Efficacy and Safety of Remdesivir over Two Waves of the SARS-CoV-2 Pandemic.

The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment (p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.

Cure of recurring Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae septic shock episodes due to complicated soft tissue infection using a ceftazidime and avibactam-based regimen: a case report.

BACKGROUND: Infections caused by multidrug-resistant Enterobacteriaceae are hard to treat and life-threatening due to reduced therapeutic options. Systemic infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae strains have increased in many European regions, becoming frequent in many clinical settings, and are associated with high mortality. The co-formulation of ceftazidime, a third-generation cephalosporin, with avibactam, a new suicide inhibitor beta-lactamase inhibitor able to block most Klebsiella pneumoniae carbapenemases, has been recently licensed, with promising results in patients with limited or absent therapeutic options. Little is known, however, as to the efficacy of such a combination in patients with soft tissue infections caused by multidrug-resistant Klebsiella pneumoniae carbapenemase-producing strains of Klebsiella pneumoniae. CASE PRESENTATION: A Caucasian 53-year-old man with paraplegia suffered multiple vertebral fractures due to a car crash. He was treated with external fixators that became infected early after insertion and were repeatedly and inefficiently treated with multiple antibiotics. He suffered repeated septic episodes caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae strains with a multidrug-resistant profile. Meropenem, tigecycline, and colistin combinations allowed only temporary improvements, but septic shock episodes recurred, in spite of removal of infected external fixators. After approval of pre-marketing prescription by our local Ethics Committee, full clinical resolution was obtained with a compassionate treatment using meropenem and ceftazidime/avibactam in combination for 16 days. CONCLUSIONS: Our experience provides additional evidence that ceftazidime/avibactam, possibly in combination with meropenem rescued by avibactam, may be an efficacious treatment option also for complicated skin and soft tissue infections caused by multidrug-resistant strains of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae.

Prevalence of HBV genotypes in South American immigrants affected by HBV-related chronic active hepatitis.

This study evaluated the prevalence of HBV infection in a population of South American immigrants in Italy and to determine in patients with detectable serum HBV-DNA the HBV genotypes. Between April 2005 and April 2006 a total of 130 South American immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV genotype was determined by INNOLiPA. Among the 130 subjects tested, 14 (10.7%) resulted HBsAg positive. All were men, with a mean age of 22 years (range 19-37) and 12 (85.7 %) came from Brazil, while 2 (14.3%) came from Ecuador. All patients infected by HBV had elevated alanine-aminotransferase serum levels (mean level was 127 IU/L, range 74-312) and serum HBV DNA detectable by PCR-Real Time (mean level 1,037,652 copies/mL, range 19,876-1,377,648). Genotype distribution was as follow: genotype D, 9 (64.2%), genotype A, 5 (35.8%). All patients infected by genotype D came from Brazil, while among the patients infected by genotype A, three came from Brazil and two from Ecuador. Our study evidences a moderate prevalence of HBV-infection in South American immigrants with the identification of two genotypes, D and A. These genotypes are not the most prevalent in the South America and this is probably the expression of a possible geographical redistribution of HBV genotypes.

Prevalence of HBV-genotypes in immigrants affected by HBV-related chronic active hepatitis.

BACKGROUND: The genetic heterogeneity of the HBV genome has been established and eight genotypes can be classified according to the criterion of >8% differences in the complete nucleotide sequence of the viral genome. AIMS: To evaluate the prevalence of HBV-infection in a population of immigrants and to determine in patients with detectable serum HBV-DNA the HBV-genotypes. METHODS: Between January 2005 and December 2005 a total of 556 immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV-genotype was determined by INNOLiPA. RESULTS: Among the 556 subjects tested, 60 (10.7%) resulted HBsAg positive. All were men, and 42 (70%) come from Africa, 10 (16.6%) from Asia and 9 (14.4%) from East-Europe. 28/60 (46.6%) patients presented normal ALT levels (<40 IU/L) and undetectable serum HBV DNA (<100 copies/mL in real-time PCR), while 32 (53.4%) patients had ALT levels above laboratory normal values and detectable serum HBV DNA. Genotype distribution was as follow: genotype E, 16 (50%), genotype D, 9 (28.1%), genotype A, 7 (21.9%). CONCLUSION: Our study evidences a moderate prevalence of HBV-infection in immigrants, particularly in sub-Saharan African people, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus, potentially characterized by a different natural history and, possibly, a different response to antiviral treatment.

