Serosurvey of Tick-Borne Encephalitis Virus Infection in Romania.

BACKGROUND: Tick-borne encephalitis (TBE) is a disease with mandatory declaration in the EU since 2012. Information regarding the seroprevalence of the disease across Romania is limited, and only sporadic cases are rarely reported. We aimed to identify new areas of TBEV infection in different counties of Romania. METHODS: We conducted a serosurvey assessing the immune response to TBEV infection in adult populations from rural areas in different counties of the country. Seropositivity was defined by a positive TBEV IgM/IgG ELISA test and confirmed by serum neutralization. RESULTS: We collected 1116 samples from 15 different localities in 10 counties (divided into endemic/border/non-endemic counties) across Romania. Overall, 26 (2.3%) of the samples were tested positive using the TBEV ELISA assay in six counties. In those counties, 3.7% of sera were positive, varying from 1.4% to 6.9% per county. After performing the neutralization assay, seven (0.6%) samples were confirmed positive, interestingly all from one site in Sibiu County, where the seroprevalence was 9.7%. CONCLUSIONS: The identification of positive serum samples in serosurveys appears to rely on the discovery of TBEV microfoci. Further serological surveys should be conducted in Romania, especially after the identification of positive TBEV patients presenting for medical care.

Dynamics of serum cross-neutralization capacity against SARS-CoV-2 Delta variant in convalescent COVID-19 patients.

The magnitude and breadth of the neutralizing antibody response against variants of concern following natural infection would provide valuable insights regarding the immune response induced by severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection. Herein, 25 patients were followed at 30 ±7 (Visit 1), 90± 15 (Visit 2), and 180 ± 15 (Visit 3) days post symptom onset (PSO). The neutralization titers against both Wuhan-Hu-1 (WT) and Delta variant were analyzed in parallel along with anti-Spike antibodies (anti-S1/S2 immunoglobulin G [IgG]). The median values of half-maximal neutralization titer (NT50 ) for the WT and Delta variants decreased by 75.8% and 82.2% at Visit 2 and by 85.4% and 81.4% at Visit 3, respectively. At Visit 1, the correlation between the anti-S1/S2 IgG and Nabs titers for the Delta variant was moderate for WT (r = 0.58) and weak for the Delta variant (r = 0.39). However, the correlation coefficient consistently remained above 0.7, with a very strong correlation at Visit 3 for both WT and Delta variants (r = 0.81). The dynamics of anti-S1/S2 IgG antibodies, NT50 , and cross-neutralization index correlated at different time points PSO. Longitudinal analysis of the cross-neutralization capacity of immune sera will inform upon the durability of the immune response against SARS CoV-2 variants.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).

OBJECTIVES: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). DISCUSSION: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

Cerebellar Abscess Secondary to Cholesteatomatous Otomastoiditis-An Old Enemy in New Times.

Chronic otitis with cholesteatoma is a potentially dangerous disease that can lead to the development of intracranial abscesses. Although cerebellar abscess is half as common as cerebral abscess, it is known for its particularly difficult diagnosis, which requires the visualization of the pathological process continuity from the mastoid to the posterior fossa. In this article, we present an extremely rare case from the literature of cholesteatomatous otomastoiditis complicated with meningitis and cerebellar abscess, along with the description of technical surgical details for the plugging of the bony defect between the mastoid and posterior fossa with muscle and surgical glue. The particularity of this case lies in the late presentation to the doctor of an immunocompetent patient, through a dramatic symptomatology of life-threatening complications. We emphasize the importance of responsibly treating any episode of middle ear infection and considering the existence of underlying pathologies. In such cases, we recommend additional neuroimaging explorations, which can prevent potentially lethal complications. The treatment of such intracranial complications must be carried out promptly and requires collaboration between a neurosurgeon and an ENT surgeon.

Brain Tuberculosis: An Odyssey through Time to Understand This Pathology.

