环丙沙星与其它6种抗菌药物对临床常见致病菌抗菌活性的比较

用琼脂平板稀释法测定了环丙沙星（ＣＰＬＸ）与６种抗菌药物对２１５株临床常见致病的最低抑菌浓度（ＭＩＣ），并统计了敏感率。结果表明７种抗菌药物对大多数受试菌均显示了较高的抗菌活性。ＣＰＬＸ与其他抗菌药物对不同受试菌呈现２．３８％￣１９．０５％的交叉耐药率。该结果提示对其他β－内酰胺类抗菌药物耐药的致病菌引起的严重感染，应根据药敏实验结果慎重选用ＣＰＬＸ。     

5种致病菌对环丙沙星,泰能的耐药性变迁

本实验采用琼脂平板稀释法测定了１９９５年泰能（ＩＭＰ／ＣＳ）和环丙沙星（ＣＰＬＸ）对５种１２９株临床常见致病菌的最低抑菌浓度（ＭＩＣ），并与１９９２年从临床标本分离的５种２１５株致病菌的实验结果进行了对比。实验结果表明，与１９９２年相比，５种致病菌对两药的ＭＩＣ值有较大幅度增高；致病菌对两药的敏感性降低，耐药菌株增多；致病菌对两药的交叉耐药现象更明显，交叉耐药率由１９９２年２．３％增加到１９９５年的１３．２％。     

泰宁等7种抗菌药物对临床常见致病菌抗菌活性的比较

用琼脂平板稀释法测定泰宁等７种抗菌药物对５种２１５株临床常见致病菌的最低抑菌浓度（ＭＩＣ），井统计敏感率。结果表明７种抗菌药物对大多数受试菌均显示较高的抗菌活性，其中泰宁的抗菌活性最强。金葡球菌、变形杆菌、大肠埃希氏菌、肺炎克雷白氏菌对泰宁的敏感率达９７．６～１００％；绿脓假单胞菌１７．０２％耐药，绿脓假单胞菌４．２６～１２．７７％和肺炎克雷白氏菌１株对泰宁和其他抗菌药物呈现部分交叉耐药性，而ＣＰＬＸ与其他抗菌药物对不同受试菌呈现２．３８～１９．０５％的交叉耐药率。该结果提示对其他β－内酰胺类抗菌药物耐药的致病引起的严重感染，可考虑选用泰宁，但ＣＰＬＸ的选用还应根据药敏试验决定。     

Gi蛋白βγ亚单位在氨甲酰胆碱所致CCL137细胞磷脂酰A_2激活中的作用

为研究氨甲酰胆碱（ＣＣｈ）所致ＣＣＬ１３７细胞中毒蕈碱型乙酰胆碱受体（ｍＡＣｈＲ）失敏时磷脂酶Ａ２（ＰＬＡ２）激活的机理，应用百日咳杆菌毒素（ＰＴＸ），抗－βγ血清和纯化的Ｇｉβγ，分别观察了它们对ＰＬＡ２活性的影响．当在培养液中加入ＰＴＸ或抗－βγ血清时，可见ＣＣｈ不再能引起ＣＣＬ１３７细胞中ｍＡＣｈＲ失敏和ＰＬＡ２激活．反之，加入Ｇｉβγ或ＧＴＰ－γ－Ｓ则使ＰＬＡ２激活，且呈剂量依赖关系，前者尤为明显．结果表明，Ｇｉβγ在ＣＣｈ所致ＣＣＬ１３７细胞的ＰＬＡ２激活中起重要作用．     