Prevalence of HBV genotypes in South American immigrants affected by HBV-related chronic active hepatitis

This study evaluated the prevalence of HBV infection in a population of South American immigrants in Italy and to determine in patients with detectable serum HBV-DNA the HBVgenotypes. Between April 2005 and April 2006 a total of 130 South American immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV genotype was determined by INNOLiPA. Among the 130 subjects tested, 14 (10.7 percent) resulted HBsAg positive. All were men, with a mean age of 22 years (range 19-37) and 12 (85.7 percent) came from Brazil, while 2 (14.3 percent) came from Ecuador. All patients infected by HBV had elevated alanine-aminotransferase serum levels (mean level was 127 IU/L, range 74-312) and serum HBV DNA detectable by PCR-Real Time (mean level 1,037,652 copies/mL, range 19,876-1,377,648). Genotype distribution was as follow: genotype D, 9 (64.2 percent), genotype A, 5 (35.8 percent). All patients infected by genotype D came from Brazil, while among the patients infected by genotype A, three came from Brazil and two from Ecuador. Our study evidences a moderate prevalence of HBV-infection in South American immigrants with the identification of two genotypes, D and A. These genotypes are not the most prevalent in the South America and this is probably the expression of a possible geographical redistribution of HBV genotypes.

Prevalence of HBV-genotypes in immigrants affected by HBV-related chronic active hepatitis

BACKGROUND: The genetic heterogeneity of the HBV genome has been established and eight genotypes can be classified according to the criterion of >8 percent differences in the complete nucleotide sequence of the viral genome. AIMS: To evaluate the prevalence of HBV-infection in a population of immigrants and to determine in patients with detectable serum HBV-DNA the HBV-genotypes. METHODS: Between January 2005 and December 2005 a total of 556 immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV-genotype was determined by INNOLiPA. RESULTS: Among the 556 subjects tested, 60 (10.7 percent) resulted HBsAg positive. All were men, and 42 (70 percent) come from Africa, 10 (16.6 percent) from Asia and 9 (14.4 percent) from East-Europe. 28/60 (46.6 percent) patients presented normal ALT levels (<40 IU/L) and undetectable serum HBV DNA (<100 copies/mL in real-time PCR), while 32 (53.4 percent) patients had ALT levels above laboratory normal values and detectable serum HBV DNA. Genotype distribution was as follow: genotype E, 16 (50 percent), genotype D, 9 (28.1 percent), genotype A, 7 (21.9 percent). CONCLUSION: Our study evidences a moderate prevalence of HBV-infection in immigrants, particularly in sub-Saharan African people, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus, potentially characterized by a different natural history and, possibly, a different response to antiviral treatment.

RACIONAL: A heterogeneidade do genoma do vírus da hepatite B (VHB) foi estabelecida e oito genótipos podem ser classificados de acordo com o critério de diferenças de percentagem maior ou igual a 8 na seqüência completa do nucleotídeo do genoma vira!. OBJETIVOS: Verificar a prevalência da infecção pelo vírus da hepatite B (VHB) em uma população de imigrantes na Itália e determinar os genótipos do VHB em pacientes com níveis séricos detectáveis do VHB-DNA. MÉTODOS: Entre janeiro e dezembro de 2005, o total de 556 imigrantes foram testados para o HbsAg. Se positivos, a atividade bioquímica e viral da infecção e a possível presença de co-infecções (HVC, HVD e HIV) foram examinadas. Nos pacientes positivos para o VHB-DNA, o genótipo do VHB foi determinado pelo método INNOLiPA. RESULTADOS: Entre os 556 pacientes, 60 (10,7 por cento) tinham HbsAg positivo. Todos eram do sexo masculino e 42 (70 por cento), provenientes da Africa, 10 (16,6 por cento) da Asia e 9 (14,4 por cento) do Leste Europeu. 28/60 (46,6 por cento) apresentaram níveis de ALT normais (<40 UI/L) e soro negativo ou indetectável para o VHB-DNA (<100 copies/mL PCR "real-time"), enquanto 32 (53,4 por cento) tinham níveis mais elevados de ALT e soro positivo para VHB-DNA. A distribuição do genótipo foi a seguinte: genótipo E, 16 (50 por cento), genótipo D, 9 (28,1 por cento), genótipo A, 7 (21,1 por cento). CONCLUSÃO: O estudo evidencia a prevalência moderada do HVB em imigrantes, particularmente na população africana, sub-Sahara e o potencial fluxo migratório na introdução da hepatite B, genótipo não-D, potencialmente caracterizada pela história natural e possivelmente levar à diferença no tratamento anti-viral.

