Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Update on the Pharmacological Actions of Enoxaparin in Nonsurgical Patients.

Low-molecular-weight heparins are a class of drugs derived from the enzymatic depolymerization of unfractionated heparin that includes enoxaparin. Several studies have been performed on enoxaparin in recent years, in particular for the prevention and treatment of venous thromboembolism and for the treatment of acute coronary syndrome. Furthermore, the use of enoxaparin has been extended to other clinical situations that require antithrombotic pharmacological prevention, such as hemodialysis and recurrent abortion. In this review, we report the main clinical experiences of using enoxaparin in the prevention of VTE in nonsurgical patients.

Invasive aspergillosis in solid organ transplant patients: diagnosis, prophylaxis, treatment, and assessment of response.

BACKGROUND: Invasive aspergillosis (IA) is a rare complication in solid organ transplant (SOT) recipients. Although IA has significant implications on graft and patient survival, data on diagnosis and management of this infection in SOT recipients are still limited. METHODS: Discussion of current practices and limitations in the diagnosis, prophylaxis, and treatment of IA and proposal of means of assessing treatment response in SOT recipients. RESULTS: Liver, lung, heart or kidney transplant recipients have common as well as different risk factors to the development of IA, thus each category needs a separate evaluation. Diagnosis of IA in SOT recipients requires a high degree of awareness, because established diagnostic tools may not provide the same sensitivity and specificity observed in the neutropenic population. IA treatment relies primarily on mold-active triazoles, but potential interactions with immunosuppressants and other concomitant therapies need special attention. CONCLUSIONS: Criteria to assess response have not been sufficiently evaluated in the SOT population and CT lesion dynamics, and serologic markers may be influenced by the underlying disease and type and severity of immunosuppression. There is a need for well-orchestrated efforts to study IA diagnosis and management in SOT recipients and to develop comprehensive guidelines for this population.

Impact of direct acting antivirals (DAAs) on cardiovascular events in HCV cohort with pre-diabetes.

BACKGROUND AND AIMS: Beyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort. METHODS AND RESULTS: In this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19-34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148-1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44-53.95; p = 0.016). CONCLUSIONS: HCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors.

Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study.

BACKGROUND: An unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals. METHODS: According to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up. RESULTS: Nine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p < 0.0001, OR: 5.686, 95% CI 2.455-13.169). CONCLUSIONS: Our data suggest that early HCC occurrence appears more frequently related to Sofosbuvir-based therapy without Ribavirin which, indeed, seems to play a protective role on HCC onset. Therefore, a careful follow-up should be mandatory, especially in those regimens including Sofosbuvir without Ribavirin.

Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response.

PURPOSE: Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. METHODS: Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients RESULTS: Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. CONCLUSIONS: The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined.

Role of Liver Stiffness Measurement in Predicting HCC Occurrence in Direct-Acting Antivirals Setting: A Real-Life Experience.

PURPOSE: The aim of this study was to evaluate the relationship between the liver stiffness measurement and the risk of developing hepatocellular carcinoma (HCC) in HCV cirrhotic patients undergoing new direct-acting antivirals. METHODS: From April 2015 to April 2017, all consecutive HCV cirrhotic patients treated by direct-acting antivirals were enrolled. A liver stiffness measurement was computed at baseline, and an ultrasound evaluation was provided for all patients at baseline and every 6 months until 1 year after the stopping of the antiviral therapy. The diagnosis of HCC was performed according to international guidelines by imaging technique workup. RESULTS: Two hundred and fifty-eight HCV patients with a diagnosis of cirrhosis were identified. The median liver stiffness was 25.5 kPa. Thirty-five patients developed HCC. Patients were divided into three groups, based on their liver stiffness: < 20 kPa (n = 72), between 20 and 30 kPa (n = 92) and > 30 kPa (n = 94). Compared to the < 20 kPa and 20-30 kPa groups, the > 30 kPa group showed a statistically significant increased risk of HCC (p = 0.019; HR 0.329; 95% CI 0.131-0.830). A ROC curve analysis to assess the overall predictive performance of liver stiffness measurement on the HCC risk was performed. The results allow us to identify a cutoff value of liver stiffness measurement equal to 27.8 kPa, which guarantees the highest sensitivity and specificity (respectively, 72% and 65%). CONCLUSIONS: The data underline that the baseline liver stiffness measurement and ultrasound surveillance is a valuable tool for assessing the risk of HCC in cirrhotic patients undergoing the direct-acting antivirals treatment.

