The case for precision dosing: medical conservatism does not justify inaction

Author:

Scheetz Marc H123ORCID,Lodise Thomas P4,Downes Kevin J567ORCID,Drusano George8,Neely Michael9

Affiliation:

1. Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA

2. Pharmacometric Center of Excellence, Midwestern University, Downers Grove, IL, USA

3. College of Graduate Studies, Midwestern University, Downers Grove, IL, USA

4. Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA

5. Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA

6. Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA

7. Center for Clinical Pharmacology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

8. Institute for Therapeutic Innovation, College of Medicine, University of Florida, Orlando, FL, USA

9. Children’s Hospital Los Angeles and University of Southern California, Los Angeles, CA, USA

Abstract

Abstract The need for precision dosing has been challenged on the basis of insufficient evidence. Herein, we argue that adequate evidence exists to conduct therapeutic drug monitoring (TDM) and precisely target antibiotic exposures. While achievement of any antibiotic concentration does not guarantee efficacy sans toxicity for any single patient, stochastic control optimizes the probability of achieving favourable responses across patients. We argue that variability in targets (such as the organism’s MIC) can be considered with models. That is, complexity alone does not relegate the decision-making framework to ‘clinician intuition’. We acknowledge the exposure–response relationships are modified by patient-specific factors (other drugs, baseline organ functional status etc.) and describe how precision dosing can inform clinical decision making rather than protocolize it. Finally, we call for randomized, controlled trials; however, we suggest that these trials are not necessary to make TDM standard of care for multiple classes of antibiotics.

Funder

Eunice Kennedy Shriver National Institute of Child Health & Human Development

National Institutes of Health

Merck, Inc

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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