RESUMEN
Listeria monocytogenes is a Gram-positive bacteria and etiological agent of listeriosis. It has the ability to colonize the intestinal lumen and cross the intestinal, blood-brain, and placental barriers, leading to invasive listeriosis responsible for septicemia and meningitis in subjects at risk such as patients with diabetes mellitus, the elderly, and immunocompromised individuals and, for maternal-neonatal infection in pregnant women. We report a rare case of L. monocytogenes septicemia and meningitis complicated by Candida glabrata fungemia on a patient with a history of type 2 diabetes mellitus, hypothyroidism, hypertension, chronic kidney failure, chronic ischemic vascular encephalopathy, and atrial fibrillation. Although adequate therapy was rapidly started with an initial partial clinical improvement, the patient suddenly experienced clinical worsening concomitantly with Candida septicemia resulting in a fatal outcome. To our knowledge, this is the first described case of an invasive L. monocytogenes infection complicated by Candida sepsis. We hypothesize that concomitant Candida infection may play a significant role in the pathogenesis and virulence of L. monocytogenes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Fungemia , Listeria monocytogenes , Listeriosis , Meningitis , Sepsis , Recién Nacido , Femenino , Humanos , Embarazo , Anciano , Candida glabrata , Fungemia/complicaciones , Fungemia/tratamiento farmacológico , Placenta , Listeriosis/complicaciones , Listeriosis/diagnóstico , Listeriosis/tratamiento farmacológico , Sepsis/complicacionesRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0215783.].
RESUMEN
BACKGROUND AND OBJECTIVES: The pangenotypic single tablet regimen of NS5B inhibitor sofobuvir (SOF) and NS5A inhibitor velpatasvir (VEL) is advised for 12 weeks in HCV-infected patients including those with compensated cirrhosis. Addition of ribavirin (RBV) may be considered in genotype 3 (GT3) with compensated and is recommended in decompensated cirrhosis. Real-life results with SOF/VEL are limited. To evaluate efficacy and safety in a large real-world-cohort including patients with different GTs and various fibrosis stages. DESIGN: In total, 1429 patients were treated with SOF/VEL 400/100 mg for 12 weeks in the Puglia registry between June 2017 and May 2018. 1319 (92.3%) reached week 12 post-treatment (SVR12) at the moment. Only 41 received RBV. Diagnosis of cirrhosis was based on transient elastography and/or APRI or FIB-4 scores. Sensitivity analysis in the population including all patients except non virological failure was conducted. Primary efficacy endpoint was the percentage of patients with SVR12. RESULTS: Patients' mean age was 63.8 years, 42.3% had GT1. The majority were naïve and 735 (55.5%) F0/F2. Of the remaining 587, 282 had cirrhosis. SVR12 was 98.5%, 98.0% in GT1, 99.4% in GT2, 97.1% in GT3, 100% in GT4. Overall, SVR12 by sensitivity analysis was 99.4%; 99.7% among F0-F1. Among 218 PWID, SVR12 was 94.5%. Discontinuation rates were 3.7% among PWID and 0.7% among non-PWID (p = 0.004). CONCLUSIONS: SOF/VEL treatment of chronic HCV infection reaches very high cure rates in a variety of patients; including those with F0/F1 and PWID.
Asunto(s)
Carbamatos/uso terapéutico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Cirrosis Hepática/complicaciones , Sofosbuvir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carbamatos/efectos adversos , Interacciones Farmacológicas , Femenino , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Humanos , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Seguridad , Sofosbuvir/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16weeks duration were associated with a 90% sustained virological response at 12weeks (SVR12). Real life cohorts showed lower SVR12 rates. METHODS: SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed. RESULTS: Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68years (18-87); 163 were treatment naïve. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm3 and 62 albumin <3.5g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67-31.25; p=0.0022 and OR 0.1; 95% CI 0.01-0.72; p=0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse. CONCLUSIONS: In GT2 cirrhotic patients, SOF/RBV for 16 or 20weeks is associated with real life SVR12 rates of 95%. LAY SUMMARY: A duration of treatment of 16-20weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available.