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Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a common and severe disease responsible for approximately 65 000 deaths every year in Europe. Intravenous antistaphylococcal penicillins (ASP) such as cloxacillin are the current recommended antibiotics. However, incre...

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Autores principales: Burdet, Charles, Loubet, Paul, Le Moing, Vincent, Vindrios, William, Esposito-Farèse, Marina, Linard, Morgane, Ferry, Tristan, Massias, Laurent, Tattevin, Pierre, Wolff, Michel, Vandenesch, François, Grall, Nathalie, Quintin, Caroline, Mentré, France, Duval, Xavier, Lescure, François-Xavier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120654/
https://www.ncbi.nlm.nih.gov/pubmed/30173161
http://dx.doi.org/10.1136/bmjopen-2018-023151
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author Burdet, Charles
Loubet, Paul
Le Moing, Vincent
Vindrios, William
Esposito-Farèse, Marina
Linard, Morgane
Ferry, Tristan
Massias, Laurent
Tattevin, Pierre
Wolff, Michel
Vandenesch, François
Grall, Nathalie
Quintin, Caroline
Mentré, France
Duval, Xavier
Lescure, François-Xavier
author_facet Burdet, Charles
Loubet, Paul
Le Moing, Vincent
Vindrios, William
Esposito-Farèse, Marina
Linard, Morgane
Ferry, Tristan
Massias, Laurent
Tattevin, Pierre
Wolff, Michel
Vandenesch, François
Grall, Nathalie
Quintin, Caroline
Mentré, France
Duval, Xavier
Lescure, François-Xavier
author_sort Burdet, Charles
collection PubMed
description INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a common and severe disease responsible for approximately 65 000 deaths every year in Europe. Intravenous antistaphylococcal penicillins (ASP) such as cloxacillin are the current recommended antibiotics. However, increasing reports of toxicity and recurrent stock-outs of ASP prompted healthcare providers to seek for alternative antibiotic treatment. Based on retrospective studies, cefazolin, a first-generation cephalosporin, is recommended in patients at risk of severe ASP-associated toxicity. We hypothesised that cefazolin has a non-inferior efficacy in comparison to cloxacillin, with a better safety profile for the treatment of MSSA bacteraemia. METHODS AND ANALYSIS: The CloCeBa trial is an open-label, randomised, controlled, non-inferiority trial conducted in academic centres throughout France. Eligible patients are adults with MSSA bacteraemia without intravascular device or suspicion of central nervous system infection. Patients will be randomised (1:1) to receive either cloxacillin or cefazolin by the intravenous route, for the first 14 days of therapy. The evaluation criteria is a composite criteria of negative blood cultures at day 5, survival, absence of relapse and clinical success at day 90 after randomisation. Secondary evaluation criteria include both efficacy and safety assessments. Three ancillary studies are planned to describe the epidemiology of β-lactamase encoding genes, the ecological impact and pharmacokinetic/pharmacodynamic parameters of cefazolin and cloxacillin. Including 300 patients will provide 80% power to demonstrate the non-inferiority of cefazolin over cloxacillin, assuming 85% success rate with cloxacillin and taking into account loss-to-follow-up, with a 0.12 non-inferiority margin and a one-sided type I error of 0.025. ETHICS AND DISSEMINATION: This protocol received authorisation from the ethics committee Sud-Est I on 13 November 2017 (2017-87-PP)and French National Agency for Medicines and Health Products (170661A-43). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03248063 and 2017-003967-36.
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spelling pubmed-61206542018-09-05 Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial Burdet, Charles Loubet, Paul Le Moing, Vincent Vindrios, William Esposito-Farèse, Marina Linard, Morgane Ferry, Tristan Massias, Laurent Tattevin, Pierre Wolff, Michel Vandenesch, François Grall, Nathalie Quintin, Caroline Mentré, France Duval, Xavier Lescure, François-Xavier BMJ Open Infectious Diseases INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a common and severe disease responsible for approximately 65 000 deaths every year in Europe. Intravenous antistaphylococcal penicillins (ASP) such as cloxacillin are the current recommended antibiotics. However, increasing reports of toxicity and recurrent stock-outs of ASP prompted healthcare providers to seek for alternative antibiotic treatment. Based on retrospective studies, cefazolin, a first-generation cephalosporin, is recommended in patients at risk of severe ASP-associated toxicity. We hypothesised that cefazolin has a non-inferior efficacy in comparison to cloxacillin, with a better safety profile for the treatment of MSSA bacteraemia. METHODS AND ANALYSIS: The CloCeBa trial is an open-label, randomised, controlled, non-inferiority trial conducted in academic centres throughout France. Eligible patients are adults with MSSA bacteraemia without intravascular device or suspicion of central nervous system infection. Patients will be randomised (1:1) to receive either cloxacillin or cefazolin by the intravenous route, for the first 14 days of therapy. The evaluation criteria is a composite criteria of negative blood cultures at day 5, survival, absence of relapse and clinical success at day 90 after randomisation. Secondary evaluation criteria include both efficacy and safety assessments. Three ancillary studies are planned to describe the epidemiology of β-lactamase encoding genes, the ecological impact and pharmacokinetic/pharmacodynamic parameters of cefazolin and cloxacillin. Including 300 patients will provide 80% power to demonstrate the non-inferiority of cefazolin over cloxacillin, assuming 85% success rate with cloxacillin and taking into account loss-to-follow-up, with a 0.12 non-inferiority margin and a one-sided type I error of 0.025. ETHICS AND DISSEMINATION: This protocol received authorisation from the ethics committee Sud-Est I on 13 November 2017 (2017-87-PP)and French National Agency for Medicines and Health Products (170661A-43). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03248063 and 2017-003967-36. BMJ Publishing Group 2018-09-01 /pmc/articles/PMC6120654/ /pubmed/30173161 http://dx.doi.org/10.1136/bmjopen-2018-023151 Text en © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Infectious Diseases
Burdet, Charles
Loubet, Paul
Le Moing, Vincent
Vindrios, William
Esposito-Farèse, Marina
Linard, Morgane
Ferry, Tristan
Massias, Laurent
Tattevin, Pierre
Wolff, Michel
Vandenesch, François
Grall, Nathalie
Quintin, Caroline
Mentré, France
Duval, Xavier
Lescure, François-Xavier
Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial
title Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial
title_full Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial
title_fullStr Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial
title_full_unstemmed Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial
title_short Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial
title_sort efficacy of cloxacillin versus cefazolin for methicillin-susceptible staphylococcus aureus bacteraemia (cloceba): study protocol for a randomised, controlled, non-inferiority trial
topic Infectious Diseases
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120654/
https://www.ncbi.nlm.nih.gov/pubmed/30173161
http://dx.doi.org/10.1136/bmjopen-2018-023151
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