Skip to main content
Erschienen in: Intensive Care Medicine 11/2010

01.11.2010 | Original

Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock

verfasst von: Caroline Landelle, Alain Lepape, Nicolas Voirin, Eve Tognet, Fabienne Venet, Julien Bohé, Philippe Vanhems, Guillaume Monneret

Erschienen in: Intensive Care Medicine | Ausgabe 11/2010

Einloggen, um Zugang zu erhalten

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Annane D, Aegerter P, Jars-Guincestre MC, Guidet B, Network ft C-R (2003) Current epidemiology of septic shock. The CUB-Réa Network. Am J Respir Crit Care Med 168:165–172CrossRefPubMed Annane D, Aegerter P, Jars-Guincestre MC, Guidet B, Network ft C-R (2003) Current epidemiology of septic shock. The CUB-Réa Network. Am J Respir Crit Care Med 168:165–172CrossRefPubMed
2.
Zurück zum Zitat Landelle C, Lepape A, Français A, Tognet E, Thizy H, Voirin N, Timsit JF, Monneret G, Vanhems P (2008) Nosocomial infection after septic shock among intensive care unit patients. Infect Control Hosp Epidemiol 29:1054–1065CrossRefPubMed Landelle C, Lepape A, Français A, Tognet E, Thizy H, Voirin N, Timsit JF, Monneret G, Vanhems P (2008) Nosocomial infection after septic shock among intensive care unit patients. Infect Control Hosp Epidemiol 29:1054–1065CrossRefPubMed
3.
Zurück zum Zitat Friedman G, Silva E, Vincent JL (1998) Has the mortality of septic shock changed with time. Crit Care Med 26:2078–2086CrossRefPubMed Friedman G, Silva E, Vincent JL (1998) Has the mortality of septic shock changed with time. Crit Care Med 26:2078–2086CrossRefPubMed
5.
Zurück zum Zitat Reddy RC, Chen GH, Tekchandani PK, Standiford TJ (2001) Sepsis-induced immunosuppression: from bad to worse. Immunol Res 24:273–287CrossRefPubMed Reddy RC, Chen GH, Tekchandani PK, Standiford TJ (2001) Sepsis-induced immunosuppression: from bad to worse. Immunol Res 24:273–287CrossRefPubMed
6.
Zurück zum Zitat Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348:138–150CrossRefPubMed Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348:138–150CrossRefPubMed
7.
Zurück zum Zitat Munford RS, Pugin J (2001) Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 163:316–321PubMed Munford RS, Pugin J (2001) Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 163:316–321PubMed
8.
Zurück zum Zitat Pugin J (2007) Immunostimulation is a rational therapeutic strategy in sepsis. Novartis Found Symp 280:21–27; discussion 27–36, 160–164CrossRefPubMed Pugin J (2007) Immunostimulation is a rational therapeutic strategy in sepsis. Novartis Found Symp 280:21–27; discussion 27–36, 160–164CrossRefPubMed
9.
Zurück zum Zitat Monneret G, Venet F, Pachot A, Lepape A (2008) Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med 14:64–78CrossRefPubMed Monneret G, Venet F, Pachot A, Lepape A (2008) Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med 14:64–78CrossRefPubMed
10.
Zurück zum Zitat Schefold JC, Hasper D, Volk HD, Reinke P (2008) Sepsis: time has come to focus on the later stages. Med Hypotheses 71:203–208CrossRefPubMed Schefold JC, Hasper D, Volk HD, Reinke P (2008) Sepsis: time has come to focus on the later stages. Med Hypotheses 71:203–208CrossRefPubMed
11.
Zurück zum Zitat Caille V, Chiche JD, Nciri N, Berton C, Gibot S, Boval B, Payen D, Mira JP, Mebazaa A (2004) Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock. Shock 22:521–526CrossRefPubMed Caille V, Chiche JD, Nciri N, Berton C, Gibot S, Boval B, Payen D, Mira JP, Mebazaa A (2004) Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock. Shock 22:521–526CrossRefPubMed
12.
Zurück zum Zitat Monneret G, Lepape A, Voirin N, Bohé J, Venet F, Debard AL, Thizy H, Bienvenu J, Gueyffier F, Vanhems P (2006) Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med 32:1175–1183CrossRefPubMed Monneret G, Lepape A, Voirin N, Bohé J, Venet F, Debard AL, Thizy H, Bienvenu J, Gueyffier F, Vanhems P (2006) Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med 32:1175–1183CrossRefPubMed
13.
Zurück zum Zitat Hershman MJ, Cheadle WG, Wellhausen SR, Davidson PF, Polk HC Jr (1990) Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patient. Br J Surg 77:204–207CrossRefPubMed Hershman MJ, Cheadle WG, Wellhausen SR, Davidson PF, Polk HC Jr (1990) Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patient. Br J Surg 77:204–207CrossRefPubMed
14.
Zurück zum Zitat Cheadle WG, Hershman MJ, Wellhausen SR, Polk HC Jr (1991) HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 161:639–645CrossRefPubMed Cheadle WG, Hershman MJ, Wellhausen SR, Polk HC Jr (1991) HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 161:639–645CrossRefPubMed
15.
