One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C.

BACKGROUND: Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144. AIM: To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C. METHODS: In this double-blind study, we randomly assigned patients to receive 0.5 mg/d ETV (Group A) or ETV maleate (Group B) (ratio, 1:1), each with a placebo tablet for 48 wk. Then, all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49. The primary efficacy endpoint was the reduction in HBV DNA levels from baseline. Secondary endpoints included the proportion of patients with undetectable HBV DNA (< 20 IU/mL), serologic response, serum alanine aminotransferase (ALT) normalization and development of resistance mutations. RESULTS: Two hundred eighteen patients who were hepatitis B e antigen (HBeAg) positive and 57 who were HBeAg negative were analyzed and predominantly presented with genotype B (49.82%) or C (48.73%). For the HBeAg-positive CHB patients, the mean HBV DNA level decrease (6.61 Log10 IU/mL vs 6.69 Log10 IU/mL, P > 0.05), viral suppression with HBV DNA < 20 IU/mL (83.33% vs 79.17%, P > 0.05) and HBeAg seroconversion (28.77% vs 20.00%, P > 0.05) occurred similarly between Groups A and B at week 192. However, there was a significant difference in the proportion of patients with normal ALT levels (91.14% vs 78.38%, P < 0.05). For the HBeAg-negative CHB patients, no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline (6.05 Log10 IU/mL vs 6.03 Log10 IU/mL, P > 0.05), percentages of patients who achieved undetectable HBV DNA (100% vs 100%, P > 0.05) and rates of ALT normalization (95.65% vs 100.00%, P > 0.05). Safety and adverse event profiles were similar between Groups A and B. Two HBeAg-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV. CONCLUSION: Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

A fatal case of Exophiala dermatitidis meningoencephalitis in an immunocompetent host: A case report and literature review.

BACKGROUND: Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. CASE PRESENTATION: A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600-800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. CONCLUSIONS: CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.

Erratum to: Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution.

Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2020 21(5):408-410. https://doi.org/10.1631/jzus.B2000117. The original version of this article unfortunately contained a mistake. For Fig. 1a in p.409, the citation of a reference, as well as the permission to reprint this picture, was missing. The correct version and the corresponding reference are given below: (a) Chest computed tomography (CT) image of Patient 1 on admission presents multiple ground-glass opacities distributed in the periphery of inferior lobe of both lungs. Reprinted from Zhang et al. (2020), with kind permission from Springer Nature.

Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study.

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

Clinical characteristics of different subtypes and risk factors for the severity of illness in patients with COVID-19 in Zhejiang, China.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment. METHODS: In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19. RESULTS: A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2-2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1-6.3, P <  0.001), cough (OR = 1.7, 95% CI: 1.0-2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1-10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0-3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2-5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19-40 years [OR = 12.7, 95% CI: 4.5-36.0, P < 0.001], 41-65 years [OR = 14.8, 95% CI: 5.2-42.1, P <  0.001], ≥ 66 years [OR = 56.5, 95% CI: 17.1-186.5, P < 0.001]). CONCLUSIONS: Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China.

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS: From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution.

As of Apr. 22, 2020, the World Health Organization (2020) has reported over 2.4 million confirmed coronavirus disease 2019 (COVID-19) patients and 169 151 deaths. Recent articles have uncovered genomic characteristics and clinical features of COVID-19 (Chan et al., 2020; Chang et al., 2020; Guan et al., 2020; Zhu et al., 2020), while our understanding of COVID-19 is still limited. As suggested by guidelines promoted by the General Office of National Health Commission of the People's Republic of China (2020) (from Versions 1 to 6), discharged standards for COVID-19 were still dependent on viral real-time polymerase chain reaction (RT-PCR) tests of respiratory specimens, showing that recovered COVID-19 patients with twice negative RT-PCR could meet discharge criteria. Here, we examined two cases in which nucleic acid test results were inconsistent with clinical and radiological findings, leading to suboptimal care.

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series.

OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). DESIGN: Retrospective case series. SETTING: Seven hospitals in Zhejiang province, China. PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China.

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Vitamin D deficiency in hepatitis C virus infection: what is old? what is new?

In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.

Acute-on-chronic liver failure in chronic hepatitis B: an update.

INTRODUCTION: Acute-on-chronic liver failure is a common pattern of end-stage liver disease in clinical practice and occurs frequently in patients with chronic hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a better understanding of this disease. Areas covered: This review updates the current comprehensive knowledge about HBV-ACLF from epidemiological studies, experimental studies, and clinical studies and provide new insights into the definition, diagnostic criteria, epidemiology, nature history, pathogenesis, treatment and prognostication of HBV-ACLF. Expert commentary: Patients with chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on-chronic liver failure, with multi-organ failure and high short-term mortality. The precipitating events can be intra-hepatic or extra-hepatic and the underlying chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is the driver of HBV-ACLF, which can be attributed to non-sterile and sterile factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell therapy is a promising alternative to LT, but requires validation and still has concern of long-term safety. Other medical therapies, such as nucleoside analogue, artificial liver supporting and glucocorticoid may improve survival in a specific subgroup. New scoring systems improve the accuracy of prognostication in HBV-ACLF, which is critical for early identification of candidates for LT.