Tuberculosis is a contagious disease that has been a concern for humanity throughout history, being recognized and referred to as the white plague. Since ancient times, starting with Hippocrates and Galen of Pergamon, doctors and scientists have attempted to understand the pathogenesis of tuberculosis and its manifestations in the brain. If, in the medieval period, it was believed that only the touch of a king could cure the disease, it was only in the early 17th and 18th centuries that the first descriptions of tuberculous meningitis and the first clinico-pathological correlations began to emerge. While the understanding of neurotuberculosis progressed slowly, it was only after the discovery of the pathogenic agent in the late 19th century that there was an upward curve in the occurrence of treatment methods. This review aims to embark on an odyssey through the centuries, from ancient Egypt to the modern era, and explore the key moments that have contributed to the emergence of a new era of hope in the history of neurotuberculosis. Understanding the history of treatment methods against this disease, from empirical and primitive ones to the emergence of new drugs used in multi-drug-resistant tuberculosis, leads us, once again, to realize the significant contribution of science and medicine in treating a disease that was considered incurable not long ago.

Pulmonary Thrombosis despite Therapeutic Anticoagulation in COVID-19 Pneumonia: A Case Report and Literature Review.

The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.

Quantitative chest CT imaging characteristics and outcome of patients with COVID-19 associated pulmonary artery thrombosis: A single-center retrospective cohort study.

Coronavirus disease 2019 (COVID-19)-associated pulmonary thrombotic events occur frequently and are associated with disease severity and worse clinical outcomes. We aimed to describe the clinical and quantitative chest computed tomography (CT) imaging characteristics based on density ranges (Hounsfield units) and the outcomes of patients with COVID-19 associated pulmonary artery thrombosis. This retrospective cohort study included all patients with COVID-19 hospitalized in a tertiary care hospital between March 2020 and June 2022 who underwent a CT pulmonary angiography. We included 73 patients: 36 (49.3%) with and 37 (50.7%) without pulmonary artery thrombosis. The in-hospital all-cause mortality was 22.2 versus 18.9% ( P  = .7), and the intensive care unit admission rates were 30.5 versus 8.1% ( P  = .01) at the time of diagnosis of pulmonary artery thrombosis. Except for D-dimers (median of 3142 vs 533, P  = .002), the other clinical, coagulopathy, and inflammatory markers were similar. Logistic regression analysis revealed that only D-dimers were associated with pulmonary artery thrombosis ( P  = .012). ROC curve analysis of D-dimers showed that a value greater than 1716 ng/mL predicted pulmonary artery thrombosis with an area under the curve of 0.779, 72.2% sensitivity, and 73% specificity (95% CI 0.672-0.885). Peripheral distribution of pulmonary artery thrombosis was recorded in 94.5% of cases. In the lower lobes of the lungs, the incidence of pulmonary artery thrombosis was 6 times higher than that in the upper lobes (58-64%), with a percentage of lung injury of 80% to 90%. Analysis of the distribution of arterial branches with filling defects revealed that 91.6% occurred in lung areas with inflammatory lesions. Quantitative chest CT imaging provides valuable information regarding the extent of COVID-19 associated lung damage and can be used to anticipate the co-location of pulmonary immunothrombotic events. In patients with severe COVID-19, in-hospital all-cause mortality was similar regardless of the presence of associated distal pulmonary thrombosis.

Challenges in the diagnosis of leptomeningeal dissemination of glioblastoma in a patient with fever and xanthochromic CSF: a case report.

