Optimizing β-lactams treatment in critically-ill patients using pharmacokinetics/pharmacodynamics targets: are first conventional doses effective?

References

• Goncalves-Pereira J, Povoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of beta-lactams. Crit Care. 2011;15:R206.
   PubMed Web of Science ®Google Scholar
• Pea F, Viale P, Furlanut M. Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability. Clin Pharmacokinet. 2005;44:1009–1034.
   PubMed Web of Science ®Google Scholar
• Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009;37:840–851.
   PubMed Web of Science ®Google Scholar
• Roberts JA, Ulldemolins M, Roberts MS, et al. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents. 2010;36:332–339.
   PubMed Web of Science ®Google Scholar
• Pea F, Viale P. Bench-to-bedside review: appropriate antibiotic therapy in severe sepsis and septic shock–does the dose matter? Crit Care. 2009;13:214.
   PubMed Web of Science ®Google Scholar
• 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;42:1764–1771.
   PubMed Web of Science ®Google Scholar
• Scaglione F. Can PK/PD be used in everyday clinical practice. Int J Antimicrob Agents. 2002;19:349–353.
   PubMed Web of Science ®Google Scholar
• Hyatt JM, McKinnon PS, Zimmer GS, et al. The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome. Focus on antibacterial agents. Clin Pharmacokinet. 1995;28:143–160.
   PubMed Web of Science ®Google Scholar
• Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1–10.
   PubMed Web of Science ®Google Scholar
• Wong G, Brinkman A, Benefield RJ, et al. An international, multicentre survey of beta-lactam antibiotic therapeutic drug monitoring practice in intensive care units. J Antimicrob Chemother. 2014;69:1416–1423.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Roberts JA, Kruger P, Paterson DL, et al. Antibiotic resistance–what’s dosing got to do with it? Crit Care Med. 2008;36:2433–2440.
   PubMed Web of Science ®Google Scholar
• Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995;22:89–96.
   PubMed Web of Science ®Google Scholar
• Zeitlinger MA, Derendorf H, Mouton JW, et al. Protein binding: do we ever learn? Antimicrob Agents Chemother. 2011;55:3067–3074.
   PubMed Web of Science ®Google Scholar
• Andes D, Craig WA. Animal model pharmacokinetics and pharmacodynamics: a critical review. Int J Antimicrob Agents. 2002;19:261–268.
   PubMed Web of Science ®Google Scholar
• Sinnollareddy MG, Roberts MS, Lipman J, et al. Beta-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review. Clin Exp Pharmacol Physiol. 2012;39:489–496.
   PubMed Web of Science ®Google Scholar
• Muller AE, Punt N, Mouton JW. Optimal exposures of ceftazidime predict the probability of microbiological and clinical outcome in the treatment of nosocomial pneumonia. J Antimicrob Chemother. 2013;68:900–906.
   PubMed Web of Science ®Google Scholar
• MacVane SH, Kuti JL, Nicolau DP. Clinical pharmacodynamics of antipseudomonal cephalosporins in patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2014;58:1359–1364.
   PubMed Web of Science ®Google Scholar
• Li C, Du X, Kuti JL, et al. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother. 2007;51:1725–1730.
   PubMed Web of Science ®Google Scholar
• Rhodes NJ, Kuti JL, Nicolau DP, et al. Defining clinical exposures of cefepime for gram-negative bloodstream infections that are associated with improved survival. Antimicrob Agents Chemother. 2015;60:1401–1410.
   PubMed Web of Science ®Google Scholar
• Ariano RE, Nyhlén A, Donnelly JP, et al. Pharmacokinetics and pharmacodynamics of meropenem in febrile neutropenic patients with bacteremia. Ann Pharmacother. 2005;39:32–38.
   PubMed Web of Science ®Google Scholar
• McKinnon PS, Paladino JA, Schentag JJ. 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. 2008;31:345–351.
   PubMed Web of Science ®Google Scholar
• Crandon JL, Bulik CC, Kuti JL, et al. Clinical pharmacodynamics of cefepime in patients infected with Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010;54:1111–1116.
   PubMed Web of Science ®Google Scholar
• Mouton JW, Vinks AA. 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. 2005;44:201–210.
   PubMed Web of Science ®Google Scholar
• Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis Suppl. 1990;74:63–70.
