J. Poissy

Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections

ABSTRACT We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Here, we compare the performance of MS-DS for the diagnosis of IC, invasive aspergillosis (IA), and mucormycosis (MM) with those of commercially available antigen detection tests. This retrospective study included 48 patients (23 IC patients [74 serum samples], 15 IA patients [40 serum samples], and 10 MM patients [15 serum samples]) and 49 appropriate controls (102 serum samples). MS-DS, mannan (Mnn), galactomannan (GM), and (1,3)-β-d-glucan (BDG) were detected by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS, Platelia, and Fungitell assays, respectively. For IC, the sensitivity and specificity of the MS-DS index, BDG detection, and Mnn detection were 62% and 84%, 82% and 60%, and 33% and 94% per serum sample and 83% and 69%, 96% and 31%, and 39% and 86% per patient, respectively. For IA, the corresponding values in comparison to BDG and GM detection were 83% and 81%, 62% and 95%, and 62% and 100% per serum sample and 93% and 76%, 87% and 90%, and 93% and 100% per patient, respectively. Nine of the 10 MM patients had a positive MS-DS result. MS-DS gave an early diagnosis in IC (73% positivity before blood culture), IA (positive before GM detection in six patients), and MM (positivity mainly preceded the date of diagnosis) patients. For IC, persisting MS-DS was associated with a poor prognosis. The different biomarkers were rarely detected simultaneously, suggesting different kinetics of release and clearance. For IA, MS-DS provided better complementation to GM monitoring than BDG monitoring. MS-DS detects panfungal molecules circulating during invasive fungal infections. The performance of MS-DS compared favorably with those of biological tests currently recommended for monitoring at-risk patients. Further validation of this test in multicenter studies is required.

Mannose-Binding Lectin Levels and Variation During Invasive Candidiasis

The high morbi-mortality associated with invasive candidiasis (IC) is a persistent problem in hospitals. Mannose-binding lectin (MBL) plays a role in innate immunity through its interaction with mannosylated molecules of Candida albicans. A correlation between MBL deficiency and vulvovaginal candidiasis or peritonitis has been reported. We investigated circulating MBL levels and their evolution during the course of IC. Sixty-eight patients with proven IC, 82 hospitalized patients (HP) without evidence of infection, and 70 healthy subjects (HS) were studied in order to examine the relationship between serum MBL and IC. Serum MBL levels were measured by enzyme-linked immunosorbent assay (ELISA). MBL levels were significantly higher in IC patients than in HP and HS (pu2009<u20090.0001, pu2009<u20090.0055, respectively). A change in MBL concentrations was observed during the course of IC, with a dramatic decrease during the 2xa0days before positive blood culture sampling. This decrease was concomitant with the presence of high levels of circulating mannan (Mn). Like MBL levels, anti-mannan antibodies (AMn) increased after the mannanemia/blood culture period. These findings suggest a possible role of MBL during the early stage of IC. The mechanisms that regulate these observations in terms of effect and consequences on innate and adaptive immunity and the prognosis of IC require further investigation.

Tracheal Tube Design and Ventilator-Associated Pneumonia

Microaspiration of contaminated oropharyngeal and gastric secretions is the main mechanism for ventilator-associated pneumonia (VAP) in critically ill patients. Improving the performance of tracheal tubes in reducing microaspiration is one potential means to prevent VAP. The aim of this narrative review is to discuss recent findings on the impact of tracheal tube design on VAP prevention. Several randomized controlled studies have reported that subglottic secretion drainage (SSD) is efficient in VAP prevention. Meta-analyses have reported conflicting results regarding the impact of SSD on duration of mechanical ventilation, and one animal study raised concern about SSD-related tracheal lesions. However, this measure appears to be cost-effective. Therefore, SSD should probably be used in all patients with expected duration of mechanical ventilation > 48 h. Three randomized controlled trials have shown that tapered-cuff tracheal tubes are not useful to prevent VAP and should probably not be used in critically ill patients. Further studies are required to confirm the promising effects of continuous control of cuff pressure, polyurethane-cuffed, silver-coated, and low-volume low-pressure tracheal tubes. There is moderate evidence for the use of SSD and strong evidence against the use of tapered-cuff tracheal tubes in critically ill patients for VAP prevention. However, more data on the safety and cost-effectiveness of these measures are needed. Other tracheal tube-related preventive measures require further investigation.

