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Objective:To compare the efficacy and safety of omacycline with meropenem plus linezolid in the treatment of patients with pulmonary infection.Methods:The clinical data of 58 patients with pulmonary infection admitted to the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou Red Cross Hospital and Jiande First People’s Hospital from December 2021 to May 2022 were retrospectively analyzed. The patients were divided into the omacycline group ( n=29) and the meropenem combined with linezolid group (combined group, n=29). The omacycline group was given intravenous omacycline 200 mg or 100 mg, q. d, and the combined group was given intravenous meropenem (1 000 mg, t.i.d) and linezolid (600 mg, b. i.d). The clinical efficacy and drug-related adverse events of two groups were observed. SPSS 22.0 statistical software was used for data analysis. Results:In the omacycline group, 8 cases (27.6%, 8/29) were cured, 19 cases (65.5%, 19/29) were improved, and 2 cases (6.9%, 2/29) were worsened. In the combined group, 1 case (3.4%, 1/29) was cured, 26 cases (89.7%, 26/29) were improved, and 2 cases (6.9%, 2/29) died. There was a statistically significant difference between the two groups ( χ2=6.533, P=0.038). The respiratory failure occurred in 3 cases (10.3%, 3/29) of the omacycline group and 5 cases (17.2%, 5/29) of the combined group ( χ2=0.580, P=0.446). In those patients who were cured or improved, the median time from treatment initiation to disease remission was 3.0 (2.0, 5.5) d in the omacycline group and 5.0 (4.0, 6.0) d in the combined group ( Z=-2.122, P=0.034). There was no significant difference in the incidence of adverse reactions between the two groups [6.9% (2/29) vs. 13.8% (4/29), χ2=0.744, P=0.389]. Conclusion:Omacycline exhibits a good efficacy and safety in the treatment of patients with pulmonary infection, which may be prioritized for the treatment of pulmonary infections.
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COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.
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In recent years, great progress has been made in small molecule therapeutic drugs and monoclonal neutralizing antibody preparations against 2019-nCoV. At least 5 oral drugs (Monupavir, AT-527, Proclutamide, Paxlovid and S-217622) and 2 monoclonal antibodies (Ambavirumab/Romisevirumab combination and Sotrovimab) have completed phase Ⅲ clinical trials exhibiting excellent antiviral effects. This article reviews the research progress of these 7 drugs to provide reference for clinical application.
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The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
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The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as and , so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
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Humans , Betacoronavirus , China , Epidemiology , Coronavirus Infections , Diagnosis , Epidemiology , Therapeutics , Virology , Disease Management , Early Diagnosis , Feces , Virology , Pandemics , Pneumonia, Viral , Diagnosis , Epidemiology , Therapeutics , Virology , Sputum , VirologyABSTRACT
Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on ( 6), and -19: , we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.
Subject(s)
Humans , Adrenal Cortex Hormones , Therapeutic Uses , Anti-Bacterial Agents , Therapeutic Uses , Antiviral Agents , Therapeutic Uses , Betacoronavirus , Coronavirus Infections , Drug Therapy , Critical Illness , Drug Therapy , Nutritional Support , Pandemics , Pneumonia, Viral , Drug Therapy , ProbioticsABSTRACT
OBJECTIVE@#To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19).@*METHODS@#The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed.@*RESULTS@#There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring.@*CONCLUSIONS@#The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.
Subject(s)
Female , Humans , Pregnancy , Antiviral Agents , Therapeutic Uses , Betacoronavirus , Cesarean Section , Coronavirus Infections , Drug Therapy , Glucocorticoids , Therapeutic Uses , Oxygen , Therapeutic Uses , Pandemics , Pneumonia, Viral , Drug Therapy , Pregnancy Complications, Infectious , Drug Therapy , Pathology , Pregnancy Outcome , Retrospective Studies , Treatment Outcome , gamma-Globulins , Therapeutic UsesABSTRACT
Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.
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Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.
