Longitudinal Evaluation of Plasma Cytokine Levels in Patients with Invasive Candidiasis.

Stefanie Wunsch,Oliver Cornely,Martin Hoenigl,Gebhard Feierl,Andreas Meinitzer,Thomas Valentin,Gudrun Pregartner,Robert Krause,Wilfried Posch,Ines Zollner-Schwetz,Juergen Prattes,Jasmin Rabensteiner,Cornelia Lass-Flörl,Christoph Zurl,Heimo Strohmaier,Elisabeth König

doi:10.3390/jof7020101

Abstract

Interleukin (IL) 17A plays a decisive role in anti-Candida host defense. Previous data demonstrated significantly increased IL-17A values in candidemic patients. We evaluated levels and time courses of IL-17A, and other cytokines suggested to be involved in Candida-specific immunity (IL-6, IL-8, IL-10, IL-17F, IL-22, IL-23, interferon-γ, tumor necrosis factor-α, Pentraxin-related protein 3, transforming growth factor-β) in patients with invasive candidiasis (IC) compared to bacteremic patients (Staphylococcus aureus, Escherichia coli) and healthy controls (from previous 4 days up to day 14 relative to the index culture (−4; 14)). IL-17A levels were significantly elevated in all groups compared to healthy controls. In IC, the highest IL-17A values were measured around the date of index sampling (−1; 2), compared to significantly lower levels prior and after sampling the index culture. Candidemic patients showed significantly higher IL-17A values compared to IC other than candidemia at time interval (−1; 2) and (3; 7). No significant differences in IL-17A levels could be observed for IC compared to bacteremic patients. Candidemic patients had higher IL-8, IL-10, IL-22, IFN-γ, PTX3 and TNF-α values compared to non-candidemic. Based on the limited discriminating competence between candidemia and bacteremia, IL-17A has to be considered a biomarker for blood stream infection rather than invasive Candida infection.

Highlights

Candida species rank as the fourth most common cause of nosocomial bloodstream infections [1,2,3,4]
A total of 184 patients were prospectively enrolled in this study; 101 patients with invasive candidiasis (IC), 23 patients with S. aureus bacteremia, 28 patients with E. coli bacteremia, and 32 healthy controls
This observation was further supported by an observational, prospective clinical trial, showing significantly elevated IL-17A levels in patients with Candida sepsis compared to patients with bacterial sepsis or septic patients with fungal colonization [22]

Summary

Introduction

Candida species (spp.) rank as the fourth most common cause of nosocomial bloodstream infections [1,2,3,4]. Since invasive Candida infections primarily occur in patients with serious underlying diseases, it is often difficult to differentiate between attributable mortality of candidemia and mortality owing to comorbidities [5]. Diagnosis and subsequent initiation of antifungal therapy are crucial for survival in patients with IC [5,6,9,10,11,12,13,14], since a delay of one to two days in initiation of adequate antifungal therapy results in doubled mortality rates [1]. The clinical diagnosis of IC is complicated by the fact that no signs or symptoms are specific for invasive Candida infection [1,11,15]. No single test or decision rule is able to precisely distinguish between contamination, commensalism, colonization or infection [16]

Objectives

Methods

Discussion

Conclusion