氟喹诺酮类药物对粪肠球菌的防耐药突变浓度研究

目的通过测定4种氟喹诺酮类药物(FQ)对粪肠球菌ATCC29212及其同源耐药突变体、粪肠球菌临床分离株的最低抑菌浓度(MIC)、防耐药突变浓度(MPC)和突变选择窗(MSW),比较其抗菌活性及防耐药突变的能力。方法采用4种FQs(环丙沙星、左氧氟沙星、莫西沙星和加替沙星)筛选粪肠球菌ATCC29212同源的第一步耐药突变体,用加替沙星筛选第二步耐药突变体;采用琼脂二倍稀释法测定粪肠球菌ATCC29212及其同源耐药突变体、粪肠球菌临床分离株的MIC、暂定MPC(MPCpr)和MPC,并计算MIC90、MPCpr90、选择指数SI(MPCpr90/MIC90及MPC/MIC)。结果加替沙星、莫西沙星、左氧氟沙星和环丙沙星对粪肠球菌ATCC29212的MPC分别为1.2、1.2、5.6和6.4μg/m L,选择指数分别为3.4、6、8和8;对30株环丙沙星敏感的粪肠球菌临床分离株的MPCpr90分别为2、1、4和4μg/m L,选择指数分别为4、4、8和8;而加替沙星和莫西沙星对15株环丙沙星中介耐药株的MPCpr90分别为32和16μg/m L,选择指数均达到了32。4种FQs药物对ATCC29212第一步耐药突变体的MIC及MPC值均较其源菌株升高;加替沙星和莫西沙星对第二步耐药突变体的MPC已高达32μg/m L;加替沙星、莫西沙星和左氧氟沙星对第一步耐药突变体的MSW较源菌株增宽。结论对于粪肠球菌临床分离株、ATCC29212及其同源的耐药突变体,加替沙星和莫西沙星的抗菌活性均高于左氧氟沙星和环丙沙星,且加替沙星和莫西沙星限制粪肠球菌耐药突变体被选择出来的能力强于左氧氟沙星和环丙沙星,结合药动学参数,加替沙星和莫西沙星能限制下一步耐药突变株的产生,而环丙沙星和左氧氟沙星则很容易筛选出下一步耐药突变株。但对于第二步耐药突变株,加替沙星和莫西沙星则很容易筛选出对这两种药物也耐药的菌株。因此,临床上为延长加替沙星和莫西沙星的使用寿命,对于环丙沙星非敏感的菌株应避免应用加替沙星和莫西沙星单药治疗。     

莫西沙星对224株肠球菌的体外抗菌活性研究

目的观察莫西沙星对224株肠球菌的体外抗菌活性。方法采用二倍琼脂稀释法对224株肠球菌进行体外抗菌实验．并与意大利Aventis公司生产的替考拉宁和Lilly公司生产的万古霉素进行抗菌效果对比。结果莫西沙星的抗菌效果较好，对169株粪肠球菌和51株屎肠球菌的MIC90均为4mg／L，替考拉宁和万古霉素对169株粪肠球菌的MIC90分别为1、2mg／L；对51株屎肠球菌的MIC90分别为0．5和2mg／L。结论莫西沙星对224株肠球菌的抗菌效果较好，肠球菌对莫西沙星的敏感率均为76．34％。莫西沙星的抗菌效果低于替考拉宁和万古霉素。     

粪肠球菌Ⅱ型拓扑异构酶QRDR基因突变与耐氟喹诺酮类药物关系的研究

目的 检测临床分离的粪肠球菌对6种氟喹诺酮类药物的敏感性,研究粪肠球菌Ⅱ型拓扑异构酶基因突变与对氟喹诺酮类药物耐药性的关系,以了解粪肠球菌对氟喹诺酮类药物的耐药机制.方法 采用CLSI M7-A8方案推荐的琼脂稀释法检测临床分离的112株粪肠球菌对6种氟喹诺酮类药物的MIC;筛选出环丙沙星耐药株,PCR扩增其gyrA、gyrB,parC和parE基因的喹诺酮耐药决定区(QRDR),并与标准敏感株核苷酸序列进行比较,分析基因突变与耐药的相关性.结果 6种FQs药物对112株粪肠球菌的抗菌活性(MIC50,MIC90)从强到弱依次为:莫西沙星＞加替沙星＞左氧氟沙星＞环丙沙星、氧氟沙星＞诺氟沙星.5株耐环丙沙星粪肠球菌的Ⅱ型拓扑异构酶QRDR基因都发生了突变:有4株的gyrA基因QRDR发生了点突变,其中3株表现为Ser83→Ile(AGT→ATT),1株表现为Glu87→Gly(GAA→GGA),4株parC基因QRDR发生突变,突变方式为Ser80→ Ile(AGC →ATC),gyrB和par基因未发现突变.     