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Objective@#Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.@*Methods@#A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.@*Results@#The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05).@*Conclusions@#The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.
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Objective@#To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.@*Methods@#A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.@*Results@#The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group.@*Conclusions@#Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.
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Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China displayed distinct clinical characteristics compared to patients in endemic countries.To standardize the diagnosis and treatment of dengue fever,the experts of the Society of Infectious Diseases,Society of Tropical Medicine and Parasitology of Chinese Medical Association,and the Society of Emergency Medicine,China Association of Chinese Medicine have reached this guideline based on guidelines for diagnosis,treatment,prevention and control of dengue (World Health Organization,2009);guidelines for diagnosis and treatment of dengue (National Health and Family Planning Commission of the People's Republic of China,2014,Edition 2),health industry standard of the People's Republic of China "diagnosis for dengue fever (WS216-2018)" and systemic reports on dengue.The guideline includes 8 aspects:introduction,terminology,epidemiology and prevention,etiology and pathogenesis,clinical features,diagnosis,treatment and problems to be solved.
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Objective To examine the short-term prognostic value of procalcitonin ( PCT ) combined with coagulation factors for cirrhotic patients complicated with spontaneous bacterial peritonitis (SBP).Methods Clinical data of 128 cirrhotic patients complicated with SBP admitted in Jinhua Central Hospital from June 2014 to October 2017 were retrospectively analyzed .In 3 months after admission , 83 patients survived ( survival group ) and 45 patients died ( fatal group ) .The factors related to prognosis were analyzed with Logistic regression and the prediction model was constructed with the weights derived from regression coefficients.The ROC curve and the area under the curve (AUC) of combination of PCT with coagulation factors were used to predict the survival of patients .Results Univariate analysis indicated that the level of PCT , total bilirubin ( TBil ) , serum creatinine ( Scr ) , prothrombin time ( PT ) , prothrombin activity ( PTA ) , blood coagulation factor Ⅱ, Ⅴ, Ⅶ, Ⅸ, Ⅹ, Ⅺ and Ⅻ were factors affecting the prognosis of cirrhotic patients complicated with SBP (P<0.01).Multivariate analysis showed that PCT , blood coagulation factors Ⅴ and Ⅸ were independent factors of short-term prognosis of cirrhotic patients complicated with SBP.The constructed predictive model was Logit (P) =1.200+0.099 ×PCT-0.026 × clotting factor Ⅴ-0.038 ×clotting factor Ⅸ.The sensitivity and specificity of the model were 0.822 and 0.675, respectively, and the AUC was 0.829.Compared with the classic MELD score , the difference was not statistically significant (P>0.05).Conclusions The predictive model based on PCT and coagulation factors Ⅴand Ⅸcan effectively predict the short-term survival of cirrhotic patients complicated with SBP . The overall prognostic ability is not different from MELD score , but the model is more simple and easier to apply.
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Objective@#To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control.@*Methods@#This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data.@*Results@#A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events.@*Conclusion@#In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.
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Objective@#To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control.@*Methods@#A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed.@*Results@#A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group.@*Conclusion@#In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.
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Objective To provide the guidance for the control and treatment of blood stream infec-tion caused by Serratia marcescens strains through analyzing the homology and drug resistant genes of the iso-lates collected from the Intensive Care Unit ( ICU) of Shaoxing County Central Hospital.Methods Serratia marcescens strains were isolated from ICU patients with blood stream infection and also from the hands of health care providers in the ICU from June 1st to September 30th, 2013.The antibiotic susceptibilities of the Serratia marcescens isolates were tested.PCR was performed to amplify the common drug resistant genes. Pulse-field gel electrophoresis ( PFGE) was carried out for analyzing the homology of all isolates.The com-plete clinical data of the patients were collected and statistically analyzed with Spearman′s rank correlation coefficient.Results Seventeen strains were isolated in this study.All of the 17 strains were resistant to the first and second generation Cephalosporin, Gentamicin and Ciprofloxacin, and sensitive to Amikacin and Ceftazidime.The drug resistant rates to Carbapenems ranged from 11.76%to 35.29%.One of the isolates (5.88%) carried the TEM gene.The results of PFGE showed that the phenotypes of all isolates were identi-cal.Conclusion Serratia marcescens strains were critical hospital infectious pathogens.They were able to spread in the hospital and were resistant to multiple antibiotics.Clinical physicians should properly use anti-biotics for the patients based on the result of drug susceptibility test.A control regulation for Serratia marces-cens infection within hospital should be enforced to avoid the cross infection and the outbreak of resistant strains.