BACKGROUND: Leptomeningeal spread with carcinomatous meningitis is a severe complication of glioblastoma, with a poor prognosis. Diagnosis is challenging, as the sensitivity of classic diagnostic investigations remains low for detecting cerebrospinal fluid (CSF) tumor spread and exclusion of infectious causes is mandatory, especially if unusual clinical findings are present. CASE PRESENTATION: A 71-year-old woman was admitted to our hospital for recurrent episodes of high fever and xanthochromic meningitis, with subacute onset. Her past medical history was significant for a left temporal glioblastoma, treated with surgical resection and adjuvant chemo- and radiotherapy, with associated systemic immunosuppression secondary to chemotherapy. An extensive workup especially with molecular microbiology testing for exclusion of infectious causes was performed. CSF was analyzed for typical bacterial and viral causes, but also pathogens associated with immunosuppression, such as Listeria monocytogenes and Cryptococcus neoformans. A therapeutic trial of standard antituberculous drugs with repeated lumbar punctures were needed in order to exclude Mycobacterium tuberculosis and to confirm the diagnosis of carcinomatous meningitis by cytopathological examination of the CSF. CONCLUSIONS: The case describes an unusual clinical presentation of a patient with glioblastoma associated leptomeningeal dissemination, as high fever and xanthochromic CSF could raise important diagnostic and therapeutic challenges in the clinical practice. The diagnosis of carcinomatous meningitis requires an extensive workup for exclusion of infectious causes which is important for urgent oncologic treatment.

Peripheral nervous system involvement associated with COVID-19. A systematic review of literature.

There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate the characteristics, management and outcomes of patients with PNS, including the types and severity of cranial nerves (CN) involvement. We systematically searched on PubMed for studies reporting adult patients diagnosed with COVID-19 and PNS involvement until July 2021. From 1670 records, 225 articles matched the inclusion criteria, with a total of 1320 neurological events, in 1004 patients. There were 805 (61%) CN, 350 (26.5%) PNS, and 165 (12.5%) PNS plus CN events. The most frequently involved CN were the facial, vestibulo-cochlear and olfactory nerve in 27.3%, 25.4% and 16.1%, respectively. Guillain-Barre syndrome spectrum was identified in 84.2% of PNS events. We analysed 328 patients reported in 225 articles with CN, PNS, and PNS plus CN involvement. The patients with CN involvement were younger (mean age 46.2±17.1, p = .003), and were more frequently treated as outpatients (p < .001), mostly with glucocorticoids (p < .001). Patients that had PNS with or without CN involvement were more likely to be hospitalized (p < .001), and to receive intravenous immunoglobulins (p = .002) or plasma exchange (p = .002). Patients with CN, PNS, and PNS plus CN had severe COVID -19 disease in 24.8%, 37.3%, 34.9% respectively. The most common neurological outcome was mild/moderate sequelae in patients with CN, PNS, and PNS plus CN in 54.7%, 67.5% and 67.8% respectively (p = .1) and no significant difference was found between the three categories regarding death, disease severity, time from disease onset to neurological symptoms, lack of improvement and complete recovery. CN involvement was the most frequent PNS finding. All three categories of PNS involvement were rather associated to non-severe COVID-19 but it may be an important cause of hospitalization and post COVID-19 sequelae.

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA).

Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-ß-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation: The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics. Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review.

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated "cytokine storm", platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.

The outcome and risk factors associated with central and peripheral nervous system involvement in hospitalized COVID-19 patients: a retrospective cohort study.

