Pharmacokinetic parameters of CAZ-AVI in the normal lung and in models of pneumonia: lessons for treatment optimization in critical care.

The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to β-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-β-lactam β-lactamase inhibitor avibactam, which exhibits broad-spectrum β-lactamase inhibition , are combined to form ceftazidime-avibactam (CAZ-AVI).

Clinical correlates of circulating small dense low-density lipoproteins in acute infective endocarditis.

Background And Aim: Infective endocarditis (IE) is a complex thrombo-inflammatory disorder, the pathogenesis of which involves a multifaceted interplay between vascular damage and bacterial virulence factors. This study aimed to assess the prognostic role of small dense low-density lipoprotein (sdLDL) cholesterol in patients with IE and its correlation with various disease-related features.

Methods: A cohort of 198 patients with definite IE was included in this study.

Clinical results with the use of ceftaroline and ceftobiprole: real-life experience in a tertiary care hospital.

Introduction: Ceftaroline and ceftobiprole show activity against resistant Gram-positive cocci as well as good tolerability and are increasingly used in diverse infections. No comparative data on the efficacy and safety of ceftaroline and ceftobiprole in real-life are available.

Methods: In this single-centre, observational, retrospective clinical study, the outcomes of patients treated with ceftaroline or ceftobiprole in our hospital were compared, assessing clinical data, use and drug exposure of study antibiotics, and outcomes.

Long-Term Outcome of Infective Endocarditis Involving Cardiac Implantable Electronic Devices: Impact of Comorbidities and Lead Extraction.

(1) Background: Management of cardiac implantable electronic device-related infective endocarditis (CIED-IE) hinges on complete hardware removal. We assessed whether long-term prognosis is affected by device removal, considering baseline patient comorbid conditions; (2) Methods: A total of 125 consecutive patients hospitalized for CIED-IE were included in this retrospective analysis. Outcomes were in-hospital, one-year, and long-term mortality.

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified.

Incidence, Risk Factors and Clinical Implications of Glucose Metabolic Changes after Heart Transplant.

Diabetes mellitus (DM) arising after transplant is a common complication, sharing many features with type 2 DM but also specific causes, such as administration of steroids and immunosuppressive drugs. Although post-transplant DM (PTDM) is generally assumed to worsen recipients' outcomes, its impact on renal function, cardiac allograft vasculopathy and mortality remains understudied in heart transplant (HT). We evaluated incidence and risk factors of PTDM and studied glucose metabolic alterations in relation to major HT outcomes.

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores.

Dissecting the correlates of N-terminal prohormone brain natriuretic peptide in acute infective endocarditis.

Purpose: To explore the prognostic value and the correlates of NT-proBNP in patients with acute infective endocarditis, a life-threatening disease, with an often unpredictable outcome given by the lack of reliable prognostic parameters.

Methods: We retrospectively studied 337 patients admitted to our centre between January 1, 2006 and September 30, 2020 with available NT-proBNP level at admission. Our analyses were performed considering NT-proBNP as both a categorical variable, using the median value as the cut-off level, and numerical variable.

Prognostic Value of Decreased High-Density Lipoprotein Cholesterol Levels in Infective Endocarditis.

(1) Background: Simple parameters to be used as early predictors of prognosis in infective endocarditis (IE) are lacking. The aim of this study was to evaluate the prognostic role of high-density-lipoprotein cholesterol (HDL-C) and also of total-cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and triglycerides, in relation to clinical features and mortality, in IE. (2) Methods: Retrospective analysis of observational data from 127 consecutive patients with a definite diagnosis of IE between 2016 and 2019.

Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance.

Objectives: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries.

Methods: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed.

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified.

Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis.

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed.

Predictors of long-term mortality in left-sided infective endocarditis: an historical cohort study in 414 patients.

Introduction: Very limited data are available on the long-term outcome of infective endocarditis (IE) and its determinants. The aim of this study was to identify the predictors of long-term mortality in patients affected by left sided IE (LSIE).

