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PURPOSE: Non-tuberculous mycobacteria (NTM) account for high clinical burden, and treatment can be challenging. Moreover, accessibility of NTM medications varies across centers. These challenges may lead to unplanned therapeutic changes, discontinuations, potentially affecting patient outcomes. Aim of this survey was to evaluate the accessibility of NTM-targeting drugs in Italy (with a particular focus on clofazimine) in centers associated with the IRENE Registry, a collaborative network of healthcare professionals. METHODS: A cross-sectional, internet-based, questionnaire-survey on the use and availability of clofazimineand other NTM-targeting drugs was sent to 88 principal investigators of the IRENE network in Italyin 2020. The questionnaires were designed with closed-ended and open-ended questions and distributed using the SurveyMonkey® platform. RESULTS: The surveys underscore the more frequent involvement of pulmonologists (42%) and infectious disease specialists (34%) in NTM treating strategies. Respondents were distributed across 18 out of20 Italian regions, with a significant concentration in the north, encompassing university hospitalsand outpatient clinics. Molecular testing is available in 40% of the involved centers, while phenotypic in 30% of the centers. Centers have a multidisciplinary team and an appointed pharmacy service for NTM drugs distribution in 10 and 75% of the cases, respectively. Substantial variability was observed in drug availability and accessibility, drug regimen composition, and drug dosage, particularly for medications like clofazimine. CONCLUSIONS: This study shows the high heterogeneity of anti-NTM drug availability in Italy and prompts toward a harmonization in antibiotic prescription and access; it also emphasizes the challenges in determining the optimal therapeutic strategies for treating NTM-infections.
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Background and Objectives: the principal purpose of this literature review is to cluster adults with hematological malignancies after treatment or on maintenance with obinutuzumab who experienced disseminated EV infection to understand clinical characteristics and outcome of this rare condition in these patients. We report the first clinical case of a male affected by follicular lymphoma treated with immune-chemotherapy including obinutuzumab who was affected by disseminated EV infection with cardiovascular involvement. Materials and Methods: this narrative review summarizes all the research about disseminated EV infection in immunosuppressed adult patients treated with obinutuzumab from January 2000 to January 2024 using the Scale for the Assessment of Narrative Review Articles (SANRA) flow-chart. We performed a descriptive statistic using the standard statistical measures for quantitative data. Results: we included six studies, five case reports, and one case report with literature analysis. We collected a total of seven patients, all female, with disseminated EV infection. The most common signs and clinical presentations of EV infection were fever and encephalitis symptoms (N = 6, 85.7%), followed by hepatitis/acute liver failure (N = 5, 71.4%). Conclusions: onco-hematological patients who receive immune-chemotherapy with a combination of treatments which depress adaptative immunity, which includes the antiCD20 obinutuzumab, could be at higher risk of disseminated EV infection, including CNS and cardiac involvement.
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Infecções por Enterovirus , Linfoma Folicular , Adulto , Humanos , Masculino , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Enterovirus/complicações , Infecções por Enterovirus/tratamento farmacológico , Linfoma Folicular/complicações , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologiaRESUMO
Background and Objectives: Stenotrophomonas maltophilia is a ubiquitous, aerobic, Gram-negative bacillus causing increasing concern in patients affected by haematological malignancies. Materials and Methods: We report a case series from two centres in Northern Italy to describe the characteristics, outcome and microbiological response of S. maltophilia infections in patients with haematological malignancies and/or allogenic hematopoietic stem cell transplantation (aHSCT). Results: Ten patients were included. The median age was 67 years, and seven patients (70%) were males. The median Charlson Comorbidity Index was 6 (IQR: 4-8). The most frequent haematological comorbidities were acute myeloid leukaemia (AML; n = 3; 30%) and non-Hodgkin's lymphoma (n = 3; 30%). Three (30%) patients underwent aHSCT before infection, all for AML. All the patients had undergone a recent antibiotics course and had an indwelling central venous catheter before infection. The main clinical presentations were nosocomial pneumonia, with (2; 20%) or without (4; 40%) secondary bloodstream infection and CRBSI (3; 30%). Four patients were treated with cefiderocol in monotherapy or combinations therapy with cotrimoxazole. The rest of the patients were treated with cotrimoxazole or levofloxacin in monotherapy. Conclusions: Despite a high rate of clinical improvement (90%) after starting antimicrobial therapy, we faced high 30-day mortality (30%) and in-hospital mortality (50%) rates in a highly comorbid population.