氟喹诺酮药物对金黄色葡萄球菌同源耐药突变株的耐药突变选择窗研究

目的通过测定不同氟喹诺酮（FQ）药物对同源金黄色葡萄球菌耐药突变株的MIC和防耐药突变浓度（mutant prevention concentration。MPC），分析不同药物的抗菌活性及限制耐药突变株选择的能力。方法分别采用环丙沙星和加替沙星琼脂平板筛选金黄色葡萄球菌ATCC25923同源的第一步和第二步耐药突变株。采用琼脂平板稀释法测定各耐药突变株的MIC和MPC。计算选择指数（MPC／MIC）。结果加替沙星和莫西沙星对金黄色葡萄球菌ATCC25923第一步耐药突变的MPC值（1—2μg／ml）明显低于环丙沙星、左氧氟沙星和帕珠沙星（4—16μg／m1），以上5种FQ药物对第一步耐药突变的MPC值和选择指数分别为ATCC25923的2—8倍和1-4倍。加替沙星和莫西沙星对第二步耐药突变的MPC值为8—16μg／ml。结论对于金黄色葡萄球菌ATCC25923同源的第一步耐药突变株。加替沙星和莫西沙星限制下一步耐药突变株选择的能力强于环丙沙星、左氧氟沙星和帕珠沙星，结合药动学参数，环丙沙星、左氧氟沙星和帕珠沙星很容易选择出下一步耐药突变株；而加替沙星和莫西沙星则能够限制下一步耐药突变株的选择。对于第二步耐药突变株，加替沙星和莫西沙星则很容易筛选出对这两种药物也耐药的菌株。临床上为延长加替沙星和莫西沙星的应用时间，对于已对左氧氟沙星耐药的菌株应避免应用加替沙星和莫西沙星单药治疗。     

三种新的喹诺酮与阿奇霉素体外抗菌活性的比较

Wenzler等测定了莫西沙星和加替沙星对从呼吸道和腹部伤口感染中分离的病原菌的体外抗菌活性并与左氧氟沙星和阿奇霉素体外抗菌活性进行比较。方法　从呼吸道和腹部伤口感染中分离的 5 0株甲氧西林敏感的金黄色葡萄球菌、屎肠球菌、粪肠球菌、肺炎链球菌、酿脓链球菌、大肠埃希氏菌、铜绿假单胞菌和流感嗜血菌 ,根据美国国家临床试验室标准委员会指南推荐的琼脂稀释法测定MIC ,金黄色萄萄球菌ATCC2 92 13、屎肠球菌ATCC2 92 12、肺炎链球菌ATCC2 96 19、大肠埃希氏菌ATCC2 5 92 2、铜绿假单胞菌ATCC2 785 3和流感嗜血菌ATCC4 92…     

喹诺酮类抗菌药物的严重不良反应

喹诺酮类是人工化学合成抗菌药物,目前临床常用的喹诺酮类药物有诺氟沙星、氧氟沙星、环丙沙星、左氧氟沙星、培氟沙星、加替沙星、莫西沙星、洛美沙星、氟罗沙星和依诺沙星等。与其他抗生素相比,其价格低廉,口服吸收良好,     

多重耐药泵抑制剂提高肠球菌对氟喹诺酮药物敏感性的研究

目的　研究临床分离肠球菌对诺氟沙星、环丙沙星、氧氟沙星等氟喹诺酮药物耐药的主动泵出机制。方法　收集临床分离肠球菌 ;用琼脂二倍稀释法测定多重耐药泵抑制剂利舍平或维拉帕米应用前后 ,菌株对氟喹诺酮药物 MIC的变化。结果　利舍平使所有被检测的 2 9株肠球菌对诺氟沙星的敏感性增加 (MIC下降至原值的 1/ 2或以下 ) ,使 2 3株肠球菌对环丙沙星的敏感性增加 ,但仅能增加 3株肠球菌对氧氟沙星的敏感性。应用利舍平以后 ,12株耐诺氟沙星粪肠球菌对诺氟沙星 MIC值均下降 ,11株耐环丙沙星粪肠球菌有7株对环丙沙星 MIC值下降。维拉帕米的抑制效果和利舍平相比略有差异。结论　诺氟沙星、环丙沙星的主动泵出机制普遍存在于临床分离肠球菌 ,并且是粪肠球菌对诺氟沙星、环丙沙星的耐药机制之一。     

