Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Inflammatory Response in COVID-19 Depending on the Severity of the Disease and the Vaccination Status.

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive patients, divided into four groups according to the severity of the disease as follows: 30 patients in the mild form group, 49 in the moderate form group, 28 in the severe form group, and 30 in the critical form group. The tested parameters were correlated with COVID-19 severity. Significant differences were registered between the form of COVID-19 depending on the vaccination status, between LDH concentrations depending on the virus variant, and in IL-6, CRP, and ferritin concentrations and vaccination status depending on the gender. ROC analysis revealed that D-dimer best predicted COVID-19 severe forms and LDH predicted the virus variant. Our findings confirmed the interdependence relationships observed between inflammation markers in relation to the clinical severity of COVID-19, with all the tested biomarkers increasing in severe and critical COVID-19. IL-6, CRP, ferritin, LDH, and D-dimer were increased in all COVID-19 forms. These inflammatory markers were lower in Omicron-infected patients. The unvaccinated patients developed more severe forms compared to the vaccinated ones, and a higher proportion of them needed hospitalization. D-dimer could predict a severe form of COVID-19, while LDH could predict the virus variant.

Antibiotic Usage in the COVID-19 Intensive Care Unit of an Infectious Diseases Hospital from Nord-Eastern Romania.

Background and Objectives. The intensive care unit (ICU), especially in an infectious disease hospital, is both an area with a high consumption of antibiotics (atb) and a "reservoir" of multidrug-resistant bacteria. We proposed the analysis of antibiotic therapy practices in such a department that treated, in conditions of a pandemic wave, patients with COVID-19 and its complications. Materials and Methods. This was a retrospective transversal study of 184 COVID-19 patients treated in the ICU of a regional infectious disease hospital of Iasi, Romania, in a 3-month interval of 2020 and 2021. Results. All the included patients (Caucasians, 53% males, with a median age of 68 years, and a Charlton comorbidity index of 3) received at least one antibiotic during their stay in the ICU (43% also had antibiotics prior to hospital admission and 68% in the Infectious Diseases ward). Only 22.3% of the ICU patients had only one antibiotic. A total of 77.7% of them started with an association of two antibiotics, and 19.6% of them received more than three antibiotics. The most-used ones were linezolid (77.2%), imipenem (75.5%), and ceftriaxone (33.7%). The median atb duration was 9 days. No change in the number or type of atb prescription was seen in 2021 (compared to 2020). Only 9.8% of the patients had a microbiological confirmation of bacterial infection. A total of 38.3% of the tested patients had elevated procalcitonin levels at ICU admission. The overall fatality rate was 68.5%, with no significant differences between the two analyzed periods or the number of administered antibiotics. More than half (51.1%) of the patients developed oral candidiasis during their stay in the ICU, but only 5.4% had C. difficile colitis. Conclusion. Antibiotics were widely used in our ICU patients in the presence of a reduced microbiological confirmation of a bacterial co-infection, and were justified by other clinical or biological criteria.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

A novel id-iri score: development and internal validation of the multivariable community acquired sepsis clinical risk prediction model.

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.

Diagnosis and treatment challenges in a rare Clostridium infection: A case report.

The Clostridium genus includes >180 species of Gram-positive, anaerobic, sporulating bacteria. Under certain conditions, these can cause a wide range of invasive infections in humans. Clostridium paraputrificum occurs in the commensal intestinal flora and related bacteremia typically occurs secondary to an injury to the intestinal mucosa and in the presence of predisposing conditions, such as gastrointestinal disorders, malignancies, diabetes, HIV infection or neutropenia. The current study presents the case of a 70-year-old male patient, a rural resident living in poverty, with a history of alchohol consumption and cardiovascular pathology. Several initial and subsequent diagnoses were ruled out by successive investigations (e.g., stroke, meningitis, localized tetanus). Blood cultures were eventually found positive for Clostridium paraputrificum and the patient developed septic shock despite treatment with metronidazole and penicillin G. Once switched to carbapenem, the patient progressed favorably, suggesting that carbapenem could work as a first-line antibiotic treatment for Clostridium paraputrificum infections.

Distinct soluble immune checkpoint profiles characterize COVID-19 severity, mortality and SARS-CoV-2 variant infections.

