Clinical And Experimental Study On Curing Ureaplasma Urealyticum Infection In Female Genital Tract By Invigorating Spleen

ObjectivesUreaplasma urealyticum(Uu)infection,which continues to rise in recent years,is closely related to diseases of female reproductive organs.Its clinical treatment is becoming more and more difficult due to drug resistance,high relapse rate and mixed infection caused by repeated migration infection,antibiotics abuse and irregular treatments,etc.Some domestic studies have showed that TCM has great advantage in the treatment of Uu infection.Uu as one of dwelling bacterias in the female genital tract,is opportunistic pathogens,which most women in the state to carry but no discomfort,only a few human cases.This is considered to be related to healthy trends.Human healthy trends need the support of spleen.This clinical study focus on invigorating spleen,to find effective therapy against Uu infection in female genital tract through comparing clinical effect and safety of Zhidai tablets,Doxycycline and combination of both,and to explore the possible effect mechanism of Zhidai tablets compound gainst Uu by inhibition test in vitro at the same time.Methods1.Clinical study on randomized,non-blinded,and positive controlled is adopted in this test,with Doxycycline as a positive control.150 female cases infected by Uu in genital tract with syndrome of splenic asthenia and wet accumulation and blood stasis are divided into three groups on average:Zhidai tablets group,Doxycycline group and Combination group.Patients in Zhidai tablets group are treated only with Zhidai tablets and those in Doxycycline group with Doxycycline.And patients of combination group are treated with both treatments above mentioned.Changes of symptoms and signs and TCM syndrome,together with laboratory examination indexes such as Uu and leucorrhea conventional are recorded to compare clinical effects of these three different therapies.Meanwhile,examination results of blood,urine,stool,hepatorenal function,electrocardiogram and adverse reaction caused by drugs will be recorded for the safety assessment of treatment.Cases cured have been tracked for at least one month and re-examined to compare relapse rates of different groups.2.Use medicine liquid made from Zhidai tablets compound and 8 prescription herbs to test their Minimum Inhibition Concentration(MIC)on Uu clinical strains and Standard strains to know if they suppress Uu in vitro.Results1.Results of clinical study(1)Clinical effects:according to the research results,Zhidai tablets,doxycycline and drug combination all improve clinical symptoms and symptom assessment of cases infected by Uu in female genital significantly.Score difference among three groups before and after the treatment has statistical significance(P<0.01).As per clinical effect evaluation,the total effective rates of Zhidai group,Doxycycline group and Combination group are 77.8%,89.5%and 95.7%.The difference has statistical significance(?2=7.160,P<0.05).By rank sum test,clinical effects of three groups also differ(P<0.01),among which the Doxycycline group and Combination group work better,and Combination group is the best.(2)TCM symptoms effects:according to the research results,Zhidai tablets,doxycycline and drug combination all improve TCM symptoms assessment efficiently.Score difference among three groups before and after the treatment has statistical significance(P<0.01).In terms of TCM symptoms effect evaluation,the total effective rates of Zhidai group,Doxycycline group and Combination group are 88.9%,70.8%and 95.7%.The difference has statistical significance(?2 =12.345,P<0.05).By rank sum test,TCM symptoms effects of three groups also differ(P<0.01),among which Zhidai group and Combination group work better,and Combination group is the best.(3)Uu negative conversion rates:according to the research results,Uu negative conversion rates of Zhidai group,Doxycycline group and Combination group are 48.9%,79.2%and 89.4%.The difference has statistical significance(?2=20.513,P<0.01)Uu negative conversion rate of Doxycycline group and Combination group is more than that of Zhidai group(P<0.01).However,the difference of Uu negative conversion rate between Doxycycline group and Combination group was not statistically significant(P>0.05).(4)Vulvovaginal Candidiasis(VVC)morbidity rates:according to the research results,VC morbidity rates of Zhidai group,Doxycycline group and Combination group are 6.7%,27.1%and 10.6%.The difference has statistical significance(?2=8.649,P<0.05).WC morbidity rates of Zhidai group and Combination group are less than that of Doxycycline group(P<0.05).However,the difference of VVC morbidity rate between Zhidai group and Combination group was not statistically significant(P>0.05).(5)Uu relapse rates:according to the research results,Uu relapse rates of Zhidai group,Doxycycline group and Combination group are 9.1%,34.2%and 11.9%.The difference has statistical significance(?2=6.900,P<0.05).Uu relapse rates of Zhidai group and Combination group are less than that of Doxycycline group(P<0.05).However,the difference of Uu replase rate between Zhidai group and Combination group was not statistically significant(P>0.05).(6)Before and after treatment no obvious abnormal case of Three groups of patients was found in all safety index,such as blood,urine,stool routine,liver and kidney function,electrocardiogram.Adverse reaction,3 cases in Doxycycline group for nausea,1 case in Doxycycline group for dizziness;1 case in Zhidai group for Constipation;1 case in Combination group for bloating?There were no serious adverse reactions in three groups.Groups of medicine were safe.2.Results of experimental study(1)The MIC of Zhidai tablets compound preparation against clinical strains and Uu Serotype ?(ATCC27618)with concentration of 102CCU/ml are both 50mg/ml while that against Uu Serotype IV(ATCC29557)with relative concentration of 102CCU/ml is no more than 20mg/ml.(2)There are 59 clinical strains in TCM inhibition test in vitro,of which 14 strains are resistant to 4 or more antibiotics,accounting for 23.7%.(3)The difference between Zhidai tablets compound MIC of clinical drug-resistant strains and that of non-resistant strains has not statistical significance(P>0.05).Among 4 strains resistant to doxycycline,of which 2 are sensitive to Zhidai tablets compound,with MIC 25mg/ml.(4)Here are the MIC of Zhidai tablets compound and 8 herbals contained against 59 clinical strains:compound preparation 50mg/ml,herba houttuyniae?5mg/ml,glabrous greenbrier rhizome?5mg/ml,white paeony 50mg/ml,,Alisma orientale>50mg/ml,herba plantaginis 100mg/ml,Rhizoma Dioscoreae Hypoglaucae 200mg/ml,largehead atractylodes>200mg/ml,common yam>300mg/ml.(5)Here are the MIC of Zhidai tablets compound and 8 herbals contained against Uu Serotype IV(ATCC29557)with concentration of 104CCU/ml:compound preparation?20mg/ml,herba houttuyniae?5mg/ml,glabrous greenbrier rhizome?5mg/ml-20mg/ml,white paeony 20-25mg/ml,Alisma orientale 10-50mg/ml,herba plantaginis 50mg/ml,Rhizoma Dioscoreae Hypoglaucae?25-100mg/ml,largehead atractylodes 25-200mg/ml,common yam 100-300mg/ml.(6)Here are the MIC of Zhidai tablets compound and 8 herbals contained against Uu Serotype ?(ATCC27618)with concentration of 102CCU/ml:compound preparation 50mg/ml,glabrous greenbrier rhizome 10-20mg/ml,white paeony?15-20mg/ml,herba houttuyniae 20mg/ml,Alisma orientale?50mg/ml,Rhizoma Dioscoreae Hypoglaucae 50-100mg/ml,herba plantaginis 100mg/ml,largehead atractylodes200mg/ml,common yam?300mg/ml.Conclusions1.Zhidai Tablets which focus on invigorating spleen combined with Doxycycline can not only improve clinical effect and TCM symptoms,but also reduce WC morbidity and relapse rate of Uu at the same time.It can be concluded that the combination therapy is worthy of clinical application.2.Multi-drug resistance of Uu is serious in clinical?Zhidai tablets compound can suppress Uu in vitro to some extent.Among these 8 herbals contained in Zhidai tablets,herba houttuyniae and glabrous greenbrier rhizome show stronger suppression than others while largehead atractylodes and common yam have none suppression nearly.The difference of MIC with Zhidai tablets compound between standard strains and clinical isolates is small.The difference between Zhidai tablets compound MIC of clinical drug-resistant strains and that of non-resistant strains has not statistical significance.This tells us that antibiotic-resistant strains is not resistant to Zhidai tablets compound and Zhidai tablets compound is worthy of further research and development.