一种新的幽门螺杆菌克拉霉素耐药相关基因

目的:分析不同克拉霉素浓度下H pylori菌株耐药的发生机制,以期发现新的耐药基因．方法:以H pylori 26695株为初发菌株,经抗生素压力筛选、转座子Tn5插入失活、E-test检测等实验方法探讨H pyolri对克拉霉素的耐药机制．结果:经12次传代,在0．5 mg／L克拉霉素浓度下培养出的耐药株经-80℃冻存30 d复苏,仍为抗性菌株;克拉霉素抗性的转座插入株于 700 bp左右出现条带;经96-168 h培养,单纯经抗生素选择压力筛选的低浓度耐药株E-test 出现椭圆形抑菌环,而经Tn5插入的克拉霉素抗性菌株无抑菌环出现．对插入位点基因的测序发现该片段与H pylori 26695菌株中“H pylori 1469”完全同源,为编码Omp3l的基因．结论:H pylori对克拉霉素的低浓度耐药,经转座后可转化为高浓度耐药,其耐药性的发生与23S rRNA点突变以外的Omp31基因有关．

瑞倍加用克拉霉素治疗幽门螺杆菌相关消化性溃疡31例

应用瑞倍加用克拉霉素治疗幽门螺杆菌(Hp)相关消化性溃疡,对照观察该方案对缓解消化性溃疡、促进溃疡愈合及根除Hp的疗效。结果其疗效与常规三联疗法相近,无显著差异。

观察奥美拉唑、阿莫西林和克拉霉索联合治疗胃溃疡的疗效

目的观察对胃溃疡患者行以奥美拉唑、阿莫西林、克拉霉素联合治疗的疗效。方法从乡镇卫生院消化内科择取22例胃溃疡患者,将其随机分成两组,对照组11例患者行以奥美拉唑、阿莫西林治疗,研究组11例患者行以奥美拉唑、阿莫西林和克拉霉素联合治疗,对照分析两组临床效果。结果从治疗效果上分析,研究组优于对照组,P<0.05;从不良反应上对比,组间并无统计学差异,P>0.05。结论对胃溃疡患者行以奥美拉唑、阿莫西林、克拉霉素联合治疗的疗效确切,而且安全性良好,临床价值显著。

观察雷贝拉唑、阿莫西林和克拉霉素联合治疗胃溃疡的效果

目的:观察雷贝拉唑、阿莫西林和克拉霉素三者联合治疗胃溃疡的效果。方法:收治胃溃疡患者100例,随机分为观察组(50例)及对照组(50例)。对观察组行雷贝拉唑、阿莫西林和克拉霉素三种药物联合治疗;对对照组使用雷贝拉唑、阿莫西林和甲硝唑三种药物联合治疗,对比、观察两组疗效。结果:观察组不适现象发生率4%,明显低于对照组的18%(P<0.05);观察组优良率98%(49/50),明显高于对照组的80%(40/50)(P<0.05)。结论:雷贝拉唑、阿莫西林和克拉霉素联合治疗胃溃疡,能够对临床症状进行有效缓解,减少家庭经济负担,效果较好,且安全性较高。

克拉霉素片溶出度的HPLC测定

用HPLC法测定克拉霉素片的溶出度,方法可靠,选择性好,灵敏度高,回收率为99.33％,变异系数为1.02％。

奥美拉唑、阿莫西林和克拉霉索联合治疗胃溃疡的疗效

目的观察奥美拉唑、阿莫西林和克拉霉索三者联合用药治疗胃溃疡的疗效。方法选择2012年7月至2013年11月于永城市中心医院治疗的胃溃疡患者100例作为研究对象,以随机数表法分为观察组和对照组(各50例)。观察组行奥美拉唑、阿莫西林和克拉霉索三种药物联合治疗;对照组使用奥美拉唑、阿莫西林和甲硝唑三者药物联合诊治,对比观察两组的疗效。结果比较两组患者不适现象发生情况,观察组发生率较对照组明显更低。两组患者进行治疗后,观察组疗效为优者占78.00%(39/50)、优良率达到98.00%(49/50),均显著高于对照组的56.00%(28/50)、80.00%(40/50)。差异均有统计学意义(P<0.05)。结论奥美拉唑、阿莫西林和克拉霉索联合使用对胃溃疡进行治疗,能够有效缓解患者临床症状,减轻家庭经济负担,效果较好,且安全性较高,值得临床推荐。

长期低剂量克拉霉素治疗慢性鼻窦炎

目的：观察长期低剂量克拉霉素治疗慢性鼻窦炎的疗效。方法：2002年4月至2003年1月我们用低剂量克拉霉素治疗63例慢性鼻窦炎，检测治疗前后糖镜传输时间，观察治疗3、6个月后患者症状、鼻内镜检查、鼻窦CT检查及鼻窦黏膜病例的改善情况。结果：治疗3、6个月后鼻腔通气改善分别为66．7％、73．0％；鼻涕量减少65．1％、74．6％；头痛减轻73．5％、85．3％；嗅觉改善30．0％、35．0％：鼻内经检查好转55．8％、69．2％：CT扫描结果较用药前改善61．4％、68．4％；病例检查示鼻窦黏膜炎症减轻38．5％、61．5％。治疗前平均ST为（35．5±6．3）min，用药3个月后为（27．8±6．6）min．

Outcomes of CAG Regimen for Refractory Biphenotypic Acute Leukemia Patients

Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor （CAG） regimen for refractory biphenotypic acute leukemia （BAL）. Methods We treated 5 refractory BAL patients by CAG regimen （10 mg.m 2 cytosine arabinoside subcutaneously administrated every 12 hours, day 1-14; 5-7 mg·m^-2 aclarubicin intravenously administrated daily, day 1-8; and concurrently used 200 μg·m^-2·d^-1 granulocyte colony-stimulating factor subcutaneously） from November 2002 to April 2007. The efficacy of the regimen was evaluated by response rate, and the side effects were also measured. Results The complete remission rate was 80%, median duration of absolute neutrophil count〈5.0×10^8/L and platelet count〈2.0×10^10/L was day 13 and day 1, respectively; and the infection rate was low （Ⅲ-Ⅳ infection rate, 20.00%）.

Clinical role and importance of fluorescence in situ hybridization method in diagnosis of H pylori infection and determination of clarithromycin resistance in H pylori eradication therapy

H pylori is etiologically associated with gastritis, gas-tric and duodenal ulcers, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Eradicating H pylori may convert rapidly the outcome of related diseases with the use of more accurate diagnostic molecular tests. Indeed some of the tests cannot give the evidence of current infection; H pylori can be detected by noninvasive and invasive methods, the latter requiring an endoscopy. Eradication failure is a big problem in H pylori infection. Recently, clarithromycin resistance in H pylori strains is increasing and eradicati-on therapy of this bacterium is becoming more difficult. Molecular methods have frequently been applied besides phenotypic methods for susceptibility testing to detect clarithromycin resistance due to mutations in the 2143 and 2144 positions of 23S rRNA gene. Fluorescence in situ hybridization (FISH) method on paraffin embedded tissue is a rapid, accurate and cost-effective method for the detection of H pylori infection and to determine clarithromycin resistance within three hours according to the gold standards as a non-culture method. This method can also be applied to fresh biopsy samples and the isolated colonies from a culture of H pylori, detecting both the culturable bacillary forms and the coccoid forms of H pylori, besides the paraffin embedded tissue secti-ons. This technique is helpful for determining the bac-terial density and the results of treatment where clarith-romycin has been widely used in populations to increase the efficacy of the treatment and to clarify the treatment failure in vitro.

Omeprazole-based triple therapy with low-versus high-dose of clarithromycin plus amoxicillin for H pylori eradication in Iranian population

AIM： To investigate the efficacy and tolerability of H pylori eradication in an omeprazole-based triple therapy with high and low dose of clarithromycin and amoxicillin. METHODS： One hundred and sixty H pylori positive patients were randomly assigned to two groups based on the following 2 wk investigation; （1） group A or low-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 250 mg b.i.d and amoxicillin 500 mg b.i.d; and （2） group B or high-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d and amoxicillin 1000 mg b.i.d. During the study Hpylori status was assessed by histology and rapid urease test prior and by 13C-urea breath test 6 wk after the therapy. Standard questionnaires were administered to determine the compliance to treatment and possible adverse events of therapy. Data were subject to x^2 to compare the eradication rates in the two groups. The significant level of 95% （P ≤ 0.05） was considered statistically different. RESULTS： We found that the per-protocol eradication rate was 88% （68/77） in group A, and 89% （67/75） in group B. The intension-to-treat eradication rate was 85% （68/80） in group A and 83.75% （67180） in group B. Overall adverse events were 26% in group A and 31% in group B. The adverse events were generally mild in nature and tolerated well in both groups with a compliance of 98% in group A vs 96% in group B. CONCLUSION： The omeprazole-based low dose regimen of darithromycin and amoxicillin for two weeks in Hpylori eradication is as effective as high dose regimen in Iranian population.

Characterization of clarithromycin resistance in Malaysian isolates of Helicobacter pylori

AIM： To characterize the types of mutations present in the 23S rRNA genes of Malaysian isolates of clarithromycin-resistant Helicobacter pylori （H pylorl~. METHODS： Clarithromycin susceptibility of H pylori isolates was determined by E test. Analyses for point mutations in the domain V of 23S rRNA genes in clarithromycin-resistant and -sensitive strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using Bsa I and MboI enzymes to detect restriction sites that correspond to the mutations in the clarithromycin- resistant strains. RESULTS： Of 187 isolates from 120 patients, four were resistant to clarithromycin, while 183 were sensitive. The MIC of the resistant strains ranged from 1.5 to 24 pg/mL. Two isolates had an A2142G mutation and another two had A2143G mutations. A T2182C mutation was detected in two out of four clarithromycin-resistant isolates and in 13 of 14 clarithromycin-sensitive isolates. Restriction enzyme analyses with Bsa I and Mbo I were able to detect the mutations. CONCLUSION： Clarithromycin resistance is an uncommon occurrence among Malaysian isolates of Hpylori strains and the mutations A2142G and A2143G detected were associated with low-level resistance.

Antibiotic resistance and cagA gene correlation:A looming crisis of Helicobacter pylori

AIM:To determine antibiotic resistance of Helicobacter pylori(H.pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS:A total of 178 strains of H.pylori were isolated from gastric biopsies of dyspeptic patients.Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period,gastric conditions and cagA gene carriage.The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.RESULTS:The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole,36% for clarithromycin,37% for amoxicillin,18.5% for ofloxacin and 12% for tetracycline.Furthermore,clarithromycin resistance was on the rise from 2005 to 2008(32% vs 38%,P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis,gastric ulcer and duodenal ulcer cases(53% vs 20%,18% and 19%,P = 0.000).On the contrary,metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases.Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.CONCLUSION:The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H.pylori strains.

泮托拉唑对幽门螺杆菌相关性十二指肠溃疡的疗效观察

目的观察泮托拉唑治疗幽门螺杆菌(Hp)相关性十二指肠溃疡的临床疗效。方法48例Hp阳性感染的十二指肠溃疡患者随机接受泮托拉唑联合羟氨苄青霉素和克拉霉素治疗或仅服用雷尼替丁治疗。4周后观察临床症状情况,并经胃镜检查观察溃疡愈合和Hp清除。结果经4周治疗发现,泮托拉唑治疗组患者明显改善临床症状(如反酸、烧心、上腹部疼痛等)并使溃疡愈合。胃窦部炎症分级明显降低,Hp也得到有效清除(P<0.05)。结论泮托拉唑联合抗Hp治疗可有效地控制十二指肠溃疡的临床症状,加速溃疡愈合,清除Hp的感染,是治疗十二指肠溃疡的一种有效、价廉的方法。

Preparation and evaluation of liposomal clarithromycin with antimicrobial effect

In this study, we developed a novel liposomal delivery system modified by Tat peptide and wheat germ agglutinin（WGA） with antimicrobial effect. Physicochemical parameters, in vitro antimicrobial, time-kill study, cellular uptake, biofilm formation inhibition and in vivo antibacterial efficacy against Methicillin-resistant Staphylococcus aureus（MRSA） were investigated. Minimum inhibitory concentrations（MICs） and colony-forming units（CFUs） in the time-kill study for Tat-WGA-modified liposomal clarithromycin（CLA-Tat WGALip） were lower than those of free and other modified liposomal CLA. Flow cytometry analysis disclosed that Tat WGALip delivered more coumarin 6 into bacteria. Furthermore, Tat-WGA-modified liposomal CLA efficiently inhibited the formation of MRSA biofiom. CFU of MRSA in the abscess of mice treated with CLA-Tat WGALip was significantly lower than that of any others（P〈0.01）. Collectively, liposomal delivery system modified by Tat and WGA could be a promising anti-resistant infection strategy.

Coordination of glycerol utilization and clavulanic acid biosynthesis to improve clavulanic acid production in Streptomyces clavuligerus

The glycerol utilization (gyl) operon is involved in clavulanic acid (CA) production by Streptomyces clavuligerus, and possibly supplies the glyceraldehyde-3-phosphate (G3P) precursor for CA biosynthesis. The gyl operon is regulated by GylR and is induced by glycerol. To enhance CA production in S. clavuligerus, an extra copy of ccaR expressed from Pgyl (the gyl promoter) was integrated into the chromosome of S. clavuligerus NRRL 3585. This construct coordinated the transcription of CA biosynthetic pathway genes with expression of the gyl operon. In the transformants carrying the Pgyl-controlled regulatory gene ccaR, CA production was enhanced 3.19-fold in glycerol-enriched batch cultures, relative to the control strain carrying an extra copy of ccaR controlled by its own promoter (PccaR). Consistent with enhanced CA production, the transcription levels of ccaR, ceas2 and claR were significantly up-regulated in the transformants containing Pgyl-controlled ccaR.