DNA persistence and relapses questions on the treatment strategies of Enterococcus infections of prosthetic valves
Authors: Gilbert Habib
Franck Thuny
Jean-Paul Casalta
Didier Raoult
Hubert Lepidi
Pierre-Edouard Fournier
Dominique Grisoli
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: 16S rRNA gene; bacterial DNA; heart valve tissue; infective endocarditis; relapse
Affiliations: URMITE, Aix Marseille Université, UMR CNRS 7278, IRD 198, INSERM 1095, Faculté de Médecine, Marseille, France.

Abstract:  We used amplification of the 16S rRNA gene followed by sequencing to evaluate the persistence of bacterial DNA in explanted heart valve tissue as part of the routine work of a clinical microbiology laboratory, and we analyzed the role of this persistence in the relapses observed in our center. We enrolled 286 patients treated for infective endocarditis (IE) who had valve replacement surgery and were diagnosed according to the modified Duke's criteria described by Li et al. from a total of 579 IE cases treated in our center. The patients were grouped based on the infecting bacteria, and we considered the 4 most common bacterial genus associated with IE separately (144 were caused by Streptococcus spp., 52 by Enterococcus spp., 58 by Staphylococcus aureus and 32 by coagulase-negative Staphylococcus). Based on our cohort, the risk of relapse in patients with enterococcal prosthetic valve infections treated with antibiotics alone was 11%. Bacterial DNA is cleared over time, but this might be a very slow process, especially with Enterococcus spp. Based on a comprehensive review of the literature performed on Medline, most reports still advise combined treatment with penicillin and an aminoglycoside for as long as 4-6 weeks, but there has been no consensus for the treatment of enterococcal infection of prostheses in IE patients. 

Retracted: No

PubPeer comments:
 The authors don t provide the date of recruitments of the participants. The author mention that * verbal consent is required for patients. These patients arrive in the emergency and cardiology department and are not able to sign any consent whatsoever. The ethics committee approved this procedure consents. * In accordance with the EU Directive 2001 20 (aka EU Clinical Trials Directive) which has been implemented in France, * A clinical trial may be undertaken only if, in particular: the trial subject or, when the person is not able to give informed consent, his legal representative has given his written consent after being informed of the nature, significance, implications and risks of the clinical trial; if the individual is unable to write, oral consent in the presence of at least one witness may be given in exceptional cases, as provided for in national legislation * In France, French Law has implemented this provision in 2006 as followed:  informed consent must be provided by written documents, or, if impossible, certified by a third person, independent from the investigator and the sponsor. Furthermore, the French law required that the written consent of the participant should be obtained as soon as the participant becomes able to give it in order to continue the study. [Source:Article L1122-1-2] There is no mention in the study regarding the involvement of a witness independent from the sponsor and the investigator. Can the authors explain how they comply with this obligation? The authors don t mention that written informed consents have been signed once participants was able to do it. Furthermore, the authors mention that the * Ethic Committee of the Institute Fu00e9du00e9ratif de Recherche 48, Marseilles, France (Agreement #07u2013015) *. This local Ethic Committee is not on the list of the certified IRB with the ability to approve a prospective and interventional study in humans. Can the author explain if they have obtained an approval from a certified IRB before to start the study ? , 
 This paper is part of a set of 4 papers from the Aix-Marseille Universitu00e9 Institut Hospitalo-Universitaire Mu00e9diterranu00e9e-Infection (IHU) in Marseille, France, that all describe a prospective study performed from 2001 and using the same ethics approval number #07-015. **Prospective study, prospective recruitment** As mentioned in the title of the paper [Comprehensive Diagnostic Strategy for Blood Culture-Negative Endocarditis: A Prospective Study of 819 New Cases] , the study and the recruitment is prospective. This is also mentioned in other papers with the same ethics approval number 07-015. **The recruitment started in 2001** As mentioned in the paper [Comprehensive Diagnostic Strategy for Blood Culture-Negative Endocarditis: A Prospective Study of 819 New Cases] , the recruitment started in 2001. *From 1 June 2001 to 1 September 2009, we prospectively included all patients with suspected BCNE for whom specimens were referred to our laboratory* This is also mentioned in other papers with the same ethics approval number 07-015. **The 4 papers use the same ethics approval number 07-015 and was obtained or requested in 2007** Considering the same ethics approval number, the 4 papers are related to the same study with the same protocol. The format of this ethics committee described the Year and a incremental number following this template : Year-Incremental Number. 07 = 2007 015 = 15th approval request this year. Based on this ethics approval number, it can be assumed that the ethics committee approval has been requested or obtained in 2007. **Retrospective ethics approval is a cause for a manuscript rejection** According to point 23 of the Helsinki declaration, an approval from an ethics committee should have been obtained before undertaking the research. Retrospective ethics approval is usually a cause for rejection according to Editors Policies. As mentioned above, it can be assumed that the ethics approval 07-015 has been requested or obtained in 2007. But, as mentioned in the papers, the recruitment started in 2001, before to obtain the ethics approval. As a consequence, the ethics approval is retrospective. According to the Editor Policy and the Helsinki Declaration, these papers should have been rejected by the Editor before to be peer-reviewed. It would be interesting to know why it was not the case. Considering the retrospective ethics approval, can the Editor explain why a study which not comply with the Helsinki Declaration was peer-reviewed ? **LIST OF THE PAPERS** - [Comprehensive Diagnostic Strategy for Blood Culture-Negative Endocarditis: A Prospective Study of 819 New Cases] - [Blood culture-negative endocarditis - Improving the diagnostic yield using new diagnostic tools] - [Investigation of blood culture-negative early prosthetic valve endocarditis reveals high prevalence of fungi] - [DNA Persistence and Relapses Questions on the Treatment Strategies of Enterococcus Infections of Prosthetic Valves] ,