We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventil...We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventilator days. We also examined pathogens, rate of progression from VAT to VAP, and impact of antibiotic therapy for VAT. Data analysis included 234 patients, 100 patients (43%) had at least moderate (+++) bacterial growth in their semi-quantitative endotracheal aspirate (SQ-ETA) cultures. VAT and VAP were each diagnosed in 34 (15%) patients. Staphylococcus aureus was the most common pathogen isolated and had the highest rate of progression from VAT to VAP. Seven (21%) of the 34 patients were diagnosed with VAT that later progressed to VAP in averaged 3 days. Patients diagnosed with VAT had significantly more ventilator days (9 vs 6, p p < 0.001) and hospital days (22 vs 17, p < 0.001). No significant difference was observed in the clinical outcomes of the 25 VAT patients with timely, appropriate antibiotics compared to the 9 VAT patients who did not receive timely appropriate antibiotics. VAT was a risk factor for increased ventilator days, longer length of ICU and hospital stay. The time window from VAT to VAP allowed physicians to identify the pathogens and sensitivity profile needed to treat VAT with appropriate antibiotics. Data from well-designed studies were needed to assess the impact of early, appropriate antibiotic therapy for VAT, the choice of antibiotics, as well as the duration and route of administration.展开更多
Objective:To validate whether orally administered capsules of alkaloids from the leaves of Alstonia scholaris(CALAS)can improve the clinical indices of acute bronchitis and to investigate the alterations in the relati...Objective:To validate whether orally administered capsules of alkaloids from the leaves of Alstonia scholaris(CALAS)can improve the clinical indices of acute bronchitis and to investigate the alterations in the relationship between its composition and pharmacodynamic markers,thereby providing a clinical reference for the administration of this medication.Methods:This is a prospectively planned,blinded,placebo-controlled,parallel-grouped clinical trial with aggregated population pharmacokinetics/pharmacodynamics(PPK/PPD)data.A total of 55 subjects will be randomly allocated into 4 arms;specifically,10 of the 55 subjects will be selected randomly for the placebo arm,and will be orally administered placebo(Tid),and 45 subjects will be randomly assigned to CALAS treatment groups(20 mg,40 mg,and 80 mg Tid,at 15 subjects per group).The medication,presence of cough and phlegm,as well as body temperature of every subject,will be recorded daily during treatment.About 3–4 blood samples will be collected from each subject at the following points for PPK/PPD parameters analysis:at pre-dose(0 h)and post-dose at 15 minutes,40 minutes,1 hour,1.5 hours,2 hours,3 hours,4 hours,6 hours,8 hours,12 hours,24 hours,30 hours,and 48 hours after last dosing.All the subjects will be subjected to a laboratory examination and efficacy evaluation on day 8.Discussion:A new integrating strategy to explore the relationship among drug components,action pathways,and clinical efficacy will be established through this study.We aim to explore the mechanism of action of CALAS in the treatment of acute bronchitis on the premise of definite active ingredients and reliable clinical efficacy.It is difficult to enroll patients in classic pharmacokinetics research because it adopts an intensive sampling method,and it cannot quantify the variability of pharmacokinetics parameters(intraindividual variation,interindividual variation,and weekly variation).Moreover,the extrapolation and prediction of dosage regimens in different species and populations cannot be achieved.Therefore,the PPK/PPD method,which takes advantage of sparse data(3–5 time points sampling per patient),is adopted to determine the measurable pathologic and physiological factors that can influence dose concentration to guide reasonable dose adjustment toward achieving optimal clinical effects.展开更多
文摘We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventilator days. We also examined pathogens, rate of progression from VAT to VAP, and impact of antibiotic therapy for VAT. Data analysis included 234 patients, 100 patients (43%) had at least moderate (+++) bacterial growth in their semi-quantitative endotracheal aspirate (SQ-ETA) cultures. VAT and VAP were each diagnosed in 34 (15%) patients. Staphylococcus aureus was the most common pathogen isolated and had the highest rate of progression from VAT to VAP. Seven (21%) of the 34 patients were diagnosed with VAT that later progressed to VAP in averaged 3 days. Patients diagnosed with VAT had significantly more ventilator days (9 vs 6, p p < 0.001) and hospital days (22 vs 17, p < 0.001). No significant difference was observed in the clinical outcomes of the 25 VAT patients with timely, appropriate antibiotics compared to the 9 VAT patients who did not receive timely appropriate antibiotics. VAT was a risk factor for increased ventilator days, longer length of ICU and hospital stay. The time window from VAT to VAP allowed physicians to identify the pathogens and sensitivity profile needed to treat VAT with appropriate antibiotics. Data from well-designed studies were needed to assess the impact of early, appropriate antibiotic therapy for VAT, the choice of antibiotics, as well as the duration and route of administration.
基金supported by the National Science of China Academy of Chinese Medical Sciences(No.zz0908022)the National Natural Science Foundation of China(81603505)+1 种基金the National Science and Technology major project(2017ZX09304003)the National Key Research and Development Program(2018YFC1706006).
文摘Objective:To validate whether orally administered capsules of alkaloids from the leaves of Alstonia scholaris(CALAS)can improve the clinical indices of acute bronchitis and to investigate the alterations in the relationship between its composition and pharmacodynamic markers,thereby providing a clinical reference for the administration of this medication.Methods:This is a prospectively planned,blinded,placebo-controlled,parallel-grouped clinical trial with aggregated population pharmacokinetics/pharmacodynamics(PPK/PPD)data.A total of 55 subjects will be randomly allocated into 4 arms;specifically,10 of the 55 subjects will be selected randomly for the placebo arm,and will be orally administered placebo(Tid),and 45 subjects will be randomly assigned to CALAS treatment groups(20 mg,40 mg,and 80 mg Tid,at 15 subjects per group).The medication,presence of cough and phlegm,as well as body temperature of every subject,will be recorded daily during treatment.About 3–4 blood samples will be collected from each subject at the following points for PPK/PPD parameters analysis:at pre-dose(0 h)and post-dose at 15 minutes,40 minutes,1 hour,1.5 hours,2 hours,3 hours,4 hours,6 hours,8 hours,12 hours,24 hours,30 hours,and 48 hours after last dosing.All the subjects will be subjected to a laboratory examination and efficacy evaluation on day 8.Discussion:A new integrating strategy to explore the relationship among drug components,action pathways,and clinical efficacy will be established through this study.We aim to explore the mechanism of action of CALAS in the treatment of acute bronchitis on the premise of definite active ingredients and reliable clinical efficacy.It is difficult to enroll patients in classic pharmacokinetics research because it adopts an intensive sampling method,and it cannot quantify the variability of pharmacokinetics parameters(intraindividual variation,interindividual variation,and weekly variation).Moreover,the extrapolation and prediction of dosage regimens in different species and populations cannot be achieved.Therefore,the PPK/PPD method,which takes advantage of sparse data(3–5 time points sampling per patient),is adopted to determine the measurable pathologic and physiological factors that can influence dose concentration to guide reasonable dose adjustment toward achieving optimal clinical effects.
