Vitamin D deficiency is a risk factor for infections in patients affected by HCV-related liver cirrhosis

Objectives: To evaluate the prevalence of vitamin D deficiency and its impact on infections in HCV-related liver cirrhosis. Methods: We enrolled 291 patients affected by HCV-related liver cirrhosis. Serum vitamin D levels were dosed at enrolment. The presence of infection was assessed at baseline and during follow-up based on physical examination and laboratory analyses. Results: Vitamin D deficiency (15 (p = 0.003), Child-Pugh class B/C vs A (p < 0.001), and active hepatocellular carcinoma (HCC) (p < 0.001). At multivariate analysis, vitamin D deficiency (p < 0.01), HCC (p < 0.05), hospitalization (p < 0.001) and exposure to immunosuppressant agents (p < 0.05) were independent risk factors for infection at baseline. Conclusions: Vitamin D may play a role in the development of infections in patients affected by liver cirrhosis, and preventive strategies with vitamin D supplementation are to be evaluated in randomized controlled trials

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Present and Future of Siderophore-Based Therapeutic and Diagnostic Approaches in Infectious Diseases

Iron is an essential micronutrient required for the growth of almost all aerobic organisms; the iron uptake pathway in bacteria therefore represents a possible target for novel antimicrobials, including hybrids between antimicrobials and siderophores. Siderophores are low molecular weight iron chelators that bind to iron and are actively transported inside the cell through specific binding protein complexes. These binding protein complexes are present both in Gram negative bacteria, in their outer and inner membrane, and in Gram positive bacteria in their cytoplasmic membrane. Most bacteria have the ability to produce siderophores in order to survive in environments with limited concentrations of free iron, however some bacteria synthetize natural siderophore-antibiotic conjugates that exploit the siderophore-iron uptake pathway to deliver antibiotics into competing bacterial cells and gain a competitive advantage. This approach has been referred to as a Trojan Horse Strategy. To overcome the increasing global problem of antibiotic resistance in Gram negative bacteria, which often have reduced outer membrane permeability, siderophore-antibiotic hybrid conjugates have been synthetized in vitro. Cefiderocol is the first siderophore-antibiotic conjugate that progressed to late stage clinical development so far. In studies on murine models the iron-siderophore uptake pathway has been also exploited for diagnostic imaging of infectious diseases, in which labelled siderophores have been used as specific probes. The aim of this review is to describe the research progress in the field of siderophore-based therapeutic and diagnostic approaches in infectious diseases

Present and future of siderophore-based therapeutic and diagnostic approaches in infectious diseases

Iron is an essential micronutrient required for the growth of almost all aerobic organisms; the iron uptake pathway in bacteria therefore represents a possible target for novel antimicrobials, including hybrids between antimicrobials and siderophores. Siderophores are low molecular weight iron chelators that bind to iron and are actively transported inside the cell through specific binding protein complexes. These binding protein complexes are present both in Gram negative bacteria, in their outer and inner membrane, and in Gram positive bacteria in their cytoplasmic membrane. Most bacteria have the ability to produce siderophores in order to survive in environments with limited concentrations of free iron, however some bacteria synthetize natural siderophore-antibiotic conjugates that exploit the siderophore-iron uptake pathway to deliver antibiotics into competing bacterial cells and gain a competitive advantage. This approach has been referred to as a Trojan Horse Strategy. To overcome the increasing global problem of antibiotic resistance in Gram negative bacteria, which often have reduced outer membrane permeability, siderophore-antibiotic hybrid conjugates have been synthetized in vitro. Cefiderocol is the first siderophore-antibiotic conjugate that progressed to late stage clinical development so far. In studies on murine models the iron-siderophore uptake pathway has been also exploited for diagnostic imaging of infectious diseases, in which labelled siderophores have been used as specific probes. The aim of this review is to describe the research progress in the field of siderophore-based therapeutic and diagnostic approaches in infectious diseases

Investigational direct-acting antivirals in hepatitis C treatment: The latest drugs in clinical development

Introduction: Therapeutic options for patients with HCV-related liver disease have increased over the last two decades. In fact, the old standard of care based on the combination of pegylated interferon and ribavirin did not result in satisfactory eradication rates, particularly in patients with liver cirrhosis. With the advent of direct-acting antivirals (DAAs), higher rates of viral clearance became possible and, patients with contraindications to interferon obtained access to treatment. However, several concerns have been raised regarding first-generation DAAs, namely their high costs, and the emergence of resistant-associated variants with low susceptibility to these drugs. Areas covered: In this review, the authors discuss the data about the efficacy and safety of the main anti-HCV direct-acting antivirals currently in the pipeline. Furthermore, they evaluate the impact of these drugs on the therapeutic options currently available for HCV patients. Expert opinion: The results of trials evaluating the effectiveness of new DAAs are encouraging. These new antivirals lead to high rates of viral eradication without relevant adverse reactions and seem to be effective regardless of viral genotypes, presence of resistant-associated variants or advanced liver disease. Consequently, with the advent of this new family of drugs, chronic HCV-related hepatitis may become a curable disease

Preventing sepsis development in complicated urinary tract infections

Introduction: Urinary tract infections (UTIs) are the most prevalent infections in the community and the most common reason for antimicrobial prescribing in ambulatory care. A UTI is defined as complicated when urinary tract anatomical abnormalities or urinary devices are present, when it is recurrent and when associated with immunodeficiency. Complicated UTIs (cUTIs) have a higher risk of treatment failure and often require longer antimicrobial treatment courses. cUTIs, especially those which are healthcare-associated, are often due to multidrug resistant organisms (MDROs).Areas covered: This article will review the available evidence in relation to prevention of sepsis in cUTI, evaluating the risk factors associated with sepsis development. Published articles from January 2005 to September 2019 on UTIs and sepsis prevention in complicated UTIs were identified by using MEDLINE (National Library of Medicine Bethesda MD) and by reviewing the references of retrieved articles.Expert opinion: Prevention of sepsis relies on prompt and timely diagnosis of cUTI, early identification of the causative organism, removal of obstructions and source control, proper and adequate empirical/targeted antimicrobial treatment. In particular, source control, i.e. removal of urinary obstructions, infected stents, urinary catheters, nephrostomies, and drainage of hydronephrosis/abscess, is essential for preventing the development and progression of sepsis

Update on the Management of Surgical Site Infections

Surgical site infections are an increasingly important issue in nosocomial infections. The progressive increase in antibiotic resistance, the ever-increasing number of interventions and the ever-increasing complexity of patients due to their comorbidities amplify this problem. In this perspective, it is necessary to consider all the risk factors and all the current preventive and prophylactic measures which are available. At the same time, given multiresistant microorganisms, it is essential to consider all the possible current therapeutic interventions. Therefore, our review aims to evaluate all the current aspects regarding the management of surgical site infections