Objectives To assess the prevalence of intra-hospital mortality and associated risk factors in older people aged 75+, admitted with blood stream infections (BSI). Design: Single center retrospective study performed in an 850-bed of the academic hospital of the Université Libre de Bruxelles. Setting and Participants From January 2015 to December 2017, all inpatients over 75 years old admitted with BSI were included. Measures Demographical, clinical and microbiological data were collected. Results 212 patients were included: median age was 82 [79–85] years and 60% were female. The in-hospital mortality rate was 19%. The majority of microorganisms were Gram-negative strains, of which Escherichia coli was the most common, and urinary tract infection was the most common origin of BSI. Compared to patients who survived, the non-survivor group had a higher SOFA score (6 versus 3, p<0.0001), a higher comorbidity score (5 versus 4, p<0.0001), more respiratory tract infections (28 vs 6%, p < 0.0001) and fungal infections (5 vs 1%, p = 0.033), bedridden status (60 vs 25%, p < 0.0001), and healthcare related infections (60 vs 40%, p = 0.019). Using Cox multivariable regression analysis, only SOFA score was independently associated with mortality (HR 1.75 [95%IC 1.52–2.03], p<0.0001). Conclusions and Implications BSI in older people are severe infections associated with a significant in-hospital mortality. Severity of clinical presentation at onset remains the most important predictor of mortality for BSI in older people. BSI originating from respiratory source and bedridden patients are at greater risk of intra-hospital mortality. Further prospective studies are needed to confirm these results.

INTRODUCTION:In 2015, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus document for the selection of lung transplant candidates. In the absence of recent French recommendations, this guideline is useful in order to send lung transplant candidates to the transplantation centers and to list them for lung transplantation at the right time. BACKGROUND:The main indications for lung transplantation in adults are COPD and emphysema, idiopathic pulmonary fibrosis and interstitial diseases, cystic fibrosis and pulmonary arterial hypertension (PAH). The specific indications for each underlying disease as well as the general contraindications have been reviewed in 2015 by the ISHLT. For cystic fibrosis, the main factors are forced expiratory volume in one second, 6-MWD, PAH and clinical deterioration characterized by increased frequency of exacerbations; for emphysema progressive disease, the BODE score, hypercapnia and FEV1; for PAH progressive disease or the need of specific intravenous therapy and NYHA classification. Finally, the diagnosis of fibrosing interstitial lung disease is usually a sufficient indication for lung transplantation assessment. OUTLOOK AND CONCLUSION:These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation.

Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world. Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - <= 50, 51-60, 61-70, 71-80, >80 years. Sepsis was defined as infection plus at least one organ failure. Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (<= 50 = 25.2%: 51-60 = 30.3%; 61-70 = 32.8%; 71-80 = 30.7%; >80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients <= 50 years (493% vs 25.2%, p < .05). The maximum rate of increase in mortality was about 0.75% per year, occurring between the ages of 71 and 77 years. In multilevel analysis, age > 70 years was independently associated with increased risk of dying. Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. All rights reserved.

Colistin, used as a last-resort drug, has a narrow therapeutic range that justifies therapeutic drug monitoring. Few data are available in the literature regarding the in vivo unbound fraction of colistin. The objectives of this study were to develop a method to isolate unbound colistin in clinical samples by ultrafiltration and to quantify it. The association between unbound colistin and biological parameters (total protein, albumin, alpha-1-acid glycoprotein and creatinine) was investigated. The measured ranges were 0.036-7.160 mg/L for colistin A and 0.064-9.630 mg/L for colistin B. The process of isolation and determination of unbound colistin was applied to clinical samples (n = 30) within 40 min and no non-specific binding was observed during the ultracentrifugation step. The median unbound fractions of colistin measured were 34.3% (12.8-51.0%) and 53.4% (27.0-77.8%) for colistin A and B, respectively. High interindividual biological variation of binding was observed for colistin A and B that was not explained by the biochemical parameters studied. The method developed could be useful to improve outcomes for patients.

