Browsing by Author "Bourgeois, Marc"

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    ItemOpen Access
    Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology.
    (Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2022-04) Prattes, Juergen; Wauters, Joost; Giacobbe, Daniele Roberto; Salmanton-García, Jon; Maertens, Johan; Bourgeois, Marc; Reynders, Marijke; Rutsaert, Lynn; Van Regenmortel, Niels; Lormans, Piet; Feys, Simon; Reisinger, Alexander Christian; Cornely, Oliver A; Lahmer, Tobias; Valerio, Maricela; Delhaes, Laurence; Jabeen, Kauser; Steinmann, Joerg; Chamula, Mathilde; Bassetti, Matteo; Hatzl, Stefan; Rautemaa-Richardson, Riina; Koehler, Philipp; Lagrou, Katrien; Hoenigl, Martin; ECMM-CAPA Study Group

    Objectives

    Coronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome.

    Methods

    The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions.

    Results

    A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0-31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02-1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84-6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41-4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%-26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel-Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59-2.87, p ≤ 0.001).

    Conclusion

    Prevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.
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    ItemOpen Access
    Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial.
    (Critical care (London, England), 2022-11) Chastre, Jean; François, Bruno; Bourgeois, Marc; Komnos, Apostolos; Ferrer, Ricard; Rahav, Galia; De Schryver, Nicolas; Lepape, Alain; Koksal, Iftihar; Luyt, Charles-Edouard; Sánchez-García, Miguel; Torres, Antoni; Eggimann, Philippe; Koulenti, Despoina; Holland, Thomas L; Ali, Omar; Shoemaker, Kathryn; Ren, Pin; Sauser, Julien; Ruzin, Alexey; Tabor, David E; Akhgar, Ahmad; Wu, Yuling; Jiang, Yu; DiGiandomenico, Antonio; Colbert, Susan; Vandamme, Drieke; Coenjaerts, Frank; Malhotra-Kumar, Surbhi; Timbermont, Leen; Oliver, Antonio; Barraud, Olivier; Bellamy, Terramika; Bonten, Marc; Goossens, Herman; Reisner, Colin; Esser, Mark T; Jafri, Hasan S; COMBACTE-MAGNET EVADE Study Group

    Background

    Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects.

    Methods

    EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee.

    Results

    Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) μg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 μg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups.

    Conclusions

    The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016.