Krankenhaushygiene up2date 2021; 16(02): 187-201
DOI: 10.1055/a-1173-5813
Antiinfektiva

Therapeutisches Drug Monitoring (TDM) in der antiinfektiven Therapie – von der Theorie zur Praxis

Alexander Brinkmann
,
Anka Röhr
,
Daniel Richter
,
Ute Chiriac
,
Otto Roman Frey

Die Medusa-Studie zeigte, dass in Deutschland nur etwa 58 % der Patienten mit schwerer Sepsis und septischem Schock eine adäquate Antibiotikatherapie erhielten [1], die einen klaren Überlebensvorteil von 11 % bot. Neben eines septischen Schocks und multiresistenter Erreger (MRE) ist eine inadäquate Antibiotikatherapie bei septischen Patienten eine unabhängige Variable der Gesamtmortalität [2].

Kernaussagen
  • Das Messen von Serumkonzentrationen im Rahmen eines therapeutischen Drug Monitorings/Managements kann den diagnostischen Blick verfeinern und die antiinfektive Therapie optimiere.

  • Mit TDM lassen sich UAWs und Arzneimittelinteraktionen verhindern.

  • Neben der kontinuierlichen Applikation, die aus unserer Sicht eine Messung der Arzneistoffkonzentrationen zwingend voraussetzt, kann alternativ die prolongierte Applikation von β-Lactam-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.



Publication History

Article published online:
18 May 2021

© 2021. Thieme. All rights reserved.

