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Multicenter Study
. 2023 Aug 24;27(1):323.
doi: 10.1186/s13054-023-04608-1.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG

Daniele Roberto Giacobbe  1   2 , Silvia Dettori  3   4 , Vincenzo Di Pilato  5 , Erika Asperges  6 , Lorenzo Ball  5   7 , Enora Berti  8 , Ola Blennow  9   10 , Bianca Bruzzone  11 , Laure Calvet  12 , Federico Capra Marzani  13 , Antonio Casabella  14 , Sofia Choudaly  15 , Anais Dartevel  16 , Gennaro De Pascale  17   18 , Gabriele Di Meco  4 , Melissa Fallon  19 , Louis-Marie Galerneau  16 , Miguel Gallego  20   21 , Mauro Giacomini  22 , Adolfo González Sáez  23   24 , Luise Hänsel  25   26 , Giancarlo Icardi  3   11 , Philipp Koehler  25   26 , Katrien Lagrou  27   28 , Tobias Lahmer  29 , P Lewis White  19   30 , Laura Magnasco  4 , Anna Marchese  5   31 , Cristina Marelli  4 , Mercedes Marín-Arriaza  23   24   32 , Ignacio Martin-Loeches  33   34 , Armand Mekontso-Dessap  8   35   36 , Malgorzata Mikulska  3   4 , Alessandra Mularoni  37 , Anna Nordlander  9   10 , Julien Poissy  15   38 , Giovanna Russelli  37 , Alessio Signori  39 , Carlo Tascini  40   41 , Louis-Maxime Vaconsin  42 , Joel Vargas  17 , Antonio Vena  3   4 , Joost Wauters  27   43 , Paolo Pelosi  5   7 , Jean-Francois Timsit  42   44 , Matteo Bassetti  3   4 ; JIR-ICU investigators (collaborators); Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESGCIP), and the Fungal Infection Study Group of the European Society of Clinical Microbiology and Infectious Diseases (EFISG)
Collaborators, Affiliations
Multicenter Study

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG

Daniele Roberto Giacobbe et al. Crit Care. .

Abstract

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored.

Materials and methods: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population.

Results: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively.

Conclusion: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Keywords: Biomarker; Diagnosis; ICU; PCR; Pneumocystis; Pneumonia; Serum β-D-Glucan.

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Conflict of interest statement

Outside the submitted work, DRG reports investigator-initiated grants from Pfizer, Shionogi, and Gilead Italia, and speaker and/or advisor fees from Pfizer and Tillotts Pharma. Outside the submitted work, MB reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from BioMérieux, Cidara, Gilead, Menarini, MSD, Pfizer, and Shionogi. Outside the submitted work, VDP reports research grant from Seegene Inc. Outside the submitted work, PLW performed diagnostic evaluations and received meeting sponsorship from Bruker; speakers fees, expert advice fees and meeting sponsorship from Gilead; expert advice fees from F2G and speaker fees from Pfizer; speakers fees and performed diagnostic evaluations for Associates of Cape Cod and IMMY. JW received meeting speakers and travel fees and investigator-initiated grants from MSD, Gilead and Pfizer, outside the scope of this manuscript. Outside the submitted work, PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online. The other authors report no conflicts of interests related to this study.

Figures

Fig. 1
Fig. 1
Flow diagram of the patients’ inclusion process. eCRF, electronic case report forms. Missing key data was defined as unavailability of information regarding both Pneumocystis polymerase chain reaction results and serum β-D-glucan results
Fig. 2
Fig. 2
PPV and NPV for presumptive/proven PJP of serum BDG and respiratory Pneumocystis PCR both separately and in combination. BDG, (1,3)-β-D-glucan; NPV, negative predictive value; PCR, polymerase chain reaction; PJP, Pneumocystis jirovecii pneumonia; PPV, positive predictive value. Criteria for positivity used for the comparisons in the graph are manufactures’ cut-offs for BDG (80 pg/mL for the Fungitell assay and 11 pg/mL for the Wako assay) and any positive result for respiratory Pneumocystis PCR (see study methods). For the combination (PCR plus BDG), the reported PPV was obtained when both markers were concordant in indicating PJP (both positive), while the reported NPV was obtained when both markers when concordant in indicating no PJP (both negative)
See this image and copyright information in PMC

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