A case of a huge aortic pseudo-aneurysm following aortic bioprosthetic endocarditis: the key role of 3D echocardiography.

Infective endocarditis (IE) is a life-threatening condition with high morbidity and mortality rates, making early diagnosis and intervention crucial. This report details the case of a 47-year-old male with a history of mechanical prosthetic aortic valve replacement, presenting with pyrexia and diagnosed with aortic bioprosthetic endocarditis leading to a massive aortic pseudoaneurysm. This shows that 3D transesophageal echocardiography is much more useful than regular 2D imaging for finding problems with IE, which makes surgical planning and intervention more precise.

Bacterial Porins and Their Procoagulant Role: Implication in the Pathophysiology of Several Thrombotic Complications during Sepsis.

The association between sepsis and thrombotic complications is still not well known. Different mechanisms have been shown to be involved in the sepsis-induced prothrombotic state, but clinical scenarios may differ. In this review, we have summarized the role that bacterial products such as porins and toxins can have in the induction of the prothrombotic state during sepsis and the interaction that they can have with each other. Furthermore, the above-mentioned mechanisms might be involved in the pattern of the clinical presentation of thrombotic events during bacterial sepsis, which would secondarily explain the association between sepsis and venous thromboembolism, the association between sepsis and disseminated intravascular coagulation, and the association between sepsis and microangiopathic venous thromboembolism.

Three-dimensional Transesophageal Echocardiography in Infective Endocarditis: What Does It Add?

Infective endocarditis (IE) diagnosis is based on a clinical suspicion supported by consistent microbiological and instrumental data. Evidence of involvement of cardiac valves (native or prosthetic) or prosthetic intracardiac material is a major diagnostic criterion of IE. Transthoracic echocardiography (TTE) is the initial technique of choice for the diagnosis while transesophageal echocardiography (TEE) is recommended in patients with an inconclusive or negative TTE, in patients with high suspicion of IE, as well as in patients with a positive TTE, in order to document local complications. Repeating TTE and/or TEE should be considered during follow-up of uncomplicated IE, in order to detect new silent complications and monitor vegetation size. In the setting of IE, the role of three-dimensional (3D) TEE is increasing; in fact, this technique has also been shown to be useful for the diagnosis of IE and its complications as it allows to obtain infinite planes and volumetric reconstructions. In this review, we will describe the usefulness of 3D-TEE and its added value in the management of IE.

Impact of ESKAPE Pathogens on Bacteremia: A Three-Year Surveillance Study at a Major Hospital in Southern Italy.

BACKGROUND/OBJECTIVES: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. METHODS: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ''Ruggi D'Aragona'' Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. RESULTS: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. CONCLUSIONS: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.

Late Hepatocellular Carcinoma Occurrence in Patients Achieving Sustained Virological Response After Direct-Acting Antiviral Therapy: A Matter of Follow-Up or Something Else?

