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ICU-acquired infections in immunocompromised patients

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Abstract

Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections—as well as on the dynamics of colonization and infection with multidrug-resistant bacteria—in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.

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References

  1. Azoulay E, Schellongowski P, Darmon M et al (2017) The Intensive Care Medicine research agenda on critically ill oncology and hematology patients. Intensive Care Med. https://doi.org/10.1007/s00134-017-4884-z

    Article  PubMed  Google Scholar 

  2. Azoulay E, Pickkers P, Soares M et al (2017) Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study. Intensive Care Med 43:1808–1819. https://doi.org/10.1007/s00134-017-4947-1

    Article  PubMed  Google Scholar 

  3. Zampieri FG, Romano TG, Salluh JIF et al (2021) Trends in clinical profiles, organ support use and outcomes of patients with cancer requiring unplanned ICU admission: a multicenter cohort study. Intensive Care Med 47:170–179. https://doi.org/10.1007/s00134-020-06184-2

    Article  PubMed  Google Scholar 

  4. Torres VBL, Vassalo J, Silva UVA et al (2016) Outcomes in critically ill patients with cancer-related complications. PLoS ONE 11:e0164537. https://doi.org/10.1371/journal.pone.0164537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dumas G, Lemiale V, Rathi N et al (2021) Survival in immunocompromised patients ultimately requiring invasive mechanical ventilation: a pooled individual patient data analysis. Am J Respir Crit Care Med 204:187–196. https://doi.org/10.1164/rccm.202009-3575OC

    Article  PubMed  Google Scholar 

  6. Salluh JIF, de Souza-Dantas VC, Martin-Loeches I et al (2010) Traqueobronquite associada à ventilação mecânica: uma atualização. Revista Brasileira de Terapia Intensiva 31:541–547

    Google Scholar 

  7. Moreau A-S, Martin-Loeches I, Povoa P et al (2018) Impact of immunosuppression on incidence, aetiology and outcome of ventilator-associated lower respiratory tract infections. Eur Respir J. https://doi.org/10.1183/13993003.01656-2017

    Article  PubMed  Google Scholar 

  8. Azoulay E, Russell L, Van de Louw A et al (2020) Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med 46:298–314. https://doi.org/10.1007/s00134-019-05906-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kreitmann L, Vasseur M, Jermoumi S et al (2023) Relationship between immunosuppression and intensive care unit-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter cohort study. Intensive Care Med. https://doi.org/10.1007/s00134-022-06954-0

    Article  PubMed  Google Scholar 

  10. Kreitmann L, Gaudet A, Nseir S (2023) Ventilator-associated pneumonia in immunosuppressed patients. Antibiotics 12:413. https://doi.org/10.3390/antibiotics12020413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tangye SG, Al-Herz W, Bousfiha A et al (2020) Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 40:24–64. https://doi.org/10.1007/s10875-019-00737-x

    Article  PubMed  PubMed Central  Google Scholar 

  12. Azoulay E, Mokart D, Kouatchet A et al (2019) Acute respiratory failure in immunocompromised adults. Lancet Respir Med 7:173–186. https://doi.org/10.1016/S2213-2600(18)30345-X

    Article  PubMed  Google Scholar 

  13. Russell L, Pène F, Martin-Loeches I (2023) Multidrug-resistant bacteria in the grey shades of immunosuppression. Intensive Care Med 49:216–218. https://doi.org/10.1007/s00134-022-06968-8

    Article  PubMed  Google Scholar 

  14. Hensley MK, Donnelly JP, Carlton EF, Prescott HC (2019) Epidemiology and outcomes of cancer-related versus non-cancer-related sepsis hospitalizations. Crit Care Med 47:1310–1316. https://doi.org/10.1097/CCM.0000000000003896

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rhee C, Wang R, Zhang Z et al (2019) Epidemiology of hospital-onset versus community-onset sepsis in U.S. hospitals and association with mortality: a retrospective analysis using electronic clinical data. Crit Care Med 47:1169–1176. https://doi.org/10.1097/CCM.0000000000003817

    Article  PubMed  PubMed Central  Google Scholar 

  16. van Vught LA, Klouwenberg PMCK, Spitoni C et al (2016) Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA 315:1469–1479. https://doi.org/10.1001/jama.2016.2691

    Article  CAS  PubMed  Google Scholar 

  17. Schmidt M, Hajage D, Demoule A et al (2021) Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med 47:60–73. https://doi.org/10.1007/s00134-020-06294-x

