TY - JOUR
T1 - Role of immunosuppression in an antibiotic stewardship intervention and its association with clinical outcomes and antibiotic use
T2 - protocol for an observational study (RISC-sepsis)
AU - Scott, Jonathan
AU - Trevi, Loredana
AU - McNeil, Hannah
AU - Ewen, Tom
AU - Mawson, Phil
AU - McDonald, David
AU - Filby, Andrew
AU - Lall, Ranjit
AU - Booth, Katie
AU - Boschman, Gert
AU - Melkebeek, Vesna
AU - Perkins, Gavin
AU - McMullan, Ronan
AU - McAuley, Daniel F
AU - McCullagh, Iain J
AU - Walsh, Timothy
AU - Rostron, Anthony
AU - Shankar-Hari, Manu
AU - Dark, Paul
AU - Simpson, A John
AU - Conway Morris, Andrew
AU - Hellyer, Thomas P
N1 - © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
PY - 2022/12/9
Y1 - 2022/12/9
N2 - INTRODUCTION: Sepsis is characterised by a dysregulated immune response to infection, with exaggerated pro-inflammatory and anti-inflammatory responses. A predominant immunosuppressive profile affecting both innate and adaptive immune responses is associated with increased hospital-acquired infection and reduced infection-free survival. While hospital-acquired infection leads to additional antibiotic use, the role of the immunosuppressive phenotype in guiding complex decisions, such as those affecting antibiotic stewardship, is uncertain. This study is a mechanistic substudy embedded within a multicentre clinical and cost-effectiveness trial of biomarker-guided antibiotic stewardship. This mechanistic study aims to determine the effect of sepsis-associated immunosuppression on the trial outcome measures.METHODS AND ANALYSIS: RISC-sepsis is a prospective, multicentre, exploratory, observational study embedded within the ADAPT-sepsis trial. A subgroup of 180 participants with antibiotics commenced for suspected sepsis, enrolled in the ADAPT-sepsis trial, will be recruited. Blood samples will be collected on alternate days until day 7. At each time point, blood will be collected for flow cytometric analysis into cell preservation tubes. Immunophenotyping will be performed at a central testing hub by flow cytometry. The primary outcome measures are monocyte human leucocyte antigen-DR; neutrophil CD88; programmed cell death-1 on monocytes, neutrophils and T lymphocytes and the percentage of regulatory T cells. Secondary outcome measures will link to trial outcomes from the ADAPT-sepsis trial including antibiotic days; occurrence of hospital-acquired infection and length of ICU-stay and hospital-stay.ETHICS AND DISSEMINATION: Ethical approval has been granted (IRAS 209815) and RISC-sepsis is registered with the ISRCTN (86837685). Study results will be disseminated by peer-reviewed publications, presentations at scientific meetings and via patient and public participation groups and social media.
AB - INTRODUCTION: Sepsis is characterised by a dysregulated immune response to infection, with exaggerated pro-inflammatory and anti-inflammatory responses. A predominant immunosuppressive profile affecting both innate and adaptive immune responses is associated with increased hospital-acquired infection and reduced infection-free survival. While hospital-acquired infection leads to additional antibiotic use, the role of the immunosuppressive phenotype in guiding complex decisions, such as those affecting antibiotic stewardship, is uncertain. This study is a mechanistic substudy embedded within a multicentre clinical and cost-effectiveness trial of biomarker-guided antibiotic stewardship. This mechanistic study aims to determine the effect of sepsis-associated immunosuppression on the trial outcome measures.METHODS AND ANALYSIS: RISC-sepsis is a prospective, multicentre, exploratory, observational study embedded within the ADAPT-sepsis trial. A subgroup of 180 participants with antibiotics commenced for suspected sepsis, enrolled in the ADAPT-sepsis trial, will be recruited. Blood samples will be collected on alternate days until day 7. At each time point, blood will be collected for flow cytometric analysis into cell preservation tubes. Immunophenotyping will be performed at a central testing hub by flow cytometry. The primary outcome measures are monocyte human leucocyte antigen-DR; neutrophil CD88; programmed cell death-1 on monocytes, neutrophils and T lymphocytes and the percentage of regulatory T cells. Secondary outcome measures will link to trial outcomes from the ADAPT-sepsis trial including antibiotic days; occurrence of hospital-acquired infection and length of ICU-stay and hospital-stay.ETHICS AND DISSEMINATION: Ethical approval has been granted (IRAS 209815) and RISC-sepsis is registered with the ISRCTN (86837685). Study results will be disseminated by peer-reviewed publications, presentations at scientific meetings and via patient and public participation groups and social media.
KW - Humans
KW - Anti-Bacterial Agents/therapeutic use
KW - Antimicrobial Stewardship/methods
KW - Prospective Studies
KW - Sepsis/drug therapy
KW - Cross Infection/drug therapy
KW - Immunosuppression Therapy
KW - Observational Studies as Topic
U2 - 10.1136/bmjopen-2022-068321
DO - 10.1136/bmjopen-2022-068321
M3 - Article
C2 - 36600326
SN - 2044-6055
VL - 12
SP - e068321
JO - BMJ Open
JF - BMJ Open
IS - 12
ER -