From the Guidelines
Severely ill adults would benefit most from the use of prolonged-infusion beta-lactam antibiotics instead of short-infusion beta-lactam antibiotics to reduce mortality or increase clinical cure. This recommendation is based on evidence showing that extended or continuous infusions of beta-lactam antibiotics provide more consistent therapeutic drug concentrations in critically ill patients, which is particularly important for time-dependent antibiotics like beta-lactams 1. In severely ill patients, physiological changes such as increased volume of distribution, augmented renal clearance, and altered protein binding can significantly impact antibiotic pharmacokinetics, potentially leading to subtherapeutic levels with traditional short infusions. Prolonged infusions help maintain drug concentrations above the minimum inhibitory concentration (MIC) for a greater percentage of the dosing interval, which correlates with improved clinical outcomes in this vulnerable population.
Some key points to consider include:
- The use of continuous or prolonged administration of beta-lactam antibiotics in the most severe patients, in case of high MIC bacteria, and in case of lower respiratory tract infection to improve clinical cure 1.
- The definition of free plasma concentration between four and eight times the MIC of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses 1.
- Common beta-lactams that benefit from prolonged infusion include piperacillin-tazobactam (typically 3.375-4.5g infused over 3-4 hours every 6-8 hours), meropenem (1-2g infused over 3 hours every 8 hours), and cefepime (1-2g infused over 3 hours every 8 hours) 1.
- The other patient populations mentioned (non-severely ill adults, obese patients, and pediatric patients) have not demonstrated the same consistent mortality benefit from prolonged infusions in clinical studies.
Overall, the evidence suggests that prolonged-infusion beta-lactam antibiotics can improve clinical outcomes in severely ill adults by providing more consistent therapeutic drug concentrations and maximizing bacteriological and clinical responses 1.
From the Research
Patient Populations for Prolonged-Infusion Beta-Lactam Antibiotics
The use of prolonged-infusion beta-lactam antibiotics has been studied in various patient populations to determine its benefits in reducing mortality or increasing clinical cure. According to the multiorganizational international consensus recommendations by Hong and colleagues, the following patient populations may benefit from prolonged-infusion beta-lactam antibiotics:
- Severely ill adults: This population is most likely to benefit from prolonged-infusion beta-lactam antibiotics, as they often have severe infections that require optimized antibiotic treatment 2, 3, 4.
- Non-severely ill adults, pediatric patients, and obese patients: While there is some evidence to suggest that these populations may also benefit from prolonged-infusion beta-lactam antibiotics, the evidence is less clear and more research is needed to determine the optimal use of this treatment in these groups 2, 3.
Key Considerations
When considering the use of prolonged-infusion beta-lactam antibiotics, several key factors must be taken into account, including:
- Pharmacokinetic and pharmacodynamic targets: Prolonged-infusion beta-lactam antibiotics can help achieve optimal pharmacokinetic and pharmacodynamic targets, particularly in patients with severe infections 5, 2.
- Therapeutic drug monitoring: Therapeutic drug monitoring can help ensure that patients are receiving optimal doses of beta-lactam antibiotics and can help minimize the risk of adverse effects 5, 2.
- Patient-specific factors: Patient-specific factors, such as renal function and body weight, must be taken into account when determining the optimal dose and administration schedule for beta-lactam antibiotics 2, 3.