4 research outputs found
Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: Study protocol for the SAFO trial
Introduction Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (=18 years) with isolation of MSSA from at least one blood culture =72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ
Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial
Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders
Fungal Planet description sheets: 1182-1283
Novel species of fungi described in this study include those from various countries as follows: Algeria, Phaeoacremonium adelophialidum from Vitis vinifera. Antarctica, Comoclathris antarctica from soil. Australia, Coniochaeta salicifolia as endophyte from healthy leaves of Geijera salicifolia, Eremothecium peggii in fruit of Citrus australis, Microdochium ratticaudae from stem of Sporobolus natalensis, Neocelosporium corymbiae on stems of Corymbia variegata, Phytophthora kelmanii from rhizosphere soil of Ptilotus pyramidatus, Pseudosydowia backhousiae on living leaves of Backhousia citriodora, Pseudosydowia indoor oopillyensis, Pseudosydowia louisecottisiae and Pseudosydowia queenslandica on living leaves of Eucalyptus sp. Brazil, Absidia montepascoalis from soil. Chile, Ilyonectria zarorii from soil under Maytenus boaria. Costa Rica, Colletotrichum filicis from an unidentified fern. Croatia, Mollisia endogranulata on deteriorated hardwood. Czech Republic, Arcopilus navicularis from tea bag with fruit tea, Neosetophoma buxi as endophyte from Buxus sempervirens, Xerochrysium bohemicum on surface of biscuits with chocolate glaze and filled with jam. France, Entoloma cyaneobasale on basic to calcareous soil, Fusarium aconidiale from Triticum aestivum, Fusarium juglandicola from buds of Juglans regia. Germany, Tetraploa endophytica as endophyte from Microthlaspi perfoliatum roots. India, Castanediella ambae on leaves of Mangifera indica, Lactifluus kanadii on soil under Castanopsis sp., Penicillium uttarakhandense from soil. Italy, Penicillium ferraniaense from compost. Namibia, Bezerromyces gobabebensis on leaves of unidentified succulent, Cladosporium stipagrostidicola on leaves of Stipagrostis sp., Cymostachys euphorbiae on leaves of Euphorbia sp., Deniquelata hypolithi from hypolith under a rock, Hysterobrevium walvisbayicola on leaves of unidentified tree, Knufia hypolithi and Knufia walvisbayicola from hypolith under a rock, Lapidomyces stipagrostidicola on leaves of Stipagrostis sp., Nothophaeotheca mirabibensis (incl. Nothophaeotheca gen. nov.) on persistent inflorescence remains of Blepharis obmitrata, Paramyrothecium salvadorae on twigs of Salvadora persica, Preussia procaviicola on dung of Procavia sp., Sordaria equicola on zebra dung, Volutella salvadorae on stems of Salvadora persica. Netherlands, Entoloma ammophilum on sandy soil, Entoloma pseudocruentatum on nutrient poor(acid)soil, Entoloma pudens on plant debris, amongst grasses. [...]Leslie W.S. de Freitas and colleagues express their
gratitude to Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq) for scholarships provided to Leslie Freitas and for the research grant
provided to André Luiz Santiago; their contribution was financed by the
projects ‘Diversity of Mucoromycotina in the different ecosystems of the
Atlantic Rainforest of Pernambuco’ (FACEPE–First Projects Program PPP/
FACEPE/CNPq–APQ–0842-2.12/14) and ‘Biology of conservation of fungi
s.l. in areas of Atlantic Forest of Northeast Brazil’ (CNPq/ICMBio 421241/
2017-9) H.B. Lee was supported by the Graduate Program for the Undiscovered
Taxa of Korea (NIBR202130202). The study of O.V. Morozova, E.F.
