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Krankenhaushygiene up2date 2017; 12(01): 59-71
DOI: 10.1055/s-0042-123738
CME-Fortbildung
Antiinfektiva
© Georg Thieme Verlag KG Stuttgart · New York

Therapeutisches Drug-Monitoring in der antiinfektiven Therapie

Alexander Brinkmann
,
Anka Christa Röhr
,
Wolfgang Artur Krüger
,
Otto Roman Frey
Subject Editor: PD Dr. med. Sebastian Schulz-Stübner
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Publication History

Publication Date:
24 March 2017 (online)

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Krankheitsprozesse im Körper haben erheblichen Einfluss auf die Pharmakokinetik von Medikamenten und können zu Störungen der Arzneistoffaufnahme, deren Verteilung, Metabolisierung und Ausscheidung führen – und somit zu unvorhersehbaren Konzentrationen im Serum und am Wirkort [7] [8] [9] [10] [11] [12]. Trotzdem kommt häufig eine Standarddosierung zum Einsatz, die beim septischen Patienten Behandlungsziele verfehlen kann. Therapeutisches Drug Monitoring (TDM) ermöglicht eine individuelle Dosierung, um die Variabilität der Pharmakokinetik bei Intensivpatienten zu berücksichtigen.

Kernaussagen

  • Das Messen von Antiinfektiva-Serumkonzentrationen im Rahmen eines therapeutischen Drug-Monitorings/-Managements kann:

    • den diagnostischen Blick verfeinern und

    • die Effektivität der antiinfektiven Therapie optimieren sowie

    • unerwünschte Wirkungen und Arzneimittelinteraktionen verhindern.

  • Neben der kontinuierlichen Applikation, die aus unserer Sicht eine Messung der Arzneistoffkonzentrationen zwingend voraussetzt, kann alternativ die prolongierte Applikation von β-Laktam-Antibiotika über einen Zeitraum von 3 – 4 h zur Optimierung der Therapie beitragen.

  • Vor allem die Antibiotikatherapie bei Intensivpatienten ist heute sicher mehr als nur eine Frage der richtigen Substanz und einer zeitnahen Applikation.

 