Borreliabacteriën zijn verantwoordelijk voor de ziekte van Lyme of Lyme-borreliose. De mens wordt besmet via een beet van een geïnfecteerde teek. De meeste besmettingen komen voort na beten van nymfen (<2 mm groot) en deze blijven vaak onopgemerkt.

BACKGROUND:Molecular assays for diagnosis of Flu A, Flu B, and RSV with short turn-around-time (TAT) are of considerable clinical importance. In addition, rapid and accurate diagnosis of a large panel of viral and atypical pathogens can be crucial in immunocompromised patients. OBJECTIVES:First, to evaluate the performance of the Simplexa™ Direct assay system in comparison with direct fluorescent antibody (DFA) and customized Taqman® Array Card (TAC) testing for RSV, Flu A, and Flu B in immunocompromised patients. Second, to evaluate different algorithms for the detection of respiratory pathogens in terms of cost, turn-around-time (TAT) and diagnostic yield. STUDY DESIGN:We collected 125 nasopharyngeal swabs (NTS) and 25 BAL samples from symptomatic immunocompromised patients. Samples for which Simplexa™ and TAC results were discordant underwent verification testing. The TAC assay is based on singleplex RT-PCR, targeting 24 viruses, 8 bacteria and 2 fungi simultaneously. RESULTS:The overall sensitivity was significantly lower for DFA testing than for the two molecular methods (p<0.05). Performance characteristics of Simplexa™ testing were not significantly different compared to TAC testing (p>0.1). For BAL samples only, the sensitivity and specificity of the Simplexa™ assay was 100%. In total, 6.7, 16 and 18% of samples were positive for Flu A, Flu B or RSV by DFA, Simplexa™ and TAC testing, respectively. When considering not only these pathogens but also all results for TAC, the method identified 93 samples with one or more respiratory pathogens (62%). A co-infection rate of 15.3% was found by TAC. The estimated costs and TAT were 8.2€ and 2h for DFA, 31.8€ and 1.5h for Simplexa™ and 55€ and 3h for TAC testing. CONCLUSIONS:Performing the Simplexa™ test 24h a day/7 days a week instead of DFA would considerably improve the overall sensitivity and time-to-result, albeit at a higher cost generated in the laboratory. Performing the TAC would increase the diagnostic yield and detection of co-infections significantly.

Lower respiratory tract infections represent one of the main causes of mortality in the world. They essentially consist of bronchitis, acute exacerbations of chronic obstructive bronchopulmonary diseases (COPD) and acute pneumonia. If acute bronchitis is mainly of viral origin, acute exacerbations of COPD and pneumonia are mainly due to a trio of bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). Other pathogens as many viruses and atypical bacteria such as Mycoplasma pneumoniae, Legionella, some Enterobacteriaceae and very rarely Pseudomonas aeruginosa are also implicated. S. pneumoniae is the pathogen associated with the greatest morbidity and mortality and empirical antibiotic treatment should always be active on this germ. According to the type of infection and factors of comorbidity, empirical antibiotic treatment should cover a number of other pathogens. Beta-lactams, associated or not with macrolides/azalides are the first line treatment. Fluoroquinolones, although highly active against all pathogens, must be used only in restricted situations in order to avoid emergence of resistance to these antibiotics.

ABSTRACT Azole-resistant Aspergillus fumigatus is an increasing worldwide problem with major clinical implications. Surveillance is warranted to guide clinicians to provide optimal treatment to patients. To investigate azole resistance in clinical Aspergillus isolates in our institution, a Belgian university hospital, we conducted a laboratory-based surveillance between June 2015 and October 2016. Two different approaches were used: a prospective culture-based surveillance using VIPcheck on unselected A. fumigatus (n = 109 patients, including 19 patients with proven or probable invasive aspergillosis [IA]), followed by molecular detection of mutations conferring azole resistance, and a retrospective detection of azole-resistant A. fumigatus in bronchoalveolar lavage fluid using the commercially available AsperGenius PCR (n = 100 patients, including 29 patients with proven or probable IA). By VIPcheck, 25 azole-resistant A. fumigatus specimens were isolated from 14 patients (12.8%). Of these 14 patients, only 2 had proven or probable IA (10.5%). Mutations at the cyp51A gene were observed in 23 of the 25 A. fumigatus isolates; TR34/L98H was the most prevalent mutation (46.7%), followed by TR46/Y121F/T289A (26.7%). Twenty-seven (27%) patients were positive for the presence of Aspergillus species by AsperGenius PCR. A. fumigatus was detected by AsperGenius in 20 patients, and 3 of these patients carried cyp51A mutations. Two patients had proven or probable IA and cyp51A mutation (11.7%). Our study has shown that the detection of azole-resistant A. fumigatus in clinical isolates was a frequent finding in our institution. Hence, a rapid method for resistance detection may be useful to improve patient management. Centers that care for immunocompromised patients should perform routine surveillance to determine their local epidemiology.

