratz E et al (2007a) Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role. Int J Antimicrob Agents 30:11–18PubMedGoogle Scholar
  173. Roberts JA, Boots R, Rickard CM et al (2007b) Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study. J Antimicrob Chemother 59:285–291PubMedGoogle Scholar
  174. Roberts JA, Kruger P, Paterson DL et al (2008) Antibiotic resistance–what’s dosing got to do with it? Crit Care Med 36:2433–2440PubMedGoogle Scholar
  175. Roberts JA, Kirkpatrick CM, Roberts MS et al (2009a) Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 64(1):142–150, Epub 2009 Apr 27PubMedGoogle Scholar
  176. Roberts JA, Roberts MS, Robertson TA et al (2009b) Piperacillin penetration into tissue of critically ill patients with sepsis–bolus versus continuous administration? Crit Care Med 37:926–933PubMedGoogle Scholar
  177. Roberts JA, Webb SA, Paterson DL et al (2009c) A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med 37:2071–2078PubMedGoogle Scholar
  178. Romano S, Fdez de Gatta MM, Calvo MV et al (1999) Population pharmacokinetics of amikacin in patients with haematological malignancies. J Antimicrob Chemother 44:235–242PubMedGoogle Scholar
  179. Roos JF, Lipman J, Kirkpatrick CM (2007) Population pharmacokinetics and pharmacodynamics of cefpirome in critically ill patients against gram-negative bacteria. Intensive Care Med 33:781–788PubMedGoogle Scholar
  180. Rule AD, Larson TS, Bergstralh EJ et al (2004) Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 141:929–937PubMedGoogle Scholar
  181. Rybak MJ (2006) The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis 42(Suppl 1):S35–S39PubMedGoogle Scholar
  182. Safdar N, Andes D, Craig WA (2004) In vivo pharmacodynamic activity of daptomycin. Antimicrob Agents Chemother 48:63–68PubMedGoogle Scholar
  183. Schentag JJ (1999) Antimicrobial action and pharmacokinetics/pharmacodynamics: the use of AUIC to improve efficacy and avoid resistance. J Chemother 11:426–439PubMedGoogle Scholar
  184. Schriever CA, Fernandez C, Rodvold KA et al (2005) Daptomycin: a novel cyclic lipopeptide antimicrobial. Am J Health Syst Pharm 62:1145–1158PubMedGoogle Scholar
  185. Sevillano D, Alou L, Aguilar L et al (2006) Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic simulation. J Antimicrob Chemother 57:1128–1133PubMedGoogle Scholar
  186. Shikuma LR, Ackerman BH, Weaver RH et al (1990a) Effects of treatment and the metabolic response to injury on drug clearance: a prospective study with piperacillin. Crit Care Med 18:37–41PubMedGoogle Scholar
  187. Shikuma LR, Ackerman BH, Weaver RH et al (1990b) Thermal injury effects on drug disposition: a prospective study with piperacillin. J Clin Pharmacol 30:632–637PubMedGoogle Scholar
  188. Shipley RE, Study RS (1951) Changes in renal blood flow, extraction of inulin, glomerular filtration rate, tissue pressure and urine flow with acute alterations of renal artery blood pressure. Am J Physiol 167:676–688PubMedGoogle Scholar
  189. Sladen RN, Endo E, Harrison T (1987) Two-hour versus 22-hour creatinine clearance in critically ill patients. Anesthesiology 67:1013–1016PubMedGoogle Scholar
  190. Snider RD, Kruse JA, Bander JJ et al (1995) Accuracy of estimated creatinine clearance in obese patients with stable renal function in the intensive care unit. Pharmacotherapy 15:747–753PubMedGoogle Scholar
  191. Stevens LA, Coresh J, Greene T et al (2006) Assessing kidney function–measured and estimated glomerular filtration rate. N Engl J Med 354:2473–2483PubMedGoogle Scholar
