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1.
目的 分析拓扑异构酶的突变和外排泵系统在大肠埃希菌(Escherichia coli)氟喹诺酮类药物耐药机制中的作用.方法 本研究通过基因重组技术对大肠埃希菌中拓扑异构酶不同点突变的功能进行了准确测定,同时也对大肠埃希菌中不同外排泵及膜蛋白的功能进行了分析.结果 在不同的菌株中,acrAB或tolC的切除所引起细菌耐药性的变化不同.对拓扑异构酶点突变的功能分析显示,gyrA中的点突变(S83和D87)在喹诺酮耐药机制中起主要作用,没有gyrA上的点突变,parC上的点突变(S80和A108)对细菌的耐药性不产生影响,但单独gyrA上的点突变(S83和D87)也仅导致敏感菌株对萘啶酸耐药,而对其他氟喹诺酮类药物仍表现为敏感.当对喹诺酮敏感的大肠埃希菌K-12同时具备gyrA(S83L和D87N)和parC(S801和A108V)上的点突变后,重组菌株对氟喹诺酮会自然产生耐药性,而并不需要过度表达的外排泵.结论 拓扑异构酶的突变在大肠埃希菌氟喹诺酮药物的耐药机制中起主要作用,对氟喹诺酮药物耐药的菌株通常应同时具备gyrA和parC上的点突变. 相似文献
2.
Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic
acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential.
Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean
biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of
the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound,19F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total
(free plus glucuronide ester) DW116 were 28.6±2.7% and 36.4±1.8% of the administered dose and the corresponding biliary recoveries
were 14.4±5.5% and 37.0±7.6%, respectively. 相似文献
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《Current medical research and opinion》2013,29(8):1175-1183
SUMMARYObjectives: To compare the efficacy and safety of ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) otic suspension with that of neomycin 0.35%/polymyxin B 10?000?IU/mL/hydrocortisone 1.0% (N/P/H) otic suspension in patients with acute otitis externa (AOE).Study Design: Randomized, observer-masked, parallel-group, multicenter study. Patients were randomized to 7 days treatment with either CIP/DEX 3–4 drops twice daily or N/P/H 3–4 drops three times daily.Population: Patients of either sex and older than 1 year, with a clinical diagnosis of mild, moderate, or severe AOE and intact tympanic membranes were recruited to participate.Outcomes Measured: Signs and symptoms of AOE, including ear inflammation, tenderness, edema and discharge (assessed on Days 3, 8 [End-of-Therapy] and 18 [Test-of-Cure]); microbiologic eradication (presumed or documented); and frequency of adverse events.Results: Patients enrolled numbered 468. In culture-positive patients who met the inclusion criteria (N = 396), clinical cure rates at Day 18 were significantly higher with CIP/DEX than with N/P/H (90.9% vs. 83.9%; p = 0.0375), as were microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057). In addition, the clinical response was significantly better with CIP/DEX than with N/P/H at Days 3 and 18 (p = 0. 0279 and p = 0. 0321, respectively), as was the reduction in ear inflammation at Day 18 (p = 0.0268). Both preparations were well tolerated in pediatric and adult patients.Conclusions: 7 days treatment with CIP/DEX otic suspension administered twice daily is clinically and microbiologically superior to N/P/H otic suspension administered 3 times daily in the treatment of mild to severe AOE, and is equally well tolerated. 相似文献
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Patricia Iraurgui María José Torres Javier Aznar 《Enfermedades infecciosas y microbiología clínica》2012
Introduction
Due to the emergence of drug-resistant pneumococcal isolates, new fluoroquinolones have been recommended for the treatment of pneumococcal infections. The purpose of this study was to establish surveillance, and to conduct molecular characterization, of fluoroquinolone-resistant Streptococcus pneumoniae in Seville.Method
Norfloxacin-resistant S. pneumoniae isolates were characterized by quinolone resistance-determining region (QRDR) substitutions, reserpine-sensitive efflux, serotype and by pulsed-field gel electrophoresis (PFGE) patterns.Results
Fourteen isolates (5.1%) showed an MIC > 16 μg/ml to norfloxacin. Eight of 10 adult isolates were susceptible to levofloxacin. The 4 infant isolates with norfloxacin MIC > 16 μg/ml were susceptible to levofloxacin. Seven of these 12 low-level-resistant isolates had mutations in ParC, while mutations both in ParC and GyrA genes were only detected in one of the two high-level-resistant isolates. All the isolates without QRDR substitutions that remained norfloxacin-resistant were positive for reserpine-inhibited efflux. The serotyping and PFGE revealed significant heterogeneity. We obtained 9 different profiles, 3 of which had two isolates each. Two of the isolates with the same pulsotype were from the same patient. The first isolate showed a mutation in the QRDR of ParC, and the second one had an additional GyrA mutation.Conclusion
In our study a levofloxacin resistance rate of 0.7% was found among invasive isolates. Although resistance level is low, surveillance is necessary, especially to prevent cases of in vivo resistance development as reported. 相似文献7.