Zurück zum Zitat Venet F, Tissot S, Debard AL, Faudot C, Crampé C, Pachot A, Ayala A, Monneret G (2007) Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: correlation with severity and secondary septic shock. Crit Care Med 35:1910–1917CrossRefPubMed Venet F, Tissot S, Debard AL, Faudot C, Crampé C, Pachot A, Ayala A, Monneret G (2007) Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: correlation with severity and secondary septic shock. Crit Care Med 35:1910–1917CrossRefPubMed
16.
Zurück zum Zitat Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRefPubMed Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRefPubMed
17.
Zurück zum Zitat Vanhems P, Lepape A, Savey A, Jambou P, Fabry J (2000) Nosocomial pulmonary infection by antimicrobial-resistant bacteria of patients hospitalized in intensive care units: risk factors and survival. J Hosp Infect 45:98–106CrossRefPubMed Vanhems P, Lepape A, Savey A, Jambou P, Fabry J (2000) Nosocomial pulmonary infection by antimicrobial-resistant bacteria of patients hospitalized in intensive care units: risk factors and survival. J Hosp Infect 45:98–106CrossRefPubMed
19.
Zurück zum Zitat Monneret G, Elmenkouri N, Bohe J, Debard AL, Gutowski MC, Bienvenu J, Lepape A (2002) Analytical requirements for measuring monocytic human lymphocyte antigen DR by flow cytometry: application to the monitoring of patients with septic shock. Clin Chem 48:1589–1592PubMed Monneret G, Elmenkouri N, Bohe J, Debard AL, Gutowski MC, Bienvenu J, Lepape A (2002) Analytical requirements for measuring monocytic human lymphocyte antigen DR by flow cytometry: application to the monitoring of patients with septic shock. Clin Chem 48:1589–1592PubMed
20.
Zurück zum Zitat Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:1141–1154CrossRef Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:1141–1154CrossRef
21.
Zurück zum Zitat Fine J, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef Fine J, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef
22.
Zurück zum Zitat R Development Core Team (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. http://www.R-project.org R Development Core Team (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. http://​www.​R-project.​org
23.
Zurück zum Zitat Vincent JL (2003) Nosocomial infections in adult intensive-care units. Lancet 361:2068–2077CrossRefPubMed Vincent JL (2003) Nosocomial infections in adult intensive-care units. Lancet 361:2068–2077CrossRefPubMed
24.
Zurück zum Zitat Brawley RL, Weber DJ, Samsa GP, Rutala WA (1989) Multiple nosocomial infections. An incidence study. Am J Epidemiol 130:769–780PubMed Brawley RL, Weber DJ, Samsa GP, Rutala WA (1989) Multiple nosocomial infections. An incidence study. Am J Epidemiol 130:769–780PubMed
25.
Zurück zum Zitat Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno R, Boulmé R, Lepage E, Le Gall R (2002) Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med 28:108–121CrossRefPubMed Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno R, Boulmé R, Lepage E, Le Gall R (2002) Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med 28:108–121CrossRefPubMed
26.
Zurück zum Zitat Wolk K, Docke WD, von Baehr V, Volk HD, Sabat R (2000) Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 96:218–223PubMed Wolk K, Docke WD, von Baehr V, Volk HD, Sabat R (2000) Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 96:218–223PubMed
27.
Zurück zum Zitat Astiz M, Saha D, Lustbader D, Lin R, Rackow E (1996) Monocyte response to bacterial toxins, expression of cell surface receptors, and release of anti-inflammatory cytokines during sepsis. J Lab Clin Med 128:594–600CrossRefPubMed Astiz M, Saha D, Lustbader D, Lin R, Rackow E (1996) Monocyte response to bacterial toxins, expression of cell surface receptors, and release of anti-inflammatory cytokines during sepsis. J Lab Clin Med 128:594–600CrossRefPubMed
28.
Zurück zum Zitat Manjuck J, Saha DC, Astiz M, Eales LJ, Rackow EC (2000) Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. J Lab Clin Med 135:153–160CrossRefPubMed Manjuck J, Saha DC, Astiz M, Eales LJ, Rackow EC (2000) Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. J Lab Clin Med 135:153–160CrossRefPubMed
29.
Zurück zum Zitat Piani A, Hossle JP, Birchler T, Siegrist CA, Heumann D, Davies G, Loeliger S, Seger R, Lauener RP (2000) Expression of MHC class II molecules contributes to lipopolysaccharide responsiveness. Eur J Immunol 30:3140–3146CrossRefPubMed Piani A, Hossle JP, Birchler T, Siegrist CA, Heumann D, Davies G, Loeliger S, Seger R, Lauener RP (2000) Expression of MHC class II molecules contributes to lipopolysaccharide responsiveness. Eur J Immunol 30:3140–3146CrossRefPubMed
30.