20种抗菌药物对肺炎链球菌的体外抗菌活性研究

目的：评价莫西沙星等20种常用抗菌药物对临床分离的60株肺炎链球菌的体外抗菌活性。方法：采用微量肉汤稀释法测定20种抗菌药物对肺炎链球菌的最低抑菌浓度（MIC）。结果：60株肺炎链球菌中有青霉素敏感的肺炎链球菌（PSSP）42株（71．7％）,青霉素不敏感肺炎链球菌（PNSSP）18株（28．3％）;其中,青霉素耐药的肺炎链球菌（PRSP）有2株（3．3％）。对PSSP菌株,20种抗菌药物中敏感率较高的药物有头孢曲松、头孢噻肟、加替沙星、莫西沙星、左氧氟沙星、阿莫西林／克拉维酸,敏感率均为100％;耐药率较高的药物有红霉素、罗红霉素、克拉霉素、阿奇霉素,耐药率分别为83-3％,83-3％,74．7％,74．7％。对PNSSP菌株,敏感率较高的药物有阿莫西林／克拉维酸、莫西沙星、头孢噻肟、加替沙星、左氧氟沙星,敏感率分别为100％,100％,88．8％,94．4％,94．4％;耐药率较高的药物有红霉素、克拉霉素、阿奇霉素,耐药率均为66．7％。20种抗菌药物对60株肺炎链球菌的累积抑菌百分率曲线显示莫西沙星和阿莫西林／克拉维酸的抑菌能力最强。结论：肺炎链球菌对大环内酯类、复方新诺明、磷霉素等抗菌药物的耐药率较高,第三、四代氟喹诺酮类药物（左氧氟沙星、莫西沙星、加替沙星）和阿莫西林／克拉维酸及第三代头孢菌素中的头孢噻肟、头孢曲松等对肺炎链球菌（包括PNSSP）有很好的抗菌活性,提示其可作为高度耐药肺炎链球菌感染的首选药物。     

25-12 新的喹诺酮抗菌剂-DX619

至从发现喹诺酮母核的 6 -氟喹诺酮可提高抗菌活性以来 ,6 -氟喹诺酮类已成为一组主要的治疗剂 ,构效关系的研究已证明加替沙星和莫西沙星比环丙沙星和氧氟沙星具有更高的抗革兰氏阳性球菌的活性。而最近研究显示去掉 6 -氟基可提高活性并降低毒性。革兰氏阳性球菌多药耐药性不     

氟喹诺酮结构及药敏测定方法对嗜麦芽寡养单胞菌敏感性的影响

目的探讨不同结构氟喹诺酮及不同药敏测定方法对嗜麦芽寡养单胞菌敏感性的影响，以指导临床合理选择抗菌药物。方法采用标准琼脂二倍稀释法测定5种氟喹诺酮对92株嗜麦芽寡养单胞菌临床分离株及20株实验室环丙沙星耐药株的最低抑菌浓度（MIC）；采用Kirby Bauer纸片扩散法测定环丙沙星对92株嗜麦芽寡养单胞菌的敏感性。结果莫西沙星、加替沙星、左氧氟沙星、洛美沙星和环丙沙星对临床分离株的敏感率分别为94．6％、90．2％、87．0％、66．3％和32．6％；莫西沙星、加替沙星、左氧氟沙星和洛美沙星对实验室耐药株的敏感率分别为75％、60％、60％和25％。与琼脂法比较，纸片法测定的环丙沙星敏感率增加、耐药率降低，均有统计学差异（P〈0．01，n=92）。结论不同结构的氟喹诺酮对嗜麦芽寡养单胞菌的敏感性不同，环丙沙星敏感性不能代替所有氟喹诺酮的敏感性；纸片法测定的敏感性不能代替琼脂法测定的敏感性。     

In vitro activity of gatifloxacin compared with gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin against uropathogens cultured from patients with complicated urinary tract infections