Introduction: Over the past four years, the COVID-19 pandemic has posed serious global health challenges. The severe form of disease and death resulted from the failure of immune regulatory mechanisms, closely highlighted by the dual proinflammatory cytokine and soluble immune checkpoint (sICP) storm. Identifying the individual factors impacting on disease severity, evolution and outcome, as well as any additional interconnections, have become of high scientific interest. Methods: In this study, we evaluated a novel panel composed of ten sICPs for the predictive values of COVID-19 disease severity, mortality and Delta vs. Omicron variant infections in relation to hyperinflammatory biomarkers. The serum levels of sICPs from confirmed SARS-CoV-2 infected patients at hospital admission were determined by Luminex, and artificial neural network analysis was applied for defining the distinct patterns of molecular associations with each form of disease: mild, moderate, and severe. Results: Notably, distinct sICP profiles characterized various stages of disease and Delta infections: while sCD40 played a central role in all defined diagrams, the differences emerged from the distribution levels of four molecules recently found and relatively less investigated (sCD30, s4-1BB, sTIM-1, sB7-H3), and their associations with various hematological and biochemical inflammatory biomarkers. The artificial neural network analysis revealed the prominent role of serum sTIM-1 and Galectin-9 levels at hospital admission in discriminating between survivors and non-survivors, as well as the role of specific anti-interleukin therapy (Tocilizumab, Anakinra) in improving survival for patients with initially high sTIM-1 levels. Furthermore, strong associations between sCD40 and Galectin-9 with suPAR defined the Omicron variant infections, while the positive match of sCD40 with sTREM-1 serum levels characterized the Delta-infected patients. Conclusions: Of importance, this study provides a comprehensive analysis of circulatory immune factors governing the COVID-19 pathology, and identifies key roles of sCD40, sTIM-1, and Galectin-9 in predicting mortality.

"Primum, non nocere": The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era-Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe.

Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the severity of the disease. Our study aims to elucidate the significance of toxigenic Clostridioides difficile (CD) strains in the clinical and therapeutic aspects of managing patients diagnosed with CDI. We conducted a single-center prospective study, including patients with CDI from north-eastern Romania. We subsequently conducted molecular biology testing to ascertain the prevalence of the presumptive 027/NAP1/BI strain within aforementioned geographic region. The patients were systematically compared and assessed both clinically and biologically, employing standardized and comparative methodologies. The study enrolled fifty patients with CDI admitted between January 2020 and June 2020. Among the investigated patients, 43 (86%) exhibited infection with toxigenic CD strains positive for toxin B genes (tcdB), binary toxin genes (cdtA and cdtB), and deletion 117 in regulatory genes (tcdC), while the remaining 7 (14%) tested negative for binary toxin genes (cdtA and cdtB) and deletion 117 in tcdC. The presence of the presumptive 027/NAP1/BI strains was linked to a higher recurrence rate (35.56%, p = 0.025), cardiovascular comorbidities (65.1% vs. 14.2%, p = 0.016), and vancomycin treatment (55.8% vs. 14.3%, p = 0.049). The findings of our investigation revealed an elevated incidence of colitis attributed to presumptive 027/NAP1/BI. Despite the prevalence of the presumptive 027 strain and its associated heightened inflammation among the patients studied, no significant differences were observed regarding the clinical course or mortality outcomes.

The Impact of Urinary Catheterization on the Antibiotic Susceptibility of ESBL-Producing Enterobacterales: A Challenging Duo.

INTRODUCTION: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns. RESULTS: We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. (p = 0.02) and Providencia stuartii (p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance (p < 0.0001) or even pandrug resistance (p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001). MATERIALS AND METHODS: We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time. CONCLUSIONS: The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies.

Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants.

C-reactive protein (CRP) has been one of the most investigated inflammatory-biomarkers during the ongoing COVID-19 pandemics caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The severe outcome among patients with SARS-CoV-2 infection is closely related to the cytokine storm and the hyperinflammation responsible for the acute respiratory distress syndrome and multiple organ failure. It still remains a challenge to determine which of the hyperinflammatory biomarkers and cytokines are the best predictors for disease severity and mortality in COVID-19 patients. Therefore, we evaluated and compared the outcome prediction efficiencies between CRP, the recently reported inflammatory modulators (suPAR, sTREM-1, HGF), and the classical biomarkers (MCP-1, IL-1ß, IL-6, NLR, PLR, ESR, ferritin, fibrinogen, and LDH) in patients confirmed with SARS-CoV-2 infection at hospital admission. Notably, patients with severe disease had higher serum levels of CRP, suPAR, sTREM-1, HGF and classical biomarkers compared to the mild and moderate cases. Our data also identified CRP, among all investigated analytes, to best discriminate between severe and non-severe forms of disease, while LDH, sTREM-1 and HGF proved to be excellent mortality predictors in COVID-19 patients. Importantly, suPAR emerged as a key molecule in characterizing the Delta variant infections.