    Article  CAS  Google Scholar 

  18. Hadjadj J, Yatim N, Barnabei L et al (2020) Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369:718–724. https://doi.org/10.1126/science.abc6027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bastard P, Rosen LB, Zhang Q, et al (2020) Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 370:eabd4585. Doi: https://doi.org/10.1126/science.abd4585

  20. Walton AH, Muenzer JT, Rasche D et al (2014) Reactivation of Multiple Viruses in Patients with Sepsis. PLoS ONE 9:e98819. https://doi.org/10.1371/journal.pone.0098819

    Article  PubMed  PubMed Central  Google Scholar 

  21. Venet F, Textoris J, Blein S et al (2022) Immune profiling demonstrates a common immune signature of delayed acquired immunodeficiency in patients with various etiologies of severe injury. Crit Care Med 50:565–575. https://doi.org/10.1097/CCM.0000000000005270

    Article  PubMed  Google Scholar 

  22. Hotchkiss RS, Monneret G, Payen D (2013) Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol 13:862–874. https://doi.org/10.1038/nri3552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Venet F, Monneret G (2018) Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol 14:121–137. https://doi.org/10.1038/nrneph.2017.165

    Article  CAS  PubMed  Google Scholar 

  24. Adrie C, Lugosi M, Sonneville R et al (2017) Persistent lymphopenia is a risk factor for ICU-acquired infections and for death in ICU patients with sustained hypotension at admission. Ann Intensive Care 7:30. https://doi.org/10.1186/s13613-017-0242-0

    Article  PubMed  PubMed Central  Google Scholar 

  25. Landelle C, Lepape A, Voirin N et al (2010) Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock. Intensive Care Med 36:1859–1866. https://doi.org/10.1007/s00134-010-1962-x

    Article  CAS  PubMed  Google Scholar 

  26. Monneret G, Venet F (2013) Immune functional testing in clinics. Crit Care Med 41:367–368. https://doi.org/10.1097/CCM.0b013e318270e6a6

    Article  PubMed  Google Scholar 

  27. Tremblay J-A, Peron F, Kreitmann L et al (2022) A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score. Ann Intensive Care 12:76. https://doi.org/10.1186/s13613-022-01051-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. de Roquetaillade C, Dupuis C, Faivre V et al (2022) Monitoring of circulating monocyte HLA-DR expression in a large cohort of intensive care patients: relation with secondary infections. Ann Intensive Care 12:39. https://doi.org/10.1186/s13613-022-01010-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang JH, Bhargava P, McCloskey D et al (2017) Antibiotic-induced changes to the host metabolic environment inhibit drug efficacy and alter immune function. Cell Host Microbe 22:757-765.e3. https://doi.org/10.1016/j.chom.2017.10.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Arulkumaran N, Routledge M, Schlebusch S et al (2020) Antimicrobial-associated harm in critical care: a narrative review. Intensive Care Med 46:225–235. https://doi.org/10.1007/s00134-020-05929-3

    Article  PubMed  PubMed Central  Google Scholar 

  31. Péju E, Llitjos J-F, Charpentier J et al (2021) Impact of blood product transfusions on the risk of ICU-acquired infections in septic shock. Crit Care Med 49:912–922. https://doi.org/10.1097/CCM.0000000000004887

    Article  PubMed  Google Scholar 

  32. Rohde JM, Dimcheff DE, Blumberg N et al (2014) Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA 311:1317–1326. https://doi.org/10.1001/jama.2014.2726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Llitjos J-F, Gassama A, Charpentier J et al (2019) Pulmonary infections prime the development of subsequent ICU-acquired pneumonia in septic shock. Ann Intensive Care 9:39. https://doi.org/10.1186/s13613-019-0515-x

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hooper LV, Littman DR, Macpherson AJ (2012) Interactions between the microbiota and the immune system. Science 336:1268–1273. https://doi.org/10.1126/science.1223490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Belkaid Y, Harrison OJ (2017) Homeostatic Immunity and the Microbiota. Immunity 46:562–576. https://doi.org/10.1016/j.immuni.2017.04.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Akrami K, Sweeney DA (2018) The microbiome of the critically ill patient. Curr Opin Crit Care 24:49–54. https://doi.org/10.1097/MCC.0000000000000469

    Article  PubMed  Google Scholar 

  37. Haak BW, Levi M, Wiersinga WJ (2017) Microbiota-targeted therapies on the intensive care unit. Curr Opin Crit Care 23:167–174. https://doi.org/10.1097/MCC.0000000000000389

