Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock
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Sepsis-induced immunosuppression is postulated to contribute to a heightened risk of nosocomial infection (NI). This prospective, single-center, observational study was conducted to assess whether low monocyte human leukocyte antigen-DR expression (mHLA-DR), proposed as a global biomarker of sepsis immunosuppression, was associated with an increased incidence of NI after septic shock.
The study included 209 septic shock patients. mHLA-DR was measured by flow cytometry at days (D) 3–4 and 6–9 after the onset of shock. After septic shock, patients were screened daily for NI at four sites (microbiologically documented pulmonary, urinary tract, bloodstream, and catheter-related infections). A competing risk approach was used to evaluate the impact of low mHLA-DR on the incidence of NI.
At D3–4, we obtained measurements in 153 patients. Non-survivors (n = 51) exhibited lower mHLA-DR values expressed as means of fluorescence intensities than survivors (n = 102) (33 vs. 67; p < 0.001). The patients who developed NI (n = 37) exhibited lower mHLA-DR values than those without NI (n = 116) (39 vs. 65; p = 0.008). mHLA-DR ≤54 remained independently associated with NI occurrence after adjustment for clinical parameters (gender, simplified acute physiology score II, sepsis-related organ failure assessment, intubation, and central venous catheterization) with an adjusted hazards ratio (aHR) of 2.52 (95% CI 1.20–5.30); p = 0.02. Similarly, at D6–9, low mHLA-DR (≤57) remained independently associated with NI with an aHR of 2.18 (95% CI 1.04–4.59); p = 0.04.
In septic shock patients, after adjustment with usual clinical confounders (including ventilation and central venous catheterization), persistent low mHLA-DR expression remained independently associated with the development of secondary NI.
KeywordsmHLA-DR Immunosuppression Nosocomial infection Sepsis Septic shock
The authors are grateful to Professor Christian Brun-Buisson, Dr. Raphaele Girard, all the intensivists of the Centre Hospitalier Lyon Sud, CCLIN Sud Est. The study was conducted thanks to the logistic support of Centre d’Investigation Clinique (CIC 201) of INSERM and Hospices Civils de Lyon. Thanks are also due to Ovid Da Silva for editing this manuscript. The present work was supported by Hospices Civils de Lyon. In addition, C. Landelle was funded by Hospices Civils de Lyon and Centre National de la Recherche Scientifique (Contrat d’Assistant Hospitalier de Recherche HCL/CNRS). C. Landelle received the International Sepsis Forum (ISF) Sepsis Award for a part of this work during the joint ESCMID (European Society of Clinical Microbiology and Infectious Disease)/ISF Sepsis Forum on May 2009 at the 19th ECCMID (European Congress of Clinical Microbiology and Infectious Disease) in Helsinki, Finland.
Conflict of interest statement
None of the authors have any financial interests or affiliations with commercial organizations whose products or services are related to the subject matter of this manuscript (i.e., no existing conflicts of interest).
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