Onset of symptoms, diagnostic confirmation, and occurrence of multiple infective foci in patients with Staphylococcus aureus bloodstream infection: a look into the order of events and potential clinical implications
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Data on the systemic dissemination in Staphylococcus aureus bloodstream infection (SAB) remain sparse. We investigated the timing and the sequence of clinical symptoms, diagnostic confirmation, and occurrence of multiple infective foci in relation to three major infective foci.
From 2006 to 2011, all adult patients with first-time SAB in Cologne and Freiburg, Germany were followed prospectively. The study was restricted to patients with short-term central venous catheter (CVC)-related SAB, vertebral osteomyelitis (VO), and infective endocarditis (IE). The collection date of the first positive blood culture was used as reference point for determining time to onset of clinical symptoms, microbiological findings, imaging results compatible with focal infection, and occurrence of additional infective foci.
We included 266 patients with first-time SAB. Among patients with CVC-related SAB, clinical onset, collection of the first positive blood culture, and microbiological confirmation almost coincided. In contrast, among patients with VO or IE, the onset of clinical symptoms most often preceded the collection of the first positive blood culture, and imaging and microbiological confirmation were most frequently obtained subsequent to the SAB diagnosis. CVC-related SAB was infrequently associated with further foci (n = 15/15.5%). Conversely, more than one infective focus was observed in 44 (56.4%) patient with VO and 68 (64.8%) patients with IE.
The sequence of clinical symptoms, diagnostic confirmation, and occurrence of multiple infective foci varied considerably with different infective foci in SAB. Based on these results, we propose a pragmatic and evidence-based terminology for the clinical course of SAB and suggest the terms “portal of entry”, “infective focus”, “multiple infective foci”, and “dominant infective focus”.
KeywordsStaphylococcus aureus bloodstream infection Infective focus Clinical course Terminology
The authors thank Christian Bernasch (Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany), Hanna Birkholz (Clinical Trials Center, University of Cologne, Germany), and Gabriele Peyerl-Hoffmann (Department of Medicine II, University Medical Center Freiburg, Germany) for providing administrative support and collecting patient data.
JS: study design, data management, analysis and interpretation, and manuscript preparation. AJK: data collection, study concept and design, data management, analysis and interpretation, and manuscript review. SRR, WVK, HS, AFW: data collection, study design, interpretation of the data, manuscript review. HCS: study design, interpretation of the data, manuscript review. All the authors have read and approved the final draft submitted.
This work was supported by the Deutsche Forschungsgemeinschaft (DFG; grant number KA 3104/1–1 to A.J.K.), the Paul-Ehrlich Gesellschaft für Chemotherapie (to HS and WVK), and the Bundesministerium für Bildung und Forschung (BMBF 01KI1017 to AJK/01KN1106 to the Clinical Trial Center Cologne). The funding organizations had no role in the design of the study, data collection, and data analysis.
Compliance with ethical standards
The study and data collection were approved by the institutional review boards of the University Medical Centers Freiburg and Cologne. We followed the ethical standards set by the Helsinki Declaration of 1975, as revised in 2004, and the research guidelines of the Universities of Freiburg and Cologne. Written informed consent was obtained from the patients at the University Medical Center Cologne. The institutional review board of the University Medical Center Freiburg considered the investigation as evaluation of service within a quality assurance program and waived the need for written informed consent. The study is registered in the German Clinical Trials Registry (DRKS00005045).
Conflict of interest
A.J.K. has received payments for lectures from BD Biosciences, bioMérieux, MSD Sharp & Dohme, Limbach Gruppe SE, and ViiV Healthcare and travel support from Janssen-Cilag. H.S. has received grants or research support from the Bundesministerium für Bildung und Forschung (BMBF), Germany, the German Centre for Infection Research (DZIF), Basilea, Novartis and Pfizer, has been a consultant for Astellas, AstraZeneca, Basilea, Cubist, Novartis, Pfizer, Tetraphase, and The Medicines Company, and has received payments for lectures from MSD, Novartis and Pfizer. S.R. has received payments for lectures from Pfizer and MSD Sharp & Dohme, as well as travel support from Astellas and MSD Sharp & Dohme. W.V.K., A.F.W., J.S and H.C.S report no conflicts.
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