    Article  PubMed  Google Scholar 

  38. Wischmeyer PE, McDonald D, Knight R (2016) Role of the microbiome, probiotics, and ‘dysbiosis therapy’ in critical illness. Curr Opin Crit Care 22:347–353. https://doi.org/10.1097/MCC.0000000000000321

    Article  PubMed  PubMed Central  Google Scholar 

  39. Zeng J, Wang C-T, Zhang F-S et al (2016) Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intensive Care Med 42:1018–1028. https://doi.org/10.1007/s00134-016-4303-x

    Article  CAS  PubMed  Google Scholar 

  40. Hempel S, Newberry SJ, Maher AR et al (2012) Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307:1959–1969. https://doi.org/10.1001/jama.2012.3507

    Article  CAS  PubMed  Google Scholar 

  41. Bo L, Li J, Tao T et al (2014) Probiotics for preventing ventilator-associated pneumonia. Cochrane Database Syst Rev 10:CD009066. https://doi.org/10.1002/14651858.CD009066.pub2

    Article  PubMed  Google Scholar 

  42. Cheema HA, Shahid A, Ayyan M et al (2022) Probiotics for the prevention of ventilator-associated pneumonia: an updated systematic review and meta-analysis of randomised controlled trials. Nutrients 14:1600. https://doi.org/10.3390/nu14081600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kassam Z, Lee CH, Yuan Y, Hunt RH (2013) Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 108:500–508. https://doi.org/10.1038/ajg.2013.59

    Article  PubMed  Google Scholar 

  44. Cammarota G, Ianiro G, Tilg H et al (2017) European consensus conference on faecal microbiota transplantation in clinical practice. Gut 66:569–580. https://doi.org/10.1136/gutjnl-2016-313017

    Article  PubMed  Google Scholar 

  45. van Doorn-Schepens MLM, Abis GSA, Oosterling SJ et al (2022) The effect of selective decontamination on the intestinal microbiota as measured with IS-pro: a taxonomic classification tool applicable for direct evaluation of intestinal microbiota in clinical routine. Eur J Clin Microbiol Infect Dis 41:1337–1345. https://doi.org/10.1007/s10096-022-04483-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bos LD, Stips C, Schouten LR et al (2017) Selective decontamination of the digestive tract halves the prevalence of ventilator-associated pneumonia compared to selective oral decontamination. Intensive Care Med 43:1535–1537. https://doi.org/10.1007/s00134-017-4838-5

    Article  PubMed  Google Scholar 

  47. Hammond NE, Myburgh J, Seppelt I et al (2022) Association between selective decontamination of the digestive tract and in-hospital mortality in intensive care unit patients receiving mechanical ventilation: a systematic review and meta-analysis. JAMA 328:1922–1934. https://doi.org/10.1001/jama.2022.19709

    Article  PubMed  PubMed Central  Google Scholar 

  48. SUDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Myburgh JA, Seppelt IM et al (2022) Effect of selective decontamination of the digestive tract on hospital mortality in critically ill patients receiving mechanical ventilation: a randomized clinical trial. JAMA 328:1911–1921. https://doi.org/10.1001/jama.2022.17927

    Article  Google Scholar 

  49. Massart N, Reizine F, Dupin C et al (2023) Prevention of acquired invasive fungal infection with decontamination regimen in mechanically ventilated ICU patients: a pre/post observational study. Infect Dis (Lond) 55:263–271. https://doi.org/10.1080/23744235.2023.2170460

    Article  CAS  PubMed  Google Scholar 

  50. Lionakis MS, Netea MG (2013) Candida and host determinants of susceptibility to invasive candidiasis. PLoS Pathog 9:e1003079. https://doi.org/10.1371/journal.ppat.1003079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Oksenhendler E, Gérard L, Fieschi C et al (2008) Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis 46:1547–1554. https://doi.org/10.1086/587669

    Article  PubMed  Google Scholar 

  52. Roblot F, Godet C, Le Moal G et al (2002) Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients. Eur J Clin Microbiol Infect Dis 21:523–531. https://doi.org/10.1007/s10096-002-0758-5

    Article  CAS  PubMed  Google Scholar 

  53. Monneret G, Venet F, Kullberg B-J, Netea MG (2011) ICU-acquired immunosuppression and the risk for secondary fungal infections. Med Mycol 49(Suppl 1):S17-23. https://doi.org/10.3109/13693786.2010.509744

    Article  PubMed  Google Scholar 

  54. Bayon C, Kreitmann L, Martin-Loeches I, et al (2023) Association between type of immunosuppression and the incidence, microbiology and outcomes of ventilator-associated lower respiratory tract infections: a retrospective multicenter study. Under review

