Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Vaccine development and technology for SARS-CoV-2: Current insight.

Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer-BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long-term effects and to assess the vaccine safety and efficacy in the general population.

Infection Control in the Era of COVID-19: A Narrative Review.

COVID-19 quickly became a pandemic causing millions of infections and mortalities. It required real-time adjustments to healthcare systems and infection prevention and control (IPC) measures to limit the spread and protect healthcare providers and hospitalized patients. IPC guidelines were adopted and developed based on experience gained during the MERS-CoV and SARS-CoV outbreaks. The aim of this narrative review is to summarize current evidence on IPC in healthcare settings and patients with COVID-19 to prevent nosocomial infections during the actual pandemic. A search was run on PubMed using the terms ('COVID-19' [Mesh]) AND ('Infection Control' [Mesh]) between 2019 and 2021. We identified 86 studies that were in accordance with our aim and summarized them under certain themes as they related to COVID-19 infection control measures. All the guidelines recommend early diagnosis and rapid isolation of COVID-19 patients. The necessary precautions should be taken comprising the whole process, starting with an infectious disease plan, administrative and engineering controls, triage, and PPE training. Guidelines should target modes of transmission, droplet, aerosol, and oral-fecal, while recommending control precautions. Healthcare facilities must promptly implement a multidisciplinary defense system to combat the outbreak.

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality.

BACKGROUND: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials. METHODS: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints). RESULTS: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; P = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95; P = .03). CONCLUSIONS: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.

COVID-19 pneumonia: do not leave the corticosteroids behind!

The host inflammatory response is critical in the progression of lung injuries in patients with SARS-CoV-2. Corticosteroids (CS) have been widely used as immunomodulating agents, but the right timing, dosage and type of molecule are unknown. In fact, the early use of CS could facilitate the viral replication but late administration may not prevent the alveolar damage. Nevertheless, a short administration of high doses of CS in the early stage of the inflammatory phase resulted in favorable outcomes. Noteworthy, some inhaled CS inhibited in vitro the viral replication of SARS-CoV-2. We aimed to define the place in therapy for CS in COVID-19 infection describing the features of patients who may benefit from their administration.

Antecedent Administration of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Antagonists and Survival After Hospitalization for COVID-19 Syndrome.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme-2 (ACE-2) receptor to enter human cells. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE-2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID-19). Methods and Results We used the Coracle registry, which contains data of patients hospitalized with COVID-19 in 4 regions of Italy, and restricted analyses to those ≥50 years of age. The primary outcome was in-hospital mortality. Among these 781 patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. While neither sex nor smoking status differed by user groups, patients on ACEI/ARB were older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. The overall mortality rate was 15.1% (118/781) and increased with age (PTrend<0.0001). The crude odds ratios (ORs) for death for ACEI users and ARB users were 0.98, 95% CI, 0.60-1.60, P=0.9333, and 1.13, 95% CI, 0.67-1.91, P=0.6385, respectively. After adjusting for age, hypertension, diabetes mellitus, and congestive heart failure, antecedent ACEI administration was associated with reduced mortality (OR, 0.55; 95% CI, 0.31-0.98, P=0.0436); a similar, but weaker trend was observed for ARB administration (OR, 0.58; 95% CI, 0.32-1.07, P=0.0796). Conclusions In those aged ≥50 years hospitalized with COVID-19, antecedent use of ACEI was independently associated with reduced risk of inpatient death. Our findings suggest a protective role of renin-angiotensin-aldosterone system inhibition in patients with high cardiovascular risk affected by COVID-19.

Mortality Risk Assessment Using CHA(2)DS(2)-VASc Scores in Patients Hospitalized With Coronavirus Disease 2019 Infection.

Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864 (82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167 (19.3%) died, 123 (14.2%) received invasive ventilation, and 249 (28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2 to 3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p <0.001) and the composite end point (18.6%, 31.9%, 43.5%, respectively; p <0.001). The odds ratios for mortality and the composite end point for T2 patients versus T1 CHA(2)DS(2)-VASc score were 3.62 (95% CI:2.29 to 5.73,p <0.001) and 2.04 (95% CI:1.42 to 2.93, p <0.001), respectively. Similarly, the odds ratios for mortality and the composite end point for T3 patients versus T1 were 5.65 (95% CI:3.54 to 9.01, p <0.001) and 3.36 (95% CI:2.30 to 4.90,p <0.001), respectively. In conclusion, among Italian patients hospitalized for COVID-19 infection, the CHA(2)DS(2)-VASc risk score for thromboembolic events enhanced the ability to achieve risk stratification for complications and death.

Microbiome in the setting of burn patients: implications for infections and clinical outcomes.

Burn damage can lead to a state of immune dysregulation that facilitates the development of infections in patients. The most deleterious impact of this dysfunction is the loss of the skin's natural protective barrier. Furthermore, the risk of infection is exacerbated by protracted hospitalization, urinary catheters, endotracheal intubation, inhalation injury, arterial lines and central venous access, among other mainstays of burn care. Currently, infections comprise the leading cause of mortality after major burn injuries, which highlights the improvements observed over the last 50 years in the care provided to burn victims. The need to implement the empirical selection of antibiotic therapy to treat multidrug-resistant bacteria may concomitantly lead to an overall pervasiveness of difficult-to-treat pathogens in burn centres, as well as the propagation of antimicrobial resistance and the ultimate dysregulation of a healthy microbiome. While preliminary studies are examining the variability and evolution of human and mice microbiota, both during the early and late phase burn injury, one must consider that abnormal microbiome conditions could influence the systemic inflammatory response. A better understanding of the changes in the post-burn microbiome might be useful to interpret the provenance and subsequent development of infections, as well as to come up with inferences on the prognosis of burn patients. This review aims to summarise the current findings describing the microbiological changes in different organs and systems of burn patients and how these alterations affect the risks of infections, complications, and, ultimately, healing.

Visceral leishmaniasis in a patient with active HBV/HDV co-infection.

Visceral leishmaniasis (VL) is an endemic infection in different regions of Italy and Europe caused by protozoan parasites of the genus Leishmania, transmitted to humans through sandflies bites. Reactivation after Solid Organ Transplantation was reported and could be a risk of organ rejection. A 48 years old woman was admitted to our hospital, complaining about low-grade fever, loss of weight and new onset pancytopenia in a known cirrhosis due to active HBV/HDV co-infection. Clinical, microbiological and anatomo-pathological elements were pivotal to define the diagnosis of VL and started an appropriate anti-infective treatment. After that she underwent liver transplantation and a therapy for VL was set. No signs of reactivation were reported in the 14 months of follow-up.

Carbapenem-sparing strategy: carbapenemase, treatment, and stewardship.

PURPOSE OF REVIEW: describing the current role of carbapenems and carbapenem-sparing strategies in the setting of antimicrobial stewardship programs. RECENT FINDINGS: sparing carbapenems with other drugs appears to be an interesting perspective for a variety of reasons in the current context of the multidrug-resistant (MDR) pandemic. Specific algorithms should also be precisely investigated to define better how to spare carbapenems within empiric and targeted regimens, with combination treatment or monotherapies, aiming at the best use of the new drugs and improving de-escalation as soon as possible for most of the patients. SUMMARY: stewardship programs may be useful in reducing probable misuse and overuse of antibiotics, which has probably contributed to the emergence of carbapenem-resistant bacteria worldwide. The proposal of carbapenem-sparing strategies has then generated substantial scientific debate and, overall, the concept of sparing these drugs is well advocated together with judicious use of novel drugs, appropriate measures of infection control and prevention as well as in stewardship programs to curb the spread of MDR and XDR-strains in healthcare facilities.

Skin and soft tissue infections after breast surgery.

