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Introduction: Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population., Methods and Analysis: This is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185<80 years and 1185≥80 years; BRAINI2-ELDERLY DIAGNOSTIC AND PROGNOSTIC STUDY) with mTBI and a brain CT scan that will undergo blood sampling within 12 hours after mTBI. The primary outcome measure is the diagnostic performance of GFAP and UCH-L1 measured using an automated assay for discriminating between patients with positive and negative findings on brain CT scans. Secondary outcome measures include the performance of both biomarkers in predicting early (1 week) and midterm (3 months) neurological status and quality of life after trauma. (2) A cohort of 480 elderly reference participants (BRAINI2-ELDERLY REFERENCE STUDY) in whom reference values for GFAP and UCHL1 will be determined., Ethics and Dissemination: Ethical approval was obtained from the Institutional Review Boards of Hospital 12 de Octubre in Spain (Re#22/027) and Southeast VI (Clermont Ferrand Hospital) (Re# 22.01782.000095) in France. The study's results will be presented at scientific meetings and published in peer-review publications., Trial Registration Number: NCT05425251., Competing Interests: Competing interests: OM and VP are employees of bioMérieux., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Clinical guidelines have been developed to standardize the management of mild traumatic brain injury (mTBI) in the emergency room, in particular the indication of brain CT scan and the use of blood biomarkers. The objective of this study was to determine the degree of adherence to guidelines in the management of these patients across four countries of Southern Europe., Methods: An electronic survey including structural and general management of mTBI patients and six clinical vignettes was conducted. In-charge physicians from France, Spain, Greece and Portugal were contacted by telephone and email. Differences among countries were searched using an unconditional approach test on contingency tables., Results: One hundred and eighty eight physicians from 131 Hospitals (78 Spain, 36 France, 12 Greece and 5 Portugal) completed the questionnaire. There were differences regarding the in-charge specialist across these countries. There was variability in the use of guidelines and their adherence. Spain was the country with the least guideline adherence. There was a global agreement in ordering a brain CT for patients receiving anticoagulation or platelet inhibitors, and for patients with seizures, altered consciousness, neurological deficit, clinical signs of skull fracture or signs of facial fracture. Aging was not an indication for CT in French centres. Loss of consciousness and posttraumatic amnesia were considered as indications for CT more frequently in Spain than in France. These findings were in line with the data from the 6 clinical vignettes. The estimated use of CT reached around 50% of mTBI cases. The use of S100B is restricted to five French centres., Conclusions: There were large variations in the guideline adherence, especially in the situations considered to order brain CT after mTBI., (© 2022. The Author(s).)

Introduction: Mild traumatic brain injury (mTBI) is a common cause of clinical consultation in the emergency department. Patients with mTBI may undergo brain CT scans based on clinical criteria. However, the proportion of patients with brain lesions on CT is very low. Two serum biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), have been shown to discriminate patients regarding the presence or absence of brain lesions on initial CT scan when assessed within the first 12 hours after TBI. However, the current technique for measuring serum concentrations of GFAP and UCH-L1 is manual and time consuming, which may hinder its use in routine clinical practice. This study assesses the diagnostic accuracy of an automated assay for the measurement of serum GFAP and UCH-L1 in a cohort of patients with mTBI who received a CT scan as the standard of care., Methods and Analysis: This is a prospective multicentre observational study of 1760 patients with mTBI recruited in France and Spain across 16 participating sites. Adult patients with an initial Glasgow Coma Scale score of 13-15 and a brain CT scan underwent blood sampling within 12 hours after TBI. The primary outcome measure is the diagnostic performance of an automated assay measuring serum concentrations of GFAP and UCH-L1 for discriminating between patients with positive and negative findings on brain CT-scans. Secondary outcome measures include the performance of these two biomarkers in predicting the neurological status and quality of life at 1 week and 3 months after the trauma., Ethics and Dissemination: Ethics approval was obtained by the Institutional Review Board of Sud-Ouest Outre Mer III in France (Re#2019-A01525-52) and Hospital 12 de Octubre in Spain (Re#19/322). The results will be presented at scientific meetings and published in peer-reviewed publications., Trial Registration Number: ClinicalTrials.gov: NCT04032509., Competing Interests: Competing interests: VB, OM and VP are employees of bioMérieux., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Antimicrobial resistance (AMR) is a major threat to human health worldwide, and the rapid detection and quantification of resistance, combined with antimicrobial stewardship, are key interventions to combat the spread and emergence of AMR. Antimicrobial susceptibility testing (AST) systems are the collective set of diagnostic processes that facilitate the phenotypic and genotypic assessment of AMR and antibiotic susceptibility. Over the past 30 years, only a few high-throughput AST methods have been developed and widely implemented. By contrast, several studies have established proof of principle for various innovative AST methods, including both molecular-based and genome-based methods, which await clinical trials and regulatory review. In this Review, we discuss the current state of AST systems in the broadest technical, translational and implementation-related scope.

The aim of this study was to describe the epidemiology and clinical impact of carbapenem-non-susceptible Pseudomonas aeruginosa (CNPA) in intensive care units (ICUs) of the national referral hospital of Indonesia. Adult patients admitted to ICUs were prospectively included. Pseudomonas aeruginosa were from clinical cultures and systematic screening. Environmental niches and healthcare workers (HCWs) were also screened. Susceptibility was determined phenotypically and the presence of carbapenemase genes was determined by PCR. Multiple loci variable-number tandem repeat analysis (MLVA) and multilocus sequence typing (MLST) were used for genotyping. Of the patients included in the study, 17/412 (4.1%) carried CNPA on admission and 34/395 (8.6%) became positive during their ICU stay. The acquisition rate was 18/1000 patient-days at risk. Of 16 environmental isolates, 12 (75.0%) were CNPA. HCWs screened negative. Acquisition of CNPA was associated with longer ICU stay (adjusted hazard ratio = 1.89, 99% confidence interval 1.12-3.13). Mortality was >40% among patients with CNPA versus <30% among those without CNPA (P = 0.019). Moreover, 83/119 (69.7%) CNPA carried either bla VIM (n = 36), bla IMP (n = 23) or bla GES-5 (n = 24). Four sequence types (STs) dominated (ST235, ST823, ST446 and ST357). Five major MLVA clusters were distinguished, two belonging to ST235 and the other three to ST823, ST446 and ST357. CNPA are introduced into these ICUs and some strains expand clonally among patients and the environment, creating endemic CNPA. VIM-, IMP- and GES-5 genes are prevalent. CNPA acquisition was associated with prolonged ICU stay and may affect ICU survival., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The prevalence of multidrug-resistant gram-negative bacteria has continuously increased over the past few years; bacterial strains producing AmpC β-lactamases and/or extended-spectrum β-lactamases (ESBLs) are of particular concern. We combined high-resolution whole genome sequencing and phenotypic data to elucidate the mechanisms of resistance to cephamycin and β-lactamase in Korean Klebsiella pneumoniae strains, in which no AmpC-encoding genes were detected by PCR. We identified several genes that alone or in combination can potentially explain the resistance phenotype. We showed that different mechanisms could explain the resistance phenotype, emphasizing the limitations of the PCR and the importance of distinguishing closely-related gene variants., Competing Interests: All the authors, except Yeon-Joon Park, are employees of bio-Mérieux, a company that develops and sells diagnostic tests in the field of infectious diseases., (© The Korean Society for Laboratory Medicine.)

Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to the global control of the disease. The purpose of this study was to characterize MDR-TB patients from Poland and to determine the extent of MDR-TB disease attributable to recent transmission. The study included all 46 patients diagnosed with MDR-TB in Poland in 2004 and followed up for 6 years (until 2011). For each patient, sociodemographic and clinical characteristics, treatment outcomes, and bacteriological data were collected by the review of medical and laboratory records. Mycobacterium tuberculosis isolates from all patients were characterized using spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing, IS6110 restriction fragment length polymorphism (RFLP) analysis, and sequencing analysis of drug resistance-associated loci (katG, mabA-inhA, rpoβ, rpsL, and embB). The majority of patients were male (86.9%), 40-64 years of age (60.8%), with a history of TB treatment (84.8%), and producing smear-positive sputa (86.9%). Twenty-two (47.8%) patients suffered from concomitant diseases and 28 (60.8%) were alcohol abusers. Treatment outcome assessment revealed that 8 (17.4%) patients were cured or completed therapy, while 15 (32.6%) died of TB, 11 (23.9%) defaulted, 8 (17.4%) failed, and 1 (2.2%) was transferred and lost to follow-up. Upon genotyping, 10 (21.7%) isolates were allocated in four clusters. These were further subdivided by mutational profiling. Overall, in 6 (13%) patients, MDR-TB was a result of recent transmission. For 4 (8.7%) of these patients, a direct epidemiological link was established. The study shows that the transmission of MDR-TB occurs at a low rate in Poland. Of urgent need is the implementation of a policy of enforced treatment of MDR-TB patients in Poland.