Browsing by Author "Rahav, Galia"

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    ItemOpen Access
    Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.
    (The Lancet. Infectious diseases, 2021-08) Hoenigl, Martin; Salmanton-García, Jon; Walsh, Thomas J; Nucci, Marcio; Neoh, Chin Fen; Jenks, Jeffrey D; Lackner, Michaela; Sprute, Rosanne; Al-Hatmi, Abdullah MS; Bassetti, Matteo; Carlesse, Fabianne; Freiberger, Tomas; Koehler, Philipp; Lehrnbecher, Thomas; Kumar, Anil; Prattes, Juergen; Richardson, Malcolm; Revankar, Sanjay; Slavin, Monica A; Stemler, Jannik; Spiess, Birgit; Taj-Aldeen, Saad J; Warris, Adilia; Woo, Patrick CY; Young, Jo-Anne H; Albus, Kerstin; Arenz, Dorothee; Arsic-Arsenijevic, Valentina; Bouchara, Jean-Philippe; Chinniah, Terrence Rohan; Chowdhary, Anuradha; de Hoog, G Sybren; Dimopoulos, George; Duarte, Rafael F; Hamal, Petr; Meis, Jacques F; Mfinanga, Sayoki; Queiroz-Telles, Flavio; Patterson, Thomas F; Rahav, Galia; Rogers, Thomas R; Rotstein, Coleman; Wahyuningsih, Retno; Seidel, Danila; Cornely, Oliver A
    With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
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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.