Michalopoulos A.,Henry Dunant Hospital |
Falagas M.E.,Alfa Institute of Biomedical science AIBS
Expert Opinion on Pharmacotherapy | Year: 2010
Importance of the field: Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. It commonly presents resistance to multiple antimicrobial agents, occasionally including carbapenems and polymyxins, and hence, it is considered the paradigm of multidrug-resistant (MDR) or pandrug-resistant (PDR) bacterium. MDR A. baumannii is a rapidly emerging pathogen, especially in the intensive care setting, causing infections including bacteremia, pneumonia/ventilator-associated pneumonia (VAP), meningitis, urinary tract infection, central venous catheter-related infection, and wound infection. Areas covered in this review: All potential antimicrobial agents that are available for the treatment of Acinetobacter infections are presented. Emphasis was given to the management of nosocomial infections due to MDR A. baumannii and its close relatives, spp. 3 and 13TU. Areas covered include bloodstream infections, pneumonia or VAP, meningitis, urinary tract infection, skin and soft-tissue or wound infections due to Acinetobacter. What the reader will gain: The antibiotics that are usually effective against A. baumannii infections include carbapenems, polymyxins E and B, sulbactam, piperacillin/tazobactam, tigecycline and aminoglycosides. Carbapenems (imipenem, meropenem, doripenem) are the mainstay of treatment for A. baumannii, though carbapenem-resistant Acinetobacter strains have increasingly been reported worldwide in recent years. However, although well-designed trials of new therapeutic approaches are certainly required, the most important factor necessary to guide clinicians in their choice of empirical or targeted therapy should be knowledge of the susceptibility patterns of strains present in their own geographical area. Take home message: Pooled data suggest that infections caused by A. baumannii, especially those with inappropriate treatment, are associated with considerable attributable mortality. The optimal treatment for A. baumannii nosocomial infections has not been established, especially for MDR strains. Therefore, well-designed clinical studies are necessary to guide clinicians on decisions regarding the best therapeutic approach for patients with MDR A. baumannii infections. In addition, new experimental studies are warranted to evaluate the activity and safety of peptides and other novel antibacterial agents for A. baumannii infections. © 2010 Informa UK Ltd.
Gonzalez C.A.,Catalan Institute of Oncology Idibell |
Sala N.,Catalan Institute of Oncology Idibell |
Rokkas T.,Henry Dunant Hospital
Helicobacter | Year: 2013
A multifactorial and multistep model of gastric cancer (GC) is currently accepted, according to which different environmental and genetic factors are involved at different stages in the cancer process. The aim of this article is to review the most relevant information published on the relative contribution of genetic and environmental factors. Large meta-analyses confirmed the association between IL8, IL10, TNF-b, TP53 and PSCA, while genetic variation at different genes such as XPG, PLCE1, HFE, ERCC5, EZH2, DOC2, CYP19A1, ALDH2, and CDH1 have been reported to be associated with GC risk. Several microRNAs have also been associated with GC and their prognosis. Cohort studies have shown the association between GC and fruit, flavonoid, total antioxidant capacity, and green tea intake. Obesity was associated with cardia GC, heme iron intake from meat with GC risk. Several large meta-analyses have confirmed the positive association of GC with salt intake and pickled foods and the negative association with aspirin use. Copyright © 2013 John Wiley & Sons Ltd 18 s1 September 2013 10.1111/hel.12082 Review Article Review Articles © 2013 John Wiley & Sons Ltd.
Liaw Y.-F.,Chang Gung University |
Brunetto M.R.,UO Epatologia |
Hadziyannis S.,Henry Dunant Hospital
Antiviral Therapy | Year: 2010
Although chronic HBV infection is a global health issue, there are geographical differences in the mode of transmission, prevalence and HBV genotype distribution. Chronic HBV infection is a dynamic state of interactions between HBV, hepatocytes and immune cells of the host. Accordingly, the natural history of chronic HBV infection typically starts with an immune tolerant phase, followed by an immune clearance phase and finally an inactive phase. The duration of the immune tolerant phase is usually long in chronic HBV infection acquired perinatally or in early childhood, otherwise the duration is very short. During the inactive phase, spontaneous hepatitis B surface antigen (HBsAg) seroclearance might occur at an annual rate of 1-2%; however, HBV reactivation with hepatitis activity could occur over time in one-quarter to one-third of HBsAg-seropositive patients. This occurs more frequently in males and in patients infected with genotypes D, C and B. The effort of active HBV replication-triggered immune clearance is the driving force of liver injury and subsequent disease progression in patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative hepatitis. Clinical studies have shown that chronic HBV infection in western countries is associated with a higher incidence of cirrhosis, but lower incidence of hepatocellular carcinoma, than in Asian countries. The geographical differences in age at the time of infection and predominant HBV genotype could account for the variance in the natural history of chronic HBV infection; however, some of these differences might actually result from comparisons between cohorts with different age, gender distribution or fibrosis stage. ©2010 International Medical Press.
Rokkas T.,Henry Dunant Hospital |
Niv Y.,Tel Aviv University
European Journal of Gastroenterology and Hepatology | Year: 2012
Background: Video capsule endoscopy (VCE) is an attractive and patient friendly tool that provides high quality images of the small bowel. The reported yield of VCE in diagnosing celiac disease (CD) has shown variable results. Objective: The aim of this study was to assess the accuracy of VCE by pooling data of existing trials. DESIGN: Meta-analysis. The fixed-effects or random-effects model was used as appropriate, based on whether homogeneity or heterogeneity, respectively, was indicated by the Cochran Q-test. PATIENTS: Studies that estimated the accuracy of VCE were identified. The two investigators independently conducted the search and data extraction. A total of 166 individuals were included in this meta-analysis. Methods: An extensive literature search was performed and studies that estimated the accuracy of VCE in CD were identified. The two investigators independently conducted the search and data extraction. Data from the eligible studies were collected and pooled; sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were computed. In addition, the results of the individual studies were displayed in a receiver operating characteristic (ROC) space to illustrate the distribution of sensitivities and specificities. A weighted symmetric summary ROC curve was computed and the area under the curve (AUC) was calculated, with perfect tests having an AUC of 1 and poor tests having an AUC close to 0.5. Results: Out of 461 titles initially generated by the literature searches, six studies met the inclusion criteria and were eligible for meta-analysis. The overall pooled VCE sensitivity was 89% [95% confidence interval (82-94%)] and specificity was 95% [95% confidence interval (89-98%)]. The AUC under the weighted symmetric summary ROC was 0.9584. Conclusion: The results of this meta-analysis mean that VCE, although it is not as accurate as pathology, could be a reasonable alternative method of diagnosing CD. Hopefully, this method will expand the portfolio of diagnostic methods available, especially in patients unwilling to undergo gastroscopy because of its perceived inconvenience and discomfort. However, larger, multicenter, and well-designed trials are needed to further establish the role of VCE in the diagnosis of CD. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Michalopoulos A.S.,Henry Dunant Hospital |
Livaditis I.G.,Henry Dunant Hospital |
Gougoutas V.,Henry Dunant Hospital
International Journal of Infectious Diseases | Year: 2011
Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969. There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use. Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis in both Gram-positive and Gram-negative bacteria by inhibiting the initial step involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Its unique mechanism of action may provide a synergistic effect to other classes of antibiotics including beta-lactams, aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the treatment of urinary tract infections, particularly those caused by Escherichia coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in combination with other antibiotics for the treatment of nosocomial infections due to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone, cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well tolerated, with a low incidence of adverse events. Further randomized controlled trials are needed in order to evaluate the efficacy of intravenous fosfomycin for the management of nosocomial infections due to MDR pathogens. © 2011 International Society for Infectious Diseases.
Michalopoulos A.S.,Henry Dunant Hospital |
Karatza D.C.,Henry Dunant Hospital
Expert Review of Anti-Infective Therapy | Year: 2010
The emergence of nosocomial infections due to multidrug-resistant Gram-negative bacteria led to the revival of 'forgotten antibiotics, such as polymyxins. Colistin, mainly colistimethate sodium (polymyxin E), has been predominantly used. Recent studies suggest that colistin administered as monotherapy or combination therapy is an effective and safe antimicrobial agent for multidrug-resistant Gram-negative bacteria infections. The reported colistin nephrotoxicity is 20% or lower. Although colistin is commonly administered intravenously, it can also be administered via inhalation for pneumonia/ventilator-associated pneumonia treatment or by the intraventricular/intrathecal route for meningitis/ventriculitis treatment. Randomized controlled trials are needed to answer clinical questions such as the appropriate colistin dose, to compare colistin monotherapy with combination therapy, and to determine the exact therapeutic role of aerosolized or intrathecal/intraventricular administration of colistin. © 2010 Expert Reviews Ltd.
Michalopoulos A.S.,Henry Dunant Hospital
Expert Opinion on Drug Delivery | Year: 2012
Inhaled antibiotics, such as TOBI (a tobramycin solution), gentamicin, colistin and aztreonam lysine (Cayston) have been effectively administered with safety and efficacy in patients with cystic fibrosis and bronchiectasis. In addition, inhaled antibiotics have been administered with safety and efficacy for the prevention and treatment of patients with ventilator-associated tracheobronchitis or pneumonia due to multidrug-resistant Gram-negative bacteria (mainly Pseudomonas aeruginosa or Acinetobacter baumannii). Original studies showed that inhaled colistin resulted in treatment success of nosocomial pneumonia or ventilator-associated pneumonia (VAP) due to multidrug-resistant Gram-negative bacteria. However, although aerosolized colistin seems to be safe and effective for the eradication of P. aeruginosa and the management of pneumonia in cystic fibrosis patients, hospital-acquired pneumonia and VAP due to multidrug-resistant Gram-negative bacteria, it is still unclear if it provides additional benefit in all-cause hospital mortality, or VAP-related mortality rates. For this reason, randomized controlled trials (RCTs) are necessary to validate the efficacy and safety of aerosolized colistin, mainly in patients with nosocomial pneumonia or VAP. In addition, RCTs are necessary to determine the appropriate inhaled colistin dose and the optimal delivery device. © 2012 Informa UK, Ltd.
Tzeis S.,Henry Dunant Hospital |
Andrikopoulos G.,Henry Dunant Hospital
Expert Opinion on Investigational Drugs | Year: 2012
Introduction: Pharmacological management of cardiac arrhythmias is limited by the reduced availability of safe and effective antiarrhythmic agents. Areas covered: Ranolazine is an agent currently used for the treatment of angina, which inhibits transmembrane ionic currents involved in several phases of the action potential in both the atrial and the ventricular cells. Due to its mechanism of action, ranolazine has been shown to exhibit antiarrhythmic properties that have been validated in the experimental models. This article recapitulates the mechanism of antiarrhythmic action of ranolazine, the existing clinical data, and the ongoing relevant clinical trials. Expert opinion: The combination of the antiischemic properties of ranolazine with its antiarrhythmic potency and minimal proarrhythmia provides a promising background that could expand its therapeutic role in the management of atrial fibrillation and ventricular tachyarrhythmias. Data derived from adequately powered randomized clinical trials will determine whether the door to a new indication will open for ranolazine in the near future. © Informa UK, Ltd.
Michalopoulos A.,Henry Dunant Hospital |
Papadakis E.,Henry Dunant Hospital
Infection | Year: 2010
The administration of antibiotics by the inhaled route is a widely recognized treatment in patients with cystic fibrosis (CF) and bronchiectasis. Tobramycin solution for inhalation (TOBI) has been available for many years and is licensed in the USA and Europe. While strong data support the use of aerosolized antibiotics for the treatment of respiratory infections in patients with CF or bronchiectasis, only a few clinical studies have examined the role of aerosolized antibiotics in the treatment of pneumonia, including ventilator-associated pneumonia (VAP) in these patients. During the last decade increasing interest has been directed towards alternative treatments to the systemic administration of antimicrobial agents for the treatment of patients with hospital-acquired pneumonia or VAP due to multidrug-resistant (MDR) Gram-negative bacteria. Recent publications demonstrate the clinical benefits from administering inhaled aminoglycosides or polymyxins in patients with hospitalacquired pneumonia or VAP. In addition to antibiotics, antifungals, and antivirals have been administered by inhalation to specific groups of critically ill patients. However, randomized controlled trials dealing with the administration of anti-infective agents via the respiratory tract are necessary in order to validate the efficacy, safety, advantages, and disadvantages of this therapeutic approach for the treatment of nosocomial pneumonia. © 2010 Urban & Vogel.
Hadziyannis S.J.,Henry Dunant Hospital
Journal of Hepatology | Year: 2011
Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic infection. Perinatal HBV infection is rare while the vast majority of chronic infections originate from horizontal HBV transmission to infants and children. HBeAg loss and seroconversion to anti-HBe occur in a few years time, usually during the second decade of life. HBeAg-negative/anti-HBe-positive chronic hepatitis B (CHB), predominates in these countries being 7-9 times more frequent than HBeAg-positive CHB. The predominance of HBeAg-negative CHB is largely linked to the molecular characteristics of HBV genotype D prevailing in European and African countries of the Mediterranean basin and of genotype E and subgenotype A1 that prevail in the other parts of Africa. The molecular characteristics of the African subgenotype A1 differ from those of European subgenotype A2 explaining the fact that patients infected subgenotype A1 demonstrate an earlier loss of HBeAg and seroconversion to anti-HBe during the natural course of HBV infection compared to those infected with subgenotype A2. It is proposed that the molecular characteristics of HBV genotypes and subgenotypes prevailing in Euro-Mediterranean and African countries acting in concert with host and environmental factors largely determine the natural history of chronic HBV infection and its significant differences from countries of HBV genotype C and B and of subgenotype Ae predominance. The knowledge of the natural history of chronic HBV infection in Euro-Mediterranean and African countries combined with wide screening programs for prompt recognition and treatment of chronic HBV infection both in its HBeAg-positive and -negative immune reactive phases can be expected to increase the efficacy of current and future therapeutic strategies. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.