22种抗生素对铜绿假单胞菌抑菌浓度研究

用ＡＭＳ法测定了２２种抗生素对铜绿假单胞菌临床菌株的抑菌浓度。ＣＰＬＸ对铜绿假单胞菌的抑菌浓度为０．６４ｍ ｇ／Ｌ,ＴＯＢ、ＩＭＰ、ＧＭ 和ＡＭＫ为１．９５～７．７３ｍｇ／Ｌ,ＣＡＺ、ＡＺ、ＣＰＺ、ＴＣ、ＰＩＰＣ、ＣＴＸ、ＣＥＺ、ＣＸＭ－Ｓ、ＣＸＭ－Ａ、ＣＥＴ和ＡＢＰＣ为９．４１～３２．００ｍｇ／Ｌ,ＣＦＸ、ＴＩＰＣ、ＴＩＰＣ／ＣＡ、ＭＺＰＣ和ＣＢＰＣ为３３．９８～１００．３０ｍ ｇ／Ｌ,ＮＦＴ为１９３．００ｍ ｇ／Ｌ。在不同标本的分离菌中,痰液与伤口、痰液与粪便和伤口与尿液有４种抗生素、痰液与尿液和伤口与粪便有５ 种抗生素、粪便与尿液有１１ 种抗生素的抑菌浓度有显著性差异（Ｐ＜０．０５０～０．００１）。     

耐甲氧西林金葡球菌对环丙沙星摄取的研究

１１株耐甲氧西林金葡球菌（ＭＲＳＡ）对１４种抗菌药物的敏感度进行了测定，除２株ＭＲＳＡ对环丙沙星敏感外，其他９株ＭＲＳＡ均对环丙沙星耐药，最低抑菌浓度（ＭＩＣ）≥１６ｍｇ／Ｌ。此组耐药菌株对其他受试的氟喹诺酮类药物也呈交叉耐药。ＭＲＳＡ对环丙沙星的摄取在２～５ｍｉｎ内达到稳定态。１９９０年以前的ＭＲＳＡ菌株对环丙沙星的摄取几乎不受氰氯苯腙（ＣＣＣＰ）影响；而１９９０年以后的菌株对环丙沙星的摄取量大多受ＣＣＣＰ影响，ＣＣＣＰ（１０ｍｇ／Ｌ）可增加ＭＲＳＡ对环丙沙星的摄取，为不加ＣＣＣＰ时的１．５３倍。此结果提示能量依赖性流出系统的改变与ＭＲＳＡ对氟喹诺酮耐药有关。诱导耐药株ＭＲＳＡ８７－９０Ｒ对环丙沙星的摄取量较诱导前（ＭＲＳＡ８７－９０）明显为少，但两者对药物的摄取均不受ＣＣＣＰ影响。     

环丙沙星在肺癌患者体内的药代动力学研究

对８例肺癌患者（伴轻度肾功能损害）和８例肺癌感染病人单剂量静滴环丙沙星（ｃｉｐｒｏｆｌｏｘａｃｉｎ,ＣＰＬＸ）４０００ｍｇ的药代动力学进行了研究。采用微生物法测定ＣＰＬＸ的血清浓度,以３Ｐ９７药代动力不程序相合计算,结果表明,与肺感染组相比,肺癌组的Ｖｃ、ＡＵＣ、Ｔ１／２０、Ｔ１／２β及ＣＬｓ等主要的药代动力学参数均坎无显著改变,提示ＣＰＬＸ在肺患者（伴轻度肾功能损害）体内的药代动力学未发生明显改     

应用环丙沙星乳剂治疗烫伤大鼠铜绿假单胞菌感染

采用大鼠１５％深Ⅲ度烫伤铜绿假单胞菌感染模型,动态观察了１％磺胺嘧啶银（ＳＤ－Ａｇ）,０．５％环丙沙星（ＣＰＬＸ）及２％ＣＰＬＸ的治疗效果。伤口细菌量和体内白细胞量的检测结果显示,在抵抗铜绿假单胞菌和提高大鼠生存率方面,２％ＣＰＬＸ优于１％ＳＤ－Ａｇ和０．５％ＣＰＬＸ,与对照组比较有显著性差异（Ｐ＜０．００１）。     

