Appropriate Antimicrobial Therapy in Critically Ill Patients

  • Fekade B. Sime
  • Jason A. Roberts
Part of the Hot Topics in Acute Care Surgery and Trauma book series (HTACST)


Appropriate antibiotic therapy in the critically ill requires more specialised considerations than just selecting the most suitable antibiotic and adhering to traditional dosing guidelines. Unfortunately, most of the guideline recommendations are based on research that either underrepresent or exclude critically ill patients. The pathophysiology of critical illness, as in the case of intraabdominal sepsis, has many unique features unseen in noncritically ill patients. These include inconsistent changes in important physiological phenomena that govern drug disposition. It follows that the disposition of several antimicrobials is markedly different and variable in the critically ill relative to that described by the drug development clinical trials often conducted on healthy volunteers or noncritically ill patients. Drug disposition determines how much of a dose to administer; thus altered disposition simply means that the dose required for critically ill patients to ensure optimal effects is likely to be different. Indeed several clinical studies have illustrated that standard doses of antimicrobials such as beta-lactam antibiotics, vancomycin, aminoglycosides, fluoroquinolones and fluconazole are largely inadequate in critically ill patients due to high variability of changes in disposition. Therefore, dosing regimens should be tailored to the unique dosing requirements of individual patients. This chapter presents a discussion on the current understandings of special dosing considerations for appropriate antimicrobials therapy of critically ill patients with intraabdominal sepsis.


  1. 1.
    Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133–64.PubMedCrossRefGoogle Scholar
  2. 2.
    Eckmann C, Dryden M, Montravers P, Kozlov R, Sganga G. Antimicrobial treatment of “complicated” intra-abdominal infections and the new IDSA guidelines? A commentary and an alternative European approach according to clinical definitions. Eur J Med Res. 2011;16(3):115–26.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Sime FB, Roberts MS, Roberts JA. Optimization of dosing regimens and dosing in special populations. Clin Microbiol Infect. 2015;21(10):886–93.PubMedCrossRefGoogle Scholar
  4. 4.
    Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, Hope WW, Farkas A, Neely MN, Schentag JJ, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Turnidge JD. The pharmacodynamics of beta-lactams. Clin Infect Dis. 1998;27(1):10–22.PubMedCrossRefGoogle Scholar
  6. 6.
    Turnidge J. Pharmacodynamics and dosing of aminoglycosides. Infect Dis Clin N Am. 2003;17(3):503–28. vCrossRefGoogle Scholar
  7. 7.
    Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26(1):1–10. quiz 11–2PubMedCrossRefGoogle Scholar
  8. 8.
    Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient – concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev. 2014;77:3–11.PubMedCrossRefGoogle Scholar
  9. 9.
    Roberts JA, Kruger P, Paterson DL, Lipman J. Antibiotic resistance—what’s dosing got to do with it? Crit Care Med. 2008;36(8):2433–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Dietch ZC, Shah PM, Sawyer RG. Advances in intra-abdominal sepsis: what is new? Curr Infect Dis Rep. 2015;17(8):497.PubMedCrossRefGoogle Scholar
  11. 11.
    Solomkin J, Hershberger E, Miller B, Popejoy M, Friedland I, Steenbergen J, Yoon M, Collins S, Yuan G, Barie PS, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin Infect Dis. 2015;60(10):1462–71.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Zhanel GG, Cheung D, Adam H, Zelenitsky S, Golden A, Schweizer F, Gorityala B, Lagace-Wiens PR, Walkty A, Gin AS, et al. Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs. 2016;76(5):567–88.PubMedCrossRefGoogle Scholar
  13. 13.
    Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, et al. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58(8):1072–83.PubMedCrossRefGoogle Scholar
  14. 14.
    Xiao Z, Wilson C, Robertson HL, Roberts DJ, Ball CG, Jenne CN, Kirkpatrick AW. Inflammatory mediators in intra-abdominal sepsis or injury – a scoping review. Crit Care. 2015;19:373.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Wakefield CH, Barclay GR, Fearon KC, Goldie AS, Ross JA, Grant IS, Ramsay G, Howie JC. Proinflammatory mediator activity, endogenous antagonists and the systemic inflammatory response in intra-abdominal sepsis. Scottish Sepsis Intervention Group. Br J Surg. 1998;85(6):818–25.PubMedCrossRefGoogle Scholar
  16. 16.
    Sautner T, Gotzinger P, Redl-Wenzl EM, Dittrich K, Felfernig M, Sporn P, Roth E, Fugger R. Does reoperation for abdominal sepsis enhance the inflammatory host response? Arch Surg. 1997;132(3):250–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Shimamoto Y, Fukuda T, Tanaka K, Komori K, Sadamitsu D. Systemic inflammatory response syndrome criteria and vancomycin dose requirement in patients with sepsis. Intensive Care Med. 2013;39(7):1247–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Udy AA, Baptista JP, Lim NL, Joynt GM, Jarrett P, Wockner L, Boots RJ, Lipman J. Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations. Crit Care Med. 2014;42(3):520–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Chung DR, Kasper DL, Panzo RJ, Chitnis T, Grusby MJ, Sayegh MH, Tzianabos AO. CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol. 2003;170(4):1958–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Bartlett JG. Experimental aspects of intraabdominal abscess. Am J Med. 1984;76(5A):91–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Barza M, Cuchural G. General principles of antibiotic tissue penetration. J Antimicrob Chemother. 1985;15(Suppl A):59–75.PubMedCrossRefGoogle Scholar
  22. 22.
