淋球菌的耐药性分析及其耐氟喹诺酮的分子机制研究

目的 检测108株临床分离淋球菌(NG)对9种药物的敏感性,并检测喹诺酮类耐药淋球菌对环丙沙星的MIC以及gyrA和parC基因突变情况.方法 用KB法检测淋球菌对9种药物的敏感性,用E-test法检测耐药菌株对环丙沙星的MIC,用PCR和DNA测序及序列比较检测基因突变.结果 淋球菌对大观霉素最敏感,其次为头孢曲松、头孢他啶、阿米卡星、四环素、红霉素和青霉素,对喹诺酮类药物高度耐药.环丙沙星的MIC范围在0.008-32μg/ml之间,10株淋球菌喹诺酮类耐药中有6株存在gyrA的Ser91→Phe突变的同时还存在gyrA的Asp95→Gly和/或parC的Aap86/Asn、Ser87→Arg/Ile,有4株只有gyrA基因Ser91→Phe的突变.结论 在淋球菌治疗中可首选大观霉素,其次为头孢曲松和头孢他啶.gyrA和parC基因突变与淋球菌耐喹诺酮类药物密切相关.     

淋球菌对大观霉素等5种抗生素的耐药性监测

目的　监测广州地区 2 0 0 2～ 2 0 0 3年度分离的淋球菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的耐药性 ,分析耐药菌株的流行特点。方法　采用琼脂稀释法测定菌株对 5种抗生素的最小抑菌浓度(MIC) ,判断敏感性按 WHO西太区淋球菌耐药性监测统一标准。用纸片酸度法检测产 β-内酰胺酶淋球菌(PPNG)菌株。结果　 10 7株淋球菌中检出 96株对青霉素耐药 (89.7% ) ,产 β-内酰胺酶淋球菌 (PPNG) 2 0株(占 18.7% ) ;四环素耐药率为 6 5 .4 % ,其中质粒介导高度耐四环素淋球菌 (TRNG)为 31株 ,占 2 9.0 % ;环丙沙星耐药率为 88.8% ;未发现对大观霉素和头孢曲松耐药菌株。青霉素 四环素和环丙沙星的 MIC50 及MIC90 均已超过耐药标准 ,尤其是青霉素为甚 ,其 MIC50 及 MIC90 均超过耐药标准的 8倍和 6 4倍。结论　淋球菌对大观霉素和头孢曲松的敏感性较高 ,可作为治疗的首选药物 ,对青霉素、四环素和环丙沙星耐药率较高 ,提示对淋病的治疗作用差     

淋病奈瑟菌4种抗生素耐药基因研究

目的检测淋病奈瑟菌(淋菌)临床分离株青霉素、四环素、环丙沙星、大观霉素耐药基因。方法对分离自常州地区的42株淋菌进行耐药相关基因TEM-1、penA、tetM、gyrA、16SrRNA基因检测分析。结果42株淋菌中31株TEM基因阳性,22株tetM基因阳性;并均存在penA、gyrA基因的突变。16SrRNA基因无突变。多种基因检测证实这些淋菌已对青霉素、四环素、环丙沙星2种或3种同时耐药。结论临床常用于治疗淋病的青霉素、四环素、环丙沙星已有较高的耐药率,大观霉素是淋病治疗的有效药物。     