PURPOSE OF REVIEW: Breast surgery is considered a clean surgical procedure; nevertheless, infection rates are often higher than those reported after other similarly considered clean surgeries (e.g., thyroid, hernia). Acute bacterial skin and soft tissue infections, mostly surgical site infections and implant-associated infections are commonest events that could complicate postoperative care. RECENT FINDINGS: Risk of infection is closely related to surgery procedure itself and patients host factors. Gram-positive bacteria with pattern of antimicrobial resistance are increasingly isolated and before today less frequent causes such as gram negative and mycobacteria infections. Impact of postoperative complications is underestimated and lacking an appropriate care and education for local and systemic management. SUMMARY: We report the current evidence on the management of infections after breast surgery. New drugs options for methicillin-resistant Staphylococcus aureus and other gram positive should have a place in this setting. Stewardship activities aiming at reducing infections risks with the correct considerations of host, microbiological and surgical risk factors.

Choosing wisely: what is the actual role of antimicrobial stewardship in Intensive Care Units?

More than two-thirds of critically ill patients receive an antimicrobial therapy with a percentage between 30% and 50% of all prescribed antibiotics reported to be unnecessary, inappropriate or misused. Since inappropriate prescription of antibiotic drugs concurs to dissemination of the multidrug resistant organisms, a reasoned antibiotics use is crucial especially in Intensive Care Unit (ICU), where up to 60% of the admitted patients develops an infection during their ICU stay. Even if the concept of antimicrobial stewardship (AS) has been clearly described as a series of coordinated interventions designed to improve antimicrobial agents use, few studies are reporting about its effectiveness to improve outcomes, reduce adverse events and costs and decrease resistance rate spread. Moreover, although it is recognized that AS programs are particularly indicated in the critical setting due to the huge number of antimicrobial drugs used, the optimal characteristics of these interventions and the best system to evaluate their effectiveness are still unclear. Specific interventions, designed tacking into account the peculiarities of the ICU setting, are hence necessary to set-up an "in-ICU-stewardship," including prompt identification of infected patients, selection of appropriate empiric treatments, optimization of dosing and route of administration, improvement of diagnostic techniques, early de-escalation to achieve shorter duration and avoid unnecessary therapies. The present narrative review summarizes the "state of art" about AS programmes and discusses the effects of the interventions possibly applied in ICU setting to optimize the patient's treatment, reduce the micro-organisms resistance and contain the hospital resources utilization.

Developing definitions for invasive fungal diseases in critically ill adult patients in intensive care units. Protocol of the FUNgal infections Definitions in ICU patients (FUNDICU) project.

BACKGROUND: The reliability of diagnostic criteria for invasive fungal diseases (IFD) developed for severely immunocompromised patients is questionable in critically ill adult patients in intensive care units (ICU). OBJECTIVES: To develop a standard set of definitions for IFD in critically ill adult patients in ICU. METHODS: Based on a systematic literature review, a list of potential definitions to be applied to ICU patients will be developed by the ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) and the ESCMID Fungal Infection Study Group (EFISG) chairpersons. The proposed definitions will be evaluated by a panel of 30 experts using the RAND/UCLA appropriateness methods. The panel will rank each of the proposed definitions on a 1-9 scale trough a dedicated questionnaire, in two rounds: one remote and one face-to-face. Based on their median rank and the level of agreement across panel members, selected definitions will be organised in a main consensus document and in an executive summary. The executive summary will be made available online for public comments. CONCLUSIONS: The present consensus project will seek to provide standard definitions for IFD in critically ill adult patients in ICU, with the ultimate aims of improving their clinical outcome and facilitating the comparison and generalizability of research findings.

First case of E. meningoseptica in Italy in a patient with necrotic hemorrhagic pancreatitis.

INTRODUCTION: Elizabethkingia meningoseptica can frequently colonizes the respiratory tract, but its pathogenetic role and its clinical significance are frequently questioned. However, recent data reported E. meningoseptica outbreaks in particular settings, as hospitalized patients. CASE REPORT: We report here the first case of Elizabethkingia meningoseptica infection in Italy in a patient with necrotic-hemorrhagic pancreatitis. E. meningoseptica was isolated from respiratory tract and treated with combination antibiotic therapy. CONCLUSION: We discuss here the role of isolation of E. meningoseptica in hospitalized patients as a sign of patient's frailty.