  55. Zebian G, Kreitmann L, Houard M, et al (2023) Immunosuppression at ICU admission is not associated with a higher incidence of ICU-acquired bloodstream infections: the COCONUT study. Under review

  56. Stansell JD, Osmond DH, Charlebois E et al (1997) Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary complications of HIV infection study group. Am J Respir Crit Care Med 155:60–66. https://doi.org/10.1164/ajrccm.155.1.9001290

    Article  CAS  PubMed  Google Scholar 

  57. Stern A, Green H, Paul M et al (2014) Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD005590.pub3

    Article  PubMed  PubMed Central  Google Scholar 

  58. Saral R, Burns WH, Laskin OL et al (1981) Acyclovir prophylaxis of herpes-simplex-virus infections. N Engl J Med 305:63–67. https://doi.org/10.1056/NEJM198107093050202

    Article  CAS  PubMed  Google Scholar 

  59. Saral R, Ambinder RF, Burns WH et al (1983) Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study. Ann Intern Med 99:773–776. https://doi.org/10.7326/0003-4819-99-6-773

    Article  CAS  PubMed  Google Scholar 

  60. Wang B, Briegel J, Krueger WA et al (2022) Ecological effects of selective oral decontamination on multidrug-resistance bacteria acquired in the intensive care unit: a case-control study over 5 years. Intensive Care Med 48:1165–1175. https://doi.org/10.1007/s00134-022-06826-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wingard JR, Eldjerou L, Leather H (2012) Use of antibacterial prophylaxis in patients with chemotherapy-induced neutropenia. Curr Opin Hematol 19:21–26. https://doi.org/10.1097/MOH.0b013e32834da9bf

    Article  CAS  PubMed  Google Scholar 

  62. Bow EJ (2011) Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis 24:545–553. https://doi.org/10.1097/QCO.0b013e32834cf054

    Article  CAS  PubMed  Google Scholar 

  63. Adrie C, Garrouste-Orgeas M, Ibn Essaied W et al (2017) Attributable mortality of ICU-acquired bloodstream infections: impact of the source, causative micro-organism, resistance profile and antimicrobial therapy. J Infect 74:131–141. https://doi.org/10.1016/j.jinf.2016.11.001

    Article  PubMed  Google Scholar 

  64. Gouel-Cheron A, Swihart BJ, Warner S et al (2022) Epidemiology of ICU-onset bloodstream infection: prevalence, pathogens, and risk factors among 150,948 ICU patients at 85 U.S. Hospitals*. Crit Care Med 50:1725–1736. https://doi.org/10.1097/CCM.0000000000005662

    Article  PubMed  PubMed Central  Google Scholar 

  65. Prowle JR, Echeverri JE, Ligabo EV et al (2011) Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality. Crit Care 15:R100. https://doi.org/10.1186/cc10114

    Article  PubMed  PubMed Central  Google Scholar 

  66. Vincent J-L, Sakr Y, Singer M et al (2020) Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 323:1478–1487. https://doi.org/10.1001/jama.2020.2717

    Article  PubMed  PubMed Central  Google Scholar 

  67. Tabah A, Koulenti D, Laupland K et al (2012) Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 38:1930–1945. https://doi.org/10.1007/s00134-012-2695-9

    Article  PubMed  Google Scholar 

  68. Tabah A, Buetti N, Staiquly Q et al (2023) Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study. Intensive Care Med 49:178–190. https://doi.org/10.1007/s00134-022-06944-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. European Centre for Disease Prevention and Control (2023) Annual Epidemiological Report for 2019 – Healthcareassociated infections acquired in intensive care units. European Centre for Disease Prevention and Control

    Google Scholar 

  70. Laporte-Amargos J, Sastre E, Bergas A et al (2023) Increasing gram-negative catheter-related bloodstream infection in cancer patients. Pathogens 12:228. https://doi.org/10.3390/pathogens12020228

    Article  PubMed  PubMed Central  Google Scholar 

  71. Islas-Muñoz B, Volkow-Fernández P, Ibanes-Gutiérrez C et al (2018) Bloodstream infections in cancer patients. Risk factors associated with mortality. Int J Infect Dis 71:59–64. https://doi.org/10.1016/j.ijid.2018.03.022

    Article  PubMed  Google Scholar 

  72. Chumbita M, Puerta-Alcalde P, Gudiol C et al (2022) Impact of empirical antibiotic regimens on mortality in neutropenic patients with bloodstream infection presenting with septic shock. Antimicrob Agents Chemother 66:e01744-e1821. https://doi.org/10.1128/AAC.01744-21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mermel LA, Allon M, Bouza E et al (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49:1–45. https://doi.org/10.1086/599376