Malysheva, V.F. Malysheva, I.V. Zmitrovich, and L.B. Kalinina was carried
out within the framework of a research project of the Komarov Botanical
Institute RAS (АААА-А19-119020890079-6) using equipment of its Core
Facility Centre ‘Cell and Molecular Technologies in Plant Science’. The work
of O. V. Morozova, L.B. Kalinina, T. Yu. Svetasheva, and E.A. Zvyagina was
financially supported by Russian Foundation for Basic Research project no.
20-04-00349. E.A. Zvyagina and T.Yu. Svetasheva are grateful to A.V. Alexandrova,
A.E. Kovalenko, A.S. Baykalova for the loan of specimens, T.Y.
James, E.F. Malysheva and V.F. Malysheva for sequencing. J.D. Reyes
acknowledges B. Dima for comparing the holotype sequence of Cortinarius
bonachei with the sequences in his database. A. Mateos and J.D. Reyes
acknowledge L. Quijada for reviewing the phylogeny and S. de la Peña-
Lastra and P. Alvarado for their support and help. Vladimir I. Kapitonov and
colleagues are grateful to Brigitta Kiss for help with their molecular studies.
This study was conducted under research projects of the Tobolsk Complex
Scientific Station of the Ural Branch of the Russian Academy of Sciences
(N АААА-А19-119011190112-5). E. Larsson acknowledges the Swedish
Taxonomy Initiative, SLU Artdatabanken, Uppsala (dha.2019.4.3-13). The
study of D.B. Raudabaugh and colleagues was supported by the Schmidt
Science Fellows, in partnership with the Rhodes Trust. Gregorio Delgado is
grateful to Michael Manning and Kamash Pillai (Eurofins EMLab P&K) for
provision of laboratory facilities. Jose G. Maciá-Vicente acknowledges support
from the German Research Foundation under grant MA7171/1-1, and
from the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer
Exzellenz (LOEWE) of the state of Hesse within the framework of the Cluster
for Integrative Fungal Research (IPF). Thanks are also due to the authorities
of the Cabañeros National Park and Los Alcornocales Natural Park
for granting the collection permit and for support during field work. The study
of Alina V. Alexandrova was carried out as part of the Scientific Project of
the State Order of the Government of Russian Federation to Lomonosov
Moscow State University No. 121032300081-7. Michał Gorczak was
financially supported by the Ministry of Science and Higher Education through
the Faculty of Biology, University of Warsaw intramural grant DSM 0117600-
13. M. Gorczak acknowledges M. Klemens for sharing a photo of the
Białowieża Forest logging site and M. Senderowicz for help with preparing
the illustration. Ivona Kautmanová and D. Szabóová were funded by the
Operational Program of Research and Development and co-financed with
the European Fund for Regional Development (EFRD). ITMS 26230120004:
‘Building of research and development infrastructure for investigation of
genetic biodiversity of organisms and joining IBOL initiative’. Ishika Bera,
Aniket Ghosh, Jorinde Nuytinck and Annemieke Verbeken are grateful to the
Director, Botanical Survey of India (Kolkata), Head of the Department of
Botany & Microbiology & USIC Dept. HNB Garhwal University, Srinagar,
Garhwal for providing research facilities. Ishika Bera and Aniket Ghosh acknowledge
the staff of the forest department of Arunachal Pradesh for facilitating
the macrofungal surveys to the restricted areas. Sergey Volobuev
was supported by the Russian Science Foundation (RSF project N 19-77-
00085). Aleksey V. Kachalkin and colleagues were supported by the Russian
Science Foundation (grant No. 19-74-10002). The study of Anna M.