   PubMedGoogle Scholar
• Manduru M, Mihm LB, White RL, et al. In vitro pharmacodynamics of ceftazidime against Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother. 1997;41:2053–2056.
   PubMed Web of Science ®Google Scholar
• 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;38:931–936.
   PubMed Web of Science ®Google Scholar
• Tam VH, McKinnon PS, Akins RL, et al. Pharmacodynamics of cefepime in patients with Gram-negative infections. J Antimicrob Chemother. 2002;50:425–428.
   PubMed Web of Science ®Google Scholar
• Tam VH, Schilling AN, Neshat S, et al. Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005;49:4920–4927.
   PubMed Web of Science ®Google Scholar
• Lee SY, Kuti JL, Nicolau DP. Cefepime pharmacodynamics in patients with extended spectrum beta-lactamase (ESBL) and non-ESBL infections. J Infect. 2007;54:463–468.
   PubMed Web of Science ®Google Scholar
• Hayashi Y, Lipman J, Udy AA, et al. Beta-lactam therapeutic drug monitoring in the critically ill: optimising drug exposure in patients with fluctuating renal function and hypoalbuminaemia. Int J Antimicrob Agents. 2013;41:162–166.
   PubMed Web of Science ®Google Scholar
• Aitken SL, Altshuler J, Guervil DJ, et al. Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia. Int J Antimicrob Agents. 2015;45:541–544.
   PubMed Web of Science ®Google Scholar
• Piccoli L, Larosa M, Marchetti F. Time-kill curves as a tool for targeting ceftazidime serum concentration during continuous infusion. J Antimicrob Chemother. 2003;52:1047–1048.
   PubMed Web of Science ®Google Scholar
• Navas D, Caillon J, Gras-Le Guen C, et al. Comparison of in vivo intrinsic activity of cefepime and imipenem in a Pseudomonas aeruginosa rabbit endocarditis model: effect of combination with tobramycin simulating human serum pharmacokinetics. J Antimicrob Chemother. 2004;54:767–771.
   PubMed Web of Science ®Google Scholar
• Huttner A, Harbarth S, Hope WW, et al. Therapeutic drug monitoring of the beta-lactam antibiotics: what is the evidence and which patients should we be using it for? J Antimicrob Chemother. 2015;70:3178–3183.
   PubMed Web of Science ®Google Scholar
• Abdul-Aziz MH, Lipman J, Akova M, et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. J Antimicrob Chemother. 2016;71:196–207.
   PubMed Web of Science ®Google Scholar
• Ulldemolins M, Martin-Loeches I, Llaurado-Serra M, et al. Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: effect of type of dialysis membrane on dosing requirements. J Antimicrob Chemother. 2016;71:1651–1659.
   PubMed Web of Science ®Google Scholar
• Tamme K, Oselin K, Kipper K, et al. Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock. Acta Anaesthesiol Scand. 2016;60:230–240.
   PubMed Web of Science ®Google Scholar
• Martínková J, Malbrain ML, Havel E, et al. A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam. Anaesthesiol Intensive Ther. 2016;48:23–28.
   PubMed Web of Science ®Google Scholar
• Öbrink-Hansen K, Juul RV, Storgaard M, et al. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations? Antimicrob Agents Chemother. 2015;59:7018–7026.
   PubMed Web of Science ®Google Scholar
• Awissi DK, Beauchamp A, Hebert E, et al. Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Pharmacotherapy. 2015;35:600–607.
   PubMed Web of Science ®Google Scholar
• Sime FB, Roberts MS, Tiong IS, et al. Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial. J Antimicrob Chemother. 2015;70:2369–2375.
   PubMed Web of Science ®Google Scholar
• Udy AA, Lipman J, Jarrett P, et al. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance? Crit Care. 2015;19:28.
   PubMed Web of Science ®Google Scholar
• Akers KS, Niece KL, Chung KK, et al. Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. J Trauma Acute Care Surg. 2014;77:S163–S170.
   PubMed Web of Science ®Google Scholar
• De Waele J, Carlier M, Hoste E, et al. Extended versus bolus infusion of meropenem and piperacillin: a pharmacokinetic analysis. Minerva Anestesiol. 2014;80:1302–1309.
   PubMed Web of Science ®Google Scholar
• Carlier M, Carrette S, Stove V, et al. 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;43:470–473.
