Evidence map›Paper›PMID 40119275›Full record

ArticleBMC infectious diseases2025

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

M M B Horstink, D R Geel, C A den Uil, P E Deetman, H Endeman, A Abdulla, T M Bosch, W J R Rietdijk, F W Thielen, J J Haringman and 7 more

Erratum issued Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06766461 (Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06766461 phase4recruitingnot on this map

Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis

TypeinterventionalSponsorErasmus Medical CenterRan2025 to 2027Enrolled980ConditionsSepsis - to Reduce Mortality in the Intensive Care Unit, Sepsis, Septic ShockArmsDouble dosing of beta-lactam antibiotic
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

M M B HorstinkDepartment of Intensive Care, Maasstad Hospital, Rotterdam, The Netherlands. m.horstink@erasmusmc.nl.
D R GeelRotterdam Clinical Pharmacometrics Group, Erasmus MC, Rotterdam, The Netherlands.
C A den UilDepartment of Intensive Care, Maasstad Hospital, Rotterdam, The Netherlands.
P E DeetmanDepartment of Intensive Care, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
H EndemanDepartment of Intensive Care, OLVG, Amsterdam, The Netherlands.
A AbdullaRotterdam Clinical Pharmacometrics Group, Erasmus MC, Rotterdam, The Netherlands.
T M BoschDepartment of Clinical Pharmacology & Toxicology Maasstadlab, Maasstad Hospital, Rotterdam, The Netherlands.
W J R RietdijkDepartment of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands.
F W ThielenSchool of Health Policy & Management, Erasmus University, Erasmus Centre for Health Economics Rotterdam, Rotterdam, The Netherlands.
J J HaringmanDepartment of Intensive Care, Isala Hospital, Zwolle, The Netherlands.
P van VlietDepartment of Intensive Care Haaglanden Medical Center, The Hague, The Netherlands.
T A RijpstraDepartment of Intensive Care, Amphia, Breda, The Netherlands.
C BethlehemDepartment of Intensive Care, Frisius MC, Leeuwarden, The Netherlands.
A BeishuizenDepartment of Intensive Care, Medisch Spectrum Twente, Enschede, The Netherlands.
A E MullerDepartment of Medical Microbiology, Haaglanden Medical Center, The Hague, The Netherlands.
B C P KochRotterdam Clinical Pharmacometrics Group, Erasmus MC, Rotterdam, The Netherlands.
BULLSEYE investigators

Funding

ZonMw 10140022310046
6 · The paper itself

Abstract

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. DISCUSSION: The 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.

Indexed as

Anti-Bacterial Agentsbeta-LactamsSepsisAgedbeta Lactam AntibioticsCritical IllnessFemaleHumansMaleMulticenter Studies as TopicRandomized Controlled Trials as TopicTreatment OutcomeAnti-Bacterial Agentsbeta Lactam Antibioticsbeta-LactamsAntibioticsBeta-lactamCost-effectiveness analysisCritically illIntensive careMortalityRandomized controlled trialSepsis

Identifiers

PMID40119275
PMCPMC11929207

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.