志贺菌临床株耐药性分析及对氟喹诺酮类抗生素耐药机制的研究

目的:了解本地区志贺菌抗生素耐药情况,探讨志贺菌对氟喹诺酮类药物的耐药机制和耐药基因的突变及流行情况。方法:K-B纸片扩散法测定2009—2010年天津地区临床分离的119株志贺菌的药敏情况,对氟喹诺酮耐药志贺菌的gyrA、parC基因及质粒介导的喹诺酮耐药(PMQR)基因qnrA、qnrB、qnrS、aac(6′)-ib-cr、qepA进行扩增、测序,将PMQR阳性菌株与大肠埃希菌J53ARZ进行质粒接合试验,比较接合前后受体菌对抗菌药物的敏感性变化。结果:119株志贺菌对萘啶酸敏感率最低(1.72%),其次为氨苄西林(2.52%)及复方磺胺甲口恶唑(3.36%)。福氏志贺菌与宋内氏志贺菌对氟喹诺酮耐药性差别较大,5株志贺菌对环丙沙星等氟喹诺酮耐药,均为福氏志贺菌,其中2株对左氧氟沙星耐药。4株同时存在gyrA83、87位点及parC80位点突变,1株缺乏gyrA87位点突变。PMQR基因阳性菌3株,包括1株qnrS及2株aac(6′)-ib-cr阳性菌,接合菌对多种抗生素的敏感性降低。结论:本地区志贺菌临床株对多种抗生素的多重耐药率较高,对氟喹诺酮耐药率低于5%。喹诺酮耐药机制既有染色体介导靶位酶突变,也存在质粒介导喹诺酮耐药。     

淋球菌对六种抗菌药物敏感性的测定

目的：观察淋球菌对6种常用抗菌药物的敏感性。方法：分离123株淋球菌,分别进行青霉素、四环素、大观霉素、环丙沙星、洛美沙星、头孢曲松的敏感性测定。结果：耐青霉素、四环素、环丙沙星、洛美沙星的菌株分别占56.9%,70.7%,22.8%,30.9%,耐大观霉素1株,未发现耐头孢曲松的菌株;青霉素、四环素、环丙沙星、洛美沙星之间存在交叉耐药及多重耐药（占14.6%)。结论：头孢曲松、大观霉素可作为武汉地区治疗淋病的首选药物,其余4种不作为首选。     

2010年～2012年某区127株淋球菌抗生素敏感性的分析

目的了解江门地区2010年²012年淋球菌对抗生素的敏感性及变化趋势。方法采用琼脂稀释法测定6种抗生素对127株淋球菌的最小抑菌浓度(MIC)及质粒介导的高度耐四环素淋球菌(TRNG),采用纸片酸度法检测菌株是否产β-内酰胺酶(PPNG)。结果淋球菌对大观霉素及头孢克肟的敏感率均为100%,头孢曲松为77.95%,环丙沙星敏感率最低,其耐药率高达92.13%;127株淋球菌中检出PPNG菌株48株(37.80%),TRNG菌株51株(40.16%)。结论淋球菌对青霉素、四环素和环丙沙星的耐药率较高,大观霉素及头孢克肟可作为治疗本地区淋病的首选药物。     

淋球菌和衣原体对抗菌药物的耐药现况

淋球菌和沙眼衣原体的耐药在临床多见.淋球菌的耐药不仅可以通过染色体和质粒介导,还可以通过主动外排系统中的基因突变引起多重可传递耐药,且耐药基因也可通过转化、接合等方式在淋球菌间传递.大观霉素和头孢曲松是我国治疗淋病的首选用药,不再推荐环丙沙星等氟喹诺酮类药物治疗淋病.沙眼衣原体为细胞内寄生菌,相对不易从其它病原体获得耐药基因,对抗生素耐药的机理与特性至今不明,但临床报道耐药多见.我国对沙眼衣原体感染的推荐治疗药物为阿奇霉素和多西环素,替代治疗药物包括红霉素和氧氟沙星等.     

惠州地区淋球菌对抗生素耐药性研究

目的探究惠州市淋球菌对四环素、环丙沙星、青霉素、大观霉素和头孢曲松的耐药情况。方法采用琼脂稀释法测定淋球菌对5种抗生素的最低抑菌浓度。用纸片酸度法检测产青霉素酶淋球菌菌株。结果 118株淋球菌对四环素、青霉素与环丙沙星的耐药率分别为77.97%（92/118）、73.73%（87/118）和39.83%（47/118）;抗菌药物的最终浓度：青霉素为0.125～8mg/L,四环素为0.25～16mg/L,环丙沙星为0.03～2mg/L,大观霉素为4～64mg/L,头孢曲松为0.002～1mg/L。4株对头孢曲松耐药的菌株,同时也对四环素、青霉素以及环丙沙星有耐药作用。结论淋球菌对四环素、环丙沙星和青霉素耐药率较高,对头孢曲松和大观霉素敏感,考虑作为临床治疗淋病的首选药物。     

山西地区91株淋球菌耐药性分析

目的检测山西地区淋病奈瑟菌（NG）对5种抗生素的敏感性,分析其耐药特点。方法K—B琼脂扩散法测定NG对抗生素的敏感性及产色头孢噻吩法检测β-内酰胺酶。结果91株淋球菌对青霉素、四环素、环丙沙星、头孢曲松和大观霉素的耐药率分别为69．23％、87．91％、97．80％、0和5．49％,检出质粒介导的产青霉素酶的淋病奈瑟菌（PPNG）38株（41．76％）,同时耐2种及2种以上抗菌药物的多重耐药率为94．51％。结论青霉素、四环素及环丙沙星已不宜用于山西地区淋病的治疗;头孢曲松和大观霉素耐药率较低,可以作为山西地区治疗淋病的首选药物。但是大观霉素已出现耐药株．应引起重视。同时山西地区多重耐药现象十分严重。持续监测淋球菌的耐药性十分必要。     

肺炎链球菌的耐药性和耐药机制

耐药性肺炎链球菌在世界范围内的广泛流行引起了医学界的普遍关注，肺炎链球菌对β－内酰胺类，大环内酯类抗生素的耐药率在世界各地以较快速度上升，不同地区差异较大，磺胺类，四环素类，氯霉素耐药率普遍较高，出现了氟喹诺酮药性临床菌株，肺炎链球菌的β－内酰胺耐药性主要由青霉素结合蛋白变异所致，非pbp基因突变也会导致β－内酰胺耐药性，大环内酯耐药性肺炎链球菌的耐药表型MLS型，M型分别由耐药基因ermB和mefA介导，23SrRNA和核糖体蛋白L4突变也是其耐药机制之一。DNA促旋酶和拓扑异构酶Ⅳ基因突变引起的靶位改变导致肺炎链球菌对氟喹诺酮类药物耐药。肺炎链球菌也存在氟喹诺酮耐药性主动排系统，pmrA基因编码了外排蛋白PmrA。     

Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype

A Neisseria gonorrhoeae strain with a reduced susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) = 0.5 microg/mL) was isolated among 398 clinical isolates obtained from 2000-2001 in Fukuoka City, Japan. The N. gonorrhoeae strain was negative for penicillinase production but it showed multidrug resistance against penicillin (MIC = 8 microg/mL), tetracycline (MIC = 4 microg/mL), azithromycin (MIC = 0.5 microg/mL) and ciprofloxacin (MIC = 16 microg/mL). The molecular mechanisms of the multidrug-resistant phenotype in this strain were analysed. Polymerase chain reaction and direct DNA sequencing were performed to identify mutations within the penA, ponA, mtrR, penB, gyrA and parC genes of the gonococcal strain, which thus explain the multidrug-resistant phenotype. The N. gonorrhoeae strain contained a significantly different sequence of the penA gene from that of the ceftriaxone-susceptible strains. Some regions of the transpeptidase domain within this penA gene were closely similar to those found in other Neisseria species such as Neisseria subflava, Neisseria flavescens or Neisseria perflava/sicca. This strain also included a ponA mutation that is associated with high-level resistance to penicillin, mtrR mutations that mediate overexpression of the MtrCDE efflux pump responsible for resistance to hydrophobic agents such as azithromycin, and penB mutations that reduce porin permeability to hydrