The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.

Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial.

BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses.

Critically Ill Patients with Visceral Nocardia Infection, France and Belgium, 2004-2023.

We studied 50 patients with invasive nocardiosis treated during 2004-2023 in intensive care centers in France and Belgium. Most (65%) died in the intensive care unit or in the year after admission. Nocardia infections should be included in the differential diagnoses for patients in the intensive care setting.

Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort.

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10-4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

Impact of corticosteroids use on midterm sequelae in survivors of COVID-19 admitted to hospital: A prospective cohort study.

An understanding of the midterm sequelae in COVID-19 and their association with corticosteroids use are needed. Between March and July 2020, we evaluated 1227 survivors of COVID-19, 3 months posthospitalization, of whom 213 had received corticosteroids within 7 days of admission. Main outcome was any midterm sequelae (oxygen therapy, shortness of breath, one major clinical sign, two minor clinical signs or three minor symptoms). Association between corticosteroids use and midterm sequelae was assessed using inverse propensity-score weighting models. Our sample included 753 (61%) male patients, and 512 (42%) were older than 65 years. We found a higher rate of sequelae among users than nonusers of corticosteroids (42% vs. 35%, odds ratio [OR] 1.40 [1.16-1.69]). Midterm sequelae were more frequent in users of low-dose corticosteroids than nonusers (64% vs. 51%, OR 1.60 [1.10-2.32]), whereas no association between higher doses (≥20 mg/day equivalent of dexamethasone) and sequelae was evidenced (OR 0.95 [0.56-1.61]). Higher risk of sequelae with corticosteroids use was observed among subjects with propensity score below the 90th percentile. Our study suggest that corticosteroids use during hospitalization for COVID-19 is associated with higher risk of midterm sequelae.

Implementation of a centralized pharmacovigilance system in academic pan-European clinical trials: Experience from EU-Response and conect4children consortia.

Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors.

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial.

BACKGROUND: The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. OBJECTIVES: To estimate the effect of remdesivir in blocking viral replication. METHODS: We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells). RESULTS: In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5-3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0-1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8-25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9-4.5 days). CONCLUSIONS: Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.

Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19.

[Figure: see text].

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study.

BACKGROUND: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. METHODS: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. RESULTS: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]). CONCLUSION: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.

Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis.

Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 µg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by Woodard in this issue.

Almitrine Infusion in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Respiratory Distress Syndrome: A Single-Center Observational Study.

OBJECTIVES: Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may be explained in part by the loss of hypoxic pulmonary vasoconstriction. The present study assessed the effect of almitrine, a selective pulmonary vasoconstrictor, on arterial oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome. DESIGN: Single-center retrospective observational study. SETTING: ICU of Lille Teaching Hospital, France, from February 27, 2020, to April 14, 2020. PATIENTS: Patients with coronavirus disease 2019 pneumonia confirmed by positive reverse transcriptase-polymerase chain reaction for severe acute respiratory syndrome-coronavirus 2 and acute respiratory distress syndrome according to Berlin definition. Data focused on clinicobiological features, ventilator settings, therapeutics, outcomes, and almitrine-related adverse events. INTERVENTIONS: Almitrine was considered in patients with severe hypoxemia (Pao2/Fio2 ratio < 150 mm Hg) in addition to the recommended therapies, at an hourly IV delivery of 10 µg/kg/min. Comparative blood gases were done before starting almitrine trial and immediately after the end of the infusion. A positive response to almitrine was defined by an increase of Pao2/Fio2 ratio greater than or equal to 20% at the end of the infusion. MEASUREMENTS AND MAIN RESULTS: A total of 169 patients were enrolled. Thirty-two patients with acute respiratory distress syndrome received an almitrine infusion trial. In most cases, almitrine was infused in combination with inhaled nitric oxide (75%). Twenty-one patients (66%) were responders. The median Pao2/Fio2 ratio improvement was 39% (9-93%) and differs significantly between the responders and nonresponders (67% [39-131%] vs 6% [9-16%], respectively; p < 0.0001). The 28-day mortality rates were 47.6% and 63.6% (p = 0.39) for the responders and nonresponders, respectively. Hemodynamic parameters remained similar before and after the trial, not suggesting acute cor pulmonale. CONCLUSIONS: Almitrine infusion improved oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome without adverse effects. In a multistep clinical approach to manage severe hypoxemia in this population, almitrine could be an interesting therapeutic option to counteract the loss of hypoxic pulmonary vasoconstriction and redistribute blood flow away from shunting zones.

Increasing morbidity and mortality of candidemia over one decade in a Swiss university hospital.