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  • Literatur

  • 1 Bloos F, Thomas-Rüddel D, Rüddel 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
  • 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
  • 3 Bloos F, Rüddel H, Thomas-Rüddel D. et al. Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial [Epub ahead of print]. Intensive Care Med 2017; 43: 1602-1612 DOI: 10.1007/s00134-017-4782-4.
  • 4 Richter DC, Heininger A, Brenner T. et al. Bacterial sepsis: Diagnostics and calculated antibiotic therapy. Anaesthesist 2019; 68: 40-62 DOI: 10.1007/s00101-017-0396-z.
  • 5 Brinkmann A, Röhr AC, Frey OR. et al. S2k-Leitlinie der PEG zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen bei Erwachsenen Fokussierte Zusammenfassung und ergänzende Informationen zur Antibiotikatherapie kritisch kranker Patienten. Anaesthesist 2018; 67: 936-949 DOI: 10.1007/s00101-018-0512-8.
  • 6 Harbarth S, Nobre V, Pittet D. Does antibiotic selection impact patient outcome?. Clin Infect Dis 2007; 44: 87-93
  • 7 Abdul-Aziz MH, Alffenaar JC, Bassetti M. et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper. Intensive Care Med 2020; 46: 1127-1153 DOI: 10.1007/s00134-020-06050-1.
  • 8 Guilhaumou R, Benaboud S, Bennis Y. et al. Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Societe Francaise de Pharmacologie et Therapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Societe Francaise d'Anesthesie et Reanimation-SFAR). Crit Care 2019; 23: 104
  • 9 Brinkmann A, Richter DC, Frey OR. et al. Applikation von ß-Lactam-Antibiotika bei kritisch Kranken: Bolus oder prolongiert/kontinuierlich?. Intensiv-News 2019; 23: 13-15
  • 10 Roberts JA, bdul-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
  • 11 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
  • 12 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
  • 13 Bodmann KF, Hohl R, Krüger W. et al. Calculated initial parenteral treatment of bacterial infections: Sepsis. GMS Infect Dis 2020; DOI: 10.3205/id000053.
  • 14 Derendorf H, Heinrichs T, Reimers T. et al. Calculated initial parenteral treatment of bacterial infections: Pharmacokinetics and pharmacodynamics. GMS Infect Dis 2020; DOI: 10.3205/id000061.
  • 15 Brinkmann A, Röhr AC, Köberer A. et al. Therapeutisches Drug Monitoring und individualisierte Dosierung von Antibiotika bei der Sepsis Modern oder nur „modisch"?. Med Klin Intensivmed Notfmed 2018; 113: 82-93
  • 16 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
  • 17 Frey OR, Köberer A, Röhr AC. et al. Therapeutisches Drug Monitoring (TDM) von Antiinfektiva bei kritisch Kranken. Intensiv-News 2013; 17: 16-18
  • 18 Brinkmann A, Röhr AC, Köberer A. et al. Adäquate Antiinfektivatherapie Bedeutung der individuellen Dosierung und Applikation [Adequate anti-infective treatment : Importance of individual dosing and application]. Anaesthesist 2018; 67: 461-476 DOI: 10.1007/s00101-018-0443-4.
  • 19 Röhr AC, Köberer A, Fuchs TH. et al. Individuelle Dosierung und Applikation von Antiinfektiva auf der Intensivstation. Intensivmedizin up2date 2018; 14: 238-243 DOI: 10.1055/a-0626-8184.
  • 20 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
  • 21 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
  • 22 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
  • 23 Brunkhorst FM, Weigand M, Pletz M. S3-Leitlinie Sepsis – Prävention, Diagnose, Therapie und Nachsorge AWMF-Registernummer: 079 001 Langversion 3.1. Deutsche Sepsis Gesellschaft e.V. (federführend); 2018 Verfügbar unter (Stand 18.02.2021): https://www.awmf.org/uploads/tx_szleitlinien/079-001m_S3_Sepsis-Praevention-Diagnose-Therapie-Nachsorge_2020-03.pdf
  • 24 de With K, Wilke K, Kern W. et al. S3- Leitlinie Strategien zur Sicherung rationaler Antibiotika-Anwendung im Krankenhaus, AWMF-Registernummer 092/001 – update 2018. Verfügbar unter (Stand 18.02.2021): https://www.awmf.org/uploads/tx_szleitlinien/092-001l_S3_Strategien-zur-Sicherung-rationaler-Antibiotika-Anwendung-im-Krankenhaus_2020-02.pdf
  • 25 Rhodes A, Evans LE, Alhazzani W. et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017; 45: 486-552
  • 26 Jacobs A, Taccone FS, Roberts JA. et al. beta-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance. Antimicrob Agents Chemother 2018; 62
  • 27 Felton TW, Ogungbenro K, Boselli E. et al. Comparison of piperacillin exposure in the lungs of critically ill patients and healthy volunteers. J Antimicrob Chemother 2018; 73: 1340-1347 DOI: 10.1093/jac/dkx541.
  • 28 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
  • 29 Blassmann U, Frey OR, Röhr AC. et al. Therapeutisches Drug-Monitoring von Antibiotika bei kritisch kranken Intensivpatienten. Krankenhauspharmazie 2020; 41: 407-415
  • 30 Roberts JA, Joynt G, Lee A. et al. The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: Data from the multinational SMARRT Study. Clin Infect Dis 2020; 1369-1378
  • 31 Richter DC, Frey O, Roehr A. et al. Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience. Infection 2019; 47: 1001-1011 DOI: 10.1007/s15010-019-01352-z.
  • 32 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
  • 33 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 DOI: 10.1093/jac/dkv201.
  • 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
  • 35 König C, Röhr AC, Frey OR. et al. In vitro removal of anti-infective agents by a novel cytokine adsorbent system. Int J Artif Organs 2018; DOI: 10.1177/0391398818812601.
  • 36 Sime FB, Roberts JA. Antibiotic Dosing In Critically Ill Patients Receiving Renal Replacement Therapy. Expert Rev Clin Pharmacol 2016; 1-3
  • 37 Imani S, Buscher H, Marriott D. et al. Too much of a good thing: a retrospective study of beta-lactam concentration-toxicity relationships. J Antimicrob Chemother 2017; 72: 2891-2897
  • 38 Bellos I, Karageorgiou V, Pergialiotis V. et al. Acute kidney injury following the concurrent administration of antipseudomonal beta-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect 2020; 26: 696-705
  • 39 Mouton JW, Meletiadis J, Voss A. et al. Variation of MIC measurements: the contribution of strain and laboratory variability to measurement precision. J Antimicrob Chemother 2018; 73: 2374-2379
  • 40 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
  • 41 Scharf C, Liebchen U, Paal M. et al. The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome. J Intensive Care 2020; 8: 86 DOI: 10.1186/s40560-020-00504-w.
  • 42 Wong G, Taccone F, Villois P. et al. beta-Lactam pharmacodynamics in Gram-negative bloodstream infections in the critically ill. J Antimicrob Chemother 2020; 75: 429-433
  • 43 Drusano GL. Antimicrobial pharmacodynamics: critical interactions of 'bug and drug'. Nat Rev Microbiol 2004; 2: 289-300
  • 44 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 DOI: 10.1093/jac/dkv165.
  • 45 Liebchen U, Paal M, Scharf C. et al. The ONTAI study - a survey on antimicrobial dosing and the practice of therapeutic drug monitoring in German intensive care units. J Crit Care 2020; 60: 260-266
  • 46 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
  • 47 Bao H, Lv Y, Wang D. et al. Clinical outcomes of extended versus intermittent administration of piperacillin/tazobactam for the treatment of hospital-acquired pneumonia: a randomized controlled trial. Eur J Clin Microbiol Infect Dis 2017; 36: 459-466 DOI: 10.1007/s10096-016-2819-1.
  • 48 Lipman J, Brett SJ, De Waele JJ. et al. A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis: BLING III. Crit Care Resusc 2019; 21: 63-68
  • 49 Bias M, Frey OR, Köberer A. HPLC-Methode zur quantitativen Bestimmung von Meronem im Serum. Krankenhauspharmazie 2010; 31: 482-486
  • 50 Woermann A. Pharmakoökonomische Überlegungen zur kontinuierlichen Infusion von ß Lactam-Antibiotika unter Serumspiegelkontrolle am Beispiel von Meropenem und Piperacillin/Tazobactam 2015; „Master of Science" im Rahmen des Masterstudiengangs „Krankenhauspharmazie". Dresden International University (DIU).