    Easter JL, Hague BA, Brumbaugh GW, Nguyen J, Chaffin MK, Honnas CM, Kemper DL. Effects of postoperative peritoneal lavage on pharmacokinetics of gentamicin in horses after celiotomy. Am J Vet Res. 1997;58(10):1166–70.PubMedGoogle Scholar
  23. 23.
    Suarez de la Rica A, Maseda E, Anillo V, Hernandez-Gancedo C, Lopez-Tofiño A, Villagran M, Gilsanz F. Risk factors for acute kidney injury in patients with complicated intra-abdominal infection. Crit Care. 2015;19(Suppl 1):P284.PubMedCentralCrossRefGoogle Scholar
  24. 24.
    Jamal JA, Udy AA, Lipman J, Roberts JA. The impact of variation in renal replacement therapy settings on piperacillin, meropenem, and vancomycin drug clearance in the critically ill: an analysis of published literature and dosing regimens. Crit Care Med. 2014;42(7):1640–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Blot S, Koulenti D, Akova M, Bassetti M, De WJJ, Dimopoulos G, Kaukonen KM, Martin C, Montravers P, Rello J, et al. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study. Crit Care. 2014;18(3):R99.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Sakoulas G, Gold HS, Cohen RA, Venkataraman L, Moellering RC, Eliopoulos GM. Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia. J Antimicrob Chemother. 2006;57(4):699–704.PubMedCrossRefGoogle Scholar
  27. 27.
    Howden BP, Ward PB, Charles PG, Korman TM, Fuller A, du Cros P, Grabsch EA, Roberts SA, Robson J, Read K, et al. Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis. 2004;38(4):521–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Cheong JY, Makmor-Bakry M, Lau CL, Abdul Rahman R. The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients. S Afr Med J. 2012;102(7):616–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Roberts JA, Taccone FS, Udy AA, Vincent JL, Jacobs F, Lipman J. Vancomycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother. 2011;55(6):2704–9.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    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):1–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Sinnollareddy MG, Roberts MS, Lipman J, Lassig-Smith M, Starr T, Robertson T, Peake SL, Roberts JA. In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis. Antimicrob Agents Chemother. 2016;60(2):827–32.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Leedahl DD, Personett HA, Gajic O, Kashyap R, Schramm GE. Predictors of mortality among bacteremic patients with septic shock receiving appropriate antimicrobial therapy. BMC Anesthesiol. 2014;14:21.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Galandiuk S, Lamos J, Montgomery W, Young S, Polk HC Jr. Antibiotic penetration of experimental intra-abdominal abscesses. Am Surg. 1995;61(6):521–5.PubMedGoogle Scholar
  34. 34.
    Shea KM, Cheatham SC, Smith DW, Wack MF, Sowinski KM, Kays MB. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009;43(11):1747–54.PubMedCrossRefGoogle Scholar
  35. 35.
    Sime FB, Roberts MS, Tiong IS, Gardner JH, Lehman S, Peake SL, Hahn U, Warner MS, Roberts JA. Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial. J Antimicrob Chemother. 2015;70(8):2369–75.PubMedCrossRefGoogle Scholar
  36. 36.
    De WJ, Carlier M, Hoste E, Depuydt P, Decruyenaere J, Wallis SC, Lipman J, Roberts JA. Extended versus bolus infusion of meropenem and piperacillin: a pharmacokinetic analysis. Minerva Anestesiol. 2014;80(12):1302–9.Google Scholar
  37. 37.
    Felton TW, Hope WW, Lomaestro BM, Butterfield JM, Kwa AL, Drusano GL, Lodise TP. Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections. Antimicrob Agents Chemother. 2012;56(8):4087–94.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Cutro SR, Holzman R, Dubrovskaya Y, Chen XJ, Ahuja T, Scipione MR, Chen D, Papadopoulos J, Phillips MS, Mehta SA. Extended-infusion versus standard-infusion piperacillin-tazobactam for sepsis syndromes at a tertiary medical center. Antimicrob Agents Chemother. 2014;58(8):4470–5.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis. 2007;44(3):357–63.PubMedCrossRefGoogle Scholar
  40. 40.
    Patel GW, Patel N, Lat A, Trombley K, Enbawe S, Manor K, Smith R, Lodise TP Jr. Outcomes of extended infusion piperacillin/tazobactam for documented Gram-negative infections. Diagn Microbiol Infect Dis. 2009;64(2):236–40.PubMedCrossRefGoogle Scholar
  41. 41.
    Yost RJ, Cappelletty DM, Group RS. The retrospective cohort of extended-infusion Piperacillin-Tazobactam (RECEIPT) study: a multicenter study. Pharmacotherapy. 2011;31(8):767–75.PubMedCrossRefGoogle Scholar
  42. 42.
