Severe sepsis often leads to multiple organ dysfunction syndromes (MODS) with acute kidney injury (AKI). AKI affects approximately, 35% of Intensive Care Unit patients, and most of these are due to sepsis. Mortality rate of sepsis-induced AKI is high. Inappropriate use of antimicrobials may be responsible for higher therapeutic failure, mortality rates, costs and toxicity as well as the emergence of resistance. Antimicrobial treatment is particularly difficult due to altered pharmacokinetic profile, dynamic changes in patient′s clinical status and, in many cases, need for renal replacement therapy. This article aims to describe the appropriate antimicrobial dosing and reviews the factors contributing to the difficulties in establishing precise guidelines for antimicrobial dosing in sepsis-induced AKI patients. Search strategy: Text material was collected by systematic search in PubMed, Google (1978-2013) for original articles.
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. 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 1992;101:1644-55.
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.
Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 1995;273:117-23.
Ostermann M, Chang RW. Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med 2007;35:1837-43.
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.
Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Crit Care 2006;10:R73.
Angus DC, Wax RS. Epidemiology of sepsis: An update. Crit Care Med 2001;29:S109-16.
Kohli HS, Bhat A, Jairam A, Aravindan AN, Sud K, Jha V, et al. Predictors of mortality in acute renal failure in a developing country: A prospective study. Ren Fail 2007;29:463-9.
Kaul A, Sharma RK, Tripathi R, Suresh KJ, Bhatt S, Prasad N. Spectrum of community-acquired acute kidney injury in India: A retrospective study. Saudi J Kidney Dis Transpl 2012;23:619-28.
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.
Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, et al. Insufficient ß-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care 2010;14:R126.
Taccone FS, Laterre PF, Spapen H, Dugernier T, Delattre I, Layeux B, et al. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care 2010;14:R53.
John AK, Norbert L, Peter A, Rashad SB, Burdmann EA, Goldstein SL, et al. KDIGO clinical practice guidelines for acute kidney injury. Kidney Int Suppl 2012;2:19-36.
Piccinni P, Cruz DN, Gramaticopolo S, Garzotto F, Dal Santo M, Aneloni G, et al. Prospective multicenter study on epidemiology of acute kidney injury in the ICU: A critical care nephrology Italian collaborative effort (NEFROINT). Minerva Anestesiol 2011;77:1072-83.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-96.
Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 2009;37:840-51.
Roberts JA, Joynt GM, Choi GY, Gomersall CD, Lipman J. How to optimise antimicrobial prescriptions in the intensive care unit: Principles of individualised dosing using pharmacokinetics and pharmacdynamics. Int J Antimicrob Agents 2012;39:187-92.
Ulldemolins M, Roberts JA, Lipman J, Rello J. Antibiotic dosing in multiple organ dysfunction syndrome. Chest 2011;139:1210-20.
Gulyassy PF, Depner TA. Impaired binding of drugs and endogenous ligands in renal diseases. Am J Kidney Dis 1983;2:578-601.
Suh B, Craig WA, England AC, Elliott RL. Effect of free fatty acids on protein binding of antimicrobial agents. J Infect Dis 1981;143:609-16.
Craig WA, Suh B. Changes in protein binding during disease. Scand J Infect Dis Suppl 1978:239-44.
Golper TA, Bennett WM. Drug removal by continuous arteriovenous haemofiltration. A review of the evidence in poisoned patients. Med Toxicol Adverse Drug Exp 1988;3:341-9.
Schetz M. Drug dosing in continuous renal replacement therapy: General rules. Curr Opin Crit Care 2007;13:645-51.
Scaglione F, Paraboni L. Influence of pharmacokinetics/pharmacodynamics of antibacterials in their dosing regimen selection. Expert Rev Anti Infect Ther 2006;4:479-90.
Choi G, Gomersall CD, Tian Q, Joynt GM, Freebairn R, Lipman J. Principles of antibacterial dosing in continuous renal replacement therapy. Crit Care Med 2009;37:2268-82.
