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  1. Article ; Online: A critical view on the current use of daptomycin in Spain: The daptomise study.

    González, Carmen Guadalupe Rodríguez / Vega, Esther Chamorro de / Martínez, Sofía De la Villa / Minero, Maricela Valerio / Urbón, José María Gutiérrez / Manzorro, Álvaro Giménez / Martínez, Edurne Fernández de Gamarra / Sacristán, Sara Cobo / Santiago, Emilio Bouza / Alonso, Ana Herranz / Paredes, Patricia Muñoz García de / Sáez, María Sanjurjo

    Journal of infection and public health

    2023  Volume 16, Issue 7, Page(s) 1115–1122

    Abstract: Background: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different ... ...

    Abstract Background: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different hospitals and the adequacy of therapy, specially focused on underdosing.
    Methods: All adult and pediatric patients who received, at least, one dose of daptomycin in a single week in 98 institutions in Spain were included. The adequacy of daptomycin use was evaluated with respect to the indication, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment.
    Results: A total of 615 patients received daptomycin during the study week. The prevalence use was 2.3 patients / 100,000 inhabitants per week, 12.4 patients / 1000 admissions and 9.2 Days of Therapy (DOT) / 1000 hospital stays. These rates varied between hospitals: from 0 to 13.9 patients / 100,000 inhabitants, from 0 to 76.1 patients / 1000 admissions and from 0 to 49.4 DOT / 1000 hospital stays. The most frequent infections were bacteremia (31.6 %) and skin and soft tissue infections (17.9 %). Microbiological results were available in only 65.4 % of infections. The most frequent microorganisms were Staphylococcus aureus (192 isolates, of which 87 were resistant to methicillin) and coagulase-negative staphylococci (124 isolates). A total of 136 prescriptions (22.1 %) were underdosed. Dosages < 8 mg/kg were used for 35.6 % of endovascular infections and for 26.2 % of osteoarticular infections. Overall, 57.2 % of prescriptions were not optimal in, at least, one item. Clinical cure rate was 76.1% and mortality attributable to the infection 8.1%.
    Conclusion: This is the first registry that identifies the prevalence of use of daptomycin in Spain and shows a high variability in the consumption between the different hospitals. Daptomycin underdosing was present in more than 20 % of cases.
    MeSH term(s) Adult ; Humans ; Child ; Daptomycin/therapeutic use ; Daptomycin/adverse effects ; Anti-Bacterial Agents ; Spain/epidemiology ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/epidemiology ; Staphylococcal Infections/microbiology ; Bacteremia/drug therapy ; Bacteremia/epidemiology ; Treatment Outcome
    Chemical Substances Daptomycin (NWQ5N31VKK) ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-05-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2467587-8
    ISSN 1876-035X ; 1876-0341
    ISSN (online) 1876-035X
    ISSN 1876-0341
    DOI 10.1016/j.jiph.2023.05.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

    Corominas, Julia / Garriga, Carme / Prenafeta, Antoni / Moros, Alexandra / Canete, Manuel / Barrero, Antonio / Gonzalez-Gonzalez, Luis / Madrenas, Laia / Guell, Irina / Clotet, Bonaventura / Izaquierdo-Useros, Nuria / Raich-Regue, Dalia / Gallemi, Marcal / Blanco, Julia / Pradenas, Edwards / Trinite, Benjamin / Prado, Julia G / Blanch-Lombarte, Oscar / Perez-Caballero, Raul /
    Plana, Montserrat / Esteban, Ignasi / Pastor-Quinones, Carmen / Nunez-Costa, Xavier / Taleb, Rachel Abu / McSkimming, Paula / Soriano, Alex / Planol, Jocelyn / Anagua, Jesse Omar / Ramos, Rafael / Lluch, Ruth Marti / Comes, Aida Corpes / Romero, Susana Otero / Gomez, Xavier Martinez / Sans-Pola, Carla / Molto, Jose / Benet, Susana / Bailon, Lucia / Arribas, Jose / Borobia, Alberto M / Parada, Javier Queiruga / Navarro-Perez, Jorge / Giner, Maria Jose Forner / Lucas, Rafael Orti / Jimenez, Maria del Mar Vazquez / Compan, Salvador Ona / Alvarez-Mon, Melchor / Troncoso, Daniel / Arana-Arri, Eunate / Meijide, Susana / Imaz-Ayo, Natale / Garcia, Patricia Munoz / Martinez, Sofia de la Villa / Fernandez, Sara Rodriguez / Prat, Teresa / Torroella, Elia / Ferrer, Laura

    medRxiv

    Abstract: Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH- ...

    Abstract Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine ̶ either heterologous (PHH-1V group) or homologous (BNT162b2 group) ̶ in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies against the ancestral Wuhan-Hu-1 strain and different variants of SARS-CoV-2 after the PHH-1V or the BNT162b2 boost, the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides and the safety and tolerability of PHH-1V as a boost. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001) and 0.87 (p=0.43) for the ancestral Wuhan-Hu-1 strain; 0.61 (p<0.0001) and 0.57 (p=0.0064) for the beta variant; 1.01 (p=0.89) and 0.52 (p=0.0003) for the delta variant; and 0.59 (p=<0.0001) and 0.56 (p=0.0026) for the omicron variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, elicits a strong and sustained neutralizing antibody response against Wuhan-Hu-1 strain, and a superior one concerning the previous circulating beta and delta SARS-CoV-2 variants, as well as the currently circulating omicron. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
    Keywords covid19
    Language English
    Publishing date 2022-07-06
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.07.05.22277210
    Database COVID19

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