    Feher C, Rovira M, Soriano A, Esteve J, Martinez JA, Marco F, Carreras E, Martinez C, Fernandez-Aviles F, Suarez-Lledo M, et al. Effect of meropenem administration in extended infusion on the clinical outcome of febrile neutropenia: a retrospective observational study. J Antimicrob Chemother. 2014;69(9):2556–62.PubMedCrossRefGoogle Scholar
  43. 43.
    Bauer KA, West JE, O'Brien JM, Goff DA. Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2013;57(7):2907–12.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Brunetti L, Poustchi S, Cunningham D, Toscani M, Nguyen J, Lim J, Ding Y, Nahass RG. Clinical and economic impact of empirical extended-infusion piperacillin-tazobactam in a community medical center. Ann Pharmacother. 2015;49(7):754–60.PubMedCrossRefGoogle Scholar
  45. 45.
    Yang H, Zhang C, Zhou Q, Wang Y, Chen L. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. PLoS One. 2015;10(1):e0116769.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Carlier M, Carrette S, Stove V, Verstraete AG, De Waele JJ. Does consistent piperacillin dosing result in consistent therapeutic concentrations in critically ill patients? A longitudinal study over an entire antibiotic course. Int J Antimicrob Agents. 2014;43(5):470–3.PubMedCrossRefGoogle Scholar
  47. 47.
    Mouton JW, Vinks AA. Is continuous infusion of beta-lactam antibiotics worthwhile?—efficacy and pharmacokinetic considerations. J Antimicrob Chemother. 1996;38(1):5–15.PubMedCrossRefGoogle Scholar
  48. 48.
    Mouton JW, Vinks AA. Continuous infusion of beta-lactams. Curr Opin Crit Care. 2007;13(5):598–606.PubMedCrossRefGoogle Scholar
  49. 49.
    Mohd Hafiz AA, Staatz CE, Kirkpatrick CM, Lipman J, Roberts JA. Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics. Minerva Anestesiol. 2012;78(1):94–104.PubMedGoogle Scholar
  50. 50.
    Roberts JA, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Piperacillin penetration into tissue of critically ill patients with sepsis—bolus versus continuous administration? Crit Care Med. 2009;37(3):926–33.PubMedCrossRefGoogle Scholar
  51. 51.
    Buijk SLCE, Gyssens IC, Mouton JW, Van Vliet A, Verbrugh HA, Bruining HA. Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections. J Antimicrob Chemother. 2002;49(1):121–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Roberts JA, Lipman J, Blot S, Rello J. Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients? Curr Opin Crit Care. 2008;14(4):390–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Mercer-Jones MA, Hadjiminas DJ, Heinzelmann M, Peyton J, Cook M, Cheadle WG. Continuous antibiotic treatment for experimental abdominal sepsis: effects on organ inflammatory cytokine expression and neutrophil sequestration. Br J Surg. 1998;85(3):385–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Lau WK, Mercer D, Itani KM, Nicolau DP, Kuti JL, Mansfield D, Dana A. Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection. Antimicrob Agents Chemother. 2006;50(11):3556–61.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Li C, Kuti JL, Nightingale CH, Mansfield DL, Dana A, Nicolau DP. Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection. J Antimicrob Chemother. 2005;56(2):388–95.PubMedCrossRefGoogle Scholar
  56. 56.
    Tessier PR, Nicolau DP, Onyeji CO, Nightingale CH. Pharmacodynamics of intermittent- and continuous-infusion cefepime alone and in combination with once-daily tobramycin against Pseudomonas aeruginosa in an in vitro infection model. Chemotherapy. 1999;45(4):284–95.PubMedCrossRefGoogle Scholar
  57. 57.
    Mouton JW, den Hollander JG. Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model. Antimicrob Agents Chemother. 1994;38(5):931–6.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Alou L, Aguilar L, Sevillano D, Gimenez MJ, Echeverria O, Gomez-Lus ML, Prieto J. Is there a pharmacodynamic need for the use of continuous versus intermittent infusion with ceftazidime against Pseudomonas aeruginosa? An in vitro pharmacodynamic model. J Antimicrob Chemother. 2005;55(2):209–13.PubMedCrossRefGoogle Scholar
  59. 59.
    Pea F, Cojutti P, Sbrojavacca R, Cadeo B, Cristini F, Bulfoni A, Furlanut M. TDM-guided therapy with daptomycin and meropenem in a morbidly obese, critically ill patient. Ann Pharmacother. 2011;45(7-8):e37.PubMedCrossRefGoogle Scholar
  60. 60.
    Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, Shirwadkar C, Eastwood GM, Myburgh J, Paterson DL, et al. A multicenter randomized trial of continuous versus intermittent beta-lactam infusion in severe sepsis. Am J Respir Crit Care. 2015;192(11):1298–305.CrossRefGoogle Scholar
  61. 61.