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Coinfecção , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Stenotrophomonas maltophilia , Masculino , Humanos , Idoso , Feminino , Cefiderocol , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapiaRESUMO
The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.
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Antibacterianos , Ceftazidima , Combinação de Medicamentos , Farmacorresistência Bacteriana , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , beta-Lactamases/genética , COVID-19/epidemiologia , Unidades de Terapia Intensiva , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Meropeném/farmacologia , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Pandemias , Estudos RetrospectivosRESUMO
Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer-BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long-term effects and to assess the vaccine safety and efficacy in the general population.
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COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Tecnologia , Desenvolvimento de VacinasRESUMO
INTRODUCTION: A lack of updated data on the burden and profile of anaerobic bloodstream infections (ABIs) exists. We assessed the incidence of ABIs and trends in antimicrobial resistance in anaerobes isolated from blood in Italy. MATERIAL AND METHODS: We conducted a retrospective study on 17 Italian hospitals (2016-2020). Anaerobes isolated from blood culture and their in vitro susceptibility profiles (EUCAST-interpreted) were registered and analyzed. RESULTS: A total of 1960 ABIs were identified. The mean age of ABIs patients was 68.6 ± 18.5 years, 57.6% were males. The overall incidence rate of ABIs was 1.01 per 10.000 patient-days. Forty-seven% of ABIs occurred in medical wards, 17% in ICUs, 14% in surgical wards, 7% in hemato-oncology, 14% in outpatients. The three most common anti-anaerobic tested drugs were metronidazole (92%), clindamycin (89%) and amoxicillin/clavulanate (83%). The three most common isolated anaerobes were Bacteroides fragilis (n = 529), Cutibacterium acnes (n = 262) and Clostridium perfringens (n = 134). The lowest resistance rate (1.5%) was to carbapenems, whereas the highest rate (51%) was to penicillin. Clindamycin resistance was >20% for Bacteroides spp., Prevotella spp. and Clostridium spp. Metronidazole resistance was 9.2% after excluding C. acnes and Actinomyces spp. Bacteroides spp. showed an increased prevalence of clindamycin resistance through the study period: 19% in 2016, 33% in 2020 (p ≤ 0.001). CONCLUSIONS: Our data provide a comprehensive overview of the epidemiology of ABIs in Italy, filling a gap that has existed since 1995. Caution is needed when clindamycin is used as empirical anti-anaerobic drug.
