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Detailed paper information
| Paper title | Optimizing β‑lactam antibiotic exposure in critically ill patients |
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| Paper code | A05 |
| Authors | |
| Form of presentation | Oral abstract presentation |
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| Abstract text |
INTRODUCTION Sepsis and septic shock are significant global healthcare challenges with high mortality rates. (1, 2) Effective management requires timely and adequate antimicrobial therapy. β‑lactam antibiotics, commonly used in patients with sepsis, are crucial for treating these infections. However, standard dosing often leads to insufficient plasma levels due to dynamic physiological changes in critically ill patients. (3) OBJECTIVES To optimize clinical outcomes in critically ill patients by improving exposure to β‑lactam antibiotics. METHODS In recent years, several changes in dosing strategies have been studied to enhance β‑lactam antibiotic exposure in the critically ill. One strategy is to shift from intermittent to continuous infusion. The latter, while being associated with higher clinical cure when using meropenem or piperacillin/tazobactam, did not translate into a mortality benefit. (4) Another strategy is the use of therapeutic drug monitoring (TDM) or model-informed precision dosing (MIPD). MIPD dosing of β‑lactams in critically ill patients was not significantly associated with hospital length of stay or mortality in all patients. (5) However, post-hoc analyses revealed that MIPD in the first phase of treatment or in patients with a lower SOFA score might be beneficial. These findings resulted in a more pragmatic approach, namely higher β‑lactam dosages in patients with severe infections. This strategy is currently under investigation by the HIT-HARD and BULLSEYE study groups. (6) The BULLSEYE study is an open-label, multicenter, randomized controlled trial that compares standard to double dosing of β‑lactam antibiotics in critically ill patients with septic shock. Participants are randomized into two arms: the control group receiving standard care, and the intervention group receiving double antibiotic doses for 48 hours, irrespective of renal function. Following this period, all patients will receive standard doses as per local protocol. The primary outcome is all cause 28-day mortality, with secondary outcomes including 90-day, 365-day, hospital and ICU mortality, hospital and ICU length of stay, SOFA scores, time to shock reversal, microbiological eradication, clinical cure, pharmacodynamic target attainment, safety, quality of life, and medical consumption. CONCLUSIONS At this moment, better β‑lactam exposure in critically ill patients is needed. Multiple strategies are and have been under investigation, from continuous infusion and therapeutic drug monitoring to improved renal‑based dosing and higher dosing, but the optimal strategy, or combination of strategies, has yet to be identified. Ongoing research, including several large clinical trials, is expected to provide valuable insights in the coming years, with the ultimate goal of improving outcomes for this vulnerable patient population. |