    Abdul-Aziz MH, Sulaiman H, Mat-Nor MB, Rai V, Wong KK, Hasan MS, Abd Rahman AN, Jamal JA, Wallis SC, Lipman J, et al. Beta-lactam infusion in severe sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med. 2016;42(10):1535–45.PubMedCrossRefGoogle Scholar
  62. 62.
    Roberts JA, Abdul-Aziz MH, Davis JS, Dulhunty JM, Cotta MO, Myburgh J, Bellomo R, Lipman J. Continuous versus intermittent beta-lactam infusion in severe sepsis: a meta-analysis of individual patient data from randomized trials. Am J Respir Crit Care Med. 2016;194(6):681–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Kasiakou SK, Sermaides GJ, Michalopoulos A, Soteriades ES, Falagas ME. Continuous versus intermittent intravenous administration of antibiotics: a meta-analysis of randomised controlled trials. Lancet Infect Dis. 2005;5(9):581–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Roberts JA, Webb S, Paterson D, Ho KM, Lipman J. A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med. 2009;37(6):2071–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Shiu J, Wang E, Tejani AM, Wasdell M. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections. Cochrane Database Syst Rev. 2013;3(3):CD008481.Google Scholar
  66. 66.
    Tamma PD, Putcha N, Suh YD, Van Arendonk KJ, Rinke ML. Does prolonged beta-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials. BMC Infect Dis. 2011;11:181.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013;56(2):272–82.PubMedCrossRefGoogle Scholar
  68. 68.
    Roberts JA, Ulldemolins M, Roberts MS, McWhinney B, Ungerer J, Paterson DL, Lipman J. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents. 2010;36(4):332–9.PubMedCrossRefGoogle Scholar
  69. 69.
    De Waele JJ, Carrette S, Carlier M, Stove V, Boelens J, Claeys G, Leroux-Roels I, Hoste E, Depuydt P, Decruyenaere J, et al. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial. Intensive Care Med. 2014;40(3):380–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Wong G, Brinkman A, Benefield RJ, Carlier M, De Waele JJ, El Helali N, Frey O, Harbarth S, Huttner A, McWhinney B, et al. An international, multicentre survey of beta-lactam antibiotic therapeutic drug monitoring practice in intensive care units. J Antimicrob Chemother. 2014;69(5):1416–23.PubMedCrossRefGoogle Scholar
  71. 71.
    Wong G, Sime FB, Lipman J, Roberts JA. How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients? BMC Infect Dis. 2014;14:288.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Felton TW, Roberts JA, Lodise TP, Van Guilder M, Boselli E, Neely MN, Hope WW. Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy. Antimicrob Agents Chemother. 2014;58(7):4094–102.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Fuchs A, Csajka C, Thoma Y, Buclin T, Widmer N. Benchmarking therapeutic drug monitoring software: a review of available computer tools. Clin Pharmacokinet. 2013;52(1):9–22.PubMedCrossRefGoogle Scholar
  74. 74.
    Buyle FM, Decruyenaere J, De Waele J, Tulkens PM, Van Audenrode T, Depuydt P, Claeys G, Robays H, Vogelaers D. A survey of beta-lactam antibiotics and vancomycin dosing strategies in intensive care units and general wards in Belgian hospitals. Eur J Clin Microbiol Infect Dis. 2013;32(6):763–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Davis SL, Scheetz MH, Bosso JA, Goff DA, Rybak MJ. Adherence to the 2009 consensus guidelines for vancomycin dosing and monitoring practices: a cross-sectional survey of U.S. hospitals. Pharmacotherapy. 2013;33(12):1256–63.PubMedCrossRefGoogle Scholar
  76. 76.
    Man SS, Carr RR, Ensom MH. Comparison of continuous and intermittent IV infusion of vancomycin: systematic review. Can J Hosp Pharm. 2010;63(5):373–81.PubMedPubMedCentralGoogle Scholar
  77. 77.
    James JK, Palmer SM, Levine DP, Rybak MJ. Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections. Antimicrob Agents Chemother. 1996;40(3):696–700.PubMedPubMedCentralGoogle Scholar
  78. 78.
    DiMondi VP, Rafferty K. Review of continuous-infusion vancomycin. Ann Pharmacother. 2013;47(2):219–27.PubMedCrossRefGoogle Scholar
  79. 79.
    Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N. Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J Antimicrob Chemother. 2012;67(1):17–24.PubMedCrossRefGoogle Scholar
  80. 80.
    Panday PN, Sturkenboom M. Continuous infusion of vancomycin less effective and safe than intermittent infusion, based on pharmacodynamic and pharmacokinetic principles. Clin Infect Dis. 2009;49(12):1964–5. author reply 1965PubMedCrossRefGoogle Scholar
  81. 81.
    Jeurissen A, Sluyts I, Rutsaert R. A higher dose of vancomycin in continuous infusion is needed in critically ill patients. Int J Antimicrob Agents. 2011;37(1):75–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Saugel B, Nowack MC, Hapfelmeier A, Umgelter A, Schultheiss C, Thies P, Phillip V, Eyer F, Schmid RM, Huber W. Continuous intravenous administration of vancomycin in medical intensive care unit patients. J Crit Care. 2013;28(1):9–13.PubMedCrossRefGoogle Scholar
  83. 83.
