| BackgroundsThe appearance of antibiotic-resistant bacteria has brought great difficulties to clinical treatment,caused huge economic losses,and has become a global issue.WHO predict we will step into "post-antibiotic" era if no solution are found.By then,no antibiotics will be available.Nowadays,scientists try to solve the problem through developing new antibiotics.But the periods of developing new antibiotics are longer than the appearance of advanced antibiotic-resistant bacteria.It is still unable to meet clinical needs.So,we thought of traditional Chinese medicine,which has rich theoretical basis and practical experience in treating infectious diseases.However clinical treatment of infectious diseases by antibiotic-resistant bacteria is still based on syndrome differentiation.It still lacks the new theory of TCM,which can guide the treatment of infectious diseases by antibiotic-resistant bacteria.In consideration of current situation,my tutor put forward a new theory "treating antibiotic-resistant bacteria as incubative pathogen" and a new formula "new Dayuan powder" to treat antibiotic-resistant bacteria.This dissertation is to discuss the above two innovation points.PurposeExolaining the theoretic foundation of the new TCM theory and new formula through looking up the literature.Observing the effect of new Dayuan powder on MRSA?Multi Drug Resistance Klebsiella Pneumonia(MDR Kp)biofilm in vitro through experimental research.Evaluating the effect of new Dayuan powder on HAP infected by MDR through clinical research.MethodsTheoretical research:?This article mainly discuss the origin and development of incubative pathogen theory,evolution of its concepts and explain the foundation and innovation point of the new theory by arranging and explaining literature related to incubative pathogen in TCM classics,including Huangdi Neijing,Nan Jing,Treatise on Febrile Diseases and the experience of six representative physicians in ancient China,including Wang Lv,Wu Youke,Zhang Lu,Jiang Baosu,Ye Tianshi,Lei Feng and Liu Baoyi.?By consulting ancient and modern literature related to herbs and formulas,four groups of herbs in the formula was discussed in detail and the whole formula was also explained profoundly.Experimental research:?XTT assays were used to study the effects of New Dayuan powder on developing MRSA?MDR Kp biofilms:100 ?L of bacterial culture and 100 ?L drug solution were added to wells of 96-well plates.After 24 h of incubation,the plates were washed and XTT-PMS was added to enable counting of the number of live bacteria in biofilms using a microplate reader.?XTT assays were also used to explore the effects of New Dayuan powder on mature MRSA?MDR Kp biofilms:100 ?L of bacterial culture were added to wells of 96-well plates.Bacteria were cultured in the plates for 24 hnd then drug solution was added.The plates were cultured for another 24 h,and then XTT-PMS was added to detect the number of live bacteria in the biofilms.?SEM was used to observe the effects of New Dayuan powder on mature MRSA?MDR Kp biofilms:washed and sterilized glass coverslips were added to 24-well plates.Bacterial culture was added.After 24 h of incubation drug solution was added.After another 24 h of incubation,the samples were observed by SEMClinical research:The study observed from January 2016 to December 2019,is a prospective,random clinical trial.The pneumonia patients were selected from department of emergency and ICU of Guang' anmen Hospital and were randomly divided into Chinese medicine group?combination group and western medicine group.All the groups were given fundamental and supportive treatment.Chinese medicine group was given New Dayuan Powder.Combination group was given New Dayuan Powder and related antibiotics.Western medicine group was given related antibiotics.All the course of treatment was 7 days.The fundamental data.laboratory indicators(WBC.NEUT%,CRP.PCT).CPIS score.sputum culture,effective rate and safety indicators were observed on day 0?3?7 in order to evaluate the effect and safety of New Davuan PowderResultsTheoretical research:?New-theor "treating antibiotic-resistant bacteria as incubative pathogen" has sufficient theoretic basis of TCM and is the inheritance and innovation of the theory of incubative pathogen.?New formula "new Dayuan powder" is the inheritanceand innovation of ancient formula "Dayuan Yin" and is more suitable for present diseases.Experimental research:?XTT assays showed that the number of live bacteria in both developing and mature MRSA?MDR Kp biofilms decreased significantly after the administration of New Dayuan powder.?SEM images showed that New Dayuan Powder could destroy the structure of MRSA?MDR Kp biofilms and bacteria.Clinical research:Finally,146 cases were selected(48 cases in Chinese medicine group,49 cases in combination group,48 cases in western medicine group).There was no statistical difference in baseline indicators(gender,age,APACHE ? score,distribution of basic diseases,results of sputum culture,use of mechanical ventilation and CRRT)among the three groups.Laboratory indicators:body temperature:Body temperature decreased in all three groups.The difference of body temperature on the three time points of combination and western medicine groups were statistically significant and the difference of combination group was most obvious(P=0.000).There was no statistical difference on the degree of decline of body temperature among three groups.The difference of recovery rate of combination and western medicine groups were statistically significant(P=0.007,0.001).WBC:WBC decreased in all three groups.The difference of WBC on the three time points of combination groups were statistically significant(P=0.048).NEUT%:NEUT%decreased in all three groups.The difference of NEUT%on the three time points of combination and western medicine groups were statistically significant(P=0.006,0.023).CRP:CRP decreased in all three groups.The difference of CRP on the three time points of combination groups were statistically significant(P=0.036).PCT:PCT decreased in all three groups.The difference of PCT on the three time points of combination groups were statistically significant(P=0.038).Oxygenation index:Oxygenation index increased in all three groups.The difference of oxygenation index on the three time points of the whole groups were statistically significant(P=0.049).There was no statistical difference on the three time points of each three groups.CPIS score:Each group showed irregular change trend.There was no statistical difference on CPIS score of the three time points of each three groups.TCM Syndrome score:TCM Syndrome score decreased in all three groups.The difference of score on the three time points of Chinese medicine and combination groups were statistically significant(P=0.000,0.000).Sputum culture:There was no statistical difference among three groups(P=0.478).Effective rate:Judged by TCM Syndrome score,the combination group had the highest effective rate(63.3%).There was no statistical difference on effective rate of three groups(P=0.278).Judged by indicators.the combination troup also had the highest effective rate(77.6%).There was no statistical difference on effective rate of three groups(P=0.103).However,the difference between combination group and Chinese medicine group were statistically significant(P=0.036)Safety indicators:No abnormal safety indicators related to experimental drugs was found 28-day case fatality rate:The combination group had the lowest rate(38.8%).However.there was no statistical difference among the three groups(P=0.450).ConclusionExperimental research showed new Dayuan powder can inhibit the bacteria embedded in MRSA?MDR Kp biofilms and destroy the structure of biofilm and bacteria in vitro Clinical research showed new Dayuan powder has positive effect on the recovery of body temperature and inflammatory indicators and improvement of oxygenation index.And it is better to combine new Dayuan powder and antibiotics,which had a higher effective rate and a downward trend in the 28 day case fatality rateHence."treating antibiotic-resistant bacteria as incubative pathogen" and "treating antibiotic-resistant bacteria with new Dayuan powder" are two major innovations which have adequate theoretical basis,positive clinical effect and great potential.It can solve part of the problem of antibiotic resistance. |
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