ＭｅｘＸＹ ＯｐｒＭ 主动外排系统在铜绿假单胞菌多重耐药机制中的作用

目的　研究ＭｅｘＸＹ ＯｐｒＭ主动外排系统在铜绿假单胞菌（ＰＡ）多重耐药机制中的作用。方法　挑选临床分离的 ＰＡ多重耐药菌株２６株、敏感菌株１５株及标准质控菌株（ＡＴＣＣ２７８５３），用ＲＴ ＰＣＲ方法扩增其内膜转运蛋白ＭｅｘＹ的结构基因 ｍｅｘＹ和内参基因１６ＳｒＲＮＡ片段，根据结构基因ｍｅｘＹ与１６ＳｒＲＮＡ扩增产物的电泳扫描比值，分析ｍｅｘＹｍＲＮＡ的表达水平，用以判 断ＭｅｘＸＹ ＯｐｒＭ的表达情况。结果　２６株多重耐药菌株对１４种常用抗菌药物都耐药，耐药率为１００００％，１５株敏感菌株对１４种 常用抗菌药物都敏感；标准质控菌株、敏感菌株和多重耐药菌株均检测出ｍｅｘＹ的ｍＲＮＡ基因，耐药菌株的ｍｅｘＹｍＲＮＡ水平高于 敏感菌株（Ｐ＜００５）。结论　ＭｅｘＸＹ ＯｐｒＭ主动外排系统表达水平的增高在ＰＡ多重耐药中起到重要的作用。     

四环素和青霉素在铜绿假单胞菌中的蓄积动力学研究及能量抑制剂（CCCP）的影

为证实国内临床分离的铜绿假单胞菌多重耐药菌株中是否存在与其多重耐药有关的主动外排机制。本文研究了＾３Ｈ－四环素和＾３Ｈ－青霉素在临床多重耐药菌（２１、２６、２８、４３５及Ｍ１２５１）、敏感菌（１７２、２２３及Ｋ７９９／６１）以及体外诱导的多重耐药突变株（１７２ｏ＋ｃ和２２３ｏ＋ｃ）中的蓄积动力学及能量抑制剂（Ｃａｒｂｏｎｙｌｃｙａｎｉｄｅ ｍ－ｃｈｌｏｒｏｐｈｅｎｙｌｈｙｄｒａｚｏｎｅ，ＣＣＣＰ）的影响。结果表明两种药物无论是在耐药还是敏感菌中，胞内均可在５～１０ｍｉｎ内达稳态浓度，而且耐药菌中的稳态浓度明显低于敏感菌。当加入ＣＣＣＰ后，耐药菌中的药物浓度明显增加，而敏感菌则降低，提示在受试的临床耐药菌中存在主动外排机制，此外，两种抗蓖药物在体外诱导多重耐药菌株中的蓄积研究及ＣＣＣＰ的影响结果与临床耐药菌相似。     

临床常见病原菌对环丙沙星耐药性趋势分析

分析临床常见病原菌对环丙沙星耐药性趋势,为临床合理应用喹诺酮类抗菌药提供依据。用whonet4(1999年版）软件对解放军总医院1994年3月至1999年3月5年间检测的临床常见病原菌环丙沙星药敏试验结果进行分析,药敏采用纸片扩散法。结果,8种临床常见菌：表葡球菌、金葡球菌、粪肠球菌、大肠埃希氏菌、肺炎克雷伯氏菌、奇异变形杆菌、阴沟肠杆菌、铜绿假单胞菌5年间对环丙沙星耐药均呈上升趋势,其中大肠埃希氏菌和表葡球菌的耐药率增长更为明显,分别达71.5%和43.2%;而分离率与大肠埃希氏菌和表葡球菌接近的铜绿假单胞菌和肺炎克雷伯氏菌耐药率仅为23%和10.8%,耐药率的增长存在明显的差异。提示临床常见病原菌对环丙沙星耐药性增长趋势不但与临床广泛应用喹诺酮类药物有关,而且与经验性应用喹诺酮类药物治疗不同部位感染也有相当密切的关系。     