Background: Despite achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs), an unexpected increase in the occurrence rate of hepatocellular carcinoma (HCC) has been observed among HCV-treated patients. This study aims to assess the long-term follow-up of HCV patients treated with DAAs who achieved an SVR to investigate the potential for late-onset HCC. Methods: In this prospective multicenter study, we enrolled consecutive HCV patients treated with DAAs following Italian ministerial guidelines between 2015 and 2018. Exclusion criteria included active HCC on imaging, prior HCC treatment, HBV or HIV co-infection, or liver transplant recipients. Monthly follow-ups occurred during treatment, with subsequent assessments every 3 months for at least 48 months. Abdominal ultrasound (US) was performed within two weeks before starting antiviral therapy, supplemented by contrast-enhanced ultrasonography (CEUS), dynamic computed tomography (CT), or magnetic resonance imaging (MRI) to evaluate incidental liver lesions. Results: Of the 306 patients completing the 48-months follow-up post-treatment (median age 67 years, 55% male), all achieved an SVR. A sofosbuvir-based regimen was administered to 72.5% of patients, while 20% received ribavirin. During follow-up, late-onset HCC developed in 20 patients (cumulative incidence rate of 6.55%). The pattern of HCC occurrence varied (median diameter 24 mm). Multivariate and univariate analyses identified liver stiffness, diabetes, body mass index, and platelet levels before antiviral therapy as associated factors for late HCC occurrence. Conclusions: Our findings suggest that late HCC occurrence may persist despite achieving SVR. Therefore, comprehensive long-term follow-up, including clinical, laboratory, and expert ultrasonography evaluations, is crucial for all HCV patients treated with DAAs.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Binding of hepatitis A virus to its cellular receptor 1 inhibits T-regulatory cell functions in humans.

BACKGROUND & AIMS: CD4+ T-regulatory (Treg) cells suppress immune responses and control self-tolerance and immunity to pathogens, cancer, and alloantigens. Most pathogens activate Treg cells to minimize immune-mediated tissue damage and prevent clearance, which promotes chronic infections. However, hepatitis A virus (HAV) temporarily inhibits Treg-cell functions. We investigated whether the interaction of HAV with its cellular receptor 1 (HAVCR1), a T-cell co-stimulatory molecule, inhibits the function of Treg cells to control HAV infection. METHODS: We studied the effects of HAV interaction with HAVCR1 on human T cells using binding, signal transduction, apoptosis, activation, suppression, cytokine production, and confocal microscopy analyses. Cytokines were analyzed in sera from 14 patients with HAV infection using bead arrays. RESULTS: Human Treg cells constitutively express HAVCR1. Binding of HAV to HAVCR1 blocked phosphorylation of Akt, prevented activation of the T-cell receptor, and inhibited function of Treg cells. At the peak viremia, patients with acute HAV infection had no Treg-cell suppression function, produced low levels of transforming growth factor-ß , which limited leukocyte recruitment and survival, and produced high levels of interleukin-22, which prevented liver damage. CONCLUSIONS: Interaction between HAV and its receptor HAVCR1 inhibits Treg-cell function, resulting in an immune imbalance that allows viral expansion with limited hepatocellular damage during early stages of infection-a characteristic of HAV pathogenesis. The mechanism by which HAV is cleared in the absence of Treg-cell function could be used as a model to develop anticancer therapies, modulate autoimmune and allergic responses, and prevent transplant rejection.

Editorial Comment on the Special Issue Discussing COVID-19 and Thrombosis, Second Edition.

The recent SARS-CoV-2 pandemic is ending after over three years, and the efforts of physicians in the daily clinical management of infection in inpatients and outpatients and vaccination campaigns allowed to medical experts to understand all possible scientific aspects of COVID-19 [...].

Retrospective Analysis of a Real-Life Use of Tixagevimab-Cilgavimab plus SARS-CoV-2 Antivirals for Treatment of COVID-19.

Tixagevimab-cilgavimab is effective for the treatment of early COVID-19 in outpatients with risk factors for progression to severe illness, as well as for primary prevention and post-exposure prophylaxis. We aimed to retrospectively evaluate the hospital stay (expressed in days), prognosis, and negativity rate for COVID-19 in patients after treatment with tixagevimab-cilgavimab. We enrolled 42 patients who were nasal swab-positive for SARS-CoV-2 (antigenic and molecular)-both vaccinated and not vaccinated for COVID-19-hospitalized at the first division of the Cotugno Hospital in Naples who had received a single intramuscular dose of tixagevimab-cilgavimab (300 mg/300 mg). All patient candidates for tixagevimab-cilgavimab had immunocompromised immune systems either due to chronic degenerative disorders (Group A: 27 patients) or oncohematological diseases (Group B: 15 patients). Patients enrolled in group A came under our observation after 10 days of clinical symptoms and 5 days after testing positivite for COVID-19, unlike the other patients enrolled in the study. The mean stay in hospital for the patients in Group A was 21 ± 5 days vs. 25 ± 5 days in Group B. Twenty patients tested negative after a median hospitalization stay of 16 days (IQR: 18-15.25); of them, five (25%) patients belonged to group B. Therefore, patients with active hematological malignancy had a lower negativization rate when treated 10 days after the onset of clinical symptoms and five days after their first COVID-19 positive nasal swab.

