Standard versus double dosing of beta-lactam antibiotics in critically ill patients with sepsis: The BULLSEYE study protocol for a multicenter randomized controlled trial

被引:0
作者
Horstink, M. M. B. [1 ,2 ]
Geel, D. R. [2 ,3 ]
Uil, C. A. den [1 ]
Deetman, P. E. [4 ]
Endeman, H. [5 ,6 ]
Abdulla, A. [2 ,3 ]
Bosch, T. M. [7 ,8 ]
Rietdijk, W. J. R. [3 ]
Thielen, F. W. [9 ]
Haringman, J. J. [10 ]
van Vliet, P. [11 ]
Rijpstra, T. A. [12 ]
Bethlehem, C. [13 ]
Beishuizen, A. [14 ]
Muller, A. E. [15 ]
Koch, B. C. P. [2 ,3 ]
BULLSEYE Investigators, C.
机构
[1] Maasstad Hosp, Dept Intens Care, Rotterdam, Netherlands
[2] Erasmus MC, Rotterdam Clin Pharmacometr Grp, Rotterdam, Netherlands
[3] Erasmus MC, Dept Hosp Pharm, Rotterdam, Netherlands
[4] Albert Schweitzer Hosp, Dept Intens Care, Dordrecht, Netherlands
[5] OLVG, Dept Intens Care, Amsterdam, Netherlands
[6] Erasmus MC, Dept Intens Care, Rotterdam, Netherlands
[7] Maasstad Hosp, Dept Clin Pharmacol & Toxicol, MaasstadLab, Rotterdam, Netherlands
[8] Maasstad Hosp, Dept Hosp Pharm, Rotterdam, Netherlands
[9] Erasmus Univ, Erasmus Ctr Hlth Econ Rotterdam, Erasmus Sch Hlth Policy & Management, Rotterdam, Netherlands
[10] Isala Hosp, Dept Intens Care, Zwolle, Netherlands
[11] Haaglanden Med Ctr, Dept Intens Care, The Hague, Netherlands
[12] Amphia Hosp, Dept Intens Care, Breda, Netherlands
[13] Med Ctr Leeuwarden Zuid, Dept Intens Care, Leeuwarden, Netherlands
[14] Med Spectrum Twente, Dept Intens Care, Enschede, Netherlands
[15] Haaglanden Med Ctr, Dept Med Microbiol, The Hague, Netherlands
关键词
Sepsis; Beta-lactam; Antibiotics; Critically ill; Intensive care; Randomized controlled trial; Mortality; Cost-effectiveness analysis; CARE; EPIDEMIOLOGY;
D O I
10.1186/s12879-025-10747-3
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
BackgroundSepsis and septic shock are significant global healthcare challenges with high mortality rates. Effective management requires timely and adequate antimicrobial therapy. Beta-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.Previous randomized controlled trials highlighted the need for timely dose adjustments to improve clinical outcomes. This is the study protocol for the BULLSEYE trial in which we aim to optimize antibiotic treatment during the initial 48 h of sepsis by comparing standard to double dosing of beta-lactam antibiotics.BackgroundSepsis and septic shock are significant global healthcare challenges with high mortality rates. Effective management requires timely and adequate antimicrobial therapy. Beta-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.Previous randomized controlled trials highlighted the need for timely dose adjustments to improve clinical outcomes. This is the study protocol for the BULLSEYE trial in which we aim to optimize antibiotic treatment during the initial 48 h of sepsis by comparing standard to double dosing of beta-lactam antibiotics.MethodsThis open-label, multicenter, randomized controlled trial will compare standard to double dosing of beta-lactam antibiotics (cefuroxime, ceftazidime, ceftriaxone, cefotaxime, amoxicillin, amoxicillin/clavulanic acid, flucloxacillin, meropenem, and piperacillin/clavulanic acid) in critically ill patients with septic shock. Participants will be randomized into two arms: the control arm receiving standard care, and the intervention arm receiving double antibiotic doses for 48 h, 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.DiscussionThe BULLSEYE trial aims to improve sepsis treatment in critically ill patients. Despite anticipated recruitment challenges, its large sample size ensures robust comparability. This pivotal trial could significantly impact sepsis treatment, leading to better clinical outcomes.Trial registrationEU_CT 2024-512950-13-00. Protocol version 2.3, protocol date 09-12-2024. Prospectively registered on 09-01-2025 at Clinicaltrails.gov nr. NCT06766461.
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