    De Waele JJ, Danneels I, Depuydt P, Decruyenaere J, Bourgeois M, Hoste E. Factors associated with inadequate early vancomycin levels in critically ill patients treated with continuous infusion. Int J Antimicrob Agents. 2013;41(5):434–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP. 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.PubMedCrossRefGoogle Scholar
  85. 85.
    Blouin RA, Bauer LA, Miller DD, Record KE, Griffen WO Jr. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother. 1982;21(4):575–80.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Brown DL, Lalla CD, Masselink AJ. AUC versus peak-trough dosing of vancomycin: applying new pharmacokinetic paradigms to an old drug. Ther Drug Monit. 2013;35(4):443–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Matsumoto K, Takesue Y, Ohmagari N, Mochizuki T, Mikamo H, Seki M, Takakura S, Tokimatsu I, Takahashi Y, Kasahara K, et al. Practice guidelines for therapeutic drug monitoring of vancomycin: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. 2013;19(3):365–80.PubMedCrossRefGoogle Scholar
  88. 88.
    Potoski BA, Paterson DL. Appropriate pharmacokinetic index for outcome in Staphylococcus aureus pneumonia. Chest. 2007;132(3):1101–2. author reply 1102–3PubMedCrossRefGoogle Scholar
  89. 89.
    Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, Lodise TP. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 2014;58(1):309–16.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Minejima E, Choi J, Beringer P, Lou M, Tse E, Wong-Beringer A. Applying new diagnostic criteria for acute kidney injury to facilitate early identification of nephrotoxicity in vancomycin-treated patients. Antimicrob Agents Chemother. 2011;55(7):3278–83.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Prabaker KK, Tran TP, Pratummas T, Goetz MB, Graber CJ. Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans. J Hosp Med. 2012;7(2):91–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med. 2006;166(19):2138–44.PubMedCrossRefGoogle Scholar
  93. 93.
    Jeffres MN, Isakow W, Doherty JA, Micek ST, Kollef MH. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. Clin Ther. 2007;29(6):1107–15.PubMedCrossRefGoogle Scholar
  94. 94.
    Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. 2008;52(4):1330–6.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Bosso JA, Nappi J, Rudisill C, Wellein M, Bookstaver PB, Swindler J, Mauldin PD. Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob Agents Chemother. 2011;55(12):5475–9.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Pritchard L, Baker C, Leggett J, Sehdev P, Brown A, Bayley KB. Increasing vancomycin serum trough concentrations and incidence of nephrotoxicity. Am J Med. 2010;123(12):1143–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf. 2010;9(1):9–14.PubMedCrossRefGoogle Scholar
  98. 98.
    Jeffres MN, Isakow W, Doherty JA, McKinnon PS, Ritchie DJ, Micek ST, Kollef MH. Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices. Chest. 2006;130(4):947–55.PubMedCrossRefGoogle Scholar
  99. 99.
    Iwamoto T, Kagawa Y, Kojima M. Clinical efficacy of therapeutic drug monitoring in patients receiving vancomycin. Biol Pharm Bull. 2003;26(6):876–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis. 2011;52(8):975–81.PubMedCrossRefGoogle Scholar
  101. 101.
    Ye ZK, Tang HL, Zhai SD. Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis. PLoS One. 2013;8(10):e77169.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Pea F, Bertolissi M, Di Silvestre A, Poz D, Giordano F, Furlanut M. TDM coupled with Bayesian forecasting should be considered an invaluable tool for optimizing vancomycin daily exposure in unstable critically ill patients. Int J Antimicrob Agents. 2002;20(5):326–32.PubMedCrossRefGoogle Scholar
  103. 103.
    Gous A, Lipman J, Scribante J, Tshukutsoane S, Hon H, Pinder M, Mathivha R, Verhoef L, Stass H. Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis. Int J Antimicrob Agents. 2005;26(1):50–5.PubMedCrossRefGoogle Scholar
  104. 104.
    Haeseker M, Stolk L, Nieman F, Hoebe C, Neef C, Bruggeman C, Verbon A. The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens. Br J Clin Pharmacol. 2013;75(1):180–5.PubMedCrossRefGoogle Scholar
  105. 105.
    Garrelts JC, Jost G, Kowalsky SF, Krol GJ, Lettieri JT. Ciprofloxacin pharmacokinetics in burn patients. Antimicrob Agents Chemother. 1996;40(5):1153–6.PubMedPubMedCentralGoogle Scholar
  106. 106.
    van Zanten AR, Polderman KH, van Geijlswijk IM, van der Meer GY, Schouten MA, Girbes AR. Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort study. J Crit Care. 2008;23(3):422–30.PubMedCrossRefGoogle Scholar
  107. 107.
    Conil JM, Georges B, de Lussy A, Khachman D, Seguin T, Ruiz S, Cougot P, Fourcade O, Houin G, Saivin S. Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches. Int J Antimicrob Agents. 2008;32(6):505–10.PubMedCrossRefGoogle Scholar
  108. 108.
    Kontou P, Chatzika K, Pitsiou G, Stanopoulos I, Argyropoulou-Pataka P, Kioumis I. Pharmacokinetics of ciprofloxacin and its penetration into bronchial secretions of mechanically ventilated patients with chronic obstructive pulmonary disease. Antimicrob Agents Chemother. 2011;55(9):4149–53.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Pea F, Poz D, Viale P, Pavan F, Furlanut M. Which reliable pharmacodynamic breakpoint should be advised for ciprofloxacin monotherapy in the hospital setting? A TDM-based retrospective perspective. J Antimicrob Chemother. 2006;58(2):380–6.PubMedCrossRefGoogle Scholar
  110. 110.
    Matsuo K, Azuma M, Kasai M, Hanji I, Kimura I, Kosugi T, Suga N, Satoh M. Investigation of the clinical efficacy and dosage of intravenous ciprofloxacin in patients with respiratory infection. J Pharm Pharm Sci. 2008;11(4):111s–7s.Google Scholar
  111. 111.
    Roberts JA, Lipman J. Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis. Clin Pharmacokinet. 2006;45(8):755–73.PubMedCrossRefGoogle Scholar
  112. 112.
    Rea RS, Capitano B, Bies R, Bigos KL, Smith R, Lee H. Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit. 2008;30(6):674–81.PubMedCrossRefGoogle Scholar
  113. 113.
    Goncalves-Pereira J, Martins A, Povoa P. Pharmacokinetics of gentamicin in critically ill patients: pilot study evaluating the first dose. Clin Microbiol Infect. 2010;16(8):1258–63.PubMedCrossRefGoogle Scholar
  114. 114.
    Delattre IK, Musuamba FT, Nyberg J, Taccone FS, Laterre PF, Verbeeck RK, Jacobs F, Wallemacq PE. Population pharmacokinetic modeling and optimal sampling strategy for Bayesian estimation of amikacin exposure in critically ill septic patients. Ther Drug Monit. 2010;32(6):749–56.PubMedCrossRefGoogle Scholar
  115. 115.
    Giuliano RA, Verpooten GA, Verbist L, Wedeen RP, De Broe ME. In vivo uptake kinetics of aminoglycosides in the kidney cortex of rats. J Pharmacol Exp Ther. 1986;236(2):470–5.PubMedGoogle Scholar
  116. 116.
    Selby NM, Shaw S, Woodier N, Fluck RJ, Kolhe NV. Gentamicin-associated acute kidney injury. QJM. 2009;102(12):873–80.PubMedCrossRefGoogle Scholar
  117. 117.
    Barza M, Ioannidis JP, Cappelleri JC, Lau J. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ. 1996;312(7027):338–45.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Ferriols-Lisart R, Alos-Alminana M. Effectiveness and safety of once-daily aminoglycosides: a meta-analysis. Am J Health Syst Pharm. 1996;53(10):1141–50.PubMedGoogle Scholar
  119. 119.
    Marik PE, Lipman J, Kobilski S, Scribante J. A prospective randomized study comparing once- versus twice-daily amikacin dosing in critically ill adult and paediatric patients. J Antimicrob Chemother. 1991;28(5):753–64.PubMedCrossRefGoogle Scholar
  120. 120.
    Avent ML, Teoh J, Lees J, Eckert KA, Kirkpatrick CM. Comparing 3 methods of monitoring gentamicin concentrations in patients with febrile neutropenia. Ther Drug Monit. 2011;33(5):592–601.PubMedGoogle Scholar
  121. 121.
    Bailey JA, Virgo KS, DiPiro JT, Nathens AB, Sawyer RG, Mazuski JE. Aminoglycosides for intra-abdominal infection: equal to the challenge? Surg Infect. 2002;3(4):315–35.CrossRefGoogle Scholar
  122. 122.
    Lau AH, Lam NP, Piscitelli SC, Wilkes L, Danziger LH. Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives. Clin Pharmacokinet. 1992;23(5):328–64.PubMedCrossRefGoogle Scholar
  123. 123.
    Karjagin J, Pahkla R, Karki T, Starkopf J. Distribution of metronidazole in muscle tissue of patients with septic shock and its efficacy against Bacteroides fragilis in vitro. J Antimicrob Chemother. 2005;55(3):341–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Ulldemolins M, Roberts JA, Lipman J, Rello J. Antibiotic dosing in multiple organ dysfunction syndrome. Chest. 2011;139(5):1210–20.PubMedCrossRefGoogle Scholar
  125. 125.
    Bouman CS, van Kan HJ, Koopmans RP, Korevaar JC, Schultz MJ, Vroom MB. 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):2013–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Farrell G, Baird-Lambert J, Cvejic M, Buchanan N. Disposition and metabolism of metronidazole in patients with liver failure. Hepatology. 1984;4(4):722–6.PubMedCrossRefGoogle Scholar
  127. 127.
    Bergan T, Thorsteinsson SB. Pharmacokinetics of metronidazole and its metabolites in reduced renal function. Chemotherapy. 1986;32(4):305–18.PubMedCrossRefGoogle Scholar
  128. 128.