BACKGROUND: The epidemiology of candidemia is evolving with raising concern about the emergence of intrinsically resistant non-albicans Candida species and acquisition of antifungal resistance. In addition to microbiological surveys, epidemiological studies including clinical data are needed to assess the impact of candidemia on morbidity and mortality. OBJECTIVES: To assess the clinical and microbiological trends of candidemia in a Swiss university hospital. PATIENTS/METHODS: This single-centre retrospective study compared the incidence of candidemia, Candida species distribution, antifungal resistance profiles, clinical characteristics and outcomes between two periods separated by one decade. RESULTS: A total of 170 candidemic episodes were included (68 from period 1, 2004-2006, and 102 from period 2, 2014-2017). Incidence of candidemia (0.85 to 0.97 episode/10,000 patient-days), species distribution (55%-57% C albicans) and antifungal susceptibilities remained unchanged. During period 2, candidemia was more frequently observed in intensive care units (ICU, 38% vs 19% in period 1, P = .01) and amongst older patients (median age 68 vs 59 years old, P < .01) with more immunosuppressive conditions (24% vs 9%, P = .01). Candidemia in period 2 was more frequently followed by septic shock (23% vs 7% in period 1, P = .01) and ICU admission (42% vs 12%, P < .01) and was associated with higher mortality (34% vs 18%, P = .03). Overall, factors associated with mortality in multivariate analyses included cirrhosis, solid malignancies and ICU stay at the time of candidemia. CONCLUSIONS: Despite stable incidence, species distribution and antifungal resistance of candidemia, an epidemiological shift of the disease towards older and more critically ill patients was observed, with higher mortality rates.

National early warning score to predict intensive care unit transfer and mortality in COVID-19 in a French cohort.

BACKGROUND: No risk stratification tool has been validated in hospitalised patients with coronavirus disease 2019 (COVID-19), despite a high rate of intensive care requirement and in-hospital mortality. We aimed to determine whether the National Early Warning Score (NEWS) at admission can accurately predict in-hospital mortality and ICU transfer. METHODS: This was a retrospective cohort study from January 24 to April 16, 2020, at Lille University Hospital. All consecutive adult patients with laboratory-confirmed COVID-19 who were initially admitted to non-ICU wards were included. The primary outcome was a composite criterion consisting of ICU transfer or in-hospital mortality. We evaluated the prognostic performance of NEWS by calculating the area under (AUC) the receiver operating characteristic curve, the optimal threshold value of NEWS, and its association with the primary outcome. RESULTS: Of the 202 COVID-19 patients, the median age was 65 (interquartile range 52-78), 38.6% were women and 136 had at least one comorbidity. The median NEWS was 4 (2-6). A total of 65 patients were transferred to the ICU or died in the hospital. Compared with patients with favourable outcome, these patients were significantly older, had more comorbidities and higher NEWS. The AUC for NEWS was 0.68 (0.60-0.77) and the best cutoff value was 6. Adjusted odds ratio for NEWS ≥ 6 as an independent predictor was 3.78 (1.94-7.09). CONCLUSIONS: In hospitalised COVID-19 patients, NEWS was an independent predictor of ICU transfer and in-hospital death. In daily practice, NEWS ≥ 6 at admission may help to identify patients who are at risk to deteriorate.

Caution With the Use of Lopinavir/Ritonavir in Severely Ill Patients for the Treatment of SARS-CoV-2: A Report of Severe Jaundice.

INTRODUCTION: We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus. METHODS: This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group. RESULTS: Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%). DISCUSSION: Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.

Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis.

The 1,3-beta-d-glucan (BDG) test is used for the diagnosis of invasive candidiasis (IC) in intensive care units (ICUs). However, its utility for patient management is unclear. This study assessed the impact of BDG test results on therapeutic decisions. This was a single-center observational study conducted in an ICU over two 6-month periods. All BDG test requests for the diagnosis of IC were analyzed. Before the second period, the ICU physicians received a pocket card instruction (algorithm) for targeted BDG testing in high-risk patients. The performance of the BDG test for IC diagnosis was assessed, as well as its impact on antifungal (AF) prescription. Overall, 72 patients had ≥1 BDG test, and 14 (19%) patients had an IC diagnosis. The BDG test results influenced therapeutic decisions in 41 (57%) cases. The impact of the BDG test was positive in 30 (73%) of them, as follows: AF abstention/interruption following a negative BDG result (n = 27), and AF initiation/continuation triggered by a positive BDG test result and subsequently confirmed IC (n = 3). In 10 (24%) cases, a positive BDG test result resulted in AF initiation/continuation with no further evidence of IC. A negative BDG result and AF abstention with subsequent IC diagnosis were observed in one case. The positive predictive value (PPV) of BDG was improved if testing was restricted to the algorithm's indications (80% versus 36%, respectively). However, adherence to the algorithm was low (26%), and no benefit of the intervention was observed. The BDG result had an impact on therapeutic decisions in more than half of the cases, which consisted mainly of safe AF interruption/abstention. Targeted BDG testing in high-risk patients improves PPV but is difficult to achieve in ICU.

Risk factors for candidemia: a prospective matched case-control study.

BACKGROUND: Candidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs. METHODS: This prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia. RESULTS: One hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia. DISCUSSION: While this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU). CONCLUSION: This study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients' management strategies and fungal epidemiology.