Diagnosis of severe respiratory infections in immunocompromised patients

Elie Azoulay^{1

2}, Lene Russell³, Andry Van de Louw⁴, Victoria Metaxa⁵, Philippe Bauer⁶, Pedro Povoa⁷, José Garnacho Montero⁸, Ignacio Martin Loeches⁹, Sangeeta Mehta¹⁰, Kathryn Puxty¹¹, Peter Schellongowski¹², Jordi Rello^{13

14}, Djamel Mokart¹⁵, Virginie Lemiale¹⁶, Adrien Mirouse^{16

17}; Nine-i Investigators

Affiliations

¹ Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France. elie.azoulay@aphp.fr.
² Université de Paris, Paris, France. elie.azoulay@aphp.fr.
³ Department of Intensive Care, Rigshospitalet and Copenhagen Academy for Medical Simulation and Education, University of Copenhagen, Copenhagen, Denmark.
⁴ Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA, USA.
⁵ Department of Critical Care, King's College Hospital NHS Foundation Trust, London, UK.
⁶ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
⁷ Polyvalent Intensive Care Unit, Hospital de São Francisco Xavier, NOVA Medical School, New University of Lisbon, Lisbon, Portugal.
⁸ Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain.
⁹ Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, St James Street, Dublin 8, Ireland.
¹⁰ Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Intensive Care, Glasgow Royal Infirmary, Glasgow, UK.
¹² Department of Medicine I, Intensive Care Unit 13i2, Comprehensive Cancer Center, Center of Excellence in Medical Intensive Care (CEMIC), Medical University of Vienna, Vienna, Austria.
¹³ Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto Salud Carlos III, Madrid, Spain.
¹⁴ CRIPS Department, Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain.
¹⁵ Critical Care Department, Institut Paoli Calmettes, Marseille, France.
¹⁶ Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France.
¹⁷ Université de Paris, Paris, France.

PMID: 32034433
PMCID: PMC7080052
DOI: 10.1007/s00134-019-05906-5

Review

Diagnosis of severe respiratory infections in immunocompromised patients

Elie Azoulay et al. Intensive Care Med. 2020 Feb.

. 2020 Feb;46(2):298-314.

doi: 10.1007/s00134-019-05906-5. Epub 2020 Feb 7.

Authors

Affiliations

¹ Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France. elie.azoulay@aphp.fr.
² Université de Paris, Paris, France. elie.azoulay@aphp.fr.
³ Department of Intensive Care, Rigshospitalet and Copenhagen Academy for Medical Simulation and Education, University of Copenhagen, Copenhagen, Denmark.
⁴ Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA, USA.
⁵ Department of Critical Care, King's College Hospital NHS Foundation Trust, London, UK.
⁶ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
⁷ Polyvalent Intensive Care Unit, Hospital de São Francisco Xavier, NOVA Medical School, New University of Lisbon, Lisbon, Portugal.
⁸ Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain.
⁹ Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, St James Street, Dublin 8, Ireland.
¹⁰ Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Intensive Care, Glasgow Royal Infirmary, Glasgow, UK.
¹² Department of Medicine I, Intensive Care Unit 13i2, Comprehensive Cancer Center, Center of Excellence in Medical Intensive Care (CEMIC), Medical University of Vienna, Vienna, Austria.
¹³ Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto Salud Carlos III, Madrid, Spain.
¹⁴ CRIPS Department, Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain.
¹⁵ Critical Care Department, Institut Paoli Calmettes, Marseille, France.
¹⁶ Médecine Intensive et Réanimation, APHP, Saint-Louis Hospital and Paris University, Paris, France.
¹⁷ Université de Paris, Paris, France.

PMID: 32034433
PMCID: PMC7080052
DOI: 10.1007/s00134-019-05906-5

Abstract

An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.

Keywords: Aspergillosis; Cytomegalovirus; Influenza; Mucormycosis; Pneumocystis pneumonia; Toxoplasmosis.

PubMed Disclaimer

Conflict of interest statement

EA has received fees for lectures from Gilead, Pfizer, Baxter, and Alexion. His research group has been supported by Ablynx, Fisher & Payckle, Jazz Pharma, and MSD. IML reports personal fees from MSD and Gilead. PV has received consultation fees from Orion, Pfizer, and Technofage. PS received honoraria from Astellas, Basilea, Fisher & Paykel, Getinge, Gilead, Hill-Rom, Jazz Pharmaceuticals, Kite, Merck, Orion, Pfizer Rokitan, and Shire. He also declares research support from Amgen, Astellas, Astro-Pharma, and Baxter. JR served a consultant or in the speakers bureau for Merck, Anchoagen, Pfizer, ROCHE and in the speakers bureau for Pfizer and MSD. JGM has received fees for lectures from Gilead. All other authors have no conflict of interest to disclose.

Figures

**Fig. 1**
Pulmonary infections according to immunosuppression. *AML* acute myeloid leukemia, *CMV* cytomegalovirus, GM galactomannan, *HSCT* hematopoietic stem-cell transplantation, *HSV* herpes simplex virus, *MDS* myelodysplastic syndrome, *PCR* polymerase in chain reaction, *SOT* solid organ transplantation, *VZV* Varicella–Zoster virus

**Fig. 2**
Etiologies of pulmonary infections according to CT-scan patterns. *CMV* cytomegalovirus, GM galactomannan, *HSV* herpes simplex virus, *MDS* myelodysplastic syndrome, IF immunofluorescence, *PCR* polymerase in chain reaction, *VZV* Varicella–Zoster virus

See this image and copyright information in PMC

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Diagnosis of severe respiratory infections in immunocompromised patients

Affiliations

Diagnosis of severe respiratory infections in immunocompromised patients

Authors

Affiliations

Abstract

Conflict of interest statement

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Medical