Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

OBJECTIVES: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). METHODS: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. RESULTS: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. CONCLUSIONS: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians.

INTRODUCTION: The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses. MATERIAL AND METHODS: Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles. RESULTS: We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff's encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barré syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients. CONCLUSION: The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.

[Predatory journals: A real threat for medical research. 2 Assess their consequences and initiate a response]. / Revues prédatrices : une vraie menace pour la recherche médicale. 2 Evaluer leurs conséquences et engager une riposte.

The deleterious consequences of "predatory" journals are numerous, whether the researcher submitted his work to them naively or knowingly: work little or not read by the international community in the absence of indexing and disappearance of any digital trace in the absence of archiving. The reputation of researchers but also of universities and research organizations and the credit of science for citizens can be sustainably damaged. These open access journals, with the author who pays as model, represent as many resources unavailable for legitimate journals. A joint mobilization of all the actors involved is necessary: researchers, universities and faculties of medicine, sections of the national university council, publishers of legitimate journals, research organizations, learned societies, ethics committees, funders, media and political decision-makers. Publishing in a predatory journal is now a scientific misconduct.

[Predatory journals: A real threat for medical research. 1. Identify these journals and understand how they work]. / Revues prédatrices : une vraie menace pour la recherche médicale. 1. Identifier ces revues et comprendre leur fonctionnement.

The "author-pay" model of open access publication, which appeared in 2002, allocates to the author or his institution the costs of processing articles due to the journal after acceptance, for an amount of a few hundred to several thousand euros. New publishers emerged towards the end of the 2000s, which used this model but with purely commercial objectives, offering naive authors and/or wishing to quickly expand their curriculum vitae by publications in "predatory journals". They are characterized by aggressive e-mail solicitations, lack of ethics, lack of details about the publisher and the editorial board, poor peer review, unspecified and low fees for processing articles, a lack of indexing and the promise of rapid publication.

Emergency ward ultrasound: clinical audit on disinfection practices during routine and sterile examinations.

CONTEXT: In the emergency ward, where the use of ultrasound is common (including for sterile procedures), ward equipment is constantly exposed to high risks of microbiological contamination. There are no clear guidelines for disinfection control practices in emergency departments, and it is not known how emergency ward doctors follow good hygiene practices. METHOD: A multi-centre audit was conducted in 16 emergency services from Northern France regional hospitals, in form of a questionnaire. It was proposed to all emergency ward physicians. We excluded questionnaires when physicians mentioned that they did not use ultrasound on a daily basis. The questionnaire was designed using existing hygiene and ultrasound disinfection practices guidelines from varying French medical societies. It included three different clinical scenarios: (a) ultrasound on healthy skin, (b) on injured skin, and (c) ultrasound-guided punctures. All questions were closed-ended, with only one answer corresponding to the guidelines. We then calculated compliance rates for each question, each clinical situation, and an overall compliance rate for all the questions. RESULTS: 104 questionnaires were collected, and 19 were excluded. For the 85 analysed questionnaires, the compliance rates were 60.4% 95% CI [56.4-64.7] for ultrasound on healthy skin, 70.9% 95% CI [66.3-76.1] on injured skin and 69.4% 95% CI [65.1-73.6] for ultrasound-guided punctures. The overall compliance rate for the compliance questions was 66.1% 95% CI [62.8-69.1]. Analysis of the questionnaires revealed severe asepsis errors, misuse of gel, ignorance of infection control practices to be applied in the context of ultrasound-guided puncture and exposure of the probe to body fluids. CONCLUSION: This study details areas for quality improvement in the disinfection of emergency ultrasound scanner use. Consequently, we propose a standardized protocol based upon the recommendations used for the questionnaire drafting, with a visual focus on the low compliance points that have been revealed in this audit. This protocol has been distributed to all the medical emergency services audited and included in the emergency resident's ultrasound learning program.

Clinical trial protocols of repurposed prophylaxis for COVID-19: A review.

Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARS-CoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis. We screened several clinical trials repositories and platforms in search of the prophylactic strategies being investigated against COVID-19 in July 2020. Up to July 5, 2020, only one clinical trial result was published, although we found 112 clinical trial protocols targeting medical workers (n=70, 63%), patients relatives (n=20, 18%) or individuals at risk of severe COVID-19 (n=14, 13%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n=69, 62%), before BCG vaccine (n=12, 11%), this followed by numerous antivirals and immune enhancers. Ninety-eight (88%) clinical trials were randomized with a median of planned inclusions of 530 (IQR 258-1299). Both pre- and post-exposure prophylaxes are investigated.