Characteristics of Tuberculous Meningitis in HIV-Positive Patients from Northeast Romania.

BACKGROUND AND OBJECTIVES: One of the most severe forms of extrapulmonary tuberculosis (EPTB) is tuberculous meningitis (TBM), which is linked to significant morbidity and high mortality. It is well recognized that human immunodeficiency virus (HIV)-positive people are more likely to develop EPTB, including TBM, especially if they have severe immunodeficiencies. We aim to highlight the profile and the characteristics of TBM in HIV-infected patients. MATERIAL AND METHODS: We conducted a retrospective clinical study based on hospital medical records of patients diagnosed with HIV/AIDS (acquired immunodeficiency syndrome) and TBM in Northeast Romania, hospitalized at "St. Parascheva" Clinical Hospital of Infectious Diseases of Iasi from 1 January 2010 to 1 December 2022. RESULTS: From a total number of 1692 patients on record in our center, 195 had a HIV-tuberculosis (TB) coinfection, and 19 cases were HIV-TBM coinfected. Six cases were newly HIV-diagnosed late presenters, and thirteen patients' names were already found in the center's records with deficient immunological viral status (median CD4 lymphocyte level 47/mm3). The average age in the study group was 27 years old. The clinical manifestations and cerebrospinal fluid (CSF) variables were typical in most cases, despite the severe immunodepression of the patients. The Thwaites scoring system correctly identified 89.5% of the patients. The median admission period was 18 days; the lethality rate was 31.6%, despite access to ART and anti-TB drugs, and was associated with a more severe immunosuppression. No rifampicin resistance was detected. CONCLUSIONS: TBM appeared in a minority of our HIV cohort and affected severely immunodepressed patients; the clinical and CSF variables had a typical aspect in most cases, and the Thwaites scoring system performed well for this type of patient. The lethality rate was high and was correlated with a more severe immunodepression.

An Overview of the Impact of Bacterial Infections and the Associated Mortality Predictors in Patients with COVID-19 Admitted to a Tertiary Center from Eastern Europe.

1. BACKGROUND: Literature data on bacterial infections and their impact on the mortality rates of COVID-19 patients from Romania are scarce, while worldwide reports are contrasting. 2. MATERIALS AND METHODS: We conducted a unicentric retrospective observational study that included 280 patients with SARS-CoV-2 infection, on whom we performed various microbiological determinations. Based on the administration or not of the antibiotic treatment, we divided the patients into two groups. First, we sought to investigate the rates and predictors of bacterial infections, the causative microbial strains, and the prescribed antibiotic treatment. Secondly, the study aimed to identify the risk factors associated with in-hospital death and evaluate the biomarkers' performance for predicting short-term mortality. 3. RESULTS: Bacterial co-infections or secondary infections were confirmed in 23 (8.2%) patients. Acinetobacter baumannii was the pathogen responsible for most of the confirmed bacterial infections. Almost three quarters of the patients (72.8%) received empiric antibiotic therapy. Multivariate logistic regression has shown leukocytosis and intensive care unit admission as risk factors for bacterial infections and C-reactive protein, together with the length of hospital stay, as mortality predictors. The ROC curves revealed an acceptable performance for the erythrocyte sedimentation rate (AUC: 0.781), and C-reactive protein (AUC: 0.797), but a poor performance for fibrinogen (AUC: 0.664) in predicting fatal events. 4. CONCLUSIONS: This study highlighted the somewhat paradoxical association of a low rate of confirmed infections with a high rate of empiric antibiotic therapy. A thorough assessment of the risk factors for bacterial infections, in addition to the acknowledgment of various mortality predictors, is crucial for identifying high-risk patients, thus allowing a timely therapeutic intervention, with a direct impact on improving patients' prognosis.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Symptoms, Treatment, and Outcomes of COVID-19 Patients Coinfected with Clostridioides difficile: Single-Center Study from NE Romania during the COVID-19 Pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has brought new challenges across medical disciplines, particularly in infectious disease medicine. In Romania, the incidence of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection increased dramatically since March 2020 until March 2022. Antibiotic administration for pulmonary superinfections in COVID-19 intensified and, consequently, increased rates of Clostridioides difficile infection (CDI) were hypothesized. We conducted a single-center, retrospective, observational study on patients from North-Eastern Romania to assess clinical characteristics and outcomes of COVID-19 and Clostridioides difficile (CD) coinfection, and to identify risk factors for CDI in COVID-19 patients. The study enrolled eighty-six CDI and COVID-19 coinfected patients admitted during March 2020-February 2021 (mean age 59.14 years, 53.49% men, 67.44% urban residents) and a group of eighty-six COVID-19 patients. On admission, symptoms were more severe in mono-infected patients, while coinfected patients associated a more intense acute inflammatory syndrome. The main risk factors for severe COVID-19 were smoking, diabetes mellitus, and antibiotic administration. Third generation cephalosporins (55%) and carbapenems (24%) were the main antibiotics used, and carbapenems were significantly associated with severe COVID-19 in patients coinfected with CD during hospitalization. Coinfection resulted in longer hospitalization and poorer outcomes. The extensive use of antibiotics in COVID-19, particularly carbapenems, contributed substantially to CD coinfection.