Minimum inhibitory concentrations (MICs) of gatifloxacin were compared with those of gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin using an agar dilution method for 400 uropathogens cultured from the urine of urological patients with complicated and/or hospital-acquired urinary tract infections (UTI). The collection of strains was made up of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). The antibacterial activity of the three newer fluoroquinolones, gatifloxacin, gemifloxacin, and moxifloxacin, were similar, but showed some drug specific differences. Gemifloxacin was most active against Escherichia coli, but less so against Proteus mirabilis. In this series all isolates of E. coli were inhibited at a MIC of 0.25 mg/l gatifloxacin and moxifloxacin and by 0.125 mg/l gemifloxacin. The MIC distribution of all fluoroquinolones showed a bimodal distribution for staphylococci, enterococci and Pseudomonas aeruginosa. The two modes for P. aeruginosa were 1 and 64 mg/l for gemifloxacin and moxifloxacin and 0.5 and 64 mg/l for gatifloxacin. For staphylococci the two modes were 0.125 and 2 mg/l for gatifloxacin, 0.03 and 4 mg/l for gemifloxacin, and 0.03 and 2 mg/l for moxifloxacin; for enterococci, 0.25 and 16 mg/l for gatifloxacin, 0.06 and 2 mg/l for gemifloxacin, and 0.25 and 8 mg/l for moxifloxacin. Compared with trovafloxacin the MICs were similar, but the newer fluoroquinolones were more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. Of the newer fluoroquinolones gatifloxacin had the highest rate of renal excretion and could be considered a promising alternative fluoroquinolone agent for the treatment of UTI.     

Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory infections

We determined the susceptibility of bacteria which were isolated from the patients with respiratory infections between January and October 2005, to tosufloxacin and other fluoroquinolones. A total of 900 isolate including 300 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 100 Moraxella catarrhalis, 200 Haemophilus influenzae, 100 Klebsiella pneumoniae and 100 Pseudomonas aeruginosa were tested. Tosufloxacin, gatifloxacin, levofloxacin, moxifloxacin, ciprofloxacin and prulifloxacin were used as the test antimicrobials. Tosufloxacin, gatifloxacin and moxifloxacin were potent antibiotics tested for the antibacterial activity against Streptococcus including penicillin-resistant S. pneumoniae; the MIC90 were 0.12-0.5/ micromL. Fluoroquinolones exerted the potent antibacterial activity against M. catarrhalis and H. influenzae; the MIC90 of fluoroquinolones tested were < or =0.06 microg/mL. Tosufloxacin, ciprofloxacin and prulifloxacin showed to be more active against K. pneumoniae and P. aeruginosa, but parts of some strains were resistant. These results indicate that tosufloxacin has the potent antibacterial activity against major organisms detected from patients with respiratory infections. Since it was approved in 1990, tosufloxacin was considered to be useful as a therapeutic antimicrobial for the treatment of respiratory infections.     

6种氟喹诺酮类药物对凝固酶阴性葡萄球菌的防耐药变异浓度分析

目的 比较6种氟喹诺酮类药物对临床分离凝固酶阴性葡萄球菌耐药突变体的选择能力.方法 选择呼吸道标本,对苯唑西林、环丙沙星敏感的凝固酶阴性葡萄球菌34株,采用标准琼脂二倍稀释法、标准琼脂平板稀释法,测定6种氟喹诺酮类药物对凝固酶阴性葡萄球菌的最低抑菌浓度(MIC)、防耐药变异浓度(MPC).结果 MPC值比较,莫西沙星最低(MPC90为1 mg/L),左氧氟沙星和环丙沙星最高(MPC90均为32 mg/L).莫西沙星、卡屈沙星和加替沙星的MPC90/MIC90较低,均为2.结论 莫西沙星、卡屈沙星和加替沙星对凝固酶阴性葡萄球菌的MPC值较低,突变选择窗范围相对较窄.     

6种氟喹诺酮类药物对临床分离金葡萄的抗菌活性比较

目的：观察临床分离金葡萄对6种氟喹诺酮类药物的耐药情况。方法：用琼脂稀释法测定诺氟沙星（NFLX）、氧氟沙星（OFLX）、氟罗沙星（FLRX）、环丙沙星（CPFX）、司帕沙星（SPFX）、托舒沙星（TFLX）6种2、3代氟喹诺桐类药物对成都地区155株临床分离金葡菌的体外抗菌活性。结果：金葡菌对6种药物的耐药率分别为诺氟沙星35.5%。氟罗沙星34.19%,环丙沙星27.75%,托舒沙星27.75% ,氧氟沙星25.81%,司帕沙星25.81%。结论：氟喹诺酮类药物的广泛应用已使细菌的耐药性明显增高,各药MIC90均超过16mg.L^-1,比以往文献报道的本地区金葡萄耐药性明显升高,提示要合理应用氟喹诺酮类药物,减少耐药菌株的增加。     

Antibacterial activity of ciprofloxacin against fresh clinical isolates from superficial suppurative foci

