Increased incidence of Campylobacter enteritis and their quinolone resistance between 2010 and 2015: Results of a French national observatory conducted in 21 general hospitals (CHG).

INTRODUCTION: In Europe, the number of cases of Campylobacter enteritis and their quinolone resistance is increasing. The aims of this work were to evaluate: (1) the hospital epidemiology of bacterial enteritis between 2010 and 2015. (2) The proportion of Campylobacter and Salmonella enteritis. (3) Resistance to quinolones in adult and paediatric populations. (4) To investigate possible regional epidemiological and bacteriological disparities. PATIENTS AND METHODS: This is a multicentric study carried out in 21 general hospitals (CHG) representing 14 French regions with a prospective collection of the results of coprocultures from 2010 to 2015 in adult and paediatric populations (children < 15 years old not exposed to quinolones). The epidemiological and bacteriological data were collected from software laboratory for positive stool cultures for Campylobacter and Salmonella. The results were compared year by year and by a period of 2 years. RESULTS: In adults, Campylobacter enteritis was each year significantly more frequent than Salmonella (P < 0.001), with a significant increase from 2010 to 2015 (P < 0.05). In children, there was also a significant and stable predominance of Campylobacter enteritis over the study period (P = 0.002). The quinolone resistance of Campylobacter was greater than 50% on the whole territory, with no North-South difference over the three periods studied. It increased significantly from 2012 to 2015 in adults (48% to 55%, P < 0.05) and in children (54% to 61%, P = 0.04). CONCLUSION: Our results confirm the increase in the prevalence of Campylobacter enteritis compared to Salmonella between 2010 and 2015. The quinolone resistance of Campylobacter is greater than 50% on the whole territory, stable between 2010 and 2015 in adults and significantly increased in children.

Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients.

AIM: To assess, in a routine practice setting, the sustained virologic response (SVR) to telaprevir (TPV) or boceprevir (BOC) in hepatitis C virus (HCV) null-responders or relapsers with severe liver fibrosis. METHODS: One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon (peg-INF) α2a + ribavirin (PR) according to standard treatment schedules without randomization. These patients were treated in routine practice settings in 10 public or private health care centers, and the data were prospectively collected. Only patients with severe liver fibrosis (Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography), genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study. RESULTS: The Metavir fibrosis scores were F3 in 35 (28%) and F4 in 90 (72%) of the patients. In total, 62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy. The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%. The SVR was 65.9% in the TPV group and 44.1% in the BOC group. Independent predictive factors of an SVR included a response to previous treatment, relapsers vs null-responders [OR = 3.9; (1.4, 10.6), P = 0.0084], a rapid virological response (RVR) [OR 6.9 (2.6, 18.2), P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2 (2.3, 29.5), P = 0.001]. During treatment, 63 patients (50.8%) had at least one severe adverse event (SAE) of grade 3 or 4. A multivariate analysis identified two factors associated with SAEs: female gender [OR = 2.4 (1.1, 5.6), P = 0.037] and a platelet count below 150 × 10(3)/ mm(3) [OR = 5.3 (2.3, 12.4), P ≤ 0.001]. CONCLUSION: More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting. The SVR rate was influenced by the response to previous PR treatment, the RVR and liver stiffness.

[Biliary lithiasis]. / Lithiase biliaire.

No treatment is recommended for silent gallstones. The diagnosis of acute cholecystitis is based on clinical and biological signs and on abdominal sonography. Early laparoscopic cholecystectomy is the treatment of choice, except in case of severe (grade III) cholecystitis where a percutaneous cholecystostomy associated with antibiotic therapy is recommended. The diagnostic accuracy of abdominal sonography for the diagnosis of common bile duct stones is poor. A second-line MR cholangiopancreatography or an endoscopic sonography is often needed to confirm the diagnosis. The treatment of acute cholangitis is based on both antibiotic therapy and biliary drainage. Results of the treatment of common bile duct stone with either laparoscopic surgery or with the combined endoscopic sphincterotomy plus laparoscopic cholecystectomy are comparable when performed by well-trained practitionners. The choice of the method should be based on the locally available treatment.

Follow-up of adverse drug reactions from peginterferon alfa-2b-ribavirin therapy.