Complete Sequence of a Novel IncR-F33:A-:B- Plasmid, pKP1034, Harboring fosA3, blaKPC-2, blaCTX-M-65, blaSHV-12, and rmtB from an Epidemic Klebsiella pneumoniae Sequence Type 11 Strain in China.

A high fosfomycin resistance rate was observed in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) in our previous study, but little is known about its mechanisms. In this study, we explored the prevalence of plasmid-mediated fosfomycin resistance determinants among fosfomycin-resistant KPC-KP strains from a Chinese university hospital and determined the complete sequence of a novel fosA3-carrying plasmid isolated from an epidemic K. pneumoniae sequence type (ST) 11 strain. A total of 97 KPC-KP strains were studied, of which 57 (58.8%) were resistant to fosfomycin, including 44 (45.4%) harboring fosA3 and 1 harboring fosA. All fosA3-positive strains belonged to the dominant ST11-pulse type (PT) A clone according to multilocus sequence typing and pulsed-field gel electrophoresis, suggesting clonal dissemination. The fosA-positive isolate belonged to ST11-PTE. The fosA3-carrying plasmid pKP1034 is 136,848 bp in length and is not self-transmissible. It is a multireplicon plasmid belonging to IncR-F33:A-: B-. Besides fosA3, a variety of other resistance determinants, including blaKPC-2, rmtB, blaCTX-M-65, and blaSHV-12, are identified in pKP1034, which would allow for coselection of fosA3 by most ß-lactams and/or aminoglycosides and facilitate its dissemination despite limited use of fosfomycin in China. Detailed comparisons with related plasmids revealed that pKP1034 is highly mosaic and might have evolved from alarming recombination of the blaKPC-2-carrying plasmid pKPC-LK30 from Taiwan and the epidemic fosA3-carrying plasmid pHN7A8 from mainland China.

Nontuberculous mycobacterial osteomyelitis.

Osteomyelitis caused by nontuberculous mycobacteria (NTM) can have severe consequences and a poor prognosis. Physicians therefore need to be alert to this condition, especially in immunocompromised patients. Although the pathogenesis of NTM osteomyelitis is still unclear, studies in immunodeficient individuals have revealed close relationships between NTM osteomyelitis and defects associated with the interleukin-12-interferon-γ-tumor necrosis factor-α axis, as well as human immunodeficiency virus infection, various immunosuppressive conditions, and diabetes mellitus. Culture and species identification from tissue biopsies or surgical debridement tissue play crucial roles in diagnosing NTM osteomyelitis. Suitable imaging examinations are also important. Adequate surgical debridement and the choice of appropriate, combined antibiotics for long-term anti-mycobacterial chemotherapy, based on in vitro drug susceptibility tests, are the main therapies for these bone infections. Bacillus Calmette-Guerin vaccination might have limited prophylactic value. The use of multiple drugs and long duration of treatment mean that the therapeutic process needs to be monitored closely to detect potential side effects. Adequate duration of anti-mycobacterial chemotherapy together with regular monitoring with blood and imaging tests are key factors determining the recovery outcome in patients with NTM osteomyelitis.

Complete nucleotide sequences of bla(CTX-M)-harboring IncF plasmids from community-associated Escherichia coli strains in the United States.

Community-associated infections due to Escherichia coli producing CTX-M-type extended-spectrum ß-lactamases are increasingly recognized in the United States. The bla(CTX-M) genes are frequently carried on IncF group plasmids. In this study, bla(CTX-M-15)-harboring plasmids pCA14 (sequence type 131 [ST131]) and pCA28 (ST44) and bla(CTX-M-14)-harboring plasmid pCA08 (ST131) were sequenced and characterized. The three plasmids were closely related to other IncFII plasmids from continents outside the United States in the conserved backbone region and multiresistance regions (MRRs). Each of the bla(CTX-M-15)-carrying plasmids pCA14 and pCA28 belonged to F31:A4:B1 (FAB [FII, FIA, FIB] formula) and showed a high level of similarity (92% coverage of pCA14 and 99% to 100% nucleotide identity), suggesting a possible common origin. The blaC(TX-M-14)-carrying plasmid pCA08 belonged to F2:A2:B20 and was highly similar to pKF3-140 from China (88% coverage of pCA08 and 99% to 100% nucleotide identity). All three plasmids carried multiple antimicrobial resistance genes and modules associated with virulence and biochemical pathways, which likely confer selective advantages for their host strains. The bla(CTX-M)-carrying IncFII-IA-IB plasmids implicated in community-associated infections in the United States shared key structural features with those identified from other continents, underscoring the global nature of this plasmid epidemic.

Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBeAg-positive chronic hepatitis B patients receiving peginterferon.

A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ≥30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy.

Complete sequence of a conjugative incn plasmid harboring blaKPC-2, blaSHV-12, and qnrS1 from an Escherichia coli sequence type 648 strain.

We sequenced a novel conjugative blaKPC-2-harboring IncN plasmid, pYD626E, from an Escherichia coli sequence type 648 strain previously identified in Pittsburgh, Pennsylvania. pYD626E was 72,800 bp long and carried four ß-lactamase genes, blaKPC-2, blaSHV-12, blaLAP-1, and blaTEM-1. In addition, it harbored qnrS1 (fluoroquinolone resistance) and dfrA14 (trimethoprim resistance). The plasmid profile and clinical history supported the in vivo transfer of this plasmid between Klebsiella pneumoniae and Escherichia coli.