The minimum inhibitory concentrations (MICs) of 5 drugs (ciprofloxacin (CPFX), and 4 drugs used as standard) were determined to investigate antibacterial potencies of CPFX against bacterial strains isolated in 1989 from superficial suppurative foci. The clinical isolates tested included 375 strains from 11 aerobic bacterial species, and 50 strains from 2 anerobic bacterial genera (group) for a total of 425 isolates. Interpreting MIC level distributions of these drugs as the expression of antibacterial potencies, the results are as follows. 1. When activities of new-quinolone antibiotics were tested, we found that, CPFX expressed far superior antibacterial potency to ofloxacin (OFLX) and norfloxacin (NFLX) against coagulase-negative staphylococci, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Pseudomonas aeruginosa and Peptostreptococcus spp., although the activity of CPFX against Bacteroides fragilis group was weaker than that of OFLX, and CPFX had similar activity against Staphylococcus aureus to OFLX. 2. In comparison to beta-lactam antibiotics, CPFX was inferior to amoxicillin (AMPC) against E. faecalis and inferior to AMPC and cefaclor (CCL) against Peptostreptococcus spp. Against all other bacterial species, however, CPFX expressed superior antibacterial potency to AMPC and CCL. 3. Scattered findings of low sensitivity or resistance to CPFX were observed among the S. aureus, E. faecalis, E. faecium, P. vulgaris, M. morganii, P. aeruginosa and B. fragilis (group) species, but with an exception of E. faecium, the incidence of resistance strains was low.     

In vitro activity of linezolid,synercid and telithromycin against genetically defined high level fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).     

Comparative in vitro activity of gemifloxacin to other fluoroquinolones and non-quinolone agents against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in the United States in 1999-2000

This study was undertaken to assess the in vitro activity of gemifloxacin, five other fluoroquinolone antimicrobial agents (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin and ofloxacin) and other non-quinolone comparator agents (ampicillin, erythromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulphamethoxazole) against Streptococcus pneumoniae collected in the United States. Susceptibility testing of 550 S. pneumoniae, 290 Haemophilus influenzae and 205 Moraxella catarrhalis showed that 38.2% of pneumococci were penicillin nonsusceptible, while 26.2 and 95.6% of H. influenzae and M. catarrhalis, respectively, produced beta-lactamase. Overall new fluoroquinolones were the most active agents. The in vitro activity (based on MIC90 in mg/l) of the six fluoroquinolones was gemifloxacin>moxifloxacin>gatifloxacin>levofloxacin>ciprofloxacin and ofloxacin.     

氟喹诺酮类抗菌药物致药物不良反应205例调查分析

目的分析氟喹诺酮类抗菌药物(FQNS)药物不良反应(ADR)的特点,为临床合理用药提供依据。方法对2001-2010年某院门、急诊及住院部应用FQNS致ADR患者205例进行回顾性统计、分析。结果男性ADR发生率高于女性,31～40岁年龄段ADR发生率最高(31.2%);引起ADR的主要给药途径为静脉注射,共105例(51.2%);共涉及10种FQNS,不良反应主要表现在神经、循环、皮肤、泌尿、消化、呼吸、血液等系统,其中以神经系统、皮肤及消化系统症状较突出。结论 FQNS致ADR因素较多,临床使用时应注意ADR的监测,合理用药,以提高用药的安全性,减少ADR的发生。     

3种氟喹诺酮类药物对鲍曼不动杆菌的防耐药突变浓度研究

目的研究3种氟喹诺酮类药物对临床分离的鲍曼不动杆菌敏感株及其环丙沙星诱导突变株的防耐药突变浓度（MPC）,比较其防耐药突变能力。方法用环丙沙星琼脂平板筛选鲍曼不动杆菌临床分离株的突变株,用琼脂平板稀释法测定各实验菌株的最低抑菌浓度（MIC）和MPC。结果加替沙星和左氧氟沙星对临床分离株及其突变株的MPC低于环丙沙星。对临床分离株的MPC,加替沙星和左氧氟沙星均为0．25μg／mL,环丙沙星为2μg／mL;对突变株的MPC,加替沙星和左氧氟沙星为1～8μg／mL,环丙沙星为4～32μg/mL。结论对临床分离的鲍曼不动杆菌敏感株及其环丙沙星诱导的突变株,加替沙星和左氧氟沙星限制其耐药突变株的选择能力强于环丙沙星;对环丙沙星敏感的鲍曼不动杆菌的临床治疗,建议要避免这3种氟喹诺酮类的单药治疗。