Efficacy and tolerability of lamivudine alone versus lamivudine plus alpha-interferon for treatment of chronic active hepatitis B in patients with a precore-mutant variant.

The aim of our study was to assess the efficacy and tolerability of lamivudine alone versus lamivudine plus alpha-interferon for treatment of chronic active hepatitis B, anti-HBe positive. In all, 59 patients were randomly divided into 3 groups: A) 21 patients received lamivudine at 100 mg/daily orally for 52 weeks; B) 20 patients received lamivudine at 100 mg/die plus alpha-interferon at 6 MU subcutaneously three times weekly for 52 weeks; C) 18 patients received the same combination therapy for 40 weeks after pre-treatment with lamivudine for 12 weeks. The complete sustained response in the three groups was 33.3% vs 35.0% vs 33.3%, respectively. Our study demonstrates that in anti-HBe positive chronic hepatitis B a 12-month course of lamivudine plus a-interferon combination therapy is as beneficial as lamivudine monotherapy. Moreover, the combination therapy for 40 weeks after pre-treatment with lamivudine for 12 weeks did not increase the sustained response.

Prolonged lamivudine treatment in patients with chronic active anti-HBe-positive hepatitis.

The efficacy of lamivudine (LAM) at 100 mg/d for 1 year in normalizing serum ALT levels and suppressing HBV DNA has been demonstrated in many studies. However, frequent relapses make long-term results modest. In the present study, we evaluated the efficacy of LAM administered for 3 years in patients with chronic active anti-HBe-positive hepatitis. Thirty-four patients with chronic active anti-HBe-positive hepatitis were treated with LAM (100 mg) once daily for 3 years. Before treatment, all patients demonstrated serum ALT levels >2 times normal levels for >6 months and HBV DNA positivity >5 pg/mL as determined by the sandwich hybridization test for nucleic acid. Both ALT and HBV DNA were monitored during therapy. After 12 months of therapy, 24 of 34 patients (70.6%) showed evidence of HBV DNA clearance and normal ALT levels; 22 of 34 (64.7%) and 19 of 34 (55.8%) patients maintained a complete response after 2 and 3 years of therapy, respectively. The long-term LAM therapy (>1 year) was not associated with an increase in the response of intially nonresponder patients. The YMDD variant emerged in 17.6% of patients in the first year, in 35.2% during the second year, and 52.9% during the third year of treatment. LAM was well tolerated during the 3-year therapy in all patients. Patients with chronic active anti-HBe-positive hepatitis demonstrated that the LAM response rate tends to decrease over time due to the emergence of YMDD variants.

Treatment of genotype 1b HCV-related chronic hepatitis: efficacy and toxicity of three different interferon alfa-2b/ribavirin combined regimens in naive patients.