次抑菌浓度的药物诱导细菌耐药与交叉耐药

铜绿假单胞菌接种于含次抑菌浓度的哌拉西林和阿米卡星的营养肉汤中，葡萄球菌接种于次抑菌浓度的氧氟沙星和环丙沙星的营养肉汤中，经传代培养可获得相对应的耐药菌株。哌拉西林诱导耐药的铜绿假单胞菌对头孢他啶亦耐药，但对阿米卡星、环丙沙星、亚胺培南／西司他丁不耐药；阿米卡星诱导耐药的铜绿假单胞菌对哌拉西林亦耐药，但对头孢他啶、环丙沙星、亚胺培南／西司他丁没有交叉耐药；氧氟沙星或环丙沙星诱导耐药的葡萄球菌对氟喹诺酮类药物都有交叉耐药，但对苯唑西林、阿米卡星、亚胺培南／西司他丁没有显著的交叉耐药性     

High prevalence of plasmid-mediated quinolone resistance determinant aac(6')-Ib-cr amongst Salmonella enterica serotype Typhimurium isolates from hospitalised paediatric patients with diarrhoea in China

In this study, the antimicrobial susceptibilities and prevalence of plasmid-mediated quinolone resistance determinants amongst Salmonella enterica serotype Typhimurium isolates from hospitalised paediatric patients with diarrhoea in China were investigated. In total, 40 (64.5%) of 62 S. Typhimurium isolates were resistant to ciprofloxacin (minimum inhibitory concentration ≥0.5 μg/mL), comprising 28 isolates with low-level resistance and 12 isolates with high-level resistance. All ciprofloxacin-resistant isolates were multiresistant to other antimicrobial agents. Four pulsed-field gel electrophoresis (PFGE) clusters were found amongst the 40 ciprofloxacin-resistant isolates, amongst which PFGE clusters A, B, E and D accounted for 7, 4, 1 and 28 isolates, respectively. Two isolates with high-level ciprofloxacin resistance had two mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC. The remaining ciprofloxacin-resistant isolates had only one mutation in the QRDR of gyrA. All 62 S. Typhimurium isolates were negative for qnr genes and qepA and 23 (37.1%) of the isolates were positive for aac(6')-Ib-cr. Nineteen isolates harbouring aac(6')-Ib-cr belonged to PFGE cluster D. A high prevalence of ciprofloxacin resistance and aac(6')-Ib-cr was found amongst S. Typhimurium isolates in China from hospitalised paediatric patients with diarrhoea not receiving quinolones. A single mutation in the QRDR of gyrA as well as production of AAC(6')-Ib-cr contributed to ciprofloxacin resistance. Clonal spread was responsible for the dissemination of aac(6')-Ib-cr amongst S. Typhimurium isolates.     

Interaction of sub-inhibitory concentrations of ciprofloxacin and rifampicin against Staphylococcus aureus

The frequency of the emergence of ciprofloxacin-resistant mutants to sub-inhibitory concentrations of ciprofloxacin, rifampicin, and ciprofloxacin plus rifampicin were compared in a subcutaneous abscess model of experimental Staphylococcus aureus infection in mice. The in vitro findings showed that the combination of ciprofloxacin and rifampicin was bacteriostatically additive for all strains tested when the combination was examined by the chequer-board technique and fractional inhibitory concentration indices determined. Animals were infected with ciprofloxacin-sensitive and ciprofloxacin-resistant test strains (6989S and 6989R) and left untreated for nine days, which showed that ciprofloxacin resistance had no effect on the pathogenicity of the organisms. In treated animals, ciprofloxacin plus rifampicin was found to be at least as effective as ciprofloxacin alone. However, in the murine model, the combination therapy produced significantly fewer high-level ciprofloxacin-resistant mutants than ciprofloxacin alone (p<0.0005). We conclude that a combination of ciprofloxacin and rifampicin was at least as efficient as either drug alone, and the additional presence of rifampicin reduced the emergence of high level ciprofloxacin-resistant sub-populations in the case of S. aureus subcutaneous abscesses in mice and so the combination may prove to be more efficient than ciprofloxacin alone.     