   PubMed Web of Science ®Google Scholar
• Asín-Prieto E, Rodríguez-Gascón A, Trocóniz IF, et al. Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. J Antimicrob Chemother. 2014;69:180–189.
   PubMed Web of Science ®Google Scholar
• Butterfield JM, Lodise TP, Beegle S, et al. Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations. J Antimicrob Chemother. 2014;69:176–179.
   PubMed Web of Science ®Google Scholar
• Sturm AW, Allen N, Rafferty KD, et al. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Pharmacotherapy. 2014;34:28–35.
   PubMed Web of Science ®Google Scholar
• Carlier M, Carrette S, Roberts JA, et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Crit Care. 2013;17:R84.
   PubMed Web of Science ®Google Scholar
• Felton TW, Hope WW, Lomaestro BM, et al. Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections. Antimicrob Agents Chemother. 2012;56:4087–4094.
   PubMed Web of Science ®Google Scholar
• Roberts JA, Kirkpatrick CM, Roberts MS, et al. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents. 2010;35:156–163.
   PubMed Web of Science ®Google Scholar
• Shea KM, Cheatham SC, Smith DW, et al. 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;43:1747–1754.
   PubMed Web of Science ®Google Scholar
• Langgartner J, Lehn N, Glück T, et al. Comparison of the pharmacokinetics of piperacillin and sulbactam during intermittent and continuous intravenous infusion. Chemotherapy. 2007;53:370–377.
   PubMed Web of Science ®Google Scholar
• Rafati MR, Rouini MR, Mojtahedzadeh M, et al. Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients. Int J Antimicrob Agents. 2006;28:122–127.
   PubMed Web of Science ®Google Scholar
• Zeitlinger MA, Erovic BM, Sauermann R, et al. Plasma concentrations might lead to overestimation of target site activity of piperacillin in patients with sepsis. J Antimicrob Chemother. 2005;56:703–708.
   PubMed Web of Science ®Google Scholar
• Georges B, Conil JM, Ruiz S, et al. Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations. Br J Clin Pharmacol. 2012;73:588–596.
   PubMed Web of Science ®Google Scholar
• Georges B, Conil JM, Seguin T, et al. Population pharmacokinetics of ceftazidime in intensive care unit patients: influence of glomerular filtration rate, mechanical ventilation, and reason for admission. Antimicrob Agents Chemother. 2009;53:4483–4489.
   PubMed Web of Science ®Google Scholar
• Mouton JW, Punt N, Vinks AA. A retrospective analysis using Monte Carlo simulation to evaluate recommended ceftazidime dosing regimens in healthy volunteers, patients with cystic fibrosis, and patients in the intensive care unit. Clin Ther. 2005;27:762–772.
   PubMed Web of Science ®Google Scholar
• Pea F, Viale P, Damiani D, et al. Ceftazidime in acute myeloid leukemia patients with febrile neutropenia: helpfulness of continuous intravenous infusion in maximizing pharmacodynamic exposure. Antimicrob Agents Chemother. 2005;49:3550–3553.
   PubMed Web of Science ®Google Scholar
• Cousson J, Floch T, Vernet-Garnier V, et al. [Pharmacodynamic interest of ceftazidime continuous infusion vs intermittent bolus administration in patients with severe nosocomial pneumonia]. Pathol Biol (Paris). 2005;53:546–550.
   PubMed Web of Science ®Google Scholar
• Traunmüller F, Schenk P, Mittermeyer C, et al. Clearance of ceftazidime during continuous venovenous haemofiltration in critically ill patients. J Antimicrob Chemother. 2002;49:129–134.
   PubMed Web of Science ®Google Scholar
• Buijk SL, Gyssens IC, Mouton JW, et al. Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections. J Antimicrob Chemother. 2002;49:121–128.
   PubMed Web of Science ®Google Scholar
• Hanes SD, Wood GC, Herring V, et al. Intermittent and continuous ceftazidime infusion for critically ill trauma patients. Am J Surg. 2000;179:436–440.
   PubMed Web of Science ®Google Scholar
• Angus BJ, Smith MD, Suputtamongkol Y, et al. Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis. Br J Clin Pharmacol. 2000;50:184–191.
   PubMed Web of Science ®Google Scholar
• Carlier M, Taccone FS, Beumier M, et al. Population pharmacokinetics and dosing simulations of cefepime in septic shock patients receiving continuous renal replacement therapy. Int J Antimicrob Agents. 2015;46:413–419.
