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: 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: 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: MARRONE, A.¹ (AUTHOR), ZAMPINO, R.¹ (AUTHOR), KARAYANNIS, P.² (AUTHOR), CIRILLO, G.³ (AUTHOR), CESARO, G.¹ (AUTHOR), GUERRERA, B.¹ (AUTHOR), RICCIOTTI, R.¹ (AUTHOR), MIRAGLIA DEL GIUDICE, E.³ (AUTHOR), UTILI, R.⁴ (AUTHOR), ADINOLFI, L. E.¹ (AUTHOR), RUGGIERO, G.¹ (AUTHOR)

المصدر: Alimentary Pharmacology & Therapeutics. Oct2005, Vol. 22 Issue 8, p707-714. 8p. 3 Charts.

مصطلحات موضوعية: *HEPATITIS B virus, *DRUG resistance, *VIRUS inhibitors, *ANTIVIRAL agents, *LIVER diseases, *VIRAL hepatitis, *GENETIC mutation, *THERAPEUTICS

مستخلص: Background : Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. Aim : To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. Methods : Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. Results : ‘Polymerase region’: M204V/I variants were found in all group A patients, but in none of group B1 ( P = 0.0007) and in four of nine of group B2 (44%; P = 0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. ‘Core promoter’: the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P = 0.03) of group B1 and one of nine (11%; P = 0.002) of group B2 patients. ‘Precore’: the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five ( P = 0.004) of group B1 and one of nine (11%; P = 0.002) of group B2. Conclusions : Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation. [ABSTRACT FROM AUTHOR]

المؤلفون: Marrone, A.¹ aldo.marrone@unina2.it, Zampino, R.¹, Portella, G.², Grimaldi, M.², Mangoni, E. D.¹, Santarpia, L.¹, Ruggiero, G.¹, Utili, R.³

المصدر: Journal of Viral Hepatitis. Mar2005, Vol. 12 Issue 2, p186-191. 6p.

مصطلحات موضوعية: *INTERFERONS, *HEPATITIS B, *ANTINEOPLASTIC agents, *LYMPHOKINES, *GLYCOPROTEINS, *ANTIVIRAL agents, *LIVER diseases

مستخلص: Alpha-interferon (IFN) or lamivudine monotherapy are ineffective in treating chronic HBeAg positive patients with high viral load and low alanine aminotransferase (ALT) levels. We investigated whether priming lamivudine treatment might enhance the antiviral and immunostimulant action of lamivudine/IFN combination in young tolerant patients. Eleven chronic HBeAg positive patients received: 100 mg/day lamivudine for 3 months followed by IFN 5 MU/m2/tiw with lamivudine 100 mg/day for 6 months and then lamivudine alone 100 mg/day for 9 months. Quantitative hepatitis B virus (HBV)-DNA was evaluated during treatment and core-promoter, precore and polymerase HBV mutants were detected by direct sequencing at the end of therapy. Serum HBV-DNA levels dropped during lamivudine monotherapy and in combination with IFN. After IFN withdrawal, viraemia transiently increased to high levels in five of 11 (45%) patients who showed rt M204V/I lamivudine mutant resistant. Two patients cleared HBeAg without anti-HBe seroconversion. One patient presented core-promoter (A1762T/G1764A) and precore stop codon mutations. Hence, three-phase sequential combined lamivudine/IFN treatment reduced HBV-DNA serum level, but did not lead to HBeAg and HBV-DNA clearance in these highly viraemic, normal ALT patients. Lamivudine/IFN combination did not prevent the emergence of YMDD lamivudine resistance. New schedules of antiviral treatments must be evaluated in this population at risk of disease progression. [ABSTRACT FROM AUTHOR]

المؤلفون: Zampino, R¹, Marrone, A¹, Cirillo, G², del Giudice, E. Miraglia², Utili, R¹, Karayiannis, P³, Liang, T. J⁴, Ruggiero, G¹

المصدر: Journal of Viral Hepatitis. May2002, Vol. 9 Issue 3, p183-188. 6p.

مصطلحات موضوعية: *HEPATITIS B, *VIRAL hepatitis, *INTERFERONS

مستخلص: We analysed the hepatitis B virus (HBV) core-promoter (CP) and precore (PC) regions before, during and after interferon treatment in young Caucasian cancer survivors who had acquired HBV infection during chemotherapy for malignancies. Fourteen patients with chronic hepatitis B [hepatitis B e antigen (HBeAg) /HBV-DNA positive] received α-2a interferon (IFN), 5 MU/m2 t.i.w. for 12 months. HBV CP and PC region sequences were analysed following polymerase chain reaction (PCR) amplification. Sera from responders were studied at: T0 (before starting IFN), T1 [at alanine aminotransferase (ALT) peak preceding HBeAg seroconversion], T2 (at ALT normalization), T3 (at end of IFN) and T4 (at one year after IFN) and in nonresponders at time points T0 , T3 and T4 . Amplified HBV-DNA was cloned and sequenced automatically. Six of 14 patients (43%) responded to IFN treatment. Five of the six (83%) responders displayed the double CP mutation A1762T/G1764A always in association with a T1753C change. None of the nonresponders showed these mutations at any time point. The G1896A change creating the PC stop codon mutation was never detected in any of the patients. In our cancer survivors, IFN-induced HBeAg/anti-HBe seroconversion appeared to correlate with CP mutations and was not influenced by previous chemotherapy. These mutations in addition to low HBV DNA levels and elevated ALT can be considered favourable factors of response to IFN-induced anti-HBe seroconversion. [ABSTRACT FROM AUTHOR]