Patel K, Roberts JA, Lipman J, Tett SE, Deldot ME, Kirkpatrick CM. Population pharmacokinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: Using Monte Carlo simulations to predict doses for specified pharmacodynamic targets. Antimicrob Agents Chemother 2011;55:5868-73.
Ulldemolins M, Roberts JA, Rello J, Paterson DL, Lipman J. The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill patients. Clin Pharmacokinet 2011;50:99-110.
Scaglione F. Can PK/PD be used in everyday clinical practice. Int J Antimicrob Agents 2002;19:349-53.
Fish DN, Teitelbaum I, Abraham E. Pharmacokinetics and pharmacodynamics of imipenem during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother 2005;49:2421-8.
Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and Applications. 3 rd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 1995.
Craig WA. Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998;26:1-10.
Craig WA. Does the dose matter? Clin Infect Dis 2001;33 Suppl 3:S233-7.
Craig WA. Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am 2003;17:479-501.
Pea F, Viale P. The antimicrobial therapy puzzle: Could pharmacokinetic-pharmacodynamic relationships be helpful in addressing the issue of appropriate pneumonia treatment in critically ill patients? Clin Infect Dis 2006;42:1764-71.
Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, et al. Continuous renal replacement therapy: A worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive Care Med 2007;33:1563-70.
Wright SE, Bodenham A, Short AI, Turney JH. The provision and practice of renal replacement therapy on adult intensive care units in the United Kingdom. Anaesthesia 2003;58:1063-9.
Mushatt DM, Mihm LB, Dreisbach AW, Simon EE. Antibiotic dosing in slow extended daily dialysis. Clin Infect Dis 2009;49:433-7.
McKenzie C. Antibiotic dosing in critical illness. J Antimicrob Chemother 2011;66 Suppl 2:ii25-31.
Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: Implications for antibacterial dosing in the critically ill. Clin Pharmacokinet 2010;49:1-16.
Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother 1999;43:1549-55.
Andes D, van Ogtrop ML, Peng J, Craig WA. In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob Agents Chemother 2002;46:3484-9.
Bergner R, Hoffmann M, Riedel KD, Mikus G, Henrich DM, Haefeli WE, et al. Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): Need for a high daily dose of 800 mg. Nephrol Dial Transplant 2006;21:1019-23.
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.
Ahern JW, Possidente CJ, Hood V, Alston WK. Cefazolin dosing protocol for patients receiving long-term hemodialysis. Am J Health Syst Pharm 2003;60:178-81.
Aronoff GR, Bennett WM, Berns JS. Drug prescribing in renal failure: Dosing guidelines for adults and children. American College of Physicians. 5 th ed. Philadelphia: PA; 2007. p. 97.
Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, 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;66:82-98.
Vilay AM, Grio M, Depestel DD, Sowinski KM, Gao L, Heung M, et al. Daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis. Crit Care Med 2011;39:19-25.
Salama NN, Segal JH, Churchwell MD, Patel JH, Gao L, Heung M, et al. Intradialytic administration of daptomycin in end stage renal disease patients on hemodialysis. Clin J Am Soc Nephrol 2009;4:1190-4.
Adembri C, Fallani S, Cassetta MI, Arrigucci S, Ottaviano A, Pecile P, et al. Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: Intermittent versus continuous infusion. Int J Antimicrob Agents 2008;31:122-9.
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-74.
Scaglione F, Paraboni L. Pharmacokinetics/pharmacodynamics of antibacterials in the intensive care unit: Setting appropriate dosing regimens. Int J Antimicrob Agents 2008;32:294-301.
Hooper D. Quinolones. In: Mandell GL, Bennett JE, Dolin RM, editors. Douglas, Bennett′s. Principles and Practice of Infectious Diseases. 5 th ed. Philadelphia: Churchill Livingstone; 2000. p. 404-23.
Greer ND. Tigecycline (Tygacil): The first in the glycylcycline class of antibiotics. Proc (Bayl Univ Med Cent) 2006;19:155-61.
Robert SP. Health care professionals: Bacteria and antibacterial drugs. The Merck Manual. 19 th ed. NJ, USA: Merck and Co. Publication; 2013.