   PubMed Web of Science ®Google Scholar
• Sime FB, Roberts MS, Tiong IS, et al. Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies. Antimicrob Agents Chemother. 2015;59:5463–5469.
   PubMed Web of Science ®Google Scholar
• Cheatham SC, Shea KM, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients. Int J Antimicrob Agents. 2011;37:46–50.
   PubMed Web of Science ®Google Scholar
• Chapuis TM, Giannoni E, Majcherczyk PA, et al. Prospective monitoring of cefepime in intensive care unit adult patients. Crit Care. 2010;14:R51.
   PubMed Web of Science ®Google Scholar
• Nicasio AM, Ariano RE, Zelenitsky SA, et al. Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2009;53:1476–1481.
   PubMed Web of Science ®Google Scholar
• Roos JF, Bulitta J, Lipman J, et al. Pharmacokinetic-pharmacodynamic rationale for cefepime dosing regimens in intensive care units. J Antimicrob Chemother. 2006;58:987–993.
   PubMed Web of Science ®Google Scholar
• Georges B, Conil JM, Cougot P, et al. Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen. Int J Clin Pharmacol Ther. 2005;43:360–369.
   PubMed Web of Science ®Google Scholar
• Lipman J, Wallis SC, Boots RJ. Cefepime versus cefpirome: the importance of creatinine clearance. Anesth Analg. 2003;97:1149–1154.
   PubMed Web of Science ®Google Scholar
• Malone RS, Fish DN, Abraham E, et al. Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother. 2001;45:3148–3155.
   PubMed Web of Science ®Google Scholar
• Mathew SK, Mathew BS, Neely MN, et al. A nonparametric pharmacokinetic approach to determine the optimal dosing regimen for 30-minute and 3-hour meropenem infusions in critically Ill patients. Ther Drug Monit. 2016;38:593–599.
   PubMed Web of Science ®Google Scholar
• Mattioli F, Fucile C, Del BV, et al. Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients. Eur J Clin Pharmacol. 2016;72:839–848.
   PubMed Web of Science ®Google Scholar
• Ulldemolins M, Soy D, Llaurado-Serra M, et al. Meropenem population pharmacokinetics in critically ill patients with septic shock and continuous renal replacement therapy: influence of residual diuresis on dose requirements. Antimicrob Agents Chemother. 2015;59:5520–5528.
   PubMed Web of Science ®Google Scholar
• Kawano S, Matsumoto K, Hara R, et al. Pharmacokinetics and dosing estimation of meropenem in Japanese patients receiving continuous venovenous hemodialysis. J Infect Chemother. 2015;21:476–478.
   PubMed Web of Science ®Google Scholar
• Pai MP, Cojutti P, Pea F. Pharmacokinetics and pharmacodynamics of continuous infusion meropenem in overweight, obese, and morbidly obese patients with stable and unstable kidney function: a step toward dose optimization for the treatment of severe gram-negative bacterial infections. Clin Pharmacokinet. 2015;54:933–941.
   PubMed Web of Science ®Google Scholar
• Jaruratanasirikul S, Thengyai S, Wongpoowarak W, et al. Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units. Antimicrob Agents Chemother. 2015;59:2995–3001.
   PubMed Web of Science ®Google Scholar
• Ramon-Lopez A, Allen JM, Thomson AH, et al. Dosing regimen of meropenem for adults with severe burns: a population pharmacokinetic study with Monte Carlo simulations. J Antimicrob Chemother. 2015;70:882–890.
   PubMed Web of Science ®Google Scholar
• Varghese JM, Jarrett P, Wallis SC, et al. Are interstitial fluid concentrations of meropenem equivalent to plasma concentrations in critically ill patients receiving continuous renal replacement therapy? J Antimicrob Chemother. 2015;70:528–533.
   PubMed Web of Science ®Google Scholar
• Frippiat F, Musuamba FT, Seidel L, et al. Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study. J Antimicrob Chemother. 2015;70:207–216.
   PubMed Web of Science ®Google Scholar
• Langan KM, Jacob J, Li J, et al. Pharmacokinetics of short versus extended infusion meropenem dosing in critically ill patients: a pilot study. Crit Care Resusc. 2014;16:190–196.