Bactericidal activity of levofloxacin and ciprofloxacin on clinical isolates of different phenotypes of Pseudomonas aeruginosa

Levofloxacin has been reported to have in vitro activity against both gram-positive and gram-negative bacteria. A recent survey carried out at our Institution showed clinical isolates of Pseudomonas aeruginosa to be more susceptible to levofloxacin than to ciprofloxacin. The in vitro activity of the two fluoroquinolones was evaluated further by looking at their bactericidal activity against two strains of each of the following antibio-phenotypes of P. aeruginosa: levofloxacin- and ciprofloxacin-susceptible, levofloxacin-susceptible/ciprofloxacin-resistant, levofloxacin-susceptible/ciprofloxacin-susceptible and ceftazidime-resistant, (National Committee for Clinical Laboratory Standards susceptibility breakpoints were used). MIC and MBC values were measured and time-kill experiments were carried out. Drugs were used at susceptibility or resistance breakpoint concentrations in the time-kill experiments and results were recorded over 12 h in an attempt to link in vitro results with the clinical situation The polypeptide profiles of outer membrane preparations of the six strains were examined by gel electrophoresis. Levofloxacin was shown to be more bactericidal than ciprofloxacin in the time-kill experiments. No differences were observed between the outer membrane proteins of the six strains. Levofloxacin showed greater bactericidal activity against P. aeruginosa clinical isolates than ciprofloxacin.     

In vitro activity of four fluoroquinolones against clinical isolates of Pseudomonas aeruginosa determined by the E test

Ciprofloxacin, levofloxacin, ofloxacin, and trovafloxacin were tested by the E-test against 100 clinical isolates of Pseudomonas aeruginosa. Ciprofloxacin was the most active of the tested agents with 82% of isolates having a MIC 8). Levofloxacin and trovafloxacin had nearly identical potency: 75% and 76% of the isolates were inhibited by 8 for levofloxacin; 0.19->8 for trovafloxacin). Ofloxacin was the least active of the four quinolones, with 43% of the isolates having a MIC >2 mg/l. All isolates resistant to ciprofloxacin were also resistant to the other agents, i.e. resistance to ciprofloxacin predicted resistance to all the quinolones tested in every case. This data demonstrates that fluoroquinolones are active agents against P. aeruginosa. In vitro susceptibility testing, however, is crucial to assess the resistance pattern in any specific location and for each individual agent.     

Transformation of ciprofloxacin-resistant Neisseria gonorrhoeae gyrA, parE and porB1b genes

In several transformation experiments, we have shown that introduction of an alteration in GyrA at position 95 of a ciprofloxacin-susceptible Neisseria gonorrhoeae strain (minimum inhibitory concentration (MIC) 0.008 mg/L) increases the MIC to 0.064 mg/L. Two alterations (positions 91 and 95) increase the MIC to 0.125-0.25 mg/L. Transformants with ciprofloxacin MICs of 0.5-16 mg/L were obtained from a moderately ciprofloxacin-resistant strain (MIC 0.25 mg/L). These transformants had alterations in the gene for PorB1b and probably other genes. In one transformant, an alteration in ParE was also introduced, which probably contributed to ciprofloxacin resistance. The ciprofloxacin-resistant transformants had the donor porB1b sequence, and most of them also had altered serovars. We conclude that alterations in N. gonorrhoeae PorB1b could be involved in ciprofloxacin resistance.     

Antimicrobial activity of BMS 284756 (T-3811) against Neisseria gonorrhoeae tested by three methods.