Hospital Antibiotic Use during COVID-19 Pandemic in Italy.

Antimicrobial resistance (AMR) represents a major issue in healthcare being correlated to global inappropriate use of antibiotics. The aim of this study was to compare the data on hospital antibiotic consumption in 2020-2021 with those related to 2019 in order to evaluate the impact of the COVID-19 pandemic on antibiotic prescriptions and appropriate use at national level and in the different geographical areas. To estimate the consumption of antibiotics, two indicators were calculated: "number of DDD per 1000 inhabitants per day" and "number of DDD per 100 hospitalisation days". Consumption data on antibiotics dispensed in public health facilities were based on the Italian "traceability of medicines" information flow. Data on hospitalisation days were extracted from the Italian "hospital discharge form" flow. Pearson correlation analysis was performed between the number of patients hospitalised for COVID-19 and the consumption of antibiotics in public healthcare facilities. During 2020, about 1.7 DDD/1000 inhabitants per day (12.3% of the overall consumption of reimbursed antibiotics) were dispensed exclusively in Italian hospitals (+0.8% compared to 2019). Considering the number of DDD per 100 hospitalisation days, consumption increased by 19.3% in 2020 compared to 2019. Comparing the first semester of 2020 and 2019, a decrease of DDD/1000 inhabitants per day was observed (-1.6%) at national level, with opposite trends in the different geographical areas; an increase in the use of azithromycin and carbapenems was also observed, with a stable consumption of third-generation cephalosporins. The use of antibiotics in the second semester of 2020 compared to the same period of 2019 showed a clear reduction at national level (-8.5%), appreciable to a similar extent in all geographic areas. In the first semester of 2021 compared to the same period of 2020, there was a huge reduction (-31.4%) in consumption at national level. However, the variations were heterogeneous between different geographical areas. To our knowledge, this study represents the most comprehensive analysis performed on antibiotic consumption data in hospital settings in Italy during the COVID-19 pandemic to date. Despite international and national guideline recommendations, a substantial overall increase in antibiotic prescriptions was observed during the COVID-19 pandemic, with variability in terms of geographical distribution and prescription strategies. These findings may be related to the dichotomy between perceived and real significance of guidelines, expert panels, or consensus. Therefore, new approaches or strategies to antimicrobial stewardship should be proposed.

Decolonization of drug-resistant Enterobacteriaceae carriers: A scoping review of the literature.

The ESCMID-EUCIC guideline on decolonization of multidrug-resistant Gram-negative bacteria carriers does not recommend routine decolonization and highlights the necessity of well-powered and designed randomized clinical trials. Based on this limited evidence, we decided to conduct a scoping review with the aim of describing and discussing the last published studies investigating the efficacy and safety of decolonization therapies in drug-resistant Enterobacteriaceae carriers. Studies published in PubMed from January 1, 2017 to December 28, 2021 were retrieved. A PICO (population, intervention, comparator, outcome) framework was used for article selection as follows: Population defined as any patient of any age in any setting with screening sample yielding for drug-resistant Enterobacteriaceae; Intervention defined as any decolonization; Controls defined as patients receiving no intervention (spontaneous decolonization) or a different decolonization therapy; Outcomes defined as a microbiological, clinical, epidemiological and adverse event. A total of 679 records were initially identified, of which 647 were excluded because they were not related to decolonization therapies. Other 18 records were excluded because not related to our aims, target bacteria, or study design. A total of 12 clinical studies were included, of which 4 were randomized clinical trials and 8 were non-randomized studies. The majority of studies evaluated selective decontamination of the digestive tract or selective oropharyngeal decontamination regimens. Selected studies were characterized by high heterogeneity. Further high-quality studies with proper design and sample size calculation are warranted.