利福昔明-双歧杆菌乳杆菌三联活菌片序贯疗法治疗肠易激综合征的临床观察

目的 探讨利福昔明-双歧杆菌乳杆菌三联活菌片序贯疗法治疗肠易激综合征（IBS）的临床效果.方法 将276例IBS患者随机分为3组,每组各92例,A组（序贯组）采用利福昔明-双歧杆菌乳杆菌三联活菌片序贯治疗＋谷维素;B组（菌剂组）采用双歧杆菌乳杆菌三联活菌片＋谷维素;C组（对照组）采用谷维素治疗;观察3组的治疗效果.结果 序贯组的总有效率为95.65％,显著高于菌剂组和对照组的79.35％、73.91％（P＜0.05）.治疗后序贯组的症状程度评分和症状频率评分为（1.48±0.87）分和（1.39±0.98）分,明显低于菌剂组与对照组的（2.24±1.23）分和（2.28±1.16）分、（2.38±1.13）分和（2.48±1.27）分（P＜0.05）.3组不良反应发生率比较差异无统计学意义（P＞0.05）.结论 利福昔明-双歧杆菌乳杆菌三联活菌片序贯治疗IBS方法简便、疗效显著,可能成为治疗IBS的新方法.     

利福昔明干混悬剂溶出度测定方法研究

目的：建立利福昔明干混悬剂溶出度的测定方法。方法：采用桨法,以900mL 0.25%十二烷基硫酸钠溶液为溶出介质,转速为50r/min,45min时取样,用紫外分光光度法在454nm波长处测定利福昔明干混悬剂的溶出量,溶出限度为标示量的70%。结果：利福昔明溶液在5.182～51.819μg/mL浓度范围内呈良好的线性关系,r=0.999 8（n=6）;平均回收率为100.84%,RSD为0.61%（n=9）。结论：该方法简便、准确、重现性好,可用于利福昔明的质量控制。     

Comparative Analysis of Azithromycin and Doxycycline Efficacy in the Treatment of Female Patients with Acute Urethral Syndrome Caused by Ureaplasma urealyticum

Abstract

Rifaximin, a poorly absorbed rifamycin derivative, exhibited time-dependent bactericidal activity and at concentrations as low as 1/32 of the minimum inhibitory concentration (MIC) caused morphological alterations in both susceptible and resistant bacterial strains. Spontaneous rifaximin-resistant clones appeared with an incidence of 2.6×10^?7. The percentage of Escherichia coli cells cured of various plasmids ranged from: 4.5-70% (Flac), 0-18% (pBP507), 7.7-43.8% (plasmid carrying ESBL genes) and 22.4-41.6% (plasmid encoding toxin from ETEC mex264). 8.4-18.2 and <0.1- 18% of Staphylococcus aureus cells were cured (plasmid-mediated penicillinase), 9.5-58.6% of Morganella morganii (ESBL), 10.6-47.1% Citrobacter freundii(ESBL), 2.3-38.7% of Proteus mirabilis (ESBL) and 14.3-66.6% of Klebsiella pneumoniae (ESBL). Rifaximin reduced plasmid transfer from donor to recipient strains by >99%. The MIC of ceftazidime was reduced (2-4 dilutions) in the presence of rifaximin (0.5xMIC) in ESBL producing strains. Rifaximin lowered the viability and virulence of the bacteria even though they developed resistance to the compound.

In conclusion, the present findings add new features to the microbiological characteristics of rifaximin and suggest that if in vivo pathogens are exposed to sub-MICs of the drug, not only are their physiological functions compromised, but gene virulence and antibiotic resistance are not fully expressed.     

利福昔明对急性细菌性肠道病原菌感染体外抗菌活性研究

目的评价利福昔明对急性细菌性肠道病原菌的体外抗菌活性。方法采用肉汤倍比稀释法测定利福昔明和环丙沙星对177株肠道病原菌的最低抑菌浓度(MIC)。结果63株金黄色葡萄球菌对利福昔明的MIC范围为0.03~2.0mg/L,MIC50和MIC90分别为0.06mg/L、0.125mg/L,环丙沙星MIC范围为0.06~64.0mg/L,MIC50和MIC90分别为1.0mg/L、16.0mg/L;肠道革兰阴性病原菌利福昔明MIC范围为2.0~32.0mg/L,MIC50和MIC90分别为8.0mg/L、16.0mg/L,环丙沙星MIC范围为0.125~64.0mg/L,MIC50和MIC90分别为1.0mg/L、16.0mg/L。结论利福昔明对金黄色葡萄球菌有较高的抗菌活性,可作为金黄色葡萄球菌肠炎的首选药物。对于革兰阴性肠道病原菌虽体外抗菌活性不高,但因它有口服不易吸收的特点可以原形由粪便排出,在肠道内充分发挥其抗菌作用。     

Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease： An observation on non-absorbable antibiotics

AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.     

Current use for old antibacterial agents: polymyxins, rifamycins, and aminoglycosides

This article reviews three classes of antibacterial agents that are uncommonly used in bacterial infections and therefore can be thought of as special-use agents. The polymyxins are reserved for gram-negative bacilli that are resistant to virtually all other classes of drugs. Rifampin is used therapeutically, occasionally as a companion drug in treatment of refractory gram-positive coccal infections, especially those involving foreign bodies. Rifaximin is a new rifamycin that is a strict enteric antibiotic approved for treatment of traveler's diarrhea and is showing promise as a possible agent for refractory Clostridium difficile infections. The aminoglycosides are used mainly as companion drugs for the treatment of resistant gram-negative bacillary infections and for gram-positive coccal endocarditis.     

利福昔明对腹泻病原菌的体外抗菌活性测定

目的　评价利福昔明 (rifaximin)、环丙沙星对腹泻病原菌的体外抗菌活性。方法　采用微量肉汤稀释法对 14 3株肠道分离病原菌进行利福昔明、环丙沙星 MIC测定。结果　利福昔明和环丙沙星对革兰氏阴性菌 (沙门菌属 31株 ,志贺菌属 2 0株 ,变形菌属 8株 ,致病性大肠埃希氏菌 5株 ,假单胞菌属 6株 ,克雷伯氏菌属 4 ,其他革兰氏阴性菌 4株 ) MIC范围 、MIC50 、MIC90 分别为 1～ >12 8、0 .0 15～ >12 8,4～ 6 4、0 .0 15～ 6 4 ,32～ 12 8、32～ 12 8mg/ L;利福昔明和环丙沙星对革兰氏阳性球菌 (金葡菌 31株 ,其他葡萄球菌 17株 ,肠球菌属 17株 ) MIC范围 、MIC50 、MIC90 分别为 0 .0 15～ 32、0 .0 15～ 6 4 ,0 .0 15～ 0 .0 3、0 .5～ 16 ,0 .0 6～ 1、16～ 6 4 mg/ L。结论　利福昔明对革兰氏阳性菌 MIC范围 、MIC50 、MIC90 均低于环丙沙星 ;革兰氏阴性菌 MIC范围 、MIC50 、MIC90虽然较环丙沙星高 ,但利福昔明在肠道中可达 80 0 0 μg/ g粪便 ,故利福昔明能有效杀灭肠道病原菌。     

Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.     

Rifaximin therapy and hepatic encephalopathy: Pros and cons

Hepatic encephalopathy(HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life.Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy.Non-absorbable antibiotics,such as neomycin and paramomycin,are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects.To overcome these limitations,rifaximin use has been proposed.Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention,with a similar incidence of side-effects.Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern.Following long-term rifaximin therapy,Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients.In addition,selection of resistant mutants of both Gram-negative and-positive bacteria in the gastrointestinal tract cannot be definitely ruled out.Electrolyte alterations(sodium and potassium) have been reported during rifaximin therapy,a warning for its long-term use in cirrhotics.Moreover,a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients.The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides.While waiting for further safety data,caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to nonabsorbable disaccharides.