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Infecções Bacterianas , Sepse , Idoso , Idoso de 80 Anos ou mais , Anaerobiose , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Anaeróbias , Infecções Bacterianas/microbiologia , Clindamicina , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Metronidazol , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Adesão à Medicação , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Feminino , Hepatite C Crônica/epidemiologia , Humanos , Análise de Intenção de Tratamento , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Resposta Viral SustentadaRESUMO
European clinical practice guidelines (EASL) on chronic hepatitis B (CHB) recently recognized the importance of migration flows in the changing hepatitis B virus (HBV) epidemiology in low-endemic European countries. The role of different genotypes in nucleos(t)ide analogue (NA) treatment is still unknown. In the case of genotype E, which is mainly circulating in West Africa, a quantitative decrease in the level of HBsAg (qHBsAg) during treatment with entecavir (ETV) predicts a longer time to HBsAg loss when compared to genotypes A and D. We prospectively evaluated qHBsAg decline in HBeAg-negative CHB patients infected with HBV genotype E who were treated with tenofovir 245 mg (TDF) or ETV 0.5 mg from 2008 to 2014. Sixty-five West African patients (58; 89.2% males) were enrolled. The median age was 29 years, and the most prevalent route of transmission was familial (25; 38.5%). Median liver stiffness was 7.4 kPa, HBV-DNA was 4.7 Log IU/ml, and qHBsAg was 3.4 Log UI/ml. According to clinical evaluation, 40 patients (61.5%) started ETV treatment, whereas 25 patients (38.5%) started TDF treatment. The decline of qHBsAg in ETV patients was significantly lower than in TDF patients after 5 years of treatment (0.31 vs. 0.68 LogIU/mL, p < 0.001). At the same time points, a significantly higher virological non-response rate was observed in ETV patients (p < 0.001). Despite the partial and non-response rates observed in the ETV group, no mutations associated with drug resistance were detected in these subjects. In genotype E infections, ETV treatment results in a significantly lower decline in qHBsAg and higher rates of virological non-response after 5 years. TDF could represent the optimal choice.
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Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Feminino , Genótipo , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: The management of non-fermentative gram-negative bloodstream infection (NFGN-BSI) offers numerous challenges. In this study the aim is to analyse a large cohort of patients with NFGN-BSI recruited in the northern Italy to describe epidemiology, etiological and susceptibility pattern, therapeutic management and outcome. METHODS: Multicentre retrospective cohort study of patients hospitalised at three large teaching hospitals in northern Italy in a fourth year period. RESULTS: 355 BSI episodes were analyzed, due to P. aeruginosa (72.7%), A. baumannii (16.6%), and Stenotrophomonas maltophilia (10.7%). Overall, 21.4% of isolates were defined as DTR, highest rate among A. baumannii (64.4%). All-cause 30-day mortality rate was 17.5%. Rates of XDR or DTR A. baumannii isolation were significantly higher in non-surviving patients. Independent risk factors for 30-day mortality were: age (HR 1.03, 95%CI 1.00-1.04, p = 0.003), septic shock (HR 2.84, 95%CI 1.67-4.82, p < 0.001) and BSI due to Acinetobacter baumannii (HR 2.23, 95%CI 1.27-3.94, p = 0.005). CONCLUSION: The overall prevalence of DTR was high in the NFGN BSI cohort analyzied, mainly among Acinetobacter baumannii episodes (64.4%). Acinetobacter baumannii is showed to be an independent predictor of mortality. These evidences marked the urgent need of new therapeutic options against this pathogen. TRIAL REGISTRATION NUMBER: 79/2017/O/OssN. Approved: March14th, 2017.
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Acinetobacter baumannii , Bacteriemia , Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Farmacorresistência Bacteriana , Humanos , Estudos RetrospectivosRESUMO
The presence of psychiatric disorders (PD) in patients affected by chronic hepatitis C (CHC) was a major contraindication for the treatment with interferon (IFN)-based regimens. The novel IFN-free approach using the direct-acting antiviral agents (DAAs) is an interesting and promising chance for these subjects. In this retrospective analysis we focused the attention on the virological response and safety of CHC patients affected by PD and treated with IFN-free regimens. 136 subjects were enrolled in this study. Treatment naïve were 78 (57.3), experienced 58 (42.6%). Major depression was present in 25 patients (18.4%), anxiety disorders in 37 (27.2%), bipolar disorders in 23 (16.9%), schizophrenia in 17 (12.5%), behavioral disturbance in 21 (15.4%), psychosis in 13 (9.5%). Psychoactive medication taken by patients were: benzodiazepines (n = 29, 21.3%), antidepressants (n = 24, 17.6%), neuroleptics (n = 29, 21.3%), mood stabilizers (n = 19, 14%), combinations of different drugs (n = 17, 12.5%). Sustained virological response at 12 weeks of follow-up (SVR12) was observed in 128 patients (94.1%), drop-out were 3 (2.2%). No adverse events or significant drug-related side-effects were reported. The treatment with novel IFN-free therapies against CHC were higher effective and well tolerated also in patients with PD taking psychoactive medications.