    Article  CAS  PubMed  Google Scholar 

  74. Timsit J-F, Ruppé E, Barbier F et al (2020) Bloodstream infections in critically ill patients: an expert statement. Intensive Care Med 46:266–284. https://doi.org/10.1007/s00134-020-05950-6

    Article  PubMed  PubMed Central  Google Scholar 

  75. Garrouste-Orgeas M, Timsit JF, Tafflet M et al (2006) Excess risk of death from intensive care unit-acquired nosocomial bloodstream infections: a reappraisal. Clin Infect Dis 42:1118–1126. https://doi.org/10.1086/500318

    Article  PubMed  Google Scholar 

  76. Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L (2014) Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014:CD003344. https://doi.org/10.1002/14651858.CD003344.pub3

    Article  PubMed  PubMed Central  Google Scholar 

  77. Paul M, Dickstein Y, Schlesinger A et al (2013) Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev 2013:CD003038. https://doi.org/10.1002/14651858.CD003038.pub2

    Article  PubMed  PubMed Central  Google Scholar 

  78. Sjövall F, Perner A, Hylander Møller M (2017) Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis - a systematic review with meta-analysis and trial sequential analysis. J Infect 74:331–344. https://doi.org/10.1016/j.jinf.2016.11.013

    Article  PubMed  Google Scholar 

  79. Martin-Loeches I, Antonelli M, Cuenca-Estrella M et al (2019) ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients. Intensive Care Med 45:789–805. https://doi.org/10.1007/s00134-019-05599-w

    Article  PubMed  Google Scholar 

  80. Mokart D, Slehofer G, Lambert J et al (2014) De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive Care Med 40:41–49. https://doi.org/10.1007/s00134-013-3148-9

    Article  CAS  PubMed  Google Scholar 

  81. Schnell D, Montlahuc C, Bruneel F et al (2019) De-escalation of antimicrobial therapy in critically ill hematology patients: a prospective cohort study. Intensive Care Med 45:743–745. https://doi.org/10.1007/s00134-019-05554-9

    Article  PubMed  Google Scholar 

  82. Freifeld AG, Bow EJ, Sepkowitz KA et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 52:e56-93. https://doi.org/10.1093/cid/cir073

    Article  PubMed  Google Scholar 

  83. Aguilar-Guisado M, Espigado I, Martín-Peña A et al (2017) Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol 4:e573–e583. https://doi.org/10.1016/S2352-3026(17)30211-9

    Article  PubMed  Google Scholar 

  84. Averbuch D, Orasch C, Cordonnier C et al (2013) European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 98:1826–1835. https://doi.org/10.3324/haematol.2013.091025

    Article  PubMed  PubMed Central  Google Scholar 

  85. Siniscalchi A, Aurini L, Benini B et al (2016) Ventilator associated pneumonia following liver transplantation: etiology, risk factors and outcome. World J Transpl 6:389–395. https://doi.org/10.5500/wjt.v6.i2.389

    Article  Google Scholar 

  86. Riera J, Caralt B, López I et al (2015) Ventilator-associated respiratory infection following lung transplantation. Eur Respir J 45:726–737. https://doi.org/10.1183/09031936.00095214

    Article  PubMed  Google Scholar 

  87. Papazian L, Klompas M, Luyt C-E (2020) Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med 46:888–906. https://doi.org/10.1007/s00134-020-05980-0

    Article  PubMed  PubMed Central  Google Scholar 

  88. Martin-Loeches I, Povoa P, Rodríguez A et al (2015) Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med 3:859–868. https://doi.org/10.1016/S2213-2600(15)00326-4

    Article  PubMed  Google Scholar 

  89. ECDC (2017) European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2015. Annual report of the European antimicrobial resistance surveillance network (EARS-Net). ECDC

    Google Scholar 

  90. Kalil AC, Metersky ML, Klompas M et al (2016) Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 63:e61–e111. https://doi.org/10.1093/cid/ciw353

    Article  PubMed  PubMed Central  Google Scholar 

  91. Torres A, Niederman MS, Chastre J et al (2017) International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. https://doi.org/10.1183/13993003.00582-2017

    Article  PubMed  Google Scholar 

  92. Azoulay É, Mokart D, Lambert J et al (2010) Diagnostic strategy for hematology and oncology patients with acute respiratory failure. Am J Respir Crit Care Med 182:1038–1046. https://doi.org/10.1164/rccm.201001-0018OC