Methods: This was an historical retrospective observational study on prospectively collected data from patients with LSIE hospitalized in our Unit (January 2000-December 2017).

Risk Factors and Outcome of Multidrug-Resistant Infections after Heart Transplant: A Contemporary Single Center Experience.

(1) Background: The aim of this study was to assess risk factors for multidrug-resistant/extensively drug-resistant (MDR/XDR) bacterial infections in heart transplant (HT) patients within three months after surgery and its impact on patient outcome. (2) Methods: Retrospective analysis of clinical, hemato-chemical, imaging, treatment and outcome data from 47 heart transplant recipients from January 2016 to December 2018. MDR/XDR infections were compared to non-MDR/XDR and noninfected patients.

In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections.

Objectives: Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections.

Methods: Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB.

Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment.

Background: Hepatitis C virus (HCV) infection affects lipid metabolism. We investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism in chronic hepatitis C (CHC), with a focus on the effects of anthropometric parameters and liver histology. We also analyzed the dynamics of metabolic indexes used to estimate cardiovascular risk.

Prognostic value of pro-adrenomedullin and copeptin in acute infective endocarditis.

Background: Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP).

Enterococcal infective endocarditis is a marker of current occult or future incident colorectal neoplasia.

Background: Few studies suggest an association between Enterococcal infective endocarditis (EIE) and colorectal disease, including colorectal neoplasia (CRN) and colorectal cancer (CRC). In this study, we analyze differences in prevalence, risk factors and outcome of CRN and CRC between EIE and Streptococcus gallolyticus infective endocarditis (SGIE).

Methods: Single center, observational study of 166 patients with definite EIE or SGIE.

Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes.

Objectives: In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.

Methods: This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin-meropenem for severe CRGN infections.

Colistin Resistance Development Following Colistin-Meropenem Combination Therapy Versus Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms.

Background: We evaluated whether carbapenem-colistin combination therapy reduces the emergence of colistin resistance, compared to colistin monotherapy, when given to patients with infections due to carbapenem-resistant Gram-negative organisms.

Methods: This is a pre-planned analysis of a secondary outcome from a randomized, controlled trial comparing colistin monotherapy with colistin-meropenem combination for the treatment of severe infections caused by carbapenem-resistant, colistin-susceptible Gram-negative bacteria. We evaluated rectal swabs taken on Day 7 or later for the presence of new colistin-resistant (ColR) isolates.

Hepatitis B core-related antigen to detect hepatitis B virus (HBV) reactivation in heart transplant recipients with past HBV infection: A pilot study.

Hepatitis B core-related antigen (HBcrAg) has been proposed as a new marker of hepatitis B virus (HBV) replication. We analyzed HBcrAg dynamics in 15 heart transplant recipients with active or prior HBV infection and correlated it with quantitative (QT)-HBsAg and HBV-DNA pre- and post-transplant. Serum HBcrAg was detected in HBsAg/HBV-DNA-positive subjects but not in recipients with past HBV infection.

Hepatitis B virus reactivation after heart transplant: Incidence and clinical impact.

Background: Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant.

Objectives: We followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features.

Clinical significance of hyperhomocysteinemia in infective endocarditis: A case-control study.

Blood coagulation plays a key role in the pathogenesis of infective endocarditis (IE). Conditions associated with thrombophilia could enhance IE vegetation formation and promote embolic complications.In this study, we assessed prevalence, correlates, and clinical consequences of hyper-homocysteinemia (h-Hcy) in IE.

Viability of pegIFNα-RBV for CHC in the direct acting antiviral era: a practical algorithm between efficacy and cost containment.

The classical pegylated interferon α (peg-IFNα) and ribavirin (RBV) treatment of chronic hepatitis C (CHC) is progressively being replaced by new direct acting antivirals, whose costs remain a major barrier to widespread use. Using baseline data and viral kinetics, we developed a predictive algorithm to allocate to DAA patients who are not going to respond to peg-IFNα/RBV. This prospective study evaluated 205 CHC patients treated with peg-IFNα/RBV.