Multidrug-Resistant (MDR) Urinary Tract Infections Associated with Gut Microbiota in CoV and Non-CoV Patients in a Urological Clinic during the Pandemic: A Single Center Experience.

The aim of the study was to compare the profile of COVID-19 (CoV)-infected patients with non-COVID-19 (non-CoV) patients who presented with a multidrug-resistant urinary tract infection (MDR UTI) associated with gut microbiota, as well as analyze the risk factors for their occurrence, the types of bacteria involved, and their spectrum of sensitivity. METHODS: We conducted a case-control study on patients admitted to the urology clinic of the "Parhon" Teaching Hospital in Iasi, Romania, between March 2020 and August 2022. The study group consisted of 22 CoV patients with MDR urinary infections associated with gut microbiota. For the control group, 66 non-CoV patients who developed MDR urinary infections associated with gut microbiota were selected. Electronic medical records were analyzed to determine demographics, characteristics, and risk factors. The types of urinary tract bacteria involved in the occurrence of MDR urinary infections and their sensitivity spectrum were also analyzed. RESULTS: Patients in both groups studied were over 60 years of age, with no differences in gender, environment of origin, and rate of comorbidities. Patients in the CoV group had a higher percentage of urosepsis (54.5% versus 21.2%, p < 0.05) and more hospitalization days (9.27 versus 6.09, p < 0.05). Regarding risk factors, the two groups had similar percentages of previous urologic interventions (95.45% versus 96.97%, p > 0.05), antibiotic therapy (77.3% versus 87.9%, p > 0.05), and the presence of permanent urinary catheters (77.27% versus 84.85%, p > 0.05). Escherichia coli (31.8% versus 42.4%, p > 0.05), Klebsiella spp. (22.7% versus 34.8%, p > 0.05), and Pseudomonas aeruginosa (27.3% versus 9.1%, p > 0.05) were the most common urinary tract bacteria found in the etiology of MDR urinary infections in CoV and non-CoV patients. A high percentage of the involved MDR urinary tract bacteria were resistant to quinolones (71.4-76.2% versus 80.3-82%, p > 0.05) and cephalosporins (61.9-81% versus 63.9-83.6%, p > 0.05), both in CoV and non-CoV patients. CONCLUSIONS: Patients with urological interventions who remain on indwelling urinary catheters are at an increased risk of developing MDR urinary infections associated with gut microbiota resistant to quinolones and cephalosporins. Patients with MDR UTIs who have CoV-associated symptoms seem to have a higher rate of urosepsis and a longer hospitalization length.

Heparin-Binding Protein (HBP), Neutrophil Gelatinase-Associated Lipocalin (NGAL) and S100 Calcium-Binding Protein B (S100B) Can Confirm Bacterial Meningitis and Inform Adequate Antibiotic Treatment.

The empirical administration of antibiotics for suspected bacterial meningitis denotes a poor bacterial stewardship. In this context, the use of biomarkers can distinguish between bacterial and viral infections before deciding treatment. Our study assesses how levels of heparin-binding protein (HBP), neutrophil gelatinase-associated lipocalin (NGAL), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) and in blood can promptly confirm bacterial etiology and the need for antibiotic treatment. The CSF and blood levels of HBP, NGAL, S100B, and NSE of 81 patients with meningitis were measured and analyzed comparatively. Statistical sensitivity, specificity, and positive and negative predictive values were evaluated. CSF levels of HBP and NGAL and the blood level of S100B in the bacterial meningitis group were significantly higher (p < 0.05). The area under curve (AUC) for predicting bacterial meningitis was excellent for the CSF level of HBP (0.808 with 93.54% sensitivity and 80.64% specificity), good for the CSF level of NGAL (0.685 with 75.00% sensitivity and 65.62% specificity), and good for the blood level of S100B (0.652 with 65.90% sensitivity and 57.14% specificity). CSF levels of HBP and NGAL, as well as the blood level of S100B, could help discriminate between bacterial and viral meningitis before considering antibiotic treatment.

A Real Pandora's Box in Pandemic Times: A Narrative Review on the Acute Cardiac Injury Due to COVID-19.

The intricate relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the cardiovascular system is an extensively studied pandemic topic, as there is an ever-increasing amount of evidence that reports a high prevalence of acute cardiac injury in the context of viral infection. In patients with Coronavirus disease 2019, COVID-19, a significant increase in serum levels of cardiac troponin or other various biomarkers was observed, suggesting acute cardiac injury, thus predicting both a severe course of the disease and a poor outcome. Pathogenesis of acute cardiac injury is not yet completely elucidated, though several mechanisms are allegedly involved, such as a direct cardiomyocyte injury, oxygen supply-demand inequity caused by hypoxia, several active myocardial depressant factors during sepsis, and endothelial dysfunction due to the hyperinflammatory status. Moreover, the increased levels of plasma cytokines and catecholamines and a significantly enhanced prothrombotic environment may lead to the destabilization and rupture of atheroma plaques, subsequently triggering an acute coronary syndrome. In the present review, we focus on describing the epidemiology, pathogenesis, and role of biomarkers in the diagnosis and prognosis of patients with acute cardiac injury in the setting of the COVID-19 pandemic. We also explore some novel therapeutic strategies involving immunomodulatory therapy, as well as their role in preventing a severe form of the disease, with both the short-term outcome and the long-term cardiovascular sequelae being equally important in patients with SARS-CoV-2 induced acute cardiac injury.

What Doesn't Kill Them Makes Them Stronger: The Impact of the Resistance Patterns of Urinary Enterobacterales Isolates in Patients from a Tertiary Hospital in Eastern Europe.

(1) Background: The evolution of bacterial resistance to antibiotics is one of the factors that make infectious pathology an extremely dynamic field, also inducing a significant burden on public health systems; therefore, continuous updates on the bacterial resistance to antibiotics and their particular regional patterns is crucial for the adequate approach of various infectious diseases. (2) Methods: We retrospectively analyzed 354 patients with Enterobacterales urinary tract infections (UTIs), determined their antibiotic resistance pattern, thus aiming to correlate them with the outcome and other specific markers of poor prognosis. (3) Results: The most frequent causative agent was Escherichia coli, representing 64.6% of all UTIs. We identified 154 patients resistant to multiple antibiotic classes, of which 126 were multidrug-resistant (MDR), 17 were extensive drug-resistant (XDR) and 11 were pandrug-resistant (PDR). Moreover, 25 isolates were resistant to carbapenems (CRE), 25 were difficult-to-treat (DTR), and 84 were extended-spectrum cephalosporin-resistant (ESC), with only 95 isolates susceptible to all tested antibiotics. Mortality ranged from 1% for UTIs caused by isolates susceptible to all tested antibiotics, to 24% for the ones caused by DTR or CRE isolates. Other significant risk factors associated with mortality were: prolonged hospital stay (p = 0.0001), Charlson comorbidity index ≥ 3 (p = 0.02), urinary catheterization (p = 0.001), associated respiratory pathologies (p = 0.004), obesity (p = 0.047), a history of previous hospitalizations (p = 0.007), inappropriate empiric antibiotic regimen (p = 0.001), or hyper inflammatory status (p = 0.006). Basically, we observed that a multiple regression model comprising urinary catheterization, inappropriate empiric anti-biotherapy, obesity, and respiratory comorbidities exhibits the best correlation with mortality rate in patients with UTI (R = 0.347, R2 = 0.12). (4) Conclusions: By focusing on the novel resistance patterns, our study provides complementary evidence concerning the resistance profiles found in an Eastern European region, as well as their prognostic implications in patients with UTI.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant. Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo). Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant. Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT).

Optimization of triplex real time PCR for detecting Staphylococcus aureus mecA, pvl and nuc genes.

Multiplex polymerase chain reaction (PCR) allows simultaneous detection of two or more genes, using the same reaction conditions, and so it is possible the rapid detection of methicillin resistant Staphylococcus aureus strains (MRSA) in clinical specimens. This study aimed to implement, for the first time in our laboratory, a triplex real time PCR (RT-PCR) technique for detection of genes encoding resistance to oxacillin and synthesis of Panton Valentine leukocidin (pvl), a pathogenicity factor characteristic for community acquired strains (CA-MRSA). The application of this method will permit the epidemiological surveillance of circulating strains and early application of prevention measures.