Introduction: SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the outcome and risk factors associated with the involvement of either CNS or PNS in a cohort of hospitalized COVID-19 patients. Methods: We performed a retrospective observational cohort study of hospitalized adult patients with COVID-19, between May 2020 and December 2022, presenting with new onset neurological disabilities any time after admission. Results: We included 115 patients, 72 with CNS manifestations and 43 with PNS involvement. The CNS manifestations were COVID-19-associated encephalopathy, headache, neurovascular events, and seizures in 80.5, 43, 31.9, and 11.1% of patients, respectively. The neurovascular events were ischemic stroke in 17 (23.6%) patients, hemorrhagic stroke in 6 (8.3%) patients, venous thrombosis in 1 (1.4%) patient, and subarachnoid hemorrhage in 1 (1.4%) patient. Cranial nerve involvement was the most frequent PNS manifestation in 34 (79%) cases, followed by mononeuritis in 5 (11.6%) patients and polyneuropathy in 4 (9.3%) patients. The affected cranial nerves were the vestibulocochlear nerve in 26 (60.5%) patients, the olfactory nerve in 24 (55.8%) patients, the oculomotor nerves in 5 (11.6%) patients, and the facial nerve in 1 (2.3%) patient. Two patients (9.3%) presented with polyneuritis cranialis. Older age (HR = 1.02, 95% CI: 1.003-1.037, p = 0.01), COVID severity (HR = 2.53, 95% CI: 1.42-4.5, p = 0.002), ischemic cardiac disease (HR = 2.42, 95% CI: 1.05-5.6, p = 0.03), and increased D-dimers (HR = 1.00, 95% CI: 1.00-1.00, p = 0.02) were independently associated with the development of CNS manifestations. The factors associated with in-hospital mortality were age (HR = 1.059, 95% CI: 1.024-1.096, p = 0.001), C-reactive protein (HR = 1.006, 95% CI: 1.00-1.011, p = 0.03), CNS involvement (HR = 9.155, 95% CI: 1.185-70.74, p = 0.03), and leucocyte number (HR = 1.053, 95% CI: 1.026-1.081, p < 0.001). Conclusion: COVID-19-associated encephalopathy was the most common CNS manifestation in our study, but neurovascular events are also important considering the overlap between inflammatory and prothrombotic pathways, especially in severe cases. CNS involvement was associated with in-hospital all-cause mortality. PNS findings were various, involving mostly the cranial nerves, especially the vestibulocochlear nerve.

Pericardial Involvement in Severe COVID-19 Patients.

Background and Objectives: SARS-CoV-2 has an extensive tissue tropism due to its ability to attach to the surfaces of cells through different receptors, leading to systemic complications. In this article, we aim to present the prevalence of pericardial effusions in patients with severe COVID-19, to identify the risk factors/predictors for pericardial involvement, and to evaluate its impact on overall mortality. Materials and Methods: We enrolled 100 patients with severe COVID-19 in our observational cohort study and divided them in two groups: Group A (27 patients with pericardial effusion) and Group B (73 patients without pericardial effusion). We recorded demographic and lifestyle parameters, anthropometric parameters, clinical parameters, inflammation markers, respiratory function parameters, complete blood count, coagulation parameters, and biochemical serum parameters. All patients were evaluated by computer tomography scans within 48 h of admission. Results: The median age was 61 years in both groups and the male/female ratio was 3.5 vs. 2.8 in Group A vs. Group B. We identified mild pericardial effusion (3-4 mm) in 62.9% patients and moderate pericardial effusion (5-9 mm) in 37.1% patients, with a median value of 4 [3;6] mm. The patients with pericardial effusion presented with higher percentages of obesity, type-2 diabetes mellitus, arterial hypertension, and congestive heart failure, without statistical significance. Increased values in cardiac enzymes (myoglobin, CK, CK-MB) and LDH were statistically associated with pericardial effusion. The overall mortality among the participants of the study was 24% (24 patients), 33.3% in Group A and 20.8% in Group B. Conclusions: Pericardial effusion has a high prevalence (27%) among patients with severe forms of COVID-19 and was associated with higher mortality. Pericardial effusion in our study was not associated with the presence of comorbidities or the extent of lung involvement. Overall mortality was 60% higher in patients with pericardial effusion.

Mortality Predictors in Severe SARS-CoV-2 Infection.

Background and Objectives: The severe forms of SARS-CoV-2 pneumonia are associated with acute hypoxic respiratory failure and high mortality rates, raising significant challenges for the medical community. The objective of this paper is to present the importance of early quantitative evaluation of radiological changes in SARS-CoV-2 pneumonia, including an alternative way to evaluate lung involvement using normal density clusters. Based on these elements we have developed a more accurate new predictive score which includes quantitative radiological parameters. The current evolution models used in the evaluation of severe cases of COVID-19 only include qualitative or semi-quantitative evaluations of pulmonary lesions which lead to a less accurate prognosis and assessment of pulmonary involvement. Materials and Methods: We performed a retrospective observational cohort study that included 100 adult patients admitted with confirmed severe COVID-19. The patients were divided into two groups: group A (76 survivors) and group B (24 non-survivors). All patients were evaluated by CT scan upon admission in to the hospital. Results: We found a low percentage of normal lung densities, PaO2/FiO2 ratio, lymphocytes, platelets, hemoglobin and serum albumin associated with higher mortality; a high percentage of interstitial lesions, oxygen flow, FiO2, Neutrophils/lymphocytes ratio, lactate dehydrogenase, creatine kinase MB, myoglobin, and serum creatinine were also associated with higher mortality. The most accurate regression model included the predictors of age, lymphocytes, PaO2/FiO2 ratio, percent of lung involvement, lactate dehydrogenase, serum albumin, D-dimers, oxygen flow, and myoglobin. Based on these parameters we developed a new score (COV-Score). Conclusions: Quantitative assessment of lung lesions improves the prediction algorithms compared to the semi-quantitative parameters. The cluster evaluation algorithm increases the non-survivor and overall prediction accuracy.COV-Score represents a viable alternative to current prediction scores, demonstrating improved sensitivity and specificity in predicting mortality at the time of admission.

Recommendations to Improve Tick-Borne Encephalitis Surveillance and Vaccine Uptake in Europe.

There has been an increase in reported TBE cases in Europe since 2015, reaching a peak in some countries in 2020, highlighting the need for better management of TBE risk in Europe. TBE surveillance is currently limited, in part, due to varying diagnostic guidelines, access to testing, and awareness of TBE. Consequently, TBE prevalence is underestimated and vaccination recommendations inadequate. TBE vaccine uptake is unsatisfactory in many TBE-endemic European countries. This review summarizes the findings of a scientific workshop of experts to improve TBE surveillance and vaccine uptake in Europe. Strategies to improve TBE surveillance and vaccine uptake should focus on: aligning diagnostic criteria and testing across Europe; expanding current vaccine recommendations and reducing their complexity; and increasing public education of the potential risks posed by TBEV infection.

Antibiotic Prescription and In-Hospital Mortality in COVID-19: A Prospective Multicentre Cohort Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, empiric antibiotics (ATBs) have been prescribed on a large scale in both in- and outpatients. We aimed to assess the impact of antibiotic treatment on the outcomes of hospitalised patients with moderate and severe coronavirus disease 2019 (COVID-19). METHODS: We conducted a prospective multicentre cohort study in six clinical hospitals, between January 2021 and May 2021. RESULTS: We included 553 hospitalised COVID-19 patients, of whom 58% (311/553) were prescribed antibiotics, while bacteriological tests were performed in 57% (178/311) of them. Death was the outcome in 48 patients-39 from the ATBs group and 9 from the non-ATBs group. The patients who received antibiotics during hospitalisation had a higher mortality (RR = 3.37, CI 95%: 1.7-6.8), and this association was stronger in the subgroup of patients without reasons for antimicrobial treatment (RR = 6.1, CI 95%: 1.9-19.1), while in the subgroup with reasons for antimicrobial therapy the association was not statistically significant (OR = 2.33, CI 95%: 0.76-7.17). After adjusting for the confounders, receiving antibiotics remained associated with a higher mortality only in the subgroup of patients without criteria for antibiotic prescription (OR = 10.3, CI 95%: 2-52). CONCLUSIONS: In our study, antibiotic treatment did not decrease the risk of death in the patients with mild and severe COVID-19, but was associated with a higher risk of death in the subgroup of patients without reasons for it.

In-Hospital Antibiotic Use for COVID-19: Facts and Rationales Assessed through a Mixed-Methods Study.