[Scientific misconduct: A major threat for medical research]. / Fraude scientifique : une menace majeure pour la recherche médicale.

Scientific misconduct (fabrication, falsification, and plagiarism) and detrimental research practices (selective reporting of data, inappropriate citation practice, ghostwriting) are admitted respectively by 2 % and 33 % of researchers. The consequences of scientific misconduct and detrimental research practices are disastrous, both for the doctors, who are the most affected researchers in view of the number of retracted articles, and for the patients, victims of false information that may have health consequences. In order to fight against the causes (promotion of doctors and allocation of resources to clinical wards and laboratories on purely quantitative research criteria, lack of training in scientific integrity in medical studies, heterogenous quality of reviewing, legal impunity), there are legislative, academic, technological and editorial solutions, but radical and urgent cultural change is needed first.

Machine learning for clinical decision support in infectious diseases: a narrative review of current applications.

BACKGROUND: Machine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID). OBJECTIVES: We aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID. SOURCES: References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019. CONTENT: We found 60 unique ML-clinical decision support systems (ML-CDSS) aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n = 24, 40%), ID consultation (n = 15, 25%), medical or surgical wards (n = 13, 20%), emergency department (n = 4, 7%), primary care (n = 3, 5%) and antimicrobial stewardship (n = 1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%). IMPLICATIONS: Considering comprehensive patient data from socioeconomically diverse healthcare settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for clinicians and patients.

Machine learning in the clinical microbiology laboratory: has the time come for routine practice?

BACKGROUND: Machine learning (ML) allows the analysis of complex and large data sets and has the potential to improve health care. The clinical microbiology laboratory, at the interface of clinical practice and diagnostics, is of special interest for the development of ML systems. AIMS: This narrative review aims to explore the current use of ML In clinical microbiology. SOURCES: References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, arXiV, ACM Digital Library and IEEE Xplore Digital Library up to November 2019. CONTENT: We found 97 ML systems aiming to assist clinical microbiologists. Overall, 82 ML systems (85%) targeted bacterial infections, 11 (11%) parasitic infections, nine (9%) viral infections and three (3%) fungal infections. Forty ML systems (41%) focused on microorganism detection, identification and quantification, 36 (37%) evaluated antimicrobial susceptibility, and 21 (22%) targeted the diagnosis, disease classification and prediction of clinical outcomes. The ML systems used very diverse data sources: 21 (22%) used genomic data of microorganisms, 19 (20%) microbiota data obtained by metagenomic sequencing, 19 (20%) analysed microscopic images, 17 (18%) spectroscopy data, eight (8%) targeted gene sequencing, six (6%) volatile organic compounds, four (4%) photographs of bacterial colonies, four (4%) transcriptome data, three (3%) protein structure, and three (3%) clinical data. Most systems used data from high-income countries (n = 71, 73%) but a significant number used data from low- and middle-income countries (n = 36, 37%). Performance measures were reported for the 97 ML systems, but no article described their use in clinical practice or reported impact on processes or clinical outcomes. IMPLICATIONS: In clinical microbiology, ML has been used with various data sources and diverse practical applications. The evaluation and implementation processes represent the main gap in existing ML systems, requiring a focus on their interpretability and potential integration into real-world settings.

Review of trials currently testing treatment and prevention of COVID-19.

BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are being undertaken all over the world. OBJECTIVES: We summarized all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS AND INTERVENTIONS: No restrictions in terms of participants' age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term 'coronavirus' or 'COVID-19' from their inception until 26 March 2020. Additional manual search of the registries was also performed. Eligible studies were summarized and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing traditional Chinese medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and three studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomized (n = 150/198, 76%) and open label (n = 73/198, 37%) with a median number of planned inclusions of 90 (interquartile range 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSIONS: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarized data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.

[The plague: An overview and hot topics]. / La peste : mise au point et actualités.

Plague is a bacterial zoonosis caused by Yersinia pestis, usually found in fleas and small rodents that constitute the reservoir of the disease. It is transmitted to humans by flea bite, contact with rodents or inhalation of infected droplets. There are three clinical forms: bubonic plague, pulmonary plague and septicemic plague. The usual presentation is a flu-like syndrome possibly accompanied by an inflammatory lymphadenopathy which appears after 1 to 7days of incubation. Bubonic plague has a case fatality rate of about 50% while other forms of plague are almost always fatal without treatment. Diagnosis can be confirmed by usual bacteriological techniques (Gram examination, culture) but also by serological examination, use of rapid diagnostic tests or PCR. Although aminoglycosides are traditionally regarded as the most effective treatment, fluoroquinolones or cyclins are currently recommended in France. Plague is one of the re-emerging diseases according to the WHO and Madagascar suffered in 2017 the most important plague epidemic of the 21st century with more than 2000 cases and 200 deaths. Peru and the Democratic Republic of Congo are also considered endemic areas. Public health measures and a relentless fight against poverty are the cornerstone of the control of the disease. Vaccine improvement in endemic areas may also play an important role.

[The plague: A disease that is still haunting our collective memory]. / La peste, une maladie qui hante encore notre mémoire collective.

Although the plague has practically disappeared from Europe since the beginning of the 20th century, it is still present in everyone's memory. Owing to three pandemics, it has left an indelible mark on mankind and has given rise to many popular phrases, paintings, books or more recently movies and video games. After a brief description of the plague as a disease, we will try to trace the history of the plague through some of the works of art it inspired and then to show how the plague is still haunting our collective memory.

Interstitial telomere repeats in translocations of hematopoietic disorders.

Cytogenetic and fluorescence in situ hybridization studies have shown the presence of telomeric repeats in translocation present in three patients with hematopoietic malignancies. One had jumping translocations, involving 1q12 and 2q, 16p, and 19q. These sequences were detected by FISH only in derivative chromosomes t(1;16) and t(1;19) in the first patient, and t(1;7) in the second. They were not seen in derivative t(1;2) and t(7;8), respectively. Interstitial telomeric sequences were observed in der(2)t(1;2) in about half of the metaphases in the third patient. The instability of interstitial telomeric DNA repeats in translocations is shown by the present findings. Moreover it supports the hypothesis that the presence of interstitial telomere repeats is not sufficient to make it functional.

Cytogenetic and molecular studies of the Philadelphia translocation t(9;22) observed in a patient with myelodysplastic syndrome.

We report here the case of a patient with refractory anemia with excess of blasts (RAEB) which evolved into RAEB in transformation. The standard Philadelphia (Ph) chromosome was found by cytogenetic study at diagnosis and during evolution. Southern blot analysis showed breakpoint cluster region (bcr) rearrangement as observed in chronic myelogenous leukemia (CML).

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

The role of methylcellulose on colony growth of human myeloid leukemic progenitors (AML-CFU).

The use of a semisolid support like methylcellulose (MC) in a clonogenic assay prevents cell migration and nonspecific aggregation. However, the inhibitory effect of MC on myeloid cell lines has been reported. To assess the effect of MC on human leukemic progenitor cell growth (acute myeloblastic leukemia colony-forming units, AML-CFU), increasing concentrations of MC (0.36%, 0.72%, and 1.44%) were added in a double-feeder culture system. T-lymphocyte-depleted leukemic cells from 12 patients with AML were cultured in the presence of 2.5% phytohemagglutinin (PHA) in a liquid and a semisolid (MC) medium over a leukocyte feeder layer. The leukemic nature of the colonies was confirmed by cytogenetic studies. The median cloning efficiency in the optimal MC assay system was significantly higher (217 leukemic colony-forming units [CFU-L]/5 x 10(4) cells) than the one obtained in the liquid assay system (72.5 CFU-L/5 x 10(4) cells). However, three patterns of growth were observed: 1) colony formation was significantly better in MC than in the liquid assay system (seven of ten cases), 2) there was no difference in growth response (three of ten cases), and 3) colony formation was significantly better in the liquid assay system (one of ten cases). In the semisolid assay system, colony growth was dependent on MC concentration and varied among individual patients. A striking feature was the partial reduction of AML-CFU growth at 1.44% MC, with complete inhibition in 4/11 cases. This phenomenon was not observed for normal progenitors cultured under the same conditions. Cytological evaluation of AML-CFU showed an incomplete maturation to the myelocyte state, accompanied occasionally by macrophagic differentiation. In contrast, maturation of the granulocyte-macrophage colony-forming unit (CFU-GM) clones was harmonious, resulting in greater than 40% polynuclear cells, even from a 7-day culture. Despite a variable clonal response of leukemic progenitors from individual patients, we conclude that 0.72% MC is the optimal concentration of MC in our system, allowing clonal growth of AML-CFU.