This prospective open-label randomized trial of chronic hepatitis C genotype-1b patients compared compared the efficacy and safety of peg-interferon alfa-2b administered once-weekly versus interferon alfa-2b thrice-weekly or daily, both in combination with ribavirin. Seventy-eight previously untreated patients, with biopsy-documented genotype 1 chronic HCV and persistently elevated ALT levels and detectable HCV RNA, were randomized (26 subjects each) to receive: interferon alfa-2b at 6MIUs.c./three-times-weekly (group A) or interferon alfa-2b, 3MIUs.c./daily (group B) or peg-interferon alfa-2b 1.5mcg/Kg s.c./once-weekly (group C). All regimens included standard weight-based doses of ribavirin (800, 1,000 or 1,200 mg/day) administered for 52-weeks. Patients in the three groups were comparable for age, sex, viral load, ALT value and histological-activity-index (HAI). Therapy was completed by 22, 20 and 23 patients in groups A, B and C, respectively. At the end of treatment, a complete (biochemical and virological) response was observed in 50.0% patients of group A, 57.7% of group B and 65.4% of group C. After an additional 24-weeks of follow-up, a sustained response was observed in 26.9%, 46.1% and 50.0% of patients in groups A, B or C, respectively. Therapy was discontinued by 4, 6 and 2 patients because of adverse events in the above three groups. In naive patients with chronic genotype-lb hepatitis C, a 48 week therapy with peg-interferon or interferon at daily doses combined with ribavirin were both more effective than treatment with thrice-weekly interferon in inducing end of treatment and sustained response. Peg-interferon treatment was better tolerated and provoked significantly fewer therapy discontinuations.

[Mixed cryoglobulinemia in HCV mono-infected and HCV/HIV co-infected patients]. / Crioglobulinemia mista in pazienti con infezione da HCV e con coinfezione HCV/HIV.

The aim of our study was to compare the prevalence of mixed cryoglobulinemia in a group of HCV positive/HIV- negative patients with respect to a group of HCV/HIV co-infected subjects. Between September 2002 and May 2003, 58 patients with proven HCV infection and 67 subjects with HIV/HCV co-infection were enrolled. Serum was assessed for detectable cryoglobulins, liver enzymes, HCV viral load and HCV genotypes. In HIV positive patients, plasma HIV RNA and CD4+ cell count were determined. A chi-square test was used to compare the prevalence of cryoglobulins in our two categories of patients. Cryoglobulinemia was detected in 14/58 HCV mono-infected patients (24.1%) and in 10/67 HCV/HIV co-infected patients (14.9%), without any significant statistical difference between the two groups (p=0.2). Only two HCV mono-infected patients complained of arthralgia. No significant correlation was found between the presence of cryoglobulinemia and ALT levels, HCV viremia and duration of HCV infection. In HIV patients circulating cryoglobulins were not correlated with plasma HIV viral load, CD4 cell count and with duration of HIV infection. In conclusion, mixed cryoglobulinemia may be detected in a similar rate in the two groups and HIV infection does not appear to play a significant role in cryoglobulin production.

[Epidemiology of tuberculosis in immigrant patients hospitalised in Infectious Diseases Units in Italy: multicentric study]. / Epidemiologia della tubercolosi tra gli immigrati ricoverati in Italia presso Unità Operative di Malattie Infettive. Uno studio multicentrico.

In order to retrospectively evaluate the prevalence of immigrant patients affected by active tuberculosis, we analysed the clinical data of 2255 immigrant patients hospitalised during 2002 in ordinary admission or in Day Hospital in 48 Clinics of Infectious Diseases. In all, 303 patients were affected by active tuberculosis (13.4% of the total immigrant hospitalised patients); 30 patients (9.9%) were also HIV-positive. There was a considerable male gender bias (62.5%); the mean age was 29.7 years; 144 patients were from Africa (47.5%), 72 (23.7%) from Asia, 47 (15.5%) from eastern Europe and 40 (13.2%) from South America. The clinical variants were: pulmonary (57.7%), lymph node (15.8%), meningitis (13.8%), intestinal (4.2%), bone (3.3%), pleurical (2.3%), peritoneal (2.3%) and renal (0.6%). We conclude that tuberculosis is a very frequent disease among immigrants, especially of African origin. The high percentage is due to several factors, such as no vaccine prophylaxis and poor, overcrowded living conditions. It is fundamental to focus on the need to provide better health support for all subjects by setting up screening plans to estimate the real incidence of this pathology and ensure medical treatment to prevent the spread of this infection among immigrants and the local host population.