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ObjectiveTo investigate the changes of hepatitis B sarfaceantigen (HBsAg) titer in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogs and pegylated interferon alfa-2a (PEG IFNα-2a) sequential therapy.Methods Among 6 HBeAg positive CHB patients,3 patients were treated with nucleos(t)ide analogs followed by PEG IFNα-2a for 48 weeks,3 patients were treated with nucleos(t)ide analog monotherapy.The serum HBsAg,anti-HBs,HBeAg,anti-HBe andanti-HBcweredetectedusingthetime-resolved immunofluorometric assay and serum hepatitis B virus (HBV) DNA levels were determined by Taqman polymerase chain reaction (PCR) every 12 weeks.Results HBsAg loss were achieved in three patients after 48-week nucleos(t)ide analogs and PEG IFNα-2a sequential therapy.However,the HBsAg titers of another 3 patients varied from 100 IU/mL to 320 IU/mL.ConclusionIn HBeAg positive CHB patients who obtain virologic response accompanied with HBsAg titer decreasing dramatically by nucleos(t) ide analog treatment,PEG IFNα-2a sequential treatment can increase HBsAg clearance rate.
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Objective To study the dynamics changes of cerebrospinal fluid (CSF) bacterial load within 48 h after infection in a rabbit meningitis model, and provide information for diagnosis,treatment and prognosis of this disease. Methods Taking New Zealand white rabbit as the study object, meningitis model was established via cerebellar cistern puncture with different concentrations of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) to explore the relationship between the mortality of animals and the subarachnoid inoculation dosage. The dynamics study of CSF bacterial load was conducted with proper inoculation bacterial dosage. Forty-eight rabbits were separated into four groups (12 each group): E. coli meningitis model group, E. coli meningitis + ceftriaxone treated group, S. aureus meningitis model group and S. aureus meningitis + vancomycin treated group. At 0,12, 24, 36 and 48 h of inoculation, CSF and blood samples were obtained for CSF bacterial quantitative culture, CSF leukocyte count and peripheral blood leukocyte count. Finally, the relationships between the early mortality of animals, the efficacy of antibiotics, CSF leukocyte counts and the dynamics changes of CSF bacterial load were analyzed in the bacterial meningitis rabbit model.The CSF bacterial load and the white blood cell count curve were compared by analysis of covariance (ANOVA). Correlation test was done using correlate partial analysis. Results The relationship between subarachnoid inoculation dosage and the mortality of rabbits presented S-curve correlation.The bacterial load in subarachnoid space peaked in 12-24 h after infection and then gradually decreased. Effective antibiotic therapy could significantly speed up the decline of this process. There were significantly different between E. coli meningitis model group and E. coli meningitis+ceftriaxone treated group (F= 27. 10, P<0. 01), between S. aureus meningitis model group and S. aureus meningitis + vancomycin treated group (F=5. 97, P = 0. 016). There was a positive correlation between CSF bacterial load and CSF leukocyte count in E. coli and S. aureus meningitis model groups (r=0. 89, 0.84, respectively; P = 0.046, 0.049, respectively). Conclusions In the treatment of bacterial meningitis, effective and sufficient antibiotics should be used as soon as possible to control the CSF bacterial load and reduce the mortality. The CSF leukocyte count can be used as indicator of CSF bacterial load and guide the antibiotic treatment in clinical bacterial meningitis.