  • Literatur

  • 1 Bloos F, Ruddel TD, Ruddel H. et al. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. Crit Care 2014; 18: R42
    CrossrefGoogle Scholar
  • 2 Vazquez-Guillamet C, Scolari M, Zilberberg MD. et al. Using the number needed to treat to assess appropriate antimicrobial therapy as a determinant of outcome in severe sepsis and septic shock. Crit Care Med 2014; 42: 2342-2349
    CrossrefGoogle Scholar
  • 3 Zilberberg MD, Shorr AF, Micek ST. et al. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 2014; 18: 596
    CrossrefGoogle Scholar
  • 4 Kumar A, Roberts D, Wood KE. 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: 1589-1596
    CrossrefGoogle Scholar
  • 5 Harbarth S, Nobre V, Pittet D. Does antibiotic selection impact patient outcome?. Clin Infect Dis 2007; 44: 87-93
    CrossrefGoogle Scholar
  • 6 Frey OR, Helbig S, Röhr AC. et al. Fragen und Antworten zur individuellen Dosierung von ß-Lactam-Antibiotika bei kritisch Kranken. Intensiv-News 2015; 19: 30-33
    Google Scholar
  • 7 Roberts JA, Abdul-Aziz MH, Lipman J. et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498-509
    CrossrefGoogle Scholar
  • 8 Abdul-Aziz MH, Lipman J, Mouton JW. et al. Applying pharmacokinetic/pharmacodynamic principles in critically ill patients: optimizing efficacy and reducing resistance development. Semin Respir Crit Care Med 2015; 36: 136-153
    Article in Thieme ConnectGoogle Scholar
  • 9 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
    CrossrefGoogle Scholar
  • 10 De Waele JJ, Lipman J, Akova M. et al. Risk factors for target non-attainment during empirical treatment with beta-lactam antibiotics in critically ill patients. Intensive Care Med 2014; 40: 1340-1351
    CrossrefGoogle Scholar
  • 11 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
    CrossrefGoogle Scholar
  • 12 Lodise TP, Sorgel F, Melnick D. et al. Penetration of meropenem into epithelial lining fluid of patients with ventilator-associated pneumonia. Antimicrob Agents Chemother 2011; 55: 1606-1610
    CrossrefGoogle Scholar
  • 13 Vincent JL, Bassetti M, Francois B. et al. Advances in antibiotic therapy in the critically ill. Crit Care 2016; 20: 133
    CrossrefGoogle Scholar
  • 14 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
    CrossrefGoogle Scholar
  • 15 Wong G, Brinkmann 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
    CrossrefGoogle Scholar
  • 16 Brinkmann A, Röhr A, Köberer A. et al. Therapeutisches Drug Monitoring und individualisierte Dosierung von Beta-Lactam-Antibiotika bei Intensivpatienten. In: Eckart J, Forst H, Briegel J. Hrsg. Intensivmedizin. 66. Aktualisierung 4/15 Edition. Landsberg am Lech: ecomed Medizin; 2015: 1-18
    Google Scholar
  • 17 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
    Google Scholar
  • 18 de With K, Allerberger F, Amann S. et al. S3-Leitlinie: Strategien zur Sicherung rationaler Antibiotika-Anwendung im Krankenhaus. AWMF. Register-Nr. 092/001, Version 15.12.2013. Im Internet: 2013 www.awmf.org/leitlinien/detail/ll/092-001.html (Stand: 2012.2016)
    Google Scholar
  • 19 van Lent-Evers NA, Mathot RA, Geus WP. et al. Impact of goal-oriented and model-based clinical pharmacokinetic dosing of aminoglycosides on clinical outcome: a cost-effectiveness analysis. Ther Drug Monit 1999; 21: 63-73
    CrossrefGoogle Scholar
  • 20 Tabah A, De WJ, Lipman J. et al. The ADMIN-ICU survey: a survey on antimicrobial dosing and monitoring in ICUs. J Antimicrob Chemother 2015; 70: 2671-2677
    CrossrefGoogle Scholar
  • 21 Abdul-Aziz MH, Sulaiman H, Mat-Nor MB. 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: 1535-1545
    CrossrefGoogle Scholar
  • 22 Eagle H, Fleischman R, Musselman AD. Effect of schedule of administration on the therapeutic efficacy of penicillin; importance of the aggregate time penicillin remains at effectively bactericidal levels. Am J Med 1950; 9: 280-299
    CrossrefGoogle Scholar
  • 23 Drusano GL. Antimicrobial pharmacodynamics: Critical interactions of 'bug and drug'. Nat Rev Microbiol 2004; 2: 289-300
    CrossrefGoogle Scholar
  • 24 Drusano GL, Lodise TP, Melnick D. et al. Meropenem penetration into epithelial lining fluid in mice and humans and delineation of exposure targets. Antimicrob Agents Chemother 2011; 55: 3406-3412
    CrossrefGoogle Scholar
  • 25 Tam VH, Gamez EA, Weston JS. et al. Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint. Clin Infect Dis 2008; 46: 862-867
    CrossrefGoogle Scholar
  • 26 George JM, Colton BJ, Rodvold KA. National survey on continuous and extended infusions of antibiotics. Am J Health Syst Pharm 2012; 69: 1895-1904
    CrossrefGoogle Scholar
  • 27 Buyle FM, Decruyenaere J, De WJ. et al. 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: 763-768
    CrossrefGoogle Scholar
  • 28 Shiu J, Wang E, Tejani AM. et al. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections. Cochrane Database Syst Rev 2013; CD008481 DOI: 10.1002/14651858.CD008481.pub2.
    Google Scholar
  • 29 Lodise Jr. TP, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis 2007; 44: 357-363
    CrossrefGoogle Scholar
  • 30 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
    CrossrefGoogle Scholar
  • 31 Roberts JA, Abdul-Aziz MH, Davis JS. et al. 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: 681-691
    CrossrefGoogle Scholar
  • 32 Yang H, Zhang C, Zhou Q. et al. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. PLoS ONE 2015; 10: 1-13 e0116769
    Google Scholar
  • 33 Rhomberg PR, Fritsche TR, Sader HS. et al. Antimicrobial susceptibility pattern comparisons among intensive care unit and general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test Information Collection Program (USA). Diagn Microbiol Infect Dis 2006; 56: 57-62
    CrossrefGoogle Scholar
  • 34 Donadello K, Antonucci E, Cristallini S. et al. beta-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study. Int J Antimicrob Agents 2015; 45: 278-282
    CrossrefPubMedGoogle Scholar
  • 35 Jamal JA, Mueller BA, Choi GY. et al. How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?. Diagn Microbiol Infect Dis 2015; 82: 92-103
    CrossrefGoogle Scholar
  • 36 Bias M, Frey OR, Köberer A. HPLC-Methode zur quantitativen Bestimmung von Meronem im Serum. Krankenhauspharmazie 2010; 31: 482-486
    Google Scholar
  • 37 Brinkmann A, Köberer A, Fuchs TH. et al. Drug Monitoring bei der Sepsis – modisch oder nur „modern“? Journal für Anästhesie und Intensivbehandlung (24. Internationales Symposium Intensivmedizin und Intensivpflege). 2014; 2: 9-14
    Google Scholar
  • 38 Frey OR. Therapeutisches Drug-Monitoring (TDM). Krankenhauspharmazie 2009; 30: 222-224
    Google Scholar
  • 39 Woermann A. Pharmakoökonomische Überlegungen zur kontinuierlichen Infusion von ß-Lactam-Antibiotika unter Serumspiegelkontrolle am Beispiel von Meropenem und Piperacillin/Tazobactam [Masterarbeit, Master of Sience]. Dresden, Germany: Dresden International University; 2015: 58
    Google Scholar