Target Audience:

Who should attend:

• Clinical faculty from the University of Pittsburgh School of Pharmacy
• Clinical staff pharmacists employed by the University of Pittsburgh Medical Center and deployed throughout the hospital campus in unit based roles and centrally in the department of pharmacy's main pharmacy
• Student pharmacy interns currently working within the department of pharmacy
• Certified Pharmacy Technicians

Abstract
Beta-Lactams are the most common antimicrobials in the intensive care unit (ICU). It is known there are several factors which predispose ICU patients to pharmacokinetic (PK) and pharmacodynamics (PD) variability. 1 Several interprofessional organizations recognize this variability and subsequently recommend therapeutic drug monitoring as a modality to optimize attainment of PK/PD targets; however, this is not routinely done in clinical practice. 1,2,6

The DALI study11 demonstrates patients who did not achieve the PK target of 50% fT>MIC were 32% less likely to achieve a positive clinical outcome. While there is a lack of randomized controlled trials to assess the efficacy and safety of therapeutic drug monitoring in ICU patients, therapeutic drug monitoring of beta-lactams currently remains controversial. This presentation seeks to describe the alterations of PK/PD in critically ill patients, to evaluate current evidence and recommendations for the use of therapeutic drug monitoring, and to recognize best practices for implementation of therapeutic drug monitoring of beta-lactams within clinical practice.

Educational Objectives:

Upon successful completion of this continuing pharmacy education program, the participant should be able to:

• Describe pharmacokinetic and pharmacodynamic changes of beta-lactams in critically ill patients.
• Discuss the available evidence for therapeutic drug monitoring of beta-lactams.
• Evaluate unique patient populations that may benefit from beta-lactam therapeutic drug monitoring.

Pharmacy Continuing Education Credits In support of improving patient care, the University of Pittsburgh is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.. The assigned universal program number(s) is JA4008223-0000-23-072-H01-P .  This knowledge-based activity provides 1  contact hours of continuing pharmacy education credit.

Suggested Additional Reading:

1. 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 (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine. Crit Care. 2019;23:104.
2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304-377.Clinical and Experimental Pharmacology and Physiology. 2012; 39(6):489-96
3. Varghese JM, Roberts JA, Lipman J. Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock. Crit Care Clin. 2011;27(1):19-34.
4. 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;36:332–9.
5. 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(3):486-552.
6. 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(6):1127-1153.
7. Wong G, Brinkman A, Benefield RJ, Carlier M, De Waele JJ, El Helali N, et al. An international, multicentre survey of β-lactam antibiotic therapeutic drug monitoring practice in intensive care units. J Antimicrob Chemother. 2014; 69:1416–23.
8. Wong G, et al. Protein binding of β-lactam antibiotics in critically Ill patients: can we successfully predict unbound concentrations? Antimicrob Agents Chemother. 2013;57(12):6165–70.
9. Power BM, Forbes AM, van Heerden PV, et al. Pharmacokinetics of drugs used in critically ill adults. Clin Pharmacokinet. 1998; 34:25–56.
10. Joukhadar C, Frossard M, Mayer BX, et al. Impaired target site penetration of beta-lactams may account for therapeutic failure in patients with septic shock. Crit Care Med 2001;29(2):385–91.
11. Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients?. Clin Infect Dis. 2014;58(8):1072-1083
12. De Waele, JS. Carrette, M. Carlier, V. et al. "Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial." Intensive Care Med. 2014;40:380-387