STUDY OBJECTIVE: To investigate the adverse drug reactions (ADRs) from peginterferon alfa-2b plus ribavirin in patients infected with the hepatitis C virus (HCV). DESIGN: Prospective, observational, pharmacovigilance study. SETTING: Gastroenterology department of a French university hospital. PATIENTS: A cohort of consecutive outpatients who were treated with peginterferon alfa-2b plus ribavirin for viral hepatitis. INTERVENTION: During the 1-year period of HCV therapy visits, a medical staff member trained in pharmacovigilance interviewed the patients about all ADRs and their use of other drugs. The ADRs assessed as serious were confirmed from regular review of the medical records. MEASUREMENTS AND MAIN RESULTS: A total of 87 patients were treated for HCV. Among these, peginterferon alfa-2b plus ribavirin therapy was started in 51 patients; one patient was lost to follow-up after 1 month. The ADRs were assessed as serious in 10 patients (20%): suicide (one patient), hospitalization (three patients), and definitive discontinuation of peginterferon alfa-2b plus ribavirin (six patients). The ADRs contributed to or were the main reason for withdrawing HCV drugs in 8 patients (16%). Dosage reductions of ribavirin and/or peginterferon alfa-2b were required in 10 patients (20%) and seemed less frequent than that needed in clinical trials. Compared with results of clinical trials, a similar frequency of hair loss, higher frequency of injection-site reactions, lower frequency of depression or insomnia, and higher frequency of endocrine ADRs or blurred vision were detected. CONCLUSION: Results suggest some differences in the frequencies of ADRs compared with data from clinical trials. A longer period of monitoring is warranted to improve knowledge about ADRs of pegylated interferon. A medical staff member trained in pharmacovigilance is useful to collect quantitative and qualitative data about ADRs.

Genetic heterogeneity of the NS5A gene of hepatitis C virus and early response to interferon-alpha.

The double-stranded RNA-activated protein kinase-binding domain (PKRbd) of the NS5A gene of hepatitis C virus (HCV) was studied by the cloning and sequencing method, in HCV-infected patients who had a primary resistance to treatment with interferon (IFN)-alpha (early nonresponders). Patients whose virus load decreased by >or=0.5 log (early responders) were similarly analyzed. In the 2 groups, the PKRbd evolved similarly over the first 24 h. Selection of resistant HCV variants is unlikely to explain primary resistance to IFN-alpha.

"A La Carte" treatment of portal hypertension: Adapting medical therapy to hemodynamic response for the prevention of bleeding.

We report the results of adapting medical therapy to the monitoring of hemodynamic response in the prevention of a first variceal bleeding or rebleeding in patients with cirrhosis. Hepatic venous pressure gradient (HVPG) was measured before and after propranolol was initiated. The patients were considered responders if HVPG decreased below 12 mm Hg or at least 20% as compared with baseline value. If patients were not responders, isosorbide-5 mononitrate (I-5MN) was added, and a third hemodynamic study was performed. Thereafter, the patients were followed for a mean of 28 months. Thirty-four consecutive patients were treated to prevent a first bleeding episode in 20 patients and a rebleeding in 14 patients. HVPG value was initially 19.8 +/- 4.6 mm Hg and decreased to 17.6 +/- 5.7 mm Hg (P <.05) after propranolol alone. Thirteen patients (38%) were responders to propranolol. I-5MN improved hemodynamic response in 7 cases. Among these 20 (59%) hemodynamic responders, only 2 (10%) experienced variceal bleeding, as compared with 9 of 14 (64%) nonresponders (P <.05). Using multivariate analysis, only hemodynamic response was found to have an independent predictive value for the risk of variceal bleeding. In conclusion, hemodynamic response to drug therapy identifies patients who are efficiently protected from variceal bleeding as well as nonresponders in whom an alternative treatment should be considered.

Genetic heterogeneity of the envelope 2 gene and eradication of hepatitis C virus after a second course of interferon-alpha.

The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was involved in the sensitivity of HCV to interferon-alpha (IFN-alpha). To assess the factors leading to virus eradication by IFN-alpha, patients whose first treatment by IFN-alpha failed and who had virus eradication after a second treatment were studied. These patients were paired with subjects in whom both treatments failed. The phosphorylation homology domain of the E2 gene (E2-PHD) had no sequence variation between the two stages in both groups of patients. Therefore, this region has no clinical predictive value within a specific genotype. The hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones per sample. Comparison of samples showed that the change in quasispecies induced by the first IFN-alpha therapy could be associated with virus elimination obtained after a second treatment. The greater proportion of nonsynonymous mutations that was noted before the second treatment in responders suggest that pretherapeutic immune response is a major factor determining virus elimination and that the immune status of these patients changed between the first and the second treatment.