目的分析和研究氟喹诺酮类药物的不良反应及应用规律,指导临床合理用药。方法归纳总结124例氟喹诺酮类药物不良反应情况。结果氟喹诺酮类药物用药后,不良反应多发生于胃肠道以及中枢神经系统,涉及不良反应较多的四类药物分别为左氧氟沙星(46.8%)、环丙沙星(28.2%)、加替沙星(18.5%),其中不良反应发生的主要给药途径为静脉注射。结论为了有效减少和防止氟喹诺酮类药物不良反应发生,临床用药中要根据规范要求用药,可有效减少不良反应,提高临床效果。 相似文献
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目的:观察急性肾盂肾炎应用左氧氟沙星的临床干预效果。方法将我院2010年4月~2013年11月确诊并收治的110例急性肾盂肾炎患者随机分为临床组和参照组各55例。临床组应用左氧氟沙星静脉滴注进而口服治疗,参照组应用氨苄青霉素静脉滴注治疗进而用磺胺甲恶唑口服治疗。比照两组症状体征消失时间、临床疗效及治疗时间。结果两组用药完成后,症状体征逐渐改善,临床组其症状体征消失速度均显著好于参照组,差异有统计学意义(P<0.05)。临床组总有效率为98.18%,参照组为96.36%,两组比较差异无统计学意义(P>0.05)。但临床组其平均治疗时长显著低于参照组,差异有统计学意义(P<0.05)。临床组1例发生恶心、呕吐,1例头晕,1例皮肤瘙痒;参照组4例发生恶心、呕吐。两组相比不良反应率差异无统计学意义(P>0.05)。结论急性肾盂肾炎应用左氧氟沙星疗效确切,迅速缓解症状体征、疗程短、安全性好。 相似文献
10.
《Current medical research and opinion》2013,29(9):2241-2249
ABSTRACTObjective: To examine in vitro resistance to azithromycin and moxifloxacin in bacterial conjunctivitis isolates.Methods: MIC90s (Minimum Inhibitory Concentration) and resistance rates to azithromycin and moxifloxacin were determined based upon microtiter broth dilution and/or antimicrobial gradient test strips in a multicenter phase III study and confirmed externally.Results: The most common isolates collected from bacterial conjunctivitis patients in the phase III study were Haemophilus influenzae (40.6%), followed by Staphylococcus epidermidis (19.3 %), Propionibacterium acnes (17.3%), Streptococcus pneumoniae (16.8%), and Staphylococcus aureus (0.06%). MIC90s for all of these organisms were well below established resistance breakpoints for moxifloxacin, indicating no bacterial resistance. On the other hand, the MIC90 for H. influenzae was 3-fold higher than the resistance breakpoint for azithromycin, ≥ 128-fold higher for S. epidermidis, 16-fold higher for S. pneumoniae and ≥ 128-fold higher for S. aureus, indicating moderate to very high bacterial resistance to azithromycin.Conclusions: Resistance to azithromycin is more common than resistance to moxifloxacin in clinical isolates causing bacterial conjunctivitis. 相似文献