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

Area of Science:

• Pharmacology
• Infectious Diseases
• Clinical Pharmacy

Background:

• Precision dosing for antibiotics is debated due to perceived insufficient evidence.
• Current practices may not fully leverage pharmacokinetic/pharmacodynamic (PK/PD) principles.
• Variability in patient factors and pathogen susceptibility complicates standard dosing.

Purpose of the Study:

• To argue that adequate evidence exists for implementing therapeutic drug monitoring (TDM) in antibiotic therapy.
• To demonstrate how TDM can precisely target antibiotic exposures for optimized clinical outcomes.
• To advocate for TDM as a standard of care, even without further large-scale trials.

Main Methods:

• Review and synthesis of existing evidence on antibiotic exposure-response relationships.
• Application of stochastic control principles to optimize probability of favorable responses.
• Modeling approaches to account for target variability (e.g., Minimum Inhibitory Concentration [MIC]).
• Consideration of patient-specific factors modifying drug exposure and effect.

Main Results:

• Adequate evidence supports the use of TDM for precise antibiotic dosing.
• Stochastic control strategies can optimize treatment success probabilities across patient populations.
• Precision dosing models can incorporate target variability and patient-specific factors.
• TDM can inform, rather than rigidly protocolize, clinical decision-making.

Conclusions:

• Therapeutic drug monitoring (TDM) is supported by sufficient evidence to become a standard of care for many antibiotics.
• Precision antibiotic dosing, informed by TDM, enhances the probability of favorable patient responses.
• Further randomized trials are not essential to establish TDM as standard practice.