比较6种氟喹诺酮类药物对金黄色葡萄球菌的防耐药变异浓度

目的比较6种氟喹诺酮类药物对临床分离金黄色葡萄球菌耐药突变体的选择能力。方法用呼吸道标本,选择对苯唑西林、环丙沙星敏感的金黄色葡萄球菌36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金黄色葡萄球菌的MIC、MPC。结果 MPC值比较,莫西沙星最低;而环丙沙星最高。选择指数(MPC90/MIC90)较低有如下4种:莫西沙星、卡屈沙星、加替沙星和帕珠沙星,均为2。6种药物MPC90值与其体内药动学参数比较,莫西沙星和卡屈沙星小于其Cmax。结论莫西沙星、卡屈沙星和加替沙星对金葡菌的MPC值较低,突变选择窗范围相对较窄。     

甲磺酸加替沙星与其他4种氟喹诺酮类药物对临床分离菌的体外抗菌活性比较

目的 :比较甲磺酸加替沙星与氧氟沙星、左氧沙星、环丙沙星、司帕沙星对 182株临床分离菌的体外抗菌活性。方法 :采用琼脂平板二倍稀释法测定加替沙星等 5种氟喹诺酮类药物对 182株临床试验分离菌株的最低抑菌浓度 (MIC)。结果 :加替沙星对葡萄球菌属的MIC90 比其他 4种氟喹诺酮类药物低。葡萄球菌属对加替沙星的敏感率显著高于其他4种氟喹诺酮类药物 ;对其他G 球菌的MICR 也较其他氟喹诺酮类药物低。G-杆菌中埃希菌属、肠杆菌属对加替沙星的敏感率明显高于其他 4种氟喹诺酮类药物 ,加替沙星对埃希菌属、肠杆菌属的MIC90比左氧沙星低 2倍 ,比其他 3种抗菌药物低 8倍 ;假单胞菌属、克雷伯菌属和其他G-杆菌对加替沙星的敏感率与左氧沙星的差异无统计学意义 ,与其他 3种氟喹诺酮类药物的差异有统计学意义。结论 :甲磺酸加替沙星具有广谱而强大的体外抗菌活性。     

耐甲氧西林金黄色葡萄球菌对三种氟喹诺酮类药物的耐药分析

目的 了解目前广州市花都区中医院的耐甲氧西林金黄色葡萄球菌(MRSA)分布情况，及其对在临床上仍较常用的抗菌药—氟喹诺酮类药物的耐药现状。方法 使用了Autoscan-4型细菌鉴定仪对受试的94株金黄色葡萄球菌进行耐苯唑西林测定，并对青霉素G，头孢唑啉等14种抗生素进行了药敏试验。结果 在94株受试菌株中，共检出66株MRSA。全院的总检出率为70.2％，这些MRSA菌株对三种氟喹诺酮类药物的耐药率，而与对四环素等抗生素的耐药率相似，但却远远高于对万古霉素等抗生素的耐药率。结论 MRSA认对氟喹诺酮类药物有明显的交叉耐药性,且氛喹诺酮类药物虽然仍具备一定的抗MRSA活性．但作用并不明显．故不应成为治疗MRSA感染症的首选药。     

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.     

喹诺酮类抗菌新药加替沙星

加替沙星(gatifloxacin)是8-甲氧基氟喹诺酮类抗菌药,现已进入临床研究后期。加替沙星对大多数G-菌显示良好活性(MIC90=2mg·L-1),而其与环丙沙星等早期同类药物相比最大特点就是拓宽了抗菌谱,对抗G 菌和厌氧菌的效力显著,其抗葡萄球菌、链球菌、肠球菌的活性是环丙沙星的2～4倍,而对抗厌氧菌(如梭状芽胞杆菌)则是环丙沙星的4～16倍。从临床应用于各种感染的研究中也充分证实了加替沙星的强有力的抗菌活性。加替沙星可渗透至骨骼、肺、皮肤、泌尿生殖和中枢等组织系统,故对这些部位的感染均能起到治疗效果。口服加替沙星400mg·d-1,对下…     

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。     

莫匹罗星对多重耐药金黄色葡萄球菌体外抗菌活性

目的 评价莫匹罗星对临床分离金黄色葡萄球菌的体外抗菌活性.方法 收集2007-2010年全国23家医院的金黄色葡萄球菌1007株,用琼脂二倍稀释法进行最低抑菌浓度(MIC)测定.结果 莫匹罗星对金黄色葡萄球菌的MIC50和MIC90分别为0.25,0.50mg·L-1,细菌耐药率为0.6％,在本试验所测药物中耐药率最低.甲氧西林耐药葡萄球菌(MRSA)对莫匹罗星耐药率为0.9％,在所测抗菌药物中耐药率同样最低.莫匹罗星对TAO(多粘菌素-新霉素-杆菌肽=50000 u:35000 u:5000 u)和夫西地酸耐药株敏感率达到80％.不同来源金黄色葡萄球菌对莫匹罗星耐药率在0～1％.来自体表分泌物的金黄色葡萄球菌对莫匹罗星耐药率为0.结论 与其他外用抗菌药比较,MRSA对莫匹罗星耐药率最低.其对其他常见抗菌药物耐药菌株甚至多重耐药的MRSA仍保持高度抗菌活性,且不易发生交叉耐药.     

痰标本金黄色葡萄球菌耐药性分析

目的 了解本院痰标本中金黄色葡萄球菌的耐药性特点及耐甲氧西林金黄色葡萄球菌(以下简称MRSA)在各科室分布情况,并将其耐药率与甲氧西林敏感的金黄色葡萄球菌(以下简称MSSA)的耐药性进行分析比较.方法 收集临床送检的痰标本,采用VITKE-Ⅱ全自动微生物分析仪进行细菌鉴定和药敏试验.分析131例次金黄色葡萄球菌的耐药性特点及MRSA所占比例和各主要科室的分布排名.结果 收集临床痰培养的金黄色葡萄球菌,其中耐甲氧西林金黄色葡萄球菌(MRSA)78例次,占59.5％;主要集中在神经外科、重症医学科和呼吸内科,分居排名前三位.抗菌药物统计显示:金黄色葡萄球菌耐药率较高,对多种抗菌药物如克林霉素、庆大霉素、环丙沙星等显示很高的耐药性.而对万古霉素、替加环素和利奈唑胺均显示较高的抗菌活性,敏感率达100％或接近100％.结论 痰标本中金黄色葡萄球菌所占比例较高,其中MRSA所占比例为59.5％(78/131),其病人抵抗力低下、住院时间长等相关科室分离率也较高.抗菌药物统计分析结果显示:金黄色葡萄球菌耐药率较高.同种抗菌药物中,MRSA就显示更高的耐药性,如MRSA与MSSA比较,对克林霉素、左氧氟沙星耐药率差异大.但对万古霉素、替加环素和利奈唑胺均显示较高的抗菌活性,仅2株MRSA对替加环素耐药,耐药率为2.7％,其余敏感率达100％.由于该菌显示多重耐药特性,致病性强.     

帕珠沙星注射剂（小针、输液、粉针）

药理毒理 本品为第三代喹诺酮类抗菌药，作用机理为DNA拓朴异构酶抑制剂，使细菌的DNA无法形成超螺旋结构，导致细菌细胞无法分裂和增殖而死亡，体内抗菌活性研究表明，本品对金黄色葡萄球菌、甲氧西林耐药株、肺炎链球菌、大肠杆菌、肺炎村菌粘质沙雷氏菌和绿脓杆菌等MIC50为、     

环丙沙星耐药性研究进展

环丙沙星属第三代喹诺酮类药物。由于其抗菌谱广、抗菌活性强、不良反应少，其应用几乎覆盖了整个临床科室，耐药菌株也逐渐增多，使其应用受到一定的限制。笔者综述了近年来国内、外环丙沙星的耐药情况及耐药机制的研究概况。     

国产米诺环素对耐甲氧西林金葡球菌的体外抗菌活性观察

用琼脂稀释法进行国产米诺环素对１０４株耐甲氧西林金葡球菌（ＭＲＳＡ）和１２０株甲氧西林敏感金葡球菌（ＭＳＳＡ）的抗菌活性研究，并与日本产米诺环素等进行了抗菌作用比较。结果表明国产米诺环素对ＭＲＳＡ和ＭＳＳＡ的抑菌效果，与日本产米诺环素基本一致。对ＭＲＳＡ的ＭＩＣ５０和ＭＩＣ９０前者分别为２和８ｍｇ／Ｌ，而后者分别为２和４ｍｇ／Ｌ。两者对ＭＳＳＡ的ＭＩＣ５０和ＭＩＣ９０均为０．５和４ｍｇ／Ｌ。国产米诺环素与其它６种抗生素比较，除去甲万古霉素外，其对ＭＲＳＡ和ＭＳＳＡ的抗菌效果，均优于头孢唑林等抗生素     

In vitro activity of clinafloxacin against fluoroquinolone resistant Spanish clinical isolates.

The in vitro activity of clinafloxacin against 162 ciprofloxacin-resistant clinical isolates was determined. Isolates were selected when their MIC to ciprofloxacin was 2 mg/l (intermediate) or > 2 mg/l (resistant). The following strains were tested: 61 Escherichia coli, 12 Klebsiella pneumoniae, 7 Proteus mirabilis, 21 Serratia marcescens, 4 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 21 Staphylococcus. aureus (resistant to methicillin) and 15 Enterococcus spp. Clinafloxacin, ciprofloxacin, ofloxacin and norfloxacin activities were evaluated by agar dilution using Müeller-Hinton agar according to NCCLS recommendations. Of the 162 isolates, 16 (9.8%) were intermediate and 146 (90.1%) resistant to ciprofloxacin. 95 of the 162 strains (58.6%) were susceptible, 27 (16.7%) intermediately susceptible, and 40 strains (24.7%) were resistant to clinafloxacin. The percentage susceptible to clinafloxacin was 65.6% for E. coli, 75% for K. pneumoniae, 71.4% for P. mirabilis, 28.6% for S. marcescens, 75% for E. cloacae, 33.3% for P. aeruginosa, 90.5% for S. aureus and 40% for Enterococcus spp. Clinafloxacin was active against 58.6% of the ciprofloxacin-resistant clinical isolates tested. It was particularly active against S. aureus strains resistant to both ciprofloxacin and methicillin.     

In vitro activity of levofloxacin against coagulase-positive and -negative staphylococci.

The in vitro activity of levofloxacin compared with that of ciprofloxacin, ofloxacin and norfloxacin were examined by conventional in vitro tests against 150 clinical isolates of staphylococci, subdivided according to species and susceptibility to methicillin. Although the minimum inhibitory concentrations (MICs) of all quinolones were highest in methicillin-resistant Staphylococcus aureus strains, the activity of levofloxacin was almost complete in methicillin-resistant S. epidermidis and methicillin-resistant S. haemolyticus when compared with ciprofloxacin and ofloxacin, which showed more than 30% resistance. Methicillin-susceptible S. aureus and S. epidermidis strains were susceptible to all quinolones with few differences between the antibiotics tested. The minimal bactericidal activity of levofloxacin was within the double dilution range of MIC values for all strains tested, demonstrating its potent role against staphylococci. In time-kill studies, levofloxacin exerted bactericidal activity within 3 h against all staphylococci. These in vitro results suggest that levofloxacin is a potent fluoroquinolone against coagulase-negative staphylococci and that it is both methicillin-susceptible and resistant. Further studies are necessary to determine the role of this drug in the treatment of infections sustained by these microorganisms.     

Synthesis and In Vitro Antibacterial Activity of 7‐(3‐Alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)‐fluoroquinolone Derivatives

A series of novel 7‐(3‐alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)fluoroquinolone derivatives were designed, synthesized, and characterized by ¹H‐NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in‐vitro antibacterial activity against representative Gram‐positive and Gram‐negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin‐sensitive Staphylococcus aureus (MSSA) and methicillin‐resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 μg/mL). In particular, compounds 14 , 19 , 28 , and 29 are fourfold more potent than ciprofloxacin against MSSA 08‐49. Compounds 23 , 26 , and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 μg/mL) against Acinetobactes calcoaceticus, which is two‐ to 16‐fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin.     

帕尼培南/倍他米隆的体外抗菌活性研究

为评价帕尼培南的体外抗菌作用，采用琼脂二倍稀释法测定帕尼培南／倍他米隆对247例临床分离菌的最低抑菌浓度（MIC），并与其它5种抗菌药物进行比较，结果表明，帕尼培与亚胺培南体外抗菌作用相仿，但帕尼培南对流感嗜血杆菌，金黄色葡萄球菌包括耐甲氧西林金葡萄球菌（MRSA）和大肠埃希氏菌体外胺培南对肺炎克雷伯氏菌、大肠埃希氏菌等革兰氏阴性菌作用略逊于美罗培南，帕尼培南体外抗菌 于头孢他啶，头孢哌酮／舒巴坦，苯唑西林等其它受试药物。帕尼培南的体外抗菌活性受接种菌量，培养基PH值和血清浓度影响。结果表明，帕尼培南是治疗多重耐药菌所致院内感染和严重需氧菌与厌氧菌混合感染的适用药物。     

Activity of gatifloxacin against strains resistant to ofloxacin and ciprofloxacin and its ability to select for less susceptible bacterial variants.

Gatifloxacin is an 8-methoxy fluoroquinolone. On quinolones, this side chain imparts increased activity against Gram-positive bacteria and enhanced killing. Gatifloxacin was tested against ofloxacin non-susceptible (ofloxacin MIC>2 mg/l) strains of Streptococcus pneumoniae (gatifloxacin MIC(90), 1 mg/l) and methicillin-resistant Staphylococcus aureus (MRSA, gatifloxacin MIC(90), 4 mg/l), and to ciprofloxacin non-susceptible (ciprofloxacin MIC>1 mg/l) strains of Escherichia coli (gatifloxacin MIC(90),>16 mg/l) and ciprofloxacin non-susceptible (ciprofloxacin MIC>0.06 mg/l) Neisseria gonorrhoeae (gatifloxacin MIC(50), 0.12 mg/l and MIC(90), 0.5 mg/l). Though gatifloxacin showed some reduced susceptibility to these populations, the MIC(50) and MIC(90) values suggest that gatifloxacin may be useful against pneumococci and some gonococcal strains not susceptible to other fluoroquinolones. Gatifloxacin did not select for less susceptible variants of MRSA and pneumococci, in contrast to the 10- to 100-fold higher selection frequencies with ciprofloxacin and ofloxacin. The single-step E. coli mutants selected by gatifloxacin and the comparator quinolones had quinolone MICs within the susceptible range. These data suggest that gatifloxacin use may hinder the development of quinolone-resistance, particularly in Gram-positive bacteria.     

In vitro activities of mutant prevention concentration-targeted concentrations of fluoroquinolones against Staphylococcus aureus in a pharmacodynamic model

To test the validity of the mutant selection window, we simulated mutant prevention concentration-targeted fluoroquinolone concentrations using an in vitro model with infected fibrin clots. Therapeutic ciprofloxacin (peak 5 microg/mL; t(1/2) 4 h), gatifloxacin (3.5 microg/mL; 8h), gemifloxacin (1.25 microg/mL; 8 h), levofloxacin (6 microg/mL; 6 h) and moxifloxacin (4.5 microg/mL; 12 h) were tested against methicillin-susceptible and -resistant Staphylococcus aureus, as were mutant prevention concentration (MPC)-targeted regimens achieving a trough of 1/4x or 2x MPC. MIC/MPC for MSSA K553 were 0.125/2, 0.03/0.125, 0.03/0.063, 0.125/1 and 0.015/0.25 microg/mL for ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin, respectively. Corresponding values for MRSA 494 were 0.125/1, 0.063/0.125, 0.03/0.063, 0.125/0.5 and 0.063/0.125 microg/mL. All regimens produced efflux mutants of MSSA K553. For MRSA 494, therapeutic and 1/4x MPC levofloxacin regimens produced resistance, whereas only 1/4x MPC regimens of gatifloxacin, gemifloxacin, and moxifloxacin produced resistance. All ciprofloxacin regimens produced resistance. Ciprofloxacin 1/4x MPC and therapeutic levofloxacin caused outgrowth of GrlA mutants (S80Y amino acid substitution); efflux mutants were isolated in all other cases. Overall, gatifloxacin, gemifloxacin, and moxifloxacin displayed a lesser propensity to select resistant isolates of S. aureus than ciprofloxacin and levofloxacin. The mutant selection window premise appeared valid for MRSA only. Additional studies are necessary to define the applicability of the MPC.     

黄芩和黄柏对耐甲氧西林金葡萄球菌的疗效对比观察

目的了解黄芩和黄柏对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性。方法用琼脂扩散法和琼脂稀释法,检测黄芩和黄柏对100株MRSA的体外抗菌活性。结果黄芩对MRSA的MIC50、MIC90分别为0.84、6.7mg。黄柏对MRSA的MIC50、MIC90分别1.48、11.8mg。结论与黄柏相比较,黄芩更适合作为MRSA敏感的抗菌药物用于临床治疗。     

In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.     

A comparison of disc agar diffusion and agar dilution for the detection of methicillin resistant staphylococci

Ninety two consecutively occurring clinical isolates of Staphylococcus aureus and 71 coagulase negative staphylococci (CONS) were tested by disc agar diffusion (DAD) and agar dilution (Mueller Hinton agar with 4% sodium chloride and 6 mcg/ml oxacillin) for methicillin resistance. There were 6 S. aureus and 33 CONS which were resistant to oxacillin. Five discrepancies (CONS) occurred between the two methods, with all indicating susceptibility by DAD and resistance by agar dilution. Four discrepancies were resolved by minimal inhibitory concentration (MIC) tests. In two of the CONS, the MIC agreed with the DAD results, and in the other two, the MIC agreed with the agar dilution results. Results of this study indicate that DAD is an accurate and acceptable method of detecting methicillin resistance in staphylococci (especially S. aureus) at this institution.