   PubMed Web of Science ®Google Scholar
• Jaruratanasirikul S, Kositpantawong N, Jullangkoon M, et al. Pharmacodynamics of meropenem in critically ill patients with ventilator-associated pneumonia. J Med Assoc Thai. 2013;96:1283–1289.
   PubMedGoogle Scholar
• Cheatham SC, Fleming MR, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit. J Clin Pharmacol. 2014;54:324–330.
   PubMed Web of Science ®Google Scholar
• Jaruratanasirikul S, Limapichat T, Jullangkoon M, et al. Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia. Int J Antimicrob Agents. 2011;38:231–236.
   PubMed Web of Science ®Google Scholar
• Crandon JL, Ariano RE, Zelenitsky SA, et al. Optimization of meropenem dosage in the critically ill population based on renal function. Intensive Care Med. 2011;37:632–638.
   PubMed Web of Science ®Google Scholar
• Doh K, Woo H, Hur J, et al. Population pharmacokinetics of meropenem in burn patients. J Antimicrob Chemother. 2010;65:2428–2435.
   PubMed Web of Science ®Google Scholar
• Bilgrami I, Roberts JA, Wallis SC, et al. Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration. Antimicrob Agents Chemother. 2010;54:2974–2978.
   PubMed Web of Science ®Google Scholar
• Isla A, Rodríguez-Gascón A, Trocóniz IF, et al. Population pharmacokinetics of meropenem in critically ill patients undergoing continuous renal replacement therapy. Clin Pharmacokinet. 2008;47:173–180.
   PubMed Web of Science ®Google Scholar
• Krueger WA, Neeser G, Schuster H, et al. Correlation of meropenem plasma levels with pharmacodynamic requirements in critically ill patients receiving continuous veno-venous hemofiltration. Chemotherapy. 2003;49:280–286.
   PubMed Web of Science ®Google Scholar
• Robatel C, Decosterd LA, Biollaz J, et al. Pharmacokinetics and dosage adaptation of meropenem during continuous venovenous hemodiafiltration in critically ill patients. J Clin Pharmacol. 2003;43:1329–1340.
   PubMed Web of Science ®Google Scholar
• Kitzes-Cohen R, Farin D, Piva G, et al. Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients. Int J Antimicrob Agents. 2002;19:105–110.
   PubMed Web of Science ®Google Scholar
• Mohd Hafiz AA, Staatz CE, Kirkpatrick CM, et al. Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics. Minerva Anestesiol. 2012;78:94–104.
   PubMed Web of Science ®Google Scholar
• Wong G, Sime FB, Lipman J, et al. How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients? BMC Infect Dis. 2014;14:288.
   PubMed Web of Science ®Google Scholar
• Taccone FS, Laterre PF, Dugernier T, et al. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14:R126.
   PubMed Web of Science ®Google Scholar
• Delattre IK, Musuamba FT, Jacqmin P, et al. Population pharmacokinetics of four beta-lactams in critically ill septic patients comedicated with amikacin. Clin Biochem. 2012;45:780–786.
   PubMed Web of Science ®Google Scholar
• Wong G, Briscoe S, Adnan S, et al. Protein binding of beta-lactam antibiotics in critically ill patients: can we successfully predict unbound concentrations? Antimicrob Agents Chemother. 2013;57:6165–6170.
   PubMed Web of Science ®Google Scholar
• Roberts JA, Paul SK, Akova M, 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;58:1072–1083.
   PubMed Web of Science ®Google Scholar
• Tam VH, Chang KT, Zhou J, et al. Determining beta-lactam exposure threshold to suppress resistance development in Gram-negative bacteria. J Antimicrob Chemother. 2017;72:1421–1428.
   PubMed Web of Science ®Google Scholar
• Riou M, Carbonnelle S, Avrain L, et al. In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains isolated from the lower respiratory tract of Intensive Care Unit patients with nosocomial pneumonia and receiving antipseudomonal therapy. Int J Antimicrob Agents. 2010;36:513–522.
   PubMed Web of Science ®Google Scholar
• Bassetti M, Welte T, Wunderink RG. Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair? Crit Care. 2016;20:19.
   PubMed Web of Science ®Google Scholar
• Nicolau DP. Pharmacodynamic optimization of beta-lactams in the patient care setting. Crit Care. 2008;12(Suppl 4):S2.
   PubMed Web of Science ®Google Scholar