  192. Sun HK, Kuti JL, Nicolau DP (2005) Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. Crit Care Med 33:2222–2227PubMedGoogle Scholar
  193. Sunder-Plassmann G, Horl WH (2004) A critical appraisal for definition of hyperfiltration. Am J Kidney Dis 43:396; author reply 396–397PubMedGoogle Scholar
  194. Tam VH, McKinnon PS, Akins RL et al (2003) Pharmacokinetics and pharmacodynamics of cefepime in patients with various degrees of renal function. Antimicrob Agents Chemother 47:1853–1861PubMedGoogle Scholar
  195. Thallinger C, Buerger C, Plock N et al (2008) Effect of severity of sepsis on tissue concentrations of linezolid. J Antimicrob Chemother 61:173–176PubMedGoogle Scholar
  196. Thomas DM, Coles GA, Williams JD (1994) What does the renal reserve mean? Kidney Int 45:411–416PubMedGoogle Scholar
  197. Thomas JK, Forrest A, Bhavnani SM et al (1998) Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy. Antimicrob Agents Chemother 42:521–527PubMedGoogle Scholar
  198. Toschlog EA, Blount KP, Rotondo MF et al (2003) Clinical predictors of subtherapeutic aminoglycoside levels in trauma patients undergoing once-daily dosing. J Trauma 55:255–260; discussion 260–252PubMedGoogle Scholar
  199. Turnidge JD (1998) The pharmacodynamics of beta-lactams. Clin Infect Dis 27:10–22PubMedGoogle Scholar
  200. Udy A, Boots R, Senthuran S et al (2010a) Augmented creatinine clearance in traumatic brain injury. Anesth Analg 111:1505–1510Google Scholar
  201. Udy AA, Putt MT, Shanmugathasan S et al (2010b) Augmented renal clearance in the Intensive Care Unit: an illustrative case series. Int J Antimicrob Agents. doi: 10.1016/j.ijantimicag.2010.02.013
  202. Udy AA, Roberts JA, Boots RJ et al (2010c) Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet 49:1–16PubMedGoogle Scholar
  203. Valdes ME, Landau SE, Shah DM et al (1979) Increased glomerular filtration rate following mannitol administration in man. J Surg Res 26:473–477PubMedGoogle Scholar
  204. Van Dalen R, Vree T, Baars IM (1987) Influence of protein binding and severity of illness on renal elimination of four cephalosporin drugs in intensive-care patients. Pharm Weekbl Sci 9:98–103PubMedGoogle Scholar
  205. Vogelman BS, Craig WA (1985) Postantibiotic effects. J Antimicrob Chemother 15(Suppl A):37–46PubMedGoogle Scholar
  206. Vogelman B, Craig WA (1986) Kinetics of antimicrobial activity. J Pediatr 108:835–840PubMedGoogle Scholar
  207. Wan L, Bellomo R, May CN (2007) The effects of normal and hypertonic saline on regional blood flow and oxygen delivery. Anesth Analg 105:141–147PubMedGoogle Scholar
  208. Wilson AP (2000) Clinical pharmacokinetics of teicoplanin. Clin Pharmacokinet 39:167–183PubMedGoogle Scholar
  209. Wysocki M, Delatour F, Faurisson F et al (2001) Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother 45:2460–2467PubMedGoogle Scholar
  210. Young RJ, Lipman J, Gin T et al (1997) Intermittent bolus dosing of ceftazidime in critically ill patients. J Antimicrob Chemother 40:269–273PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Critical Care and AnaesthesiologyThe University of QueenslandBrisbaneAustralia
  2. 2.Department of Intensive Care MedicineRoyal Brisbane and Women’s HospitalHerston, BrisbaneAustralia
  3. 3.Department of Intensive Care MedicineRoyal Brisbane and Women’s HospitalHerston, BrisbaneAustralia
  4. 4.Burns, Trauma and Critical Care Research CenterThe University of QueenslandBrisbaneAustralia

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