L’éosinopénie permet de distinguer une infection d’une pathologie inflammatoire non infectieuse en cas de maladie inflammatoire aiguë [1]. Des études de mortalité ont démontré que la persistance d’une éosinopénie est de mauvais pronostic chez les patients en sepsis [2]. Elles démontrent également que l’éosinophilie se normalise entre le 2e et 3e jour chez les patients survivants [3]. La capacité de l’éosinophilie à prédire précocement l’adéquation d’une antibiothérapie n’a jamais été étudiée. Notre objectif est de comparer l’évolution de l’éosinophilie à celle des autres marqueurs inflammatoires chez des patients présentant une bactériémie et d’évaluer si l’évolution de l’éosinophilie au cours d’une bactériémie permet de prédire précocement le caractère approprié d’une antibiothérapie empirique. Étude rétrospective, monocentrique, portant sur des patients présentant une bactériémie communautaire traitée, sans délai, par une antibiothérapie empirique. Nous avons relevé le type d’antibiotique administré, le(s) germe(s) responsable(s), la sensibilité in vitro à l’antibiotique ainsi que les valeurs de la CRP (en mg/L), de l’éosinophilie, de la lymphocytose et de la neutrophilie (en cellules/μL) avant (T0) et après le début du traitement antibiotique empirique, à deux reprises (T1 et T2). Sur base de l’antibiogramme, 2 groupes de patients ont été constitués : traitement approprié (germe sensible à l’antibiotique ; groupe 1), traitement inapproprié (sensibilité intermédiaire ou résistance à l’antibiotique ; groupe 2). Les évolutions de l’éosinophilie, de la lymphocytose, de la neutrophilie et du taux de CRP ont été comparées entre les 2 groupes. Les dossiers de 98 patients ont été retenus (groupe 1, n = 86 ; groupe 2, n = 12). Moins de 24 h après le début du traitement (T1 = 16 h), l’éosinophilie augmente significativement dans le groupe 1 alors qu’elle reste inchangée dans le groupe 2. L’analyse par une courbe de ROC indique qu’une remontée de ≥ 27 éosinophiles/μL après 16 heures de traitement est prédictive d’un traitement approprié (sensibilité : 45 % [intervalle de confiance à 95 % (IC95 %) : 35 à 57] ; spécificité : 92 % [IC95 % : 62 à 100] ; rapport de vraisemblance positif : 5,4 [IC95 % : 0,8 à 36,1]). L’évolution du compte lymphocytaire est différente entre les groupes au T1 mais la courbe ROC ne permet pas d’utiliser ce critère. Aucune différence d’évolution n’est observée entre les groupes pour la neutrophilie et la CRP. Notre étude suggère que la remontée précoce de l’éosinophilie au cours des bactériémies est un facteur prédictif du caractère approprié du traitement antibiotique, une remontée de ≥ 27 éosinophiles/μL faisant passer la probabilité a priori que l’antibiothérapie empirique soit adéquate de 88 % à une probabilité a posteriori de 98 %. A contrario, la variation de la neutrophilie, de la lymphocytose et du taux de CRP au cours des deux premiers jours de bactériémie ne permet pas d’identifier les patients recevant un traitement approprié. Le caractère rétrospectif de notre étude ainsi que l’utilisation de données uniquement bactériologiques et non cliniques constituent ses limitations. Nous suggérons, la réalisation d’une étude prospective utilisant d’autres critères pour distinguer les patients adéquatement traités, notamment des critères objectifs de l’état clinique du patient. La remontée de l’éosinophilie est le facteur prédictif le plus précoce du caractère approprié du traitement antibiotique empirique administré lors d’une bactériémie.