Glushakova was carried out as part of the Scientific Project of the State
Order of the Government of Russian Federation to Lomonosov Moscow
State University No. 121040800174-6. Tracey V. Steinrucken and colleagues
were supported by AgriFutures Australia (Rural Industries Research and
Development Corporation), through funding from the Australian Government
Department of Agriculture, Water and the Environment, as part of its Rural
Research and Development for Profit program (PRJ-010527). Neven Matočec
and colleagues thank the Croatian Science Foundation for their financial
support under the project grant HRZZ-IP-2018-01-1736 (ForFungiDNA). Ana
Pošta thanks the Croatian Science Foundation for their support under the
grant HRZZ-2018-09-7081. The research of Milan Spetik and co-authors
was supported by Internal Grant of Mendel University in Brno No. IGAZF/
2021-SI1003. K.C. Rajeshkumar thanks SERB, the Department of Science
and Technology, Government of India for providing financial support
under the project CRG/2020/000668 and the Director, Agharkar Research
Institute for providing research facilities. Nikhil Ashtekar thanks CSIR-HRDG,
INDIA, for financial support under the SRF fellowship (09/670(0090)/2020-EMRI),
and acknowledges the support of the DIC Microscopy Facility, established
by Dr Karthick Balasubramanian, B&P (Plants) Group, ARI, Pune. The research
of Alla Eddine Mahamedi and co-authors was supported by project
No. CZ.02.1.01/0.0/0.0/16_017/0002334, Czech Republic. Tereza Tejklová
is thanked for providing useful literature. A. Polhorský and colleagues were
supported by the Operational Program of Research and Development and
co-financed with the European fund for Regional Development (EFRD), ITMS
26230120004: Building of research and development infrastructure for investigation
of genetic biodiversity of organisms and joining IBOL initiative.
Yu Pei Tan and colleagues thank R. Chen for her technical support. Ernest
Lacey thanks the Cooperative Research Centres Projects scheme (CRCPFIVE000119)
for its support. Suchada Mongkolsamrit and colleagues were
financially supported by the Platform Technology Management Section,
National Center for Genetic Engineering and Biotechnology (BIOTEC),
Project Grant No. P19-50231. Dilnora Gouliamova and colleagues were
supported by a grant from the Bulgarian Science Fund (KP-06-H31/19). The
research of Timofey A. Pankratov was supported by the Russian Foundation
for Basic Research (grant No. 19-04-00297a). Gabriel Moreno and colleagues
wish to express their gratitude to L. Monje and A. Pueblas of the Department
of Drawing and Scientific Photography at the University of Alcalá for their
help in the digital preparation of the photographs, and to J. Rejos, curator of
the AH herbarium, for his assistance with the specimens examined in the
present study. Vit Hubka was supported by the Charles University Research
Centre program No. 204069. Alena Kubátová was supported by The National
Programme on Conservation and Utilization of Microbial Genetic
Resources Important for Agriculture (Ministry of Agriculture of the Czech
Republic). The Kits van Waveren Foundation (Rijksherbariumfonds Dr E. Kits
van Waveren, Leiden, Netherlands) contributed substantially to the costs of
sequencing and travelling expenses for M. Noordeloos. The work of B. Dima
was supported by the ÚNKP-20-4 New National Excellence Program of the
Ministry for Innovation and Technology from the source of the National Research,
Development and Innovation Fund, and by the ELTE Thematic Excellence
Programme 2020 supported by the National Research, Development
and Innovation Office of Hungary (TKP2020-IKA-05). The Norwegian Entoloma
studies received funding from the Norwegian Biodiversity Information
Centre (NBIC), and the material was partly sequenced through NorBOL.
Gunnhild Marthinsen and Katriina Bendiksen (Natural History Museum,
University of Oslo, Norway) are acknowledged for performing the main parts
of the Entoloma barcoding work. Asunción Morte is grateful to AEI/FEDER,
UE (CGL2016-78946-R) and Fundación Séneca - Agencia de Ciencia y
Tecnología de la Región de Murcia (20866/PI/18) for financial support.
Vladimír Ostrý was supported by the Ministry of Health, Czech Republic -
conceptual development of research organization (National Institute of
Public Health – NIPH, IN 75010330). Konstanze Bensch (Westerdijk Fungal
Biodiversity Institute, Utrecht) is thanked for correcting the spelling of various
Latin epithets.Peer reviewe
Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.
The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients