Title: Clinical factors associated with a Candida albicans Germ Tube Antibody (CAGTA) positive test in ICU patients

Transcription

1 Author's response to reviews Title: Clinical factors associated with a Candida albicans Germ Tube Antibody (CAGTA) positive test in ICU patients Authors: Javier Pemán (peman_jav@gva.es) Rafael Zaragoza (zaragozar@ono.es) Guillermo Quindós (oipquang@lg.ehu.es) Miriam Alkorta (malkorta@hcru.osakidetza.net) María S Cuétara (mcuetara.hsvo@salud.madrid.org) Juan J Camarena (juan.camarena@uv.es) Paula Ramírez (villapauleta@eresmas.com) María J Giménez (gimenez_mar@gva.es) Estrella Martín-Mazuelos (estrella.martin.sspa@juntadeandalucia.es) María J Linares-Sicilia (mi1lisim@uco.es) José Pontón (oipposaj@lg.ehu.es) Version: 2 Date: 27 December 2010 Author's response to reviews: see over

2 Manuscript ID: Title: Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients Dear Dieter Buchheidt, Thank you very much for considering that our paper may be acceptable for publication in the prestigious journal BMC Infectious Diseases after revision. The reviewers comments have been very helpful for increasing the quality of the new version of the manuscript. Moreover, we have tried as much as possible to answer their questions in a point-by-point manner and we have introduced the adequate modifications where required. All alterations in the new version of the paper have been highlighted using the MsWord tool for control of changes. Looking forward to hearing from you Editorial requests: - Please revise your Title Page. This should list: the title of the article, which should include an accurate, clear and concise description of the reported work, avoiding abbreviations; and the full names, institutional addresses, and addresses for all authors. The corresponding author should also be indicated. Recommended changes have been made. - Please be sure to clearly describe within your manuscript that the cohort is the same as that described in your previous publications and clearly describe the novel aspects reported here not included in your previous papers. Recommended description has been added to the manuscript (Methods Section). - Informed consent must also be documented. Manuscripts may be rejected if the editorial office considers that the research has not been carried out within an ethical framework, e.g. if the severity of the experimental procedure is not justified by the value of the knowledge gained. A sentence about informed consent has been added to the

3 manuscript (Methods Section). - Please include a 'Competing interests' section between the Conclusions and Authors' contributions. If there are none to declare, please write 'The authors declare that they have no competing interests'. A Competing interest section has been added to the manuscript - Please include an Authors' contributions section before the Acknowledgements and Reference list. An Authors contributions section has been included in the manuscript - We strongly encourage you to include an Acknowledgements section between the Authors contributions section and Reference list. Please acknowledge anyone who contributed towards the study by making substantial contributions to conception, design, acquisition of data, or analysis and interpretation of data, or who was involved in drafting the manuscript or revising it critically for important intellectual content, but who does not meet the criteria for authorship. Please also include their source(s) of funding. Please also acknowledge anyone who contributed materials essential for the study. Authors should obtain permission to acknowledge from all those mentioned in the Acknowledgements. Please list the source(s) of funding for the study, for each author, and for the manuscript preparation in the acknowledgements section. Authors must describe the role of the funding body, if any, in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The Acknowledgements section (with all the items suggested) has been placed in the position indicated Answers to the Reviewers comments: General comment: Referee 1: Comments to the Author:

4 1) Authors have to correlate the level of CAGTA titer with individual clinical factors. It is not clear the meaning of 1/2560 in comparison to 1/160 The possible correlation between CAGTA titers and mortality has been published previously by our group (Zaragoza R, Pemán J, Quindós G, Iruretagoyena JR, Cuetara M, Ramirez P et al.: Clinical significance of Candida albicans germ tube antibody detection in critically ill patients. Clin Microbiol Infect 2009, 15: ; and Zaragoza R, Pemán J, Quindós G, Iruretagoyena JR, Cuétara MS, Ramirez P et al.: Kinetic Patterns of Candida albicans Germ Tube Antibody (CAGTA) in Critically Ill Patients: Influence on Mortality. Clin Vaccine Immunol 2009, 16: ). However, the correlation with mortality remains unclear; due to this fact, we only have analyzed the correlation between clinical factors and the qualitative result of the test (positive or negative). The low number (2 patients) of high positivity results (1/2560) has no possible to analyse this correlation. For this reason, the meaning of 1/2560 in comparison to 1/160 is no possible to be defined in our cohort. 2) Other not so clear correlation is the CAGTA results and antifungal therapy. This correlation need to be better discussed. Is any benefit from this correlation? The reason to include the Table 2 was to analyze the possible differences in CAGTA test according the antifungal agent used. The no difference observed neither the global administration of antifungal treatment nor antifungal agent used between CAGTApositive and -negative give more value to this technique avoiding false-negative results in presence of any antifungal therapy. A brief comment has been added in Discussion Section. Minor revision: Page 11: Please change C. Albicans in C. albicans Please check all citations, particularly use of brackets Recommended changes have been made. Reviewer: 2 Comments to the Author

5 Major compulsory revisions: 1. Interpretation of the data presented is limited as no outcome data are provided. The report lacks comprehensive data on colonisation (C.albicans versus non albicans), treatment data (in vitro active therapy before onset, after onset of test positivity). As the influence of CAGTA titers on mortality has been previously published by our group (Zaragoza R, Pemán J, Quindós G, Iruretagoyena JR, Cuetara M, Ramirez P et al.: Clinical significance of Candida albicans germ tube antibody detection in critically ill patients. Clin Microbiol Infect 2009, 15: ; and Zaragoza R, Pemán J, Quindós G, Iruretagoyena JR, Cuétara MS, Ramirez P et al.: Kinetic Patterns of Candida albicans Germ Tube Antibody (CAGTA) in Critically Ill Patients: Influence on Mortality. Clin Vaccine Immunol 2009, 16: ) we have treated to avoid duplicate results in the present article. Due to the design of study only included the Corrected Colonisation Index (CCI) it is not possible to give an answer to colonisation data query. No in vitro susceptibility testing was performed to colonisation isolates. 2. Microbiologic data from sterile sites (e.g. blood, CSF etc.) are needed to understand the true incidence of proven invasive candidiasis in this patient cohort. Unfortunately, no invasive candidiasis were diagnosed in this cohort as it has been described as limitation in the Discussion Section 3. The authors should state wether this report describes consecutive patients at risk for invasive candidiasis or if the patients were selected for the analysis. All the patients were consecutively included in the study. This fact has been added to the manuscript (Methods Section) 4. A statement if this is an additional analysis on a patient cohort that has been reported previously would be welcome. Recommended description has been added to the manuscript (Methods Section). We thank you for your accurate revision of the article and kindly

6 comments, which have significantly improved our original paper. Sincerely yours, Rafael Zaragoza & Javier Pemán