BACKGROUND:Although β-lactams are considered to have a safe therapeutic profile, neurotoxicity has been reported. The aim of this study was to assess the association between β-lactam concentrations and neurological alterations in septic ICU patients.METHODS:Retrospective study on all ICU patients who were treated with meropenem (MEM), piperacillin-tazobactam (TZP) or ceftazidime/cefepime (CEF) and in whom at least one β-lactam trough concentration (C min) was determined. Drug levels were measured using high-performance liquid chromatography; C min was normalized to the clinical breakpoint of Pseudomonas aeruginosa (as determined by EUCAST) for each drug (C min/MIC). Changes in neurological status were evaluated using changes in the neurological sequential organ failure assessment score (ΔnSOFA) using the formula: ΔnSOFA = nSOFA(day of TDM) - nSOFA(ICU admission). Worsening neurological status (NWS) was defined as a ΔnSOFA ≥ 1 for an nSOFA on admission of 0-2.RESULTS:We collected 262 C min in 199 patients (130 MEM, 85 TZP, 47 CEF). Median APACHE II score and GCS on admission were 17 and 15, respectively. Overall ICU mortality was 27 %. There were no differences in the occurrence of NWS between antibiotics (39% for MEM, 32% for TZP and 35% for CEF). The occurrence of NWS increased with increasing C min/MIC ranges (P = 0.008); this correlation was found for TZP (P = 0.05) and MEM (P = 0.01), but not for CEF. C min/MIC was an independent predictive factor for NWS (OR 1.12 [1.04-1.20]).CONCLUSION:We found a correlation between high β-lactam trough concentrations and increased occurrence of neurological deterioration in septic ICU patients. Although our data cannot determine causality, monitoring of β-lactam levels should be considered when deterioration of neurological status occurs during critical illness.

Background & AimsThe pharmacokinetics of -lactam antibiotics have not been well defined in critically ill patients with cirrhosis.MethodsWe reviewed data from critically ill patients with cirrhosis and matched controls in whom routine therapeutic drug monitoring of two broad-spectrum -lactam antibiotics (piperacillin/tazobactam and meropenem) had been performed. Serum drug concentrations were measured twice by high-performance liquid chromatography. Antibiotic pharmacokinetics were calculated using a one-compartment model. We considered that therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration of Pseudomonas aeruginosa during optimal periods of time for each drug ( 50% for piperacillin/tazobactam; 40% for meropenem).ResultsWe studied 38 patients with cirrhosis (16 for piperacillin/tazobactam and 22 for meropenem) and 38 matched controls. Drug dosing was similar in the two groups. The pharmacokinetics analysis showed a lower volume of distribution of meropenem (P = 0.05) and a lower antibiotic clearance of piperacillin/tazobactam (P = 0.009) in patients with cirrhosis than in the matched controls. Patients with cirrhosis were more likely than those without cirrhosis to have excessive serum -lactam concentrations (P = 0.015), in particular for piperacillin/tazobactam.ConclusionsStandard -lactam antibiotics regimens resulted in excessive serum concentrations in two thirds of the patients with cirrhosis. This was particularly true for piperacillin/tazobactam, probably because of reduced drug clearance.

Infections caused by multi-drug resistant (MDR) Gram-negative (GN) organisms in critically ill patients are a therapeutic challenge. Few therapeutical options are available.

A patient with refractory diffuse lymphoma treated for pulmonary invasive aspergillosis developed a concomitant primary cutaneous mucormycosis. The mucormycete was identified by sequencing as Mucor circinelloides. This case confirms the importance of a rapid pathogen diagnosis in immunocompromised patients and the usefulness of molecular methods for identification of rare fungal species.