National Institute for Infectious Diseases

Rome, Italy

National Institute for Infectious Diseases

Rome, Italy
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Di Bella S.,National Institute for Infectious Diseases | Drapeau C.,King's College | Garcia-Almodovar E.,Son Espases University Hospital | Petrosillo N.,National Institute for Infectious Diseases
Infectious Disease Reports | Year: 2013

Clostridium difficile infection (CDI) is an emerging problem in terms of incidence, morbidity and mortality. Currently available treatment options are not always effective, especially in cases of recurrent/refractory or complicated CDI. The gut microbiota transplantation is a technique that has been sporadically practiced since the '50s, but its clinical efficacy has only recently been supported by scientific evidence. In the present article, we report the pathophysiological basis and the clinical indications of this technique that, in light of its low cost, and proven efficacy and safety, is likely to become part of the management guidelines of difficult cases of CDI in the near future.cases, the signs and symptoms of CDI usually reappear after discontinuation of antibiotic treatment. Actually, the current international guidelines declare the existence of a gap in the management of these clinical situations.4 Unconventional therapies have been proposed as alternative or adjunctive treatment to the classic metronidazole and vancomycin, such as the use of intravenous immunoglobulin, and others like probiotics, and chelating agents. However, the results in terms of clinical cure have been far from satisfactory. In light of these therapeutic limitations the technique of fecal bacteriotherapy was rediscovered, with the rationale of a real organ transplant. The first reported fecal transplant in humans in the literature dates back to 1958.5 The use of fecal bacteriotherapy was in fact reported in the literature for about 50 years, but until 2013 no randomized trial was ever been published. Over the last few years, the term intestinal flora (now considered obsolete) has been gradually replaced with that of gut microbiota, thus indicating the growing awareness of the existence of an actual organ responsible of multiple physiological functions (i.e. energy metabolism and immune system), similarly to what has happened with the adipose tissue in metabolic diseases. © S. Di Bella et al.

Fung S.,University of Toronto | Kwan P.,University of British Columbia | Fabri M.,University of Novi Sad | Horban A.,Medical University of Warsaw | And 11 more authors.
Gastroenterology | Year: 2014

Background & Aims Tenofovir disoproxil fumarate (TDF) is active against lamivudine-resistant hepatitis B virus (HBV) infection, but data to support its clinical efficacy in this setting are limited. Methods In a prospective, double-blind, 96-week trial, patients were randomly assigned (1:1) to groups given TDF (300 mg, n = 141) or a combination of emtricitabine (FTC, 200 mg; n = 139) and TDF (300 mg, FTC/TDF). Patients were hepatitis B e antigen (HBeAg)-positive or HBeAg-negative, with levels of HBV DNA ≥3 log10 IU/mL and lamivudine resistance mutations (HBV polymerase or reverse transcriptase amino acid substitutions rtM204I/V ± rtL180M by INNO-LiPA Multi-DR v3; Innogenetics, Inc, Alpharetta, GA). The primary end point was proportion with HBV DNA <69 IU/mL (Roche COBAS Taqman assay; Roche Molecular Systems, Inc, Pleasanton, CA). Results Patient groups were well matched for demographic and disease characteristics, including region (60% from Europe), HBV genotype (45% genotype D), HBeAg status (47% HBeAg-positive), and duration of lamivudine treatment (mean, 3.8 years). At week 96 of treatment, 89.4% of patients in the TDF group and 86.3% in the FTC/TDF group had levels of HBV DNA <69 IU/mL (P =.43). HBeAg loss and seroconversion did not differ between groups; only 1 patient (0.7%) in the FTC/TDF group lost hepatitis B surface antigen. Treatment was well tolerated; confirmed renal events (creatinine increase of ≥0.5 mg/dL [>44 umol/L], creatinine clearance <50 mL/min, or level of PO4 <2 mg/dL [<0.65 mmol/L]) were generally mild and infrequent (<1%). Small reductions (<2%) in mean bone mineral density of hip and spine were detected by dual-energy x-ray absorptiometry in both groups. No TDF resistance developed through 96 weeks of treatment. Conclusions TDF alone is safe and effective for treatment of patients with lamivudine-resistant, chronic HBV infection. Clinical No, NCT00737568. © 2014 by the AGA Institute.

Cataldo M.A.,National Institute for Infectious Diseases | Petrosillo N.,National Institute for Infectious Diseases | Cipriani M.,University Cattolica | Cauda R.,University Cattolica | Tacconelli E.,University Cattolica
Journal of Infection | Year: 2010

Over the past years there has been a significant increase in the number of joint prosthesis replacements worldwide. The most serious complication of joint prosthesis is infection with an incidence of 1.5-2.5% for primary interventions and up to 20% for revision procedures. The mortality rate ranges between 1% and nearly 3%. The economic cost of this complication is up to $50,000 per patient and $250,000 million per year. A major issue in the management of prosthetic joint infection (PJI) is the relative difficulty in making a diagnosis so to cause a significant effect on the prognosis. Goals of the treatment are to eradicate infection, prevent its recurrence and preserve mechanical joint function. In this review we focus on the value of traditional and newer diagnostic tests and we discuss management and preventive strategies. European networks are needed to define the best diagnostic and treatment strategies in order to reduce future challenge posed by PJIs. © 2010 The British Infection Association.

Lanini S.,National Institute for Infectious Diseases | Molloy A.C.,Royal Free Hospital | Fine P.E.,London School of Hygiene and Tropical Medicine | Prentice A.G.,Royal Free Hospital | And 2 more authors.
BMC Medicine | Year: 2011

Background: The addition of Rituximab (R) to standard chemotherapy (C) has been reported to improve the end of treatment outcome in patients affected by CD-20 positive malignant lymphomas (CD20+ ML). Nevertheless, given the profound and prolonged immunosuppression produced by R there are concerns that severe infections may arise. A systematic review and meta-analysis were performed to determine whether or not the addition of R to C may increase the risk of severe infections in adults undergoing induction therapy for CD20+ ML.Methods: Only randomised controlled trials comparing R-C to C standard alone in adult patients with CD20+ ML were included. Meta-analysis was performed on overall incidence of severe infection, risk of dying as the consequence of infection, risk of febrile neutropenia, risk of severe leucopenia, risk of severe granulocytopenia and overall response assuming a fixed effect model. Heterogeneity was investigated, if present and I2>20%, according to several predefined baseline characteristics of the study populations.Results: Several relevant results have emerged. First, the addition of R to standard C does not increase the overall risk of severe infections (RR = 1.00; 95% CI 0.87 to 1.14) nor does it increase the risk of dying as a consequence of infection (RR = 1.60; 95% CI 0.68 to 3.75). Second, we confirmed that the addition of R to standard C increases the proportion of overall response (RR = 1.12; 95% CI 1.09 to 1.15), but it also increases the risk of severe leucopenia (RR = 1.24; 95% CI 1.12 to 1.37) and granulocytopenia (RR = 1.07; 95% CI 1.02 to 1.12).Conclusions: R-C is superior to standard C in terms of overall response and it does not increase the overall incidence of severe infection. However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking. In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections. © 2011 Lanini et al; licensee BioMed Central Ltd.

Almodovar S.,University of Colorado at Denver | Cicalini S.,National Institute for Infectious Diseases | Petrosillo N.,National Institute for Infectious Diseases | Flores S.C.,University of Colorado at Denver
Chest | Year: 2010

The success of antiretroviral therapies in improving the survival of patients infected with HIV and reducing HIV-associated opportunistic infections is undisputed. Nevertheless, long-term outcomes such as noninfectious cardiovascular complications, including cardiomegaly, pericarditis, myocarditis, and pulmonary arterial hypertension, are now serious concerns. The lung is a frequent target organ for disorders associated with HIV infection. HIV-related pulmonary arterial hypertension (HRPAH) affects more individuals who are infected with HIV than individuals who are uninfected. Moreover, the long-standing estimated prevalence of HRPAH in developed countries (calculated at 0.5%) is increasing as more clinician-scientists unify their efforts to screen patients who are pulmonary asymptomatic for pulmonary arterial hypertension. In order to decrease mortality, efforts are directed at early detection, diagnosis, and therapeutic interventions before the disease compromises patients' quality of life. This article reviews the logistics of screening approaches for HRPAH and discusses the substantial disease burden currently faced by developing countries, where the prevalence of HIV infection is higher and complicated by hyperendemic risk factors, limited access to antiretrovirals, and lack of screening tools. We also present mechanistic insights into HRPAH, including the role of HIV proteins and their potential use as screening tools, and, finally, areas that still need intense research. © 2010 American College of Chest Physicians.

Di Sano F.,University of Rome Tor Vergata | Bernardoni P.,University of Rome Tor Vergata | Piacentini M.,University of Rome Tor Vergata | Piacentini M.,National Institute for Infectious Diseases
Experimental Cell Research | Year: 2012

The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by a specific class of curvature stabilizing proteins, the reticulons and DP1; however it is still unclear how the sheets are assembled. The ER is the cellular compartment responsible for secretory and membrane protein synthesis. The reducing conditions of ER lead to the intra/inter-chain formation of new disulphide bonds into polypeptides during protein folding assessed by enzymatic or spontaneous reactions. Moreover, ER represents the main intracellular calcium storage site and it plays an important role in calcium signaling that impacts many cellular processes. Accordingly, the maintenance of ER function represents an essential condition for the cell, and ER morphology constitutes an important prerogative of it. Furthermore, it is well known that ER undergoes prominent shape transitions during events such as cell division and differentiation. Thus, maintaining the correct ER structure is an essential feature for cellular physiology. Now, it is known that proper ER-associated proteins play a fundamental role in ER tubules formation. Among these ER-shaping proteins are the reticulons (RTN), which are acquiring a relevant position. In fact, beyond the structural role of reticulons, in very recent years new and deeper functional implications of these proteins are emerging in relation to their involvement in several cellular processes. © 2012 Elsevier Inc.

Topino S.,National Institute for Infectious Diseases | Galati V.,National Institute for Infectious Diseases | Grilli E.,National Institute for Infectious Diseases | Petrosillo N.,National Institute for Infectious Diseases
AIDS Patient Care and STDs | Year: 2010

Rhodococcus equi is a gram-positive, coryneform bacterium that causes zoonotic infection mainly in horses and foals. It sometimes affects humans presenting as cavitary pneumonia. Immunocompromised patients, including HIV-infected patients, are more susceptible to R. equi infection. We present 10 cases of R. equi infection in HIV-positive patients admitted to our institute from 1991 to June 2008. Moreover, we have reviewed 272 cases of R. equi infection in HIV-infected persons, published from 1986 through 2008. With respect to the literature data, the R. equi strains isolated in our case series showed lower sensitivity to ceftriaxone, amoxicillin/clavulanic acid, and cotrimoxazole. Prompt diagnosis, early initiation of antiretroviral treatment and combined antimicrobial treatment seem to be effective to eradicate the infection and to improve the outcome. © Mary Ann Liebert, Inc.

Delogu G.,Catholic University of the Sacred Heart | Goletti D.,National Institute for Infectious Diseases
Journal of Rheumatology | Year: 2014

The risk of developing active tuberculosis (TB) is higher in patients taking immunosuppressive drugs, either as a result of reactivation of a latent TB infection (LTBI) or following a new infection with Mycobacterium tuberculosis (Mtb). We discuss the pathogenesis and spectrum of Mtb infection in light of its implication for the management of patients following biologic regimens. Among recent findings, during LTBI, Mtb can persist in the host for decades, localizing in many tissues and assuming different metabolic states that protect the bacilli from the harsh host immune defenses. Despite the strong host T cell response against Mtb, the bacilli may also replicate and multiply in vivo, and any event impairing immune function may lead to active and uncontrolled bacteria replication and active disease. The classic dichotomy between active and latent disease is being reconsidered in favor of a continuous and dynamic spectrum extending from infection to disease that can coexist in the same individual. This TB spectrum results from the dynamic interaction between the host immune system and the bacilli and can be maintained in equilibrium for decades, although treatments affecting the host immune cells may result in disease reactivation © 2014. All rights reserved.

Cataldo M.A.,National Institute for Infectious Diseases | Petrosillo N.,National Institute for Infectious Diseases
Therapeutics and Clinical Risk Management | Year: 2011

Fungi are a frequent cause of nosocomial infections, with an incidence that has increased significantly in recent years, especially among critically ill patients who require intensive care unit (ICU) admission. Among ICU patients, postsurgical patients have a higher risk of Candida infections in the bloodstream. In consideration of the high incidence of fungal infections in these patients, their strong impact on mortality rate, and of the difficulties in Candida diagnosis, some experts suggest the use of antifungal prophylaxis in critically ill surgical patients. A clinical benefit from this strategy has been demonstrated, but the economic impact of the use of antifungal prophylaxis in surgical patients has not been systematically evaluated, and its cost-benefit ratio has not been defined. Whereas the costs associated with treating fungal infections are very high, the cost of antifungal drugs varies from affordable (ie, the older azoles) to expensive (ie, echinocandins, polyenes, and the newer azoles). Adverse drug-related effects and the possibly increased incidence of fluconazole resistance and of isolates other than Candida albicans must also be taken into account. From the published studies of antifungal prophylaxis in surgical patients, a likely economic benefit of this strategy could be inferred, but its usefulness and cost-benefits should be evaluated in light of local data, because the available evidence does not permit general recommendations. © 2011 Cataldo and Petrosillo.

Cataldo M.A.,National Institute for Infectious Diseases | Tacconelli E.,University Cattolica Sacro Cuore | Grilli E.,National Institute for Infectious Diseases | Pea F.,University of Udine | Petrosillo N.,National Institute for Infectious Diseases
Journal of Antimicrobial Chemotherapy | Year: 2012

Objectives: To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patientswith Gram-positive infections. Methods: MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration(Cmin) for InI and steady-state concentration (Css) for CoI; area under the curve at 24 h (AUC24) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I2 test was calculated to assess heterogeneity across studies. Results: One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P=0.02;I2=0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P=0.9; I2=0). Conclusions: Our meta-analysis suggests that administration of vancomycin for the treatment ofGram-positiveinfections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug.RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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