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Hepatite C Crônica , Transtornos Mentais , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Psicotrópicos/efeitos adversos , Psicotrópicos/uso terapêutico , Estudos Retrospectivos , Resposta Viral SustentadaRESUMO
PURPOSE OF REVIEW: Breast surgery is considered a clean surgical procedure; nevertheless, infection rates are often higher than those reported after other similarly considered clean surgeries (e.g., thyroid, hernia). Acute bacterial skin and soft tissue infections, mostly surgical site infections and implant-associated infections are commonest events that could complicate postoperative care. RECENT FINDINGS: Risk of infection is closely related to surgery procedure itself and patients host factors. Gram-positive bacteria with pattern of antimicrobial resistance are increasingly isolated and before today less frequent causes such as gram negative and mycobacteria infections. Impact of postoperative complications is underestimated and lacking an appropriate care and education for local and systemic management. SUMMARY: We report the current evidence on the management of infections after breast surgery. New drugs options for methicillin-resistant Staphylococcus aureus and other gram positive should have a place in this setting. Stewardship activities aiming at reducing infections risks with the correct considerations of host, microbiological and surgical risk factors.
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Mama/cirurgia , Gerenciamento Clínico , Infecções Relacionadas à Prótese/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Feminino , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Mycobacterium/classificação , Mycobacterium/isolamento & purificação , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/tratamento farmacológico , Procedimentos Cirúrgicos Operatórios/métodos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/tratamento farmacológicoRESUMO
PURPOSE OF REVIEW: describing the current role of carbapenems and carbapenem-sparing strategies in the setting of antimicrobial stewardship programs. RECENT FINDINGS: sparing carbapenems with other drugs appears to be an interesting perspective for a variety of reasons in the current context of the multidrug-resistant (MDR) pandemic. Specific algorithms should also be precisely investigated to define better how to spare carbapenems within empiric and targeted regimens, with combination treatment or monotherapies, aiming at the best use of the new drugs and improving de-escalation as soon as possible for most of the patients. SUMMARY: stewardship programs may be useful in reducing probable misuse and overuse of antibiotics, which has probably contributed to the emergence of carbapenem-resistant bacteria worldwide. The proposal of carbapenem-sparing strategies has then generated substantial scientific debate and, overall, the concept of sparing these drugs is well advocated together with judicious use of novel drugs, appropriate measures of infection control and prevention as well as in stewardship programs to curb the spread of MDR and XDR-strains in healthcare facilities.
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Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Carbapenêmicos/uso terapêutico , Resistência beta-Lactâmica , Gestão de Antimicrobianos , Bactérias/enzimologia , Bactérias/genética , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Gerenciamento Clínico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Humanos , Resultado do Tratamento , beta-Lactamases/biossíntese , beta-Lactamases/genéticaRESUMO
Chronic hepatitis delta (CHD) is the most severe chronic hepatitis, with no satisfactory treatment options and severe clinical outcomes. This infection is frequent in the migrant subjects from endemic areas, especially from Africa and East-Europe. The pegylated (PEG)-interferon α (IFN) is limited by side effects and poor response. In this retrospective analysis, we reported our experience of treatment with PEG-IFN in a cohort of immigrant patients affected by CHD. We evaluated the virological responses are as follows: complete response (CR; clearance of hepatitis B surface antigen [HBsAg] and hepatitis D virus [HDV]-RNA), partial response (PR; HBsAg clearance with HDV-RNA+), and null response (NR; HBsAg and HDV-RNA+). Clinical outcomes were clinical stabilization, disease progression, hepatic decompensation, hepatocellular carcinoma (HCC), death, and liver transplantation. Forty-six patients were included. At the end of treatment (ET), 11 patients gained a CR (23.9%), 10 were PR (21.7%), and 16 were NR (34.8%). After 1 year, 10 remained with CR (21.7%), after 2 years, 9 (19.5%), and at 3 years, 8 (17.4%). Relapse rate was 2.2%, 4.4%, and 6.5% at year 1, 2, and 3, respectively. Favorable factors were CR at the ET (odds ratio [OR] = 4.559, 95% confidence interval [CI]: 2.219-7.116; P = 0.003), PEG-IFN course greater than 1 (OR = 1.240, 95% CI: 0.998-4.839; P = 0.012), prolonged treatment (OR = 1.276, 95% CI: 0.816-3.108; P = 0.018), quantitative hepatitis B surface antigen (qHBsAg) decline at 12 weeks greater than 0.5 log IU/mL (OR = 4.816, 95% CI: 2.190-8.194; P < 0.001). The unfavorable factors were cirrhosis (OR = 3.122, 95% CI: 1.466-4.190; P = 0.012), active hepatitis B virus (OR = 2.334, 95% CI: 1.788-3.992; P = 0.018), NR at ET (OR = 6.998, 95% CI: 5.987-11.404; P < 0001). Treatment of CHD is limited by poor virological response; is NR unfavorable outcomes were unavoidable. No other treatment options were available.
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Antivirais/uso terapêutico , Emigrantes e Imigrantes , Hepatite D Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Feminino , Hepatite D Crônica/etnologia , Humanos , Itália , Masculino , Recidiva , Estudos Retrospectivos , Resultado do TratamentoAssuntos
COVID-19/patologia , Linfócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The role of different genotypes in nucleos(t)ide analogs (NAs) treatment is still debated. Previous studies conducted on special populations evidenced that the E genotype had the lower virological and serological response. This descriptive study aims to recognize the hepatitis B "s" antigen (HBsAg) decline during tenofovir disoproxil fumarate (TDF) treatment in a cohort of patient affected by chronic hepatitis B (CHB). We retrospectively included all patients with CHB treated with TDF between April 2007 and March 2012 with a duration of treatment of 7 years. Kinetics of HBsAg was determined as serological response in this cohort. We include 110 subjects; virological response was observed in all subjects with genotypes A, B, and D; in 17 patients with C genotype (94.4%) and 24 with E genotype (96%). HBeAg loss was observed in 2 patients with genotype A (50%), 3 with B (100%), 0 with C (0%), 1 with D (20%), and 1 with E genotype (25%). In multivariate analysis we observed as predictive factors of HBsAg decline the baseline level of HBsAg (OR = 1.467; 95%CI: 1.221-5.113; p = 0.017) and viral genotypes (OR = 11.218; 95%CI: 5.441-41.138; p < 0.001). This study confirmed higher HBsAg decline after 7 years of treatment in A and B genotypes, and lower in C, E, and D genotypes. However, no evidence is enough to choose a single NAs, but in special populations, as well as in genotype E, the use of TDF should be preferred to entecavir.
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Herpes zoster ophthalmicus results from the reactivation of the latent varicella zoster virus, affecting the first branch of the trigeminal nerve. In 20-70% of cases, Zoster Ophthalmicus can lead to ocular involvement, affecting various orbital structures. Orbital myositis is a rare but severe complication of herpes zoster ophthalmicus. We present a case of a 52-year-old man with no significant medical history who developed zoster-associated right ocular myositis and dacryocystitis. He was treated with intravenous acyclovir and oral steroids. A review of the literature identified 29 patients across 19 studies. The median age was 61 years, with a slight female predominance. In 55% of cases, the patients had no notable medical history. The most common presentation of myositis involved all oculomotor muscles. There were 22 cases who were treated with intravenous antiviral therapy and 19 received steroids. A full resolution of symptoms was achieved in 51.7% of patients. Zoster-related orbital myositis is a rare complication that should be considered even in immunocompetent individuals. It may occur either before or after the appearance of a vesicular rash. Magnetic resonance imaging is the preferred radiological exam for assessing orbital involvement. Intravenous antiviral therapy should be started within 72 h of symptom onset, and its combination with systemic corticosteroids appears to be an effective treatment for zoster-related ocular myositis.