Strategy for Overcoming Serum Interferences in Detection of Serum (1,3)-β-d-Glucans

The (1,3)-β-d-glucan (BG) is a cell-wall polysaccharide of most fungi. Regular measurement of BG levels in serum is recognized as a useful diagnostic marker for invasive fungal diseases in immunocompromised and intensive care unit (ICU) patients ([1][1]). Previous studies have identified several

Relationship between digestive tract colonization and subsequent ventilator-associated pneumonia related to ESBL-producing Enterobacteriaceae

Background Ventilator-associated pneumonia (VAP) is the most common ICU-acquired infection. Recently, the incidence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE) has substantially increased in critically ill patients. Identifying patients at risk for VAP related to ESBLE could be helpful to improve the rate of appropriate initial antibiotic treatment, and to reduce unnecessary exposure to carbapenems. The primary objective was to identify risk factors for VAP related to ESBLE. Secondary objective was to determine the impact of ESBLE on outcome in VAP patients. Methods This retrospective study was conducted in a single mixed intensive care unit (ICU), during a 4-year period. All patients with confirmed VAP were included. VAP was defined using clinical, radiologic and quantitative microbiological data. VAP first episodes were prospectively identified using the continuous surveillance data. Exposure to different risk factors was taken into account until the diagnosis of ESBLE VAP or until ICU discharge, in patients with ESBLE VAP and VAP related to other bacteria, respectively. In all patients, routine screening for ESBLE (rectal swab) was performed at ICU admission and once a week. Patients with ESBLE VAP were compared with those with VAP related to other bacteria using univariate analysis. All significant factors were included in the multivariate logistic regression model. Results Among the 410 patients with VAP, 43 (10.5%) had ESBLE VAP, 76 (19%) patients had polymicrobial VAP and 189 (46%) had VAP related to multidrug resistant bacteria. Multivariate analysis identified prior ESBLE colonization of the digestive tract as the only independent risk factor for ESBLE VAP (OR [95% CI] = 23 [10–55], p < 0.001). Whilst the positive predictive value of ESBLE digestive colonization was low (43.6%), its negative predictive value was excellent (97.3%) in predicting ESBLE VAP. Duration of mechanical ventilation (median [IQR], 28 [18,42] vs 23 [15,42] d, p = 0.4), length of ICU stay (31 [19,53] vs 29 [18,46] d, p = 0.6), and mortality rates (55.8% vs 50%, p = 0.48) were similar in ESBLE VAP, compared with VAP related to other bacteria. Conclusion Digestive tract colonization related to ESBLE is independently associated with ESBLE VAP. Its excellent negative predictive value suggests that patients without ESBLE colonization should not receive carbapenems as part of their initial empirical treatment to cover ESBLE.

Physiopathologie des candidoses invasivesPathophysiology of invasive candidiasis

RésuméLa physiopathologie des candidoses invasives fait intervenir une transition des levures du genre Candida d’un état de saprophyte commensal vers un état de pathogène virulent. Cette transition est en rapport avec l’expression de programmes de virulence, favorisée par des modifications environnementales et entretenue par le développement d’une réponse immunitaire inappropriée, voire facilitatrice, de l’hôte. La compréhension des mécanismes sous-tendant ce déséquilibre hôte/pathogène passe par l’analyse des deux acteurs de cette relation, ce qui pourrait permettre d’éclairer la compréhension des fonds génétiques et des terrains prédisposant à la candidose invasive.AbstractPathophysiology of invasive candidiasis relies on the transition of Candida yeasts from a saprophytic commensal state to a virulent pathogenic state. This is in link with the expression of a virulence schedule, in response to environmental changes, and is emphasized by an inappropriate immune response from the host, which can even facilitate this transition towards a pathogenic profile. The understanding of the mechanisms leading to the disequilibrium of the relation host/pathogen needs the analysis of the two actors of this relation, which could allow to understand the genetic backgrounds predisposing to invasive candidiasis.

Physiopathologie des candidoses invasives

RésuméLa physiopathologie des candidoses invasives fait intervenir une transition des levures du genre Candida d’un état de saprophyte commensal vers un état de pathogène virulent. Cette transition est en rapport avec l’expression de programmes de virulence, favorisée par des modifications environnementales et entretenue par le développement d’une réponse immunitaire inappropriée, voire facilitatrice, de l’hôte. La compréhension des mécanismes sous-tendant ce déséquilibre hôte/pathogène passe par l’analyse des deux acteurs de cette relation, ce qui pourrait permettre d’éclairer la compréhension des fonds génétiques et des terrains prédisposant à la candidose invasive.AbstractPathophysiology of invasive candidiasis relies on the transition of Candida yeasts from a saprophytic commensal state to a virulent pathogenic state. This is in link with the expression of a virulence schedule, in response to environmental changes, and is emphasized by an inappropriate immune response from the host, which can even facilitate this transition towards a pathogenic profile. The understanding of the mechanisms leading to the disequilibrium of the relation host/pathogen needs the analysis of the two actors of this relation, which could allow to understand the genetic backgrounds predisposing to invasive candidiasis.