Title:How to approach and treat viral infections in ICU patients.

Transcription

1 Author's response to reviews Title:How to approach and treat viral infections in ICU patients. Authors: Theodoros Kelesidis Ioannis Mastoris Aliki Metsini Sotirios Tsiodras Version:2Date:22 April 2014 Author's response to reviews: see over

2 Article Title: How to approach and treat viral infections in ICU patients Athens, April 21, 2014 Dear Editor, Thank you very much for your dated 4/7/14 stating that our manuscript may be considered for publication in your Journal provided that we revise it further according to your suggestions. We resubmit the manuscript entitled How to approach and treat viral infections in ICU patients by Kelesidis et al, which has been revised according to your suggestions. We would like to thank you for your comments, which prompted us to revise the manuscript extensively. Please see our specific responses to your comments in the following page. Please do not hesitate to or call me if I can be of further assistance. We believe that this paper may help in clarifying available literature on this issue and that this article will be of major interest to the global readership of BMC Infectious Diseases. This manuscript has not been previously published and is not being considered for publication elsewhere. There are no potential conflicts of interest for the participating authors. Please do not hesitate to contact me should you have any further questions regarding this manuscript. Sincerely, Sotirios Tsiodras, M.D, PhD Asst Professor of Medicine and Infectious Diseases Univ of Athens Medical School 4th Department of Internal Medicine Attikon University Hospital 1 Rimini str Xaidari, Athens Greece tel: mob: fax: tsiodras@med.uoa.gr

3 Reviewer 1 Major Compulsory Revisions This article seeks to review the epidemiology, clinical manifestations and treatment of viral infections in adults requiring intensive care unit admission. There are several reviews in the literature that examine specific clinical entities (e.g. pneumonia, encephalitis) of viral infections in the ICU and this manuscript attempts comprehensively address the spectrum of clinical presentation. Comprehensive reviews of this nature have been previously published although this is one of the first written following the widespread availability of respiratory viral polymerase chain reaction testing. We would like to thank the reviewer for his/her comments. Unfortunately, there is not enough of a discussion of how our understanding of the epidemiology of viral infections has changed over the last five years. We would like to thank the reviewer for the feedback. The focus of this mini review (< 2500 words) is on the clinical presentation and treatment of viral infections in the ICU setting. The reported incidence of viral infections reported in the ICU varies widely across studies and geographic regions and thus we could not present detailed epidemiological data regarding the different types of viral infections. However the following sentences were included in the revised manuscript to briefly address the changes in the epidemiology of viral infections over the last five years. Introduction: The reported incidence of viral infections reported in the ICU varies widely across studies and geographic regions and has changed over the recent years based on the epidemiology of emerging viral infections such as human metapneumovirus and adenovirus infections. Improved molecular detections methods have also significantly changed the epidemiology of viral infections in the ICU over the last years. Multi-institutional databases and time-series models may be useful tools to characterize and forecast the burden of severe viral infections at the local and institutional levels The discussion of viral pneumonia needs to be expanded significantly especially as it relates to viruses increasingly identified (e.g. rhinovirus, hmpv, etc) and adenovirus As we mention above the size limitations of this mini-review does not allow us to extensively present epidemiological data regarding specific viral infections such as rhinovirus, hmpv and

4 adenovirus. However the following sentences were included in the revised manuscript to further emphasize the emerging role of these viral infections: Introduction: Improved molecular detections methods have also significantly changed the epidemiology of viral infections in the ICU over the last years. Causes lf viral pneumonia: Recent molecular diagnostic methods have significantly changed the epidemiology of viral pneumonias in the ICU over the last years with the increasing detection of viruses such as human metapneumovirus and adenovirus infections Under Treatment of viral of respiratory viruses, the statement that Except for severe influenza pneumonia, treatment of viral CAP remains supportive is misleading. The following sentences were revised to clarify that influenza is the only viral infection for which there are FDA approved antivirals: Treatment of viral CAP remains largely supportive. Influenza is the only virus for which Food and Drug Administration (FDA)- approved therapeutic agents are available for adults. FDA approval aside, there is a large body of evidence investigating the use of antiviral medications (e.g. cidofovir) for a variety of at-risk populations (e.g. hematopoietic stem cell transplant). In this mini-review we focused only on FDA approved treatment of viral infections. There are numerous experimental antivirals that can be used for off-label indications that have been recently reviewed. We included these references (De,Clercq E 2013) and in addition the following sentences were added in the section Novel antivirals can be considered for treatment of respiratory viral infections : Finally, numerous antivirals such as entry inhibitors, nucleoside analogues such as cidofovir, viral enzyme inhibitors (such as terminase and helicase enzyme inhibitors), and translation inhibitors may be utilized in an off-label indication for treatment of viral infections Per #3, the Table seems present a lot more information as it relates to treatment options than is suggested within the text.

5 The Table is cited throughout the manuscript and concisely summarizes etiology, clinical presentation and treatment of viral infections in the ICU (not only treatment). While the Table has a wealth of great information, it is difficult to read across columns. This needs be edited so that the reader can read across from the first column through the third column for each syndrome or presentation We would like to clarify that we made every effort to summarize a large volume of data in a table as concisely as possible. The goal of the table is not to present separate treatment for each syndrome or presentation since the treatment of viral infections often overlaps and is rarely specific for each virus. For example supportive therapy is applicable to all viruses and it would be repetitive to mention this treatment for each syndrome or presentation separately. Minor Compulsory Revisions There are multiple abbreviations not defined (e.g. PCR, flu, HIV, etc.) The following abbreviations were spelled out: PCR: Polymerase Chain Reaction Flu was substituted for influenza throughout the manuscript HIV: Human Immunodeficiency Virus FDA: Food and Drug Administration