    Pendland SL, Piscitelli SC, Schreckenberger PC, Danziger LH. In vitro activities of metronidazole and its hydroxy metabolite against Bacteroides spp. J Antimicrob Chemother. 1988;21:195–200.CrossRefGoogle Scholar
  129. 129.
    Sartelli M, Viale P, Catena F, Ansaloni L, Moore E, Malangoni M, Moore FA, Velmahos G, Coimbra R, Ivatury R, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8(1):3.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Vardakas KZ, Rafailidis PI, Falagas ME. Effectiveness and safety of tigecycline: focus on use for approved indications. Clin Infect Dis. 2012;54(11):1672–4.PubMedCrossRefGoogle Scholar
  131. 131.
    Prasad P, Sun J, Danner RL, Natanson C. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis. 2012;54(12):1699–709.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Tasina E, Haidich AB, Kokkali S, Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis. 2011;11(11):834–44.PubMedCrossRefGoogle Scholar
  133. 133.
    Tygacil (tigecycline): drug safetycommunication-increased risk of death.
  134. 134.
    Eagye KJ, Kuti JL, Dowzicky M, Nicolau DP. Empiric therapy for secondary peritonitis: a pharmacodynamic analysis of cefepime, ceftazidime, ceftriaxone, imipenem, levofloxacin, piperacillin/tazobactam, and tigecycline using Monte Carlo simulation. Clin Ther. 2007;29(5):889–99.PubMedCrossRefGoogle Scholar
  135. 135.
    Sevillano D, Aguilar L, Alou L, Gimenez MJ, Gonzalez N, Torrico M, Cafini F, Garcia-Rey C, Garcia-Escribano N, Prieto J. Exposure-response analysis of tigecycline in pharmacodynamic simulations using different size inocula of target bacteria. Int J Antimicrob Agents. 2010;36(2):137–44.PubMedCrossRefGoogle Scholar
  136. 136.
    Falagas ME, Vardakas KZ, Tsiveriotis KP, Triarides NA, Tansarli GS. Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections. Int J Antimicrob Agents. 2014;44(1):1–7.PubMedCrossRefGoogle Scholar
  137. 137.
    Xie J, Wang T, Sun J, Chen S, Cai J, Zhang W, Dong H, Hu S, Zhang D, Wang X, et al. Optimal tigecycline dosage regimen is urgently needed: results from a pharmacokinetic/pharmacodynamic analysis of tigecycline by Monte Carlo simulation. Int J Infect Dis. 2014;18:62–7.PubMedCrossRefGoogle Scholar
  138. 138.
    Conde-Estevez D, Grau S, Horcajada JP, Luque S. Off-label prescription of tigecycline: clinical and microbiological characteristics and outcomes. Int J Antimicrob Agents. 2010;36(5):471–2.PubMedCrossRefGoogle Scholar
  139. 139.
    De Pascale G, Montini L, Pennisi M, Bernini V, Maviglia R, Bello G, Spanu T, Tumbarello M, Antonelli M. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care. 2014;18(3):R90.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Barbour A, Schmidt S, Ma B, Schiefelbein L, Rand KH, Burkhardt O, Derendorf H. Clinical pharmacokinetics and pharmacodynamics of tigecycline. Clin Pharmacokinet. 2009;48(9):575–84.PubMedCrossRefGoogle Scholar
  141. 141.
    Meagher AK, Ambrose PG, Grasela TH, Ellis-Grosse EJ. Pharmacokinetic/pharmacodynamic profile for tigecycline—a new glycylcycline antimicrobial agent. Diagn Microbiol Infect Dis. 2005;52(3):165–71.PubMedCrossRefGoogle Scholar
  142. 142.
    Muralidharan G, Micalizzi M, Speth J, Raible D, Troy S. Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob Agents Chemother. 2005;49(1):220–9.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Hoffmann M, DeMaio W, Jordan RA, Talaat R, Harper D, Speth J, Scatina J. Metabolism, excretion, and pharmacokinetics of [14C]tigecycline, a first-in-class glycylcycline antibiotic, after intravenous infusion to healthy male subjects. Drug Metab Dispos. 2007;35(9):1543–53.PubMedCrossRefGoogle Scholar
  144. 144.
    Veinstein A, Debouverie O, Gregoire N, Goudet V, Adier C, Robert R, Couet W. Lack of effect of extracorporeal membrane oxygenation on tigecycline pharmacokinetics. J Antimicrob Chemother. 2012;67(4):1047–8.PubMedCrossRefGoogle Scholar
  145. 145.
    Honore PM, Jacobs R, De Waele E, Van Gorp V, Spapen HD. The blind spot in high-dose tigecycline pharmacokinetics in critically ill patients: membrane adsorption during continuous extracorporeal treatment. Crit Care. 2015;19:24.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Bassetti M, Marchetti M, Chakrabarti A, Colizza S, Garnacho-Montero J, Kett DH, Munoz P, Cristini F, Andoniadou A, Viale P, et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med. 2013;39(12):2092–106.PubMedCrossRefGoogle Scholar
  147. 147.
    Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–50.PubMedCrossRefGoogle Scholar
  148. 148.
    Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-Akdagli S, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18(Suppl 7):19–37.PubMedCrossRefGoogle Scholar
  149. 149.
    Sinnollareddy M, Peake SL, Roberts MS, Playford EG, Lipman J, Roberts JA. Pharmacokinetic evaluation of fluconazole in critically ill patients. Expert Opin Drug Metab Toxicol. 2011;7(11):1431–40.PubMedCrossRefGoogle Scholar
  150. 150.
    Sinnollareddy MG, Roberts JA, Lipman J, Akova M, Bassetti M, De Waele JJ, Kaukonen KM, Koulenti D, Martin C, Montravers P, et al. Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients study. Crit Care. 2015;19:33.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Yagasaki K, Gando S, Matsuda N, Kameue T, Ishitani T, Hirano T, Iseki K. Pharmacokinetics and the most suitable dosing regimen of fluconazole in critically ill patients receiving continuous hemodiafiltration. Intensive Care Med. 2003;29(10):1844–8.PubMedCrossRefGoogle Scholar
  152. 152.
    Sinnollareddy MG, Roberts MS, Lipman J, Robertson TA, Peake SL, Roberts JA. Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration. Int J Antimicrob Agents. 2015;45(2):192–5.PubMedCrossRefGoogle Scholar
  153. 153.
    Jamal JA, Mueller BA, Choi GY, Lipman J, Roberts JA. How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy? Diagn Microbiol Infect Dis. 2015;82(1):92–103.PubMedCrossRefGoogle Scholar
  154. 154.
    Grau S, Luque S. Antifungal therapeutic drug monitoring: when, how, and why. Enferm Infecc Microbiol Clin. 2015;33(5):295–7.PubMedCrossRefGoogle Scholar
  155. 155.
    Alobaid AS, Wallis SC, Jarrett P, Starr T, Stuart J, Lassig-Smith M, Ordonez Mejia JL, Roberts MS, Sinnollareddy MG, Roger C, et al. What is the effect of obesity on the population pharmacokinetics of fluconazole in critically ill patients? Antimicrob Agents Chemother. 2016;60(11):6550–7.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Grau S, Luque S, Campillo N, Samso E, Rodriguez U, Garcia-Bernedo CA, Salas E, Sharma R, Hope WW, Roberts JA. Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis. J Antimicrob Chemother. 2015;70(10):2854–61.PubMedCrossRefGoogle Scholar
  157. 157.
    Maseda E, Grau S, Villagran MJ, Hernandez-Gancedo C, Lopez-Tofino A, Roberts JA, Aguilar L, Luque S, Sevillano D, Gimenez MJ, et al. Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration. J Antimicrob Chemother. 2014;69(6):1624–32.PubMedCrossRefGoogle Scholar
  158. 158.
    Weiler S, Seger C, Pfisterer H, Stienecke E, Stippler F, Welte R, Joannidis M, Griesmacher A, Bellmann R. Pharmacokinetics of caspofungin in critically ill patients on continuous renal replacement therapy. Antimicrob Agents Chemother. 2013;57(8):4053–7.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    De Waele JJ. Abdominal sepsis. Curr Infect Dis Rep. 2016;18(8):23.PubMedCrossRefGoogle Scholar
  160. 160.
    Sartelli M, Catena F, Ansaloni L, Coccolini F, Corbella D, Moore EE, Malangoni M, Velmahos G, Coimbra R, Koike K, et al. Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study. World J Emerg Surg. 2014;9:37.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Sawyer RG, Claridge JA, Nathens AB, Rotstein OD, Duane TM, Evans HL, Cook CH, O'Neill PJ, Mazuski JE, Askari R, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015;372(21):1996–2005.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Sartelli M, Catena F, Ansaloni L, Coccolini F, Di Saverio S, Griffiths EA. Duration of antimicrobial therapy in treating complicated intra-abdominal infections: a comprehensive review. Surg Infect. 2016;17(1):9–12.CrossRefGoogle Scholar
  163. 163.
    Feagins LA, Holubar SD, Kane SV, Spechler SJ. Current strategies in the management of intra-abdominal abscesses in Crohn’s disease. Clin Gastroenterol Hepatol. 2011;9(10):842–50.PubMedCrossRefGoogle Scholar
  164. 164.
    Feng Y, Hodiamont CJ, van Hest RM, Brul S, Schultsz C, Ter Kuile BH. Development of antibiotic resistance during simulated treatment of Pseudomonas aeruginosa in chemostats. PLoS One. 2016;11(2):e0149310.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Translational Anti-infective Pharmacodynamics, School of PharmacyThe University of QueenslandBrisbaneAustralia
  2. 2.Burns, Trauma and Critical Care Research CentreThe University of QueenslandBrisbaneAustralia
  3. 3.Department of Intensive Care MedicineRoyal Brisbane and Women’s HospitalBrisbaneAustralia
  4. 4.Pharmacy DepartmentRoyal Brisbane and Women’s HospitalBrisbaneAustralia

Personalised recommendations