    Article  PubMed  Google Scholar 

  93. Martin-Loeches I, Torres A, Nagavci B et al (2023) ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Intensive Care Med 49:615–632. https://doi.org/10.1007/s00134-023-07033-8

    Article  PubMed  Google Scholar 

  94. Darie AM, Khanna N, Jahn K et al (2022) Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial. Lancet Respir Med 10:877–887. https://doi.org/10.1016/S2213-2600(22)00086-8

    Article  CAS  PubMed  Google Scholar 

  95. University Hospital, Lille (2022) Impact of a Strategy Based on the Unyvero® Testing System on Appropriate and Targeted Antimicrobial Treatment in Patients With Suspected VAP or HAP Requiring Mechanical Ventilation: a Randomized Controlled Unblinded Trial. clinicaltrials.gov

  96. Dumford DM, Skalweit M (2016) Antibiotic-resistant infections and treatment challenges in the immunocompromised host. Infect Dis Clin North Am 30:465–489. https://doi.org/10.1016/j.idc.2016.02.008

    Article  PubMed  Google Scholar 

  97. Dumford D, Skalweit MJ (2020) Antibiotic-resistant infections and treatment challenges in the immunocompromised host: an update. Infect Dis Clin N Am 34:821–847. https://doi.org/10.1016/j.idc.2020.08.005

    Article  Google Scholar 

  98. Nseir S, Di Pompeo C, Diarra M et al (2007) Relationship between immunosuppression and intensive care unit-acquired multidrug-resistant bacteria: a case-control study. Crit Care Med 35:1318–1323. https://doi.org/10.1097/01.CCM.0000261885.50604.20

    Article  PubMed  Google Scholar 

  99. Ramirez JA, Musher DM, Evans SE et al (2020) Treatment of community-acquired pneumonia in immunocompromised adults: a consensus statement regarding initial strategies. Chest 158:1896–1911. https://doi.org/10.1016/j.chest.2020.05.598

    Article  PubMed  Google Scholar 

  100. Legoff J, Zucman N, Lemiale V et al (2019) Clinical significance of upper airway virus detection in critically ill hematology patients. Am J Respir Crit Care Med 199:518–528. https://doi.org/10.1164/rccm.201804-0681OC

    Article  PubMed  Google Scholar 

  101. Kakiuchi S, Tsuji M, Nishimura H et al (2018) Human parainfluenza virus type 3 infections in patients with hematopoietic stem cell transplants: the mode of nosocomial infections and prognosis. Jpn J Infect Dis 71:109–115. https://doi.org/10.7883/yoken.JJID.2017.424

    Article  CAS  PubMed  Google Scholar 

  102. Khanna N, Widmer AF, Decker M et al (2008) Respiratory syncytial virus infection in patients with hematological diseases: single-center study and review of the literature. Clin Infect Dis 46:402–412. https://doi.org/10.1086/525263

    Article  CAS  PubMed  Google Scholar 

  103. Limaye AP, Stapleton RD, Peng L et al (2017) Effect of ganciclovir on il-6 levels among cytomegalovirus-seropositive adults with critical illness. JAMA 318:731–740. https://doi.org/10.1001/jama.2017.10569

    Article  PubMed  PubMed Central  Google Scholar 

  104. Ljungman P, Boeckh M, Hirsch HH et al (2017) Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis 64:87–91. https://doi.org/10.1093/cid/ciw668

    Article  PubMed  Google Scholar 

  105. Durand CM, Marr KA, Arnold CA et al (2013) Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis 57:1550–1559. https://doi.org/10.1093/cid/cit521

    Article  PubMed  PubMed Central  Google Scholar 

  106. Fisher CE, Alexander J, Bhattacharya R et al (2016) Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Transpl Infect Dis 18:372–380. https://doi.org/10.1111/tid.12531

    Article  CAS  PubMed  Google Scholar 

  107. Bhimraj A, Morgan RL, Shumaker AH et al (2022) Infectious Diseases Society of America guidelines on the treatment and management of patients with coronavirus disease 2019 (COVID-19). Clin Infect Dis. https://doi.org/10.1093/cid/ciac724

    Article  PubMed  Google Scholar 

  108. Cornely OA, Gachot B, Akan H et al (2015) Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031). Clin Infect Dis 61:324–331. https://doi.org/10.1093/cid/civ293