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The treatment of refractory CMV is often associated with high toxicity. Maribavir (MBV) is a novel oral antiviral, known for its favourable safety profile in fragile patients. We describe a case of CMV disease with end organ damage following kidney transplantation at high risk, for recipient-donor serological mismatch. A 54-year-old female with history of obesity, hypertension, and chronic kidney disease, on prednisone and tacrolimus after kidney transplantation in November 2022, soon after developed primary CMV infection, treated with Valganciclovir and CMV Ig. In January 2023 the patient presented with fever and dyspnea. Pulmonary miliary opacities and right-upper lobe consolidation were found at CT-scan along with CMV-DNA positivity on BAL and serum. Lung biopsy confirmed CMV infection. Antiviral was switched to Ganciclovir. Despite initial benefit, fever and respiratory failure happened 8 days later, leading to intubation at day 15. Due to slow decrease serum CMV-DNA and detection of UL97 mutation, conferring resistance to valganciclovir and ganciclovir, the patient was started on foscarnet and letermovir. She was extubated after a gradual respiratory improvement and discharged from ICU to rehabilitation department with HFNC; reduction in serum CMV-DNA, but persistently elevated CMV-DNA on BAL were documented. At week 8, MBV was started and letermovir continued, for a 8 weeks course, without notable adverse effects. Respiratory function improved but soon after septic shock occurred. A bone marrow biopsy resulted in lymphoma, without indications for treatment: the patient developed coma and died 6 months after admission. MBV has recently been approved in Europe for treatment of R/R CMV in HSCT and SOT recipients. MBV showed superior rates of viraemia clearance after 8 weeks compared to SOC, demonstrating also a favourable safety profile with fewer patients discontinuing treatment and being affected by nephrotoxicity and neutropenia. Its main side effects are taste impairment, gastro-intestinal symptoms and asthenia. Based on actual promising perspectives regarding antiviral stewardship, more data are required to corroborate benefit of MBV in terms of toxicity and impact on mortality in highly fragile populations as SOT recipients. MBV received approval for the treatment of refractory or resistant CMV infections to other antiviral agents. Nevertheless, real-life data on efficacy and safety of MBV are still lacking. We conducted a narrative review of the current literature on MBV as treatment for CMV infection in kidney transplant recipients to understand clinical characteristics, safety and outcomes of MBV in this population. A search was run on the main scientific databases. 194 papers were identified, of which 188 were excluded by title and abstract evaluation. Subsequently, 6 papers were included. We performed descriptive statistics on the entire study population. The studies included in our analysis showed a higher prevalence of male subjects. The median age was 57 year. CKD was the most frequently reported comorbidity. Seven patients reported a donor/recipient mismatch (D+/R-). The case report and the cohort of patients collected from the literature show that MBV was used as an option in R/R CMV, notably for the presence or suspicion of CMV resistance to previous treatment. The clinical presentation of CMV in kidney SOT was heterogenous and varied from isolated reactivation of CMV-DNAemia, isolated fever or gastrointestinal involvement. For mild to moderate CMV disease, as with the cases reported in our review, or for proven ganciclovir, foscarnet or cidofovir resistance, MBV could be a valuable option. Outcomes of the patients treated with MBV were not reported in all the studies; however, where reported, 45.4% of the cases developed virological failure during MBV treatment with the development of specific resistance to MBV. MBV was generally well-tolerated, with low rates of toxicity, normally reversible. The introduction of new oral antivirals, such as MBV, could improve treatment, prophylaxis and preemptive treatment strategies, especially in anti-CMV treatment experienced patients.