The potency of BMS 284756, a novel des-F(6)-quinolone, was tested against 137 clinical isolates of Neisseria gonorrhoeae including 50 strains observed to be resistant to ciprofloxacin and other newer quinolones. The gonococci were tested using NCCLS methods (agar dilution, disk diffusion) and Etest. BMS 284756 potency versus N. gonorrhoeae was generally two- to four-fold greater than ciprofloxacin. Penicillin resistance in the absence of ciprofloxacin resistance did not affect BMS 284756 activity. However, elevated ciprofloxacin MICs were associated with higher BMS 284756 MIC results as follows (BMS 284756 MIC(50)/MIC range in mg/l): ciprofloxacin-susceptible strains (0.016 or 0.03/0.004-0.06), ciprofloxacin-intermediate strains (0.06 or 0.12/0.008-0.25) and ciprofloxacin-resistant strains (0.12 or 0.5/0.12-1). Etest MICs were routinely lower than those produced by the reference agar dilution method, but the correlation coefficient remained acceptable (r = 0.87). Similarly acceptable correlation was achieved with 5 microg disk zone diameters (r = 0.78), where all zones were > or = 28 mm (MIC < or = 1 mg/l). In conclusion, BMS 284756 was very active against N. gonorrhoeae (MIC(50) 0.03 mg/l overall) including ciprofloxacin-resistant strains and could be considered as a single-dose therapeutic option for gonorrhoea.     

Ciprofloxacin resistance by altered gyrase and drug efflux system inPseudomonas aeruginosa

Ciprofloxacin resistance mechanisms were studied by investigating the inhibitory effect of ciprofloxacin on the gyrase-mediated DNA supercoiling and the intracellular accumulation of ciprofloxacin in clinical isolates ofPseudomonas aeruginosa. A higher amount of ciprofloxacin was required to inhibit the gyrases purified from the ciprofloxacin-resistant strains than that from the sensitive strain. Reconstitution of heterologous gyrase subunits from different strains revealed alterations in the A and/or the B subunits of gyrase in these strains. In addition, the resistant strains accumulated approximately a half amount of ciprofloxacin inside the cells, compared to the sensitive strain. However, when the active efflux was blocked by carbonyl cyanide m-chlorophenyl hydrazone treatment, intracellular concentration of ciprofloxacin was elevated about 4–7 fold in these strains, while the sensitive strain was not significantly affected by this treatment, indicating that the ciprofloxacin-resistant strains developed a drug efflux system. Interestingly, these resistant strains expressed an envelope protein of approximately 51 kD. These studies suggest that alterations in the gyrase as well as the active drug-efflux system conferred dual ciprofloxacin resistance mechanisms to these clinical isolates ofP. aeruginosa.     

儿童阑尾炎感染病原菌的分布及耐药性

目的：研究息阑尾炎儿童感染病原菌的种类、分布特征及抗生素的耐药情况。方法：采取术中阑尾炎脓液标本作培养．利用MicroScan—Wolk／40全自动微生物分析仪进行细菌鉴定和药敏实验。结果：在患阑尾炎儿童感染病原菌中，革兰阴性杆菌以大肠埃希菌、铜绿假单孢菌、肺炎克雷伯菌为主；革兰阳性菌以金黄色葡萄球菌、粪肠球菌、屎肠球菌居多。在药敏实验中。革兰阴性杆菌对亚胺硫霉素耐药率〈10％．头孢西丁、环丙氟哌酸耐药率相对较低，金黄色葡萄球菌对万古霉素无耐药株，对亚胺硫霉素、环丙氟哌酸、复方新诺明、利复平、苯唑青霉素耐药率〈10％。结论：大肠埃希菌、铜绿假单孢菌、肺炎克雷伯菌、金黄色葡萄球菌、粪肠球菌、屎肠球菌在阑尾腔内繁殖是小儿阑尾炎症的诱发因素之一，对这些病原菌药敏分析的调查，对防治术后切口感染，合理使用抗生素有重要临床意义。