    Article  PubMed  Google Scholar 

  109. Lortholary O, Renaudat C, Sitbon K et al (2017) The risk and clinical outcome of candidemia depending on underlying malignancy. Intensive Care Med 43:652–662. https://doi.org/10.1007/s00134-017-4743-y

    Article  PubMed  PubMed Central  Google Scholar 

  110. Lortholary O, Desnos-Ollivier M, Sitbon K et al (2011) Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob Agents Chemother 55:532–538. https://doi.org/10.1128/AAC.01128-10

    Article  CAS  PubMed  Google Scholar 

  111. Pappas PG, Kauffman CA, Andes DR et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62:e1-50. https://doi.org/10.1093/cid/civ933

    Article  PubMed  Google Scholar 

  112. Wingard JR, Merz WG, Rinaldi MG et al (1993) Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. Antimicrob Agents Chemother 37:1847–1849. https://doi.org/10.1128/AAC.37.9.1847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wingard JR, Merz WG, Rinaldi MG et al (1991) Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med 325:1274–1277. https://doi.org/10.1056/NEJM199110313251803

    Article  CAS  PubMed  Google Scholar 

  114. Bergeron A, Porcher R, Sulahian A et al (2012) The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies. Blood 119:1831–1837. https://doi.org/10.1182/blood-2011-04-351601

    Article  CAS  PubMed  Google Scholar 

  115. Schauwvlieghe AFAD, Rijnders BJA, Philips N et al (2018) Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med 6:782–792. https://doi.org/10.1016/S2213-2600(18)30274-1

    Article  PubMed  Google Scholar 

  116. Gangneux J-P, Dannaoui E, Fekkar A et al (2022) Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study. Lancet Respir Med 10:180–190. https://doi.org/10.1016/S2213-2600(21)00442-2

    Article  CAS  PubMed  Google Scholar 

  117. Lugosi M, Alberti C, Zahar J-R et al (2014) Aspergillus in the lower respiratory tract of immunocompetent critically ill patients. J Infect 69:284–292. https://doi.org/10.1016/j.jinf.2014.04.010

    Article  PubMed  Google Scholar 

  118. Donnelly JP, Chen SC, Kauffman CA et al (2020) Revision and Update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 71:1367–1376. https://doi.org/10.1093/cid/ciz1008

    Article  PubMed  Google Scholar 

  119. Blot SI, Taccone FS, Van den Abeele A-M et al (2012) A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 186:56–64. https://doi.org/10.1164/rccm.201111-1978OC

    Article  PubMed  Google Scholar 

  120. Verweij PE, Brüggemann RJM, Azoulay E et al (2021) Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis. Intensive Care Med 47:819–834. https://doi.org/10.1007/s00134-021-06449-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Meersseman W, Lagrou K, Maertens J et al (2008) Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 177:27–34. https://doi.org/10.1164/rccm.200704-606OC

    Article  PubMed  Google Scholar 

  122. Lortholary O, Gangneux J-P, Sitbon K et al (2011) Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005–2007). Clin Microbiol Infect 17:1882–1889. https://doi.org/10.1111/j.1469-0691.2011.03548.x

    Article  CAS  PubMed  Google Scholar 

  123. D’Haese J, Theunissen K, Vermeulen E et al (2012) Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol 50:1258–1263. https://doi.org/10.1128/JCM.06423-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Azoulay E, Guigue N, Darmon M et al (2016) (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies. Oncotarget 7:21484–21495. https://doi.org/10.18632/oncotarget.7471

    Article  PubMed  PubMed Central  Google Scholar 

  125. Tissot F, Agrawal S, Pagano L et al (2017) ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 102:433–444. https://doi.org/10.3324/haematol.2016.152900

    Article  PubMed  PubMed Central  Google Scholar 

  126. Bodinier M, Monneret G, Casimir M et al (2023) Identification of a sub-group of critically ill patients with high risk of intensive care unit-acquired infections and poor clinical course using a transcriptomic score. Crit Care 27:158. https://doi.org/10.1186/s13054-023-04436-3

    Article  PubMed  PubMed Central  Google Scholar 

  127. Kreitmann L, Bodinier M, Fleurie A et al (2022) Mortality prediction in sepsis with an immune-related transcriptomics signature: a multi-cohort analysis. Front Med (Lausanne) 9:930043. https://doi.org/10.3389/fmed.2022.930043

    Article  PubMed  Google Scholar 

  128. Meisel C, Schefold JC, Pschowski R et al (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 180:640–648. https://doi.org/10.1164/rccm.200903-0363OC