It is well known that during the coronavirus disease 2019 (COVID-19) pandemic, antibiotics were overprescribed. However, less is known regarding the arguments that have led to this overuse. Our aim was to understand the factors associated with in-hospital antibiotic prescription for COVID-19, and the rationale behind it. We chose a convergent design for this mixed-methods study. Quantitative data was prospectively obtained from 533 adult patients admitted in six hospitals (services of internal medicine, infectious diseases and pneumology). Fifty-six percent of the patients received antibiotics. The qualitative data was obtained from interviewing 14 physicians active in the same departments in which the enrolled patients were hospitalized. Thematic analysis was used for the qualitative approach. Our study revealed that doctors based their decisions to prescribe antibiotics on a complex interplay of factors regarding the simultaneous appearance of consolidation on the chest computer tomography together with a worsening of clinical conditions suggestive of bacterial infection and/or an increase in inflammatory markers. Besides these features which might suggest bacterial co-/suprainfection, doctors also prescribed antibiotics in situations of uncertainty, in patients with severe disease, or with multiple associated comorbidities.

Acute Pulmonary Artery Thrombosis despite Anticoagulation in Patients with COVID-19 Pneumonia: A Single-Center Retrospective Cohort Study.

(1) Background: We aimed to describe the clinical and imaging characteristics of patients diagnosed with pulmonary artery thrombosis (PAT) despite receiving anticoagulation with low-molecular-weight heparin (LMWH). (2) Methods: We retrospectively studied all hospitalized COVID-19 adult patients diagnosed with PAT between March 2020 and December 2021, who received LMWH for ≥72 h until the diagnosis of PAT. Acute PAT was confirmed by a CT pulmonary angiogram. (3) Results: We included 30 severe and critical COVID-19 patients. Median age was 62 (54-74) years, with 83.3% males, and comorbidities seen in 73.3%. PAT was diagnosed despite prophylactic (23.3%), intermediate (46.6%) or therapeutic (30%) doses of LMWH for a median time of 8 (4.7-12) days. According to their Wells score, 80% of patients had a low probability of pulmonary embolism diagnosis. PAT was localized in the lower lobes of the lungs in 76.6% of cases with 33.3% having bilateral involvement, with the distal, peripheral arteries being the most affected. At the PAT diagnosis we found a worsening of respiratory function, with seven patients progressing to mechanical ventilation (p = 0.006). The in-hospital mortality was 30%. (4) Conclusions: PAT should be considered in patients with severe and critical COVID-19, mainly in elderly male patients with comorbidities, irrespective of Wells score and LMWH anticoagulation.

The Impact of Tocilizumab on Radiological Changes Assessed by Quantitative Chest CT in Severe COVID-19 Patients.

(1) Background: We aimed to analyze the characteristics associated with the in-hospital mortality, describe the early CT changes expressed quantitatively after tocilizumab (TOC), and assess TOC timing according to the oxygen demands. (2) Methods: We retrospectively studied 101 adult patients with severe COVID-19, who received TOC and dexamethasone. The lung involvement was assessed quantitatively using native CT examination before and 7−10 days after TOC administration. (3) Results: The in-hospital mortality was 17.8%. Logistic regression analysis found that interstitial lesions above 50% were associated with death (p = 0.01). The other variables assessed were age (p = 0.1), the presence of comorbidities (p = 0.9), the oxygen flow rate at TOC administration (p = 0.2), FiO2 (p = 0.4), lymphocyte count (p = 0.3), and D-dimers level (p = 0.2). Survivors had a statistically significant improvement at 7−10 days after TOC of interstitial (39.5 vs. 31.6%, p < 0.001), mixt (4.3 vs. 2.3%, p = 0.001) and consolidating (1.7 vs. 1.1%, p = 0.001) lesions. When TOC was administered at a FiO2 ≤ 57.5% (oxygen flow rate ≤ 13 L/min), the associated mortality was significantly lower (4.3% vs. 29.1%, p < 0.05). (4) Conclusions: Quantitative imaging provides valuable information regarding the extent of lung damage which can be used to anticipate the in-hospital mortality. The timing of TOC administration is important and FiO2 could be used as a clinical predictor.

European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults.

SCOPE: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults. METHODS AND QUESTIONS: Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure. RECOMMENDATIONS: Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.