Zurück zum Zitat Satoh A, Miura T, Satoh K, Masamune A, Yamagiwa T, Sakai Y, Shibuya K, Takeda K, Kaku M, Shimosegawa T (2002) Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis. Pancreas 25:245–250CrossRefPubMed Satoh A, Miura T, Satoh K, Masamune A, Yamagiwa T, Sakai Y, Shibuya K, Takeda K, Kaku M, Shimosegawa T (2002) Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis. Pancreas 25:245–250CrossRefPubMed
31.
Zurück zum Zitat Le Tulzo Y, Pangault C, Amiot L, Guilloux V, Tribut O, Arvieux C, Camus C, Fauchet R, Thomas R, Drénou B (2004) Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. Am J Respir Crit Care Med 169:1144–1151CrossRefPubMed Le Tulzo Y, Pangault C, Amiot L, Guilloux V, Tribut O, Arvieux C, Camus C, Fauchet R, Thomas R, Drénou B (2004) Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. Am J Respir Crit Care Med 169:1144–1151CrossRefPubMed
32.
Zurück zum Zitat Allen ML, Peters MJ, Goldman A, Elliott M, James I, Callard R, Klein NJ (2002) Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care. Crit Care Med 30:1140–1145CrossRefPubMed Allen ML, Peters MJ, Goldman A, Elliott M, James I, Callard R, Klein NJ (2002) Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care. Crit Care Med 30:1140–1145CrossRefPubMed
33.
Zurück zum Zitat Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B, Payen D (2009) Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med 37:2746–2752CrossRefPubMed Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B, Payen D (2009) Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med 37:2746–2752CrossRefPubMed
34.
Zurück zum Zitat Döcke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W (1997) Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 3:678–681CrossRefPubMed Döcke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W (1997) Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 3:678–681CrossRefPubMed
35.
Zurück zum Zitat Nakos G, Malamou-Mitsi VD, Lachana A, Karassavoglou A, Kitsiouli E, Agnandi N, Lekka ME (2002) Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma. Crit Care Med 30:1488–1494CrossRefPubMed Nakos G, Malamou-Mitsi VD, Lachana A, Karassavoglou A, Kitsiouli E, Agnandi N, Lekka ME (2002) Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma. Crit Care Med 30:1488–1494CrossRefPubMed
36.
Zurück zum Zitat Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, Weber-Carstens S, Hasper D, Keh D, Zuckermann H, Reinke P, Volk HD (2009) Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind randomized placebo-controlled multicenter trial. Am J Respir Crit Care Med 180:640–648CrossRefPubMed Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, Weber-Carstens S, Hasper D, Keh D, Zuckermann H, Reinke P, Volk HD (2009) Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind randomized placebo-controlled multicenter trial. Am J Respir Crit Care Med 180:640–648CrossRefPubMed
37.
Zurück zum Zitat Döcke WD, Höflich C, Davis KA, Röttgers K, Meisel C, Kiefer P, Weber SU, Hedwig-Geissing M, Kreuzfelder E, Tschentscher P, Nebe T, Engel A, Monneret G, Spittler A, Schmolke K, Reinke P, Volk HD, Kunz D (2005) Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study. Clin Chem 51:2341–2347CrossRefPubMed Döcke WD, Höflich C, Davis KA, Röttgers K, Meisel C, Kiefer P, Weber SU, Hedwig-Geissing M, Kreuzfelder E, Tschentscher P, Nebe T, Engel A, Monneret G, Spittler A, Schmolke K, Reinke P, Volk HD, Kunz D (2005) Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study. Clin Chem 51:2341–2347CrossRefPubMed
Metadaten
Titel
Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock
verfasst von
Caroline Landelle
Alain Lepape
Nicolas Voirin
Eve Tognet
Fabienne Venet
Julien Bohé
Philippe Vanhems
Guillaume Monneret
Publikationsdatum
01.11.2010
Verlag
Springer-Verlag
Erschienen in
Intensive Care Medicine / Ausgabe 11/2010
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-010-1962-x

Weitere Artikel der Ausgabe 11/2010

Intensive Care Medicine 11/2010 Zur Ausgabe

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

Delir bei kritisch Kranken – Antipsychotika versus Placebo

16.05.2024 Delir Nachrichten

Um die Langzeitfolgen eines Delirs bei kritisch Kranken zu mildern, wird vielerorts auf eine Akuttherapie mit Antipsychotika gesetzt. Eine US-amerikanische Forschungsgruppe äußert jetzt erhebliche Vorbehalte gegen dieses Vorgehen. Denn es gibt neue Daten zum Langzeiteffekt von Haloperidol bzw. Ziprasidon versus Placebo.

Klinikreform soll zehntausende Menschenleben retten

15.05.2024 Klinik aktuell Nachrichten

Gesundheitsminister Lauterbach hat die vom Bundeskabinett beschlossene Klinikreform verteidigt. Kritik an den Plänen kommt vom Marburger Bund. Und in den Ländern wird über den Gang zum Vermittlungsausschuss spekuliert.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.