    Article  CAS  PubMed  Google Scholar 

  129. Roquilly A, Francois B, Huet O et al (2023) Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial. Intensive Care Med. https://doi.org/10.1007/s00134-023-07065-0

    Article  PubMed  PubMed Central  Google Scholar 

  130. Nguyen LS, Ait Hamou Z, Gastli N et al (2021) Potential role for interferon gamma in the treatment of recurrent ventilator-acquired pneumonia in patients with COVID-19: a hypothesis. Intensive Care Med 47:619–621. https://doi.org/10.1007/s00134-021-06377-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Textoris J (2020) Immunity check should be performed for all patients with septic shock? Yes. Intensive Care Med 46:503–505. https://doi.org/10.1007/s00134-019-05909-2

    Article  PubMed  PubMed Central  Google Scholar 

  132. Stanski NL, Wong HR (2020) Prognostic and predictive enrichment in sepsis. Nat Rev Nephrol 16:20–31. https://doi.org/10.1038/s41581-019-0199-3

    Article  PubMed  Google Scholar 

  133. University Hospital, Lille (2023) Evaluation of the Incidence of Invasive Pulmonary Aspergillosis in Patients With Suspected Ventilator-associated Pneumonia. clinicaltrials.gov

  134. Woodworth MH, Conrad RE, Haldopoulos M et al (2023) Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement. Sci Transl Med 15:eabo2750. https://doi.org/10.1126/scitranslmed.abo2750

    Article  CAS  PubMed  Google Scholar 

  135. Hospices Civils de Lyon (2023) Human Recombinant Interferon Gamma in the Treatment of Ventilator-acquired Pneumonia in ICU Patients. clinicaltrials.gov

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Acknowledgements

The authors would like to thank Mehdi Mezidi for his critical appraisal of the manuscript.

Funding

There was no specific funding for this study.

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Authors and Affiliations

  1. Department of Intensive Care Medicine, Imperial College Healthcare NHS Trust, London, UK

    Louis Kreitmann

  2. Centre for Antimicrobial Optimisation, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, W12 0HS, UK

    Louis Kreitmann

  3. Service de Médecine Intensive-Réanimation, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 1, Place de l’Hôpital, 67091, Strasbourg Cedex, France

    Julie Helms

  4. ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d’Immunologie et d’Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Fédération Hospitalo-Universitaire (FHU) OMICARE, Université de Strasbourg (UNISTRA), Strasbourg, France

    Julie Helms

  5. Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), Leinster, D08NYH1, Dublin, Ireland

    Ignacio Martin-Loeches

  6. Pulmonary Intensive Care Unit, Respiratory Institute, Hospital Clinic of Barcelona, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, ICREA CIBERes, 08380, Barcelona, Spain

    Ignacio Martin-Loeches

  7. D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro, RJ, 22281-100, Brazil

    Jorge Salluh

  8. Third Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece

    Garyphallia Poulakou

  9. Médecine Intensive-Réanimation, Hôpital Cochin, Assistance Publique–Hôpitaux de Paris, Université Paris Cité, Paris, France

    Frédéric Pène

  10. Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, Paris, France

    Frédéric Pène

  11. Médecine Intensive-Réanimation, CHU de Lille, 59000, Lille, France

    Saad Nseir

  12. Inserm U1285, Université de Lille, CNRS, UMR 8576-UGSF, 59000, Lille, France

    Saad Nseir

Authors
  1. Louis Kreitmann
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  2. Julie Helms
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  3. Ignacio Martin-Loeches
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  7. Saad Nseir
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Contributions

Study conception and design: LK and SN. Statistical analysis: not applicable. Data curation: all authors. Manuscript drafting: all authors. Critical revision: all authors.

Corresponding author

Correspondence to Saad Nseir.

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Conflicts of interest

LK has received speaking fees and a research scholarship from BioMérieux, and has been employed by Transgene. JH has received honoraria for lectures from Diagnostica Stago, Pfizer PFE France, Sanofi Aventis France, Inotrem, MSD, Octapharma and Shionogi. IML, JS, and GP have no conflict of interest related to this work. FP has received speaking fees and consultancy honoraria from Gilead and Alexion, and is a member of the steering committee in a study to assess an immune diagnostic test developed by bioMérieux. SN has received speaking fees from MSD, Pfizer, BioMérieux, Fischer and Paykel, and Medtronic.

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Kreitmann, L., Helms, J., Martin-Loeches, I. et al. ICU-acquired infections in immunocompromised patients. Intensive Care Med 50, 332–349 (2024). https://doi.org/10.1007/s00134-023-07295-2

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