Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

Management of Clostridioides difficile infection: an Italian Delphi consensus.

BACKGROUND: Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs. OBJECTIVES: To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin. METHODS: An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use. RESULTS: Consensus was reached on 21 of the 25 statements addressing the management of CDI. CONCLUSIONS: Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy.

Emerging Microorganisms and Infectious Diseases: One Health Approach for Health Shared Vision.

Emerging infectious diseases (EIDs) are newly emerging and reemerging infectious diseases. The National Institute of Allergy and Infectious Diseases identifies the following as emerging infectious diseases: SARS, MERS, COVID-19, influenza, fungal diseases, plague, schistosomiasis, smallpox, tick-borne diseases, and West Nile fever. The factors that should be taken into consideration are the genetic adaptation of microbial agents and the characteristics of the human host or environment. The new approach to identifying new possible pathogens will have to go through the One Health approach and omics integration data, which are capable of identifying high-priority microorganisms in a short period of time. New bioinformatics technologies enable global integration and sharing of surveillance data for rapid public health decision-making to detect and prevent epidemics and pandemics, ensuring timely response and effective prevention measures. Machine learning tools are being more frequently utilized in the realm of infectious diseases to predict sepsis in patients, diagnose infectious diseases early, and forecast the effectiveness of treatment or the appropriate choice of antibiotic regimen based on clinical data. We will discuss emerging microorganisms, omics techniques applied to infectious diseases, new computational solutions to evaluate biomarkers, and innovative tools that are useful for integrating omics data and electronic medical records data for the clinical management of emerging infectious diseases.

Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

On the SARS-CoV-2 Variants.

The evolutionary dynamics of viruses, particularly exemplified by SARS-CoV-2 during the ongoing COVID-19 pandemic, underscore the intricate interplay between genetics, host adaptation, and viral spread. This paper delves into the genetic evolution of SARS-CoV-2, emphasizing the implications of viral variants on global health. Initially emerging from the Wuhan-Hu-1 lineage, SARS-CoV-2 rapidly diversified into numerous variants, each characterized by distinct mutations in the spike protein and other genomic regions. Notable variants such as B.1.1.7 (α), B.1.351 (ß), P.1 (γ), B.1.617.2 (δ), and the Omicron variant have garnered significant attention due to their heightened transmissibility and immune evasion capabilities. In particular, the Omicron variant has presented a myriad of subvariants, raising concerns about its potential impact on public health. Despite the emergence of numerous variants, the vast majority have exhibited limited expansion capabilities and have not posed significant threats akin to early pandemic strains. Continued genomic surveillance is imperative to identify emerging variants of concern promptly. While genetic adaptation is intrinsic to viral evolution, effective public health responses must be grounded in empirical evidence to navigate the evolving landscape of the pandemic with resilience and precision.

A One Health Platform for Future Epidemic Preparedness.

Here, we introduce the EpiConnect Intelligence Platform (ECIP), a platform facilitating rapid, transparent data sharing and analysis to support researchers and public health officials in Europe, with a focus on Italy. ECIP provides reliable, concise, machine-readable data to aid in epidemiological understanding, standardize case characteristics, and estimate key parameters. The platform adheres to FAIR (findable, accessible, interoperable, reusable) principles, offering easily accessible and downloadable datasets for researchers' endeavors. Future enhancements include involving national public health authorities, expanding data streams, and fostering collaboration between experts and users for improved epidemic risk monitoring. Shared standards among diverse surveillance systems are advocated to achieve common strategic goals, emphasizing the need for forward-looking policies to empower professionals to analyze disease dynamics in the context of evolving health crises. The recent emergencies underscore the importance of collective efforts towards shared strategic goals, highlighting the necessity for coordinated action to address mutual concerns affecting everyone's lives.

The impact of armed conflict on the development and global spread of antibiotic resistance: a systematic review.

BACKGROUND: Scant data are available on the link between armed conflicts and the development and spread of antimicrobial resistance. OBJECTIVES: We performed a systematic review with the aim to summarize the available data on the prevalence and features of antibiotic resistance and the causes of antibiotic resistance development during armed conflicts in the 21st century. METHODS: Data sources: PubMed and SCOPUS databases were searched from 1 January 2000 to 30 November 2023. STUDY ELIGIBILITY CRITERIA: Original articles reporting data on armed conflicts and antimicrobial resistance were included in this systematic review. No attempt was made to obtain information from unpublished studies. No language restriction was applied. Methods of data synthesis: Both quantitative and qualitative information were summarized by means of textual descriptions. PARTICIPANTS: Patients or soldiers deployed in armed conflict zones. TESTS: culture-dependent antibiotic sensitivity testing or molecular detection of the genetic determinants of antibiotic resistance after a confirmed diagnosis of bacterial infection. Assessment of risk of bias: To evaluate the quality of the included studies, we adapted the tool recommended by the Joanna Briggs Institute. RESULTS: Thirty-four studies were identified, published between November 2004 and November 2023. The quality of included studies was high and medium in 47% and 53% of the studies, respectively. The included studies reported high infection and colonization rates of multidrug-resistant bacteria. Studies performed during the Eastern Ukraine conflict reported high rates of New Delhi metallo-ß-lactamase producers. DISCUSSION: Our findings confirm that wars lead to a large pool of multidrug-resistant infections that could potentially spread. Infection control in healthcare facilities in conflict zones and proper antimicrobial stewardship are crucial.

Tackling Acinetobacter baumannii.

Globally, multidrug-resistant (MDR) bacteria represent a menace to public health [...].

Clostridioides difficile and Enterococci's Interplay in the Human Gut: Bacterial Alliance or Competition? A Systematic Literature Review.

Clostridioides difficile and Enterococcus spp. are two common bacterial pathogens populating the human microbiota. We possess scant data on how Clostridioides difficile interacts with Enterococcus spp. in the gut microbiota in subjects colonized with Clostridioides difficile or during a Clostridioides difficile infection. We carried out a systematic review of studies on Enterococcus spp. and Clostridioides difficile's interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI development. Studies on Enterococcus spp. and Clostridioides difficile's interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI were searched using the search terms "clostridium", "clostridioides", "difficile" and "enterococcus" on the MEDLINE and SCOPUS databases. PubMed was searched until 1 May 2023. An English language restriction was applied. The risk of bias in the included studies was not assessed. Quantitative and qualitative information was summarized in textual descriptions. Fourteen studies, published from August 2012 to November 2022, on Clostridioides difficile and Enterococcus spp.'s interaction in the gut microbiota met the inclusion criteria. The studies included in our systematic review reported evidence that the Enterococcus spp. intestinal burden represents a risk factor for the occurrence of CDI. There is supporting evidence that Enterococcus spp. play a role in CDI development and clinical outcomes.

The Medical Community's Role in Communication Strategies during Health Crises-Perspective from European Union of Medical Specialists (UEMS).

The COVID-19 pandemic was complicated by the spread of false information leading to what became widely called an "infodemic". The present opinion paper was written by an ad hoc international team united under the European Union of Medical Specialists (UEMS) umbrella and reflects the organizations' effort to contribute to the resolution of these issues, by highlighting and reflecting on them and by suggesting the medical community's necessary activities resulting in the formulation of effective future communication strategies. The importance of physicians' and other health workers' role and mission as educators and leaders in communities in critical situations should be reassessed and upgraded. We need to equip future doctors with strong and sustainable leadership and communication skills through relevant undergraduate and postgraduate education programs, in order that compliance with preventive medical advice is increased. To avoid possible politically and otherwise biased communication in health crises of the future, European nations should establish independent advisory bodies providing evidence-based advice and participate in communication campaigns. Medical and other health professional organizations should build organizational and personal capacities of their members to enable them to reliably inform and adequately educate governments, populations, civic society, employers' and employees' organizations, schools and universities, and other stakeholders.

SARS-CoV CH.1.1 Variant: Genomic and Structural Insight.

In early February 2023, the Omicron subvariant XBB.1.5, also known as "Kraken", accounted for more than 44% of new COVID-19 cases worldwide, whereas a relatively new Omicron subvariant named CH.1.1, deemed "Orthrus", accounted for less than 6% of new COVID-19 cases during the subsequent weeks. This emerging variant carries a mutation, L452R, previously observed in the highly pathogenic Delta and the highly transmissible BA.4 and BA.5 variants, necessitating a shift to active surveillance to assure adequate preparedness for likely future epidemic peaks. We provide a preliminary understanding of the global distribution of this emerging SARS-CoV-2 variant by combining genomic data with structural molecular modeling. In addition, we shield light on the number of specific point mutations in this lineage that may have functional significance, thereby increasing the risk of disease severity, vaccine resistance, and increased transmission. This variant shared about 73% of the mutations with Omicron-like strains. Our homology modeling analysis revealed that CH.1.1 may have a weakened interaction with ACE2 and that its electrostatic potential surface appears to be more positive than that of the reference ancestral virus. Finally, our phylogenetic analysis revealed that this likely-emerging variant was already cryptically circulating in European countries prior to its first detection, highlighting the importance of having access to whole genome sequences for detecting and controlling emerging viral strains.

Khosta: A Genetic and Structural Point of View of the Forgotten Virus.

Bats are well-known to be natural reservoirs of various zoonotic coronaviruses, which have caused outbreaks of severe acute respiratory syndrome (SARS) and the COVID-19 pandemic in 2002 and 2019, respectively. In late 2020, two new Sarbecoviruses were found in Russia, isolated in Rhinolophus bats, i.e., Khosta-1 in R. ferrumequinum and Khosta-2 in R. hipposideros. The potential danger associated with these new species of Sarbecovirus is that Khosta-2 has been found to interact with the same entry receptor as SARS-CoV-2. Our multidisciplinary approach in this study demonstrates that Khosta-1 and -2 currently appear to be not dangerous with low risk of spillover, as confirmed by prevalence data and by phylogenomic reconstruction. In addition, the interaction between Khosta-1 and -2 with ACE2 appears weak, and furin cleavage sites are absent. While the possibility of a spillover event cannot be entirely excluded, it is currently highly unlikely. This research further emphasizes the importance of assessing the zoonotic potential of widely distributed batborne CoV in order to monitor changes in genomic composition of viruses and prevent spillover events (if any).

Meningococcal Conjunctivitis in a 54-Year-Old Man: Case Report and Review of the Literature.

Neisseria meningitidis represents an uncommon pathogen of acute bacterial conjunctivitis. In this brief report, we describe a case of meningococcal conjunctivitis in an immunocompetent adult male, with a review of the literature. The patient went to the outpatient ophthalmology clinic complaining of severe ocular discomfort, burning, and redness for more than 2 weeks and, at slit lamp examination, he was diagnosed with a mild conjunctivitis. Microbiology cultures of ocular swabs revealed the growth of colonies, as pure culture, identified as N. meningitidis of serogroup B. A diagnosis of primary meningococcal conjunctivitis was made and treatment of patient with intramuscular injections of ceftriaxone in addition to topical moxifloxacin eye drops for 2 weeks led to clinical improvement and, finally, to a complete recovery, in accordance with microbiological findings. Ophthalmologists must be aware of the possibility of primary meningococcal conjunctivitis cases, even uncommon, and the need to treat with systemic antibiotics and their close contacts with adequate antibiotic chemoprophylaxis.

Efficacy of bezlotoxumab in preventing the recurrence of Clostridioides difficile infection: an Italian multicenter cohort study.

OBJECTIVES: Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. METHODS: A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). RESULTS: rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). CONCLUSION: Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors.

Neutralizing Antibodies against SARS-CoV-2 Beta and Omicron Variants Inhibition Comparison after BNT162b2 mRNA Booster Doses with a New PETIA sVNT Assay.

BACKGROUND: Monitoring antibody response following SARS-CoV-2 vaccination is strategic, and neutralizing antibodies represent the gold standard. The neutralizing response to Beta and Omicron VOCs was evaluated versus the gold standard by a new commercial automated assay. METHODS: Serum samples from 100 healthcare workers from the Fondazione Policlinico Universitario Campus Biomedico and the Pescara Hospital were collected. IgG levels were determined by chemiluminescent immunoassay (Abbott Laboratories, Wiesbaden, Germany) and serum neutralization assay as the gold standard. Moreover, a new commercial immunoassay, the PETIA test Nab (SGM, Rome, Italy), was used for neutralization evaluation. Statistical analysis was performed with R software, version 3.6.0. RESULTS: Anti-SARS-CoV-2 IgG titers decayed during the first ninety days after the vaccine second dose. The following booster dose significantly (p < 0.001) increased IgG levels. A correlation between IgG expression and neutralizing activity modulation was found with a significant increase after the second and the third booster dose (p < 0.05. Compared to the Beta variant of the virus, the Omicron VOC was associated with a significantly larger quantity of IgG antibodies needed to achieve the same degree of neutralization. The best Nab test cutoff for high neutralization titer (≥1:80) was set for both Beta and Omicron variants. CONCLUSION: This study correlates vaccine-induced IgG expression and neutralizing activity using a new PETIA assay, suggesting its usefulness for SARS-CoV2 infection management.