From the Guidelines
The most appropriate statement to include in the institutional guidance for therapeutic drug monitoring (TDM) regarding prolonged-infusion beta-lactam antibiotics is that important factors in the emergence of resistance to beta-lactam antibiotics with implications for TDM include the choice of antibiotics, organism burden, and minimum inhibitory concentration (MIC). This statement accurately reflects current understanding of antimicrobial resistance mechanisms and aligns with the multiorganizational international consensus recommendations 1. When implementing TDM for beta-lactam antibiotics, prescribers should consider these three key factors as they directly influence the effectiveness of therapy and the potential for resistance development. The choice of antibiotic affects target attainment based on its pharmacokinetic properties, while organism burden impacts the likelihood of resistant subpopulations emerging during treatment. The MIC is particularly crucial as it determines the concentration of antibiotic needed to inhibit bacterial growth, with higher MICs requiring more aggressive dosing strategies to maintain effective concentrations above this threshold. Understanding these relationships helps prescribers optimize beta-lactam therapy through appropriate TDM, potentially reducing treatment failures and limiting the emergence of resistance in the clinical setting.
Some key points to consider when implementing TDM for beta-lactam antibiotics include:
- The use of prolonged or continuous infusions of beta-lactam antibiotics to maximize the time that the drug concentration exceeds the MIC value, particularly for infections due to bacteria with high MIC 1.
- The importance of considering the pathophysiological status of the patient and the pharmacokinetic properties of the employed antibiotics when selecting an empiric antibiotic regimen 1.
- The need for a rational and appropriate use of antibiotics to optimize quality clinical care and reduce selection pressure on resistant pathogens 1.
- The consideration of local resistance epidemiology and individual risk factors for infection by resistant pathogens when choosing an empiric antibiotic regimen 1.
By considering these factors and implementing appropriate TDM strategies, prescribers can help to optimize beta-lactam therapy and reduce the emergence of resistance in the clinical setting.
From the Research
Prolonged-Infusion Beta-Lactam Antibiotics
- The use of prolonged-infusion beta-lactam antibiotics is a strategy to optimize antibiotic dosing and minimize the risk of antimicrobial resistance 2.
- Prolonged infusion increases the percentage of time the beta-lactam antibiotic concentration remains above the minimal inhibitory concentration (%fT>MIC), which is a key predictor of antibacterial effect 3, 4.
- However, merely increasing target attainment (or the %fT>MIC) is unlikely to lead to improved clinical outcome, as the PK/PD index and target are dynamic entities 2.
Factors Influencing Resistance
- Important factors in the emergence of resistance to beta-lactam antibiotics include the choice of antibiotics, organism burden, and minimum inhibitory concentration (MIC) 2, 4.
- The minimal inhibitory concentration is not a good denominator to describe either the emergence of resistance or toxicity, and a different approach to antibiotic dosing is necessary 2.
Therapeutic Drug Monitoring (TDM)
- TDM of beta-lactam antibiotics has shown an ability to increase the rate of target attainment, but there is currently limited evidence to suggest that it leads to improved clinical outcomes 3, 5.
- Evaluation of beta-lactam concentrations is best accomplished using population PK software and Bayesian modeling 3.
- A range of exposures between 50 and 100% fT > MIC are reasonable to define the beta-lactam TDM therapeutic window for most infections 6.