المؤلفون: Adinolfi, L.E., Utili, R., Tonziello, A., Ruggiero, G.

المصدر: Gut. May2003, Vol. 52 Issue 5, p701. 5p. 3 Charts.

مصطلحات موضوعية: *HEPATITIS C treatment, *INTERFERONS, *RIBAVIRIN

مستخلص: Background: Fifty per cent of chronic hepatitis C patients are non-responders to interferon. At present, there are no recommended therapeutic options for non- responders. Aims: The safety and long term effect of alpha interferon induction plus ribavirin with or without amantadine in the treatment of interferon non- responsive chronic hepatitis C was evaluated. Patients and methods: A total of 114 consecutive patients were randomly divided into three groups with a final 2:2:1 ratio: group A (44 patients) received interferon alfa 2b, 3 million units (MU), three times a week, and oral ribavirin (1000 mg/day); group B (46 patients) received interferon 3 MU daily for the first four weeks and subsequently 3 MU three times a week, and ribavirin as in regimen A; and group C (24 patients) received interferon and ribavirin as in regimen B, plus oral amantadine hydrochloride (200 mg/day). The duration of treatment was 12 months. Results: The end of treatment response for groups A and B was 25% and 29%, respectively, and for group C, 68% (p<0.005). At the end of one year of follow up, a sustained response was observed for six (25%) patients in group C, one (2%) patient in group A, and two (4%) patients in group B (p<0.002). The triple regimen was well tolerated and did not increase the frequency or severity of side effects. Conclusions: The study demonstrates that for the treatment of interferon non-responder hepatitis C patients, the association of interferon-ribavirin has a negligible long term effect whereas a triple regimen including interferon, ribavirin, and amantadine can be an effective and safe treatment. [ABSTRACT FROM AUTHOR]

المؤلفون: Utili, R.^1,2,3 riccardo.utili@unina2.it, Tripodi, M. F.^2,3, Ragone, E.¹, Casillo, R.¹, Pasquale, G.¹, De Santo, L.^3,4, Esposito, S.⁵

المصدر: Transplant Infectious Disease. Mar2004, Vol. 6 Issue 1, p33-36. 4p.

مصطلحات موضوعية: *CRYPTOCOCCOSIS, *CARDIAC surgery, *HEART transplantation, *HEART transplant recipients, *TOMOGRAPHY, *DYSPNEA

مستخلص: Cryptococcosis primarily occurs in patients with impaired immune response. While pulmonary and/or cerebral involvement are more often described, there is limited experience of its presence in other sites. We present a case of hepatic cryptococcosis with possible pulmonary involvement in a 54-year-old male heart transplant recipient. Two months after heart transplantation, he developed a persistent, moderate dyspnea with fever and signs of liver damage. Diagnosis was made with liver biopsy for a concurrent reactivation of chronic hepatitis B virus (HBV) infection already present before transplant. Along with a mild chronic HBV hepatitis with fibrosis, we observed sinusoidal dilation and groups of bright, rounded, colorless cells with a central nucleus suggestive of cryptococci. Periodic acid–Schiff stain clearly showed encapsulated yeasts, which supported the diagnosis. Cryptococcal antigen was positive in serum and negative in the cerebrospinal fluid. Computed tomography scan of the chest demonstrated a mild interstitial infiltrate. The patient promptly responded to reduction of immunosuppressive therapy and antifungal treatment with amphotericin B lipid complex and flucytosine followed by maintenance treatment with fluconazole. Cryptococcosis should always be considered in the differential diagnosis in immunocompromised hosts with dyspnea and signs of extrapulmonary involvement. Diagnosis of extrapulmonary and extraneural cryptococcosis is difficult and often fortuitous; a histopathological examination of tissues involved is probably warranted. [ABSTRACT FROM AUTHOR]

المؤلفون: Utili, R., Muto, P., Baiano Svizzero, G., Bifulco, M., Mattucci, I., Senese, A., D'Amico, F., Pinto, D., Agrusta, F., Malgeri, U., Andini, R., Cesaro, F., Farinaro, V., Iorio, V., Cavezza, G., Graziano, C., Battimelli, C., Savinelli, C., Trojaniello, C., De Rimini, M.

المصدر: International Journal of Antimicrobial Agents. May2013 Supplement, Vol. 41, pS17-S17. 1p.

المؤلفون: Santini, C., Utili, R., De Feo, M., Vaglio, F., Gattuso, G.

المصدر: International Journal of Antimicrobial Agents. Jun2009 Supplement 2, Vol. 33, pS8-S9. 0p.

المؤلفون: Tripodi, M.-F.^1,2, Fortunato, R.¹, Utili, R.^2,3 riccardo.utili@ospedalemonaldi.it, Triassi, M.⁴, Zarrilli, R.⁴

المصدر: Clinical Microbiology & Infection. Oct2005, Vol. 11 Issue 10, p814-819. 6p.

مصطلحات موضوعية: *STREPTOCOCCUS, *ENDOCARDITIS, *MOLECULAR epidemiology, *BACTEREMIA, *BACTERIAL diseases

مستخلص: Streptococcus bovis is being recognised increasingly as a cause of infective endocarditis, and has also been associated with underlying gastrointestinal malignancy. This study evaluated the molecular epidemiology of S. bovis isolates responsible for endocarditis or bacteraemia in Italian patients between January 1990 and August 2003. S. bovis isolates were classified on the basis of their biochemical profiles, antimicrobial susceptibilities and genotypes. Of 25 isolates studied, 20 were S. bovis I and five were S. bovis II. Seven biochemical profiles were identified. Pulsed-field gel electrophoresis (PFGE) analysis identified 22 profiles that differed by at least two DNA fragments and showed a similarity of < 87%. Most PFGE patterns represented single isolates that differed in antimicrobial susceptibility, but three PFGE types were observed, with identical profiles and antibiotypes, in isolates from two different patients. S. bovis I and II isolates grouped into two distinct genetic clusters (I and II) with a similarity coefficient of 38%. Two sub-clusters (Ia and Ib), with a similarity coefficient of 47%, included 17 S. bovis I isolates with similar biochemical profiles (15 with biotype A, and two with biotype B), but different resistance phenotypes. Based on the phenotypic and genotypic heterogeneity of the isolates, it is postulated that the increase in S. bovis endocarditis in this geographical area might have been caused by the selection of sporadic endemic clones from the endogenous intestinal flora. [ABSTRACT FROM AUTHOR]

المؤلفون: Durante-Mangoni, E.¹, Andini, R.¹, Signoriello, S.², Cavezza, G.¹, Murino, P.³, Buono, S.³, De Cristofaro, M.⁴, Taglialatela, C.⁴, Bassetti, M.⁵, Malacarne, P.⁶, Petrosillo, N.⁷, Corcione, A.³, Viscoli, C.⁸, Utili, R.¹ riccardo.utili@unina2.it, Gallo, C.²

المصدر: Clinical Microbiology & Infection. Dec2016, Vol. 22 Issue 12, p984-989. 6p.

مصطلحات موضوعية: *KIDNEY injuries, *COLISTIN, *ACINETOBACTER baumannii, *NEPHROTOXICOLOGY, *DRUG side effects, *DRUG resistance in bacteria, *SURVIVAL analysis (Biometry), *INJURY risk factors, *THERAPEUTICS, RISK factors

مستخلص: The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii . The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii . Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were ‘time to any kidney injury’ (AKI stages 1–3) and ‘time to severe kidney injury’ (considering only AKI stages 2–3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4–6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither ‘any’ nor ‘severe AKI’ were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated. [ABSTRACT FROM AUTHOR]

المؤلفون: Durante‐Mangoni, E.^1,2, Vitrone, M.¹, Parrella, A.¹, Andini, R.¹, Iossa, D.¹, Ragone, E.², Falco, E.³, Maiello, C.⁴, Utili, R.^1,2, Zampino, R.¹

المصدر: Transplant Infectious Disease. Jun2016, Vol. 18 Issue 3, p319-325. 7p.

مصطلحات موضوعية: *TENOFOVIR, *MEDICATION safety, *DRUG efficacy, *HEPATITIS B treatment, *GLOMERULAR filtration rate, *HEART transplantation, *ANTIVIRAL agents

مستخلص: Background Treatment of chronic hepatitis B ( CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. Methods In this prospective, observational study, we assessed outcomes of therapy with tenofovir ( TDF), entecavir ( ETV), and telbivudine (LdT) in 13 heart transplant recipients ( HTR) with CHB. Results Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus ( HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate ( GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF ( n = 9) or LdT ( n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed. Conclusions This study indicates that newer antivirals are effective and safe in HTR with CHB. [ABSTRACT FROM AUTHOR]

المؤلفون: Seminari, E.¹ e.seminari@smatteo.pv.it, Silvestri, A.², Ravasio, V.³, Ludovisi, S.¹, Utili, R.⁴, Petrosillo, N.⁵, Castelli, F.⁶, Bassetti, M.⁷, Barbaro, F.⁸, Grossi, P.⁹, Barzaghi, N.¹⁰, Rizzi, M.³, Minoli, L.¹

المصدر: European Journal of Clinical Microbiology & Infectious Diseases. Feb2016, Vol. 35 Issue 2, p279-284. 6p.

مصطلحات موضوعية: *LIVER failure, *LIVER diseases, *LIVER disease diagnosis, *INPATIENT care, *ENDOCARDIUM diseases, *INFECTIVE endocarditis, *PATIENTS, *GENETICS

مستخلص: Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD− patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species ( S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD− patients ( p = 0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p < 0.001); embolization (43.3 % versus 26.1 %, p < 0.001) and congestive heart failure (42 % versus 34.1 %, p = 0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD− and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required. [ABSTRACT FROM AUTHOR]

المؤلفون: Tripodi, M.-F.¹, Durante-Mangoni, E.¹, Fortunato, R.¹, Cuccurullo, S.¹, Mikami, Y.², Farina, C.³, Utili, R.¹ riccardo.utili@ospedalemonaldi.it

المصدر: Transplant Infectious Disease. Aug2011, Vol. 13 Issue 4, p335-343. 9p. 4 Charts.

مصطلحات موضوعية: *LUNG disease treatment, *NOCARDIA, *HEART transplant recipients, *ANTIBIOTICS, *ANTIBACTERIAL agents

مستخلص: M.-F. Tripodi, E. Durante-Mangoni, R. Fortunato, S. Cuccurullo, Y. Mikami, C. Farina, R. Utili. In vitro activity of multiple antibiotic combinations against Nocardia: relationship with a short-term treatment strategy in heart transplant recipients with pulmonary nocardiosis. Transpl Infect Dis 2011: 13: 335-343. All rights reserved Background/objectives. Pulmonary nocardiosis (PN) chiefly affects immunocompromised patients, particularly transplant recipients. Cotrimoxazole is still the mainstay of treatment, but it is associated with nephro- and myelo-toxicity, and can show unpredictable activity against Nocardia isolates. Methods. Over a 20-year period, Nocardia isolates were identified from 12 heart transplant (HTx) recipients with PN. The in vitro activity of various antibacterials, alone or in combination, was assessed using disk-diffusion, minimal inhibitory concentration (MIC), and time-kill methodology. The in vitro results were compared with the clinical outcome of the patients. Results. Seven different Nocardia strains were identified. Disk diffusion and MIC determinations showed that all isolates were susceptible to amikacin, netilmicin, and linezolid, and that moxifloxacin was the most active of the fluoroquinolones. All but 1 of the isolates were susceptible to imipenem. Time-kill studies showed that imipenem/amikacin and imipenem/moxifloxacin combinations were bactericidal for most isolates. Of 12 patients who received 3−4 weeks' intravenous (IV) treatment with amikacin or ciprofloxacin in combination with a beta-lactam, followed by 1−3 months' oral cotrimoxazole, moxifloxacin, or linezolid, 11 were cured; 1 patient died, but not related to Nocardia. Conclusion. Initial PN treatment in HTx recipients can be successfully carried out with bactericidal combinations such as imipenem plus amikacin or moxifloxacin, administered IV for 3-4 weeks. Within 1 month, a significant clinical and radiological improvement may be observed. In our experience, a <3 month oral regimen with cotrimoxazole, moxifloxacin, or doxycycline may then be used. This may allow a reduction of side effects and treatment-related burden, without any recurrence. [ABSTRACT FROM AUTHOR]

المؤلفون: Durante-Mangoni, E.^1,2 emanuele.durante@unina2.it, Ragone, E.^1,2, Pinto, D.^1,2, Iossa, D.^1,2, Covino, F.E.³, Maiello, C.³, Utili, R.^1,2

المصدر: Transplantation Proceedings. Jan2011, Vol. 43 Issue 1, p299-303. 5p.

مصطلحات موضوعية: *HEPATITIS C treatment, *INTERFERONS, *HEART transplant recipients, *RIBAVIRIN, *DRUG efficacy, *HEALTH outcome assessment, *TREATMENT duration, *ECHOCARDIOGRAPHY

مستخلص: Abstract: Background/aim: The combination of pegylated interferon (PEG-IFN) and ribavirin (RBV) is the current treatment for chronic hepatitis C (CHC). The treatment is thought to suppress viral replication and induce viral clearance via immunomodulatory effects. For this reason, concern exists for the use of this treatment in recipients of a solid organ transplantation. We sought to evaluate the safety and efficacy of PEG-IFN/RBV in heart transplant recipients with CHC. Methods: From June 2005 to September 2009, we treated three CHC patients with heart transplantation. PEG-IFN alpha2b and RBV doses and treatment duration were set according to the hepatitis C virus (HCV) genotype and body weight as per current recommendations. Dose reductions were dictated by individual patient tolerability. Cardiac safety was monitored by clinical examinations, echocardiography, and measurement of troponin I and B-type natriuretic peptide, as well as endomyocardial biopsies. Results: All three patients, displayed HCV genotype 1b infection, viral loads of >5 logs, and a Scheuer fibrosis score ≥ 2. Two of them completed the prescribed treatment course becoming sustained virological responders. The other patient had an initial complete virological response, but subsequently experienced a viral breakthrough after reduction of PEG-IFN and withdrawal of RBV due to severe anemia. We observed no cardiovascular adverse events nor rejection episodes. Posttreatment clinical history and examination, electrocardiography, and echocardiography did not show any sign of graft dysfunction. Conclusions: Treatment with PEG-IFN/RBV may be safely offered to stable heart transplant recipients with CHC and signs of liver disease progression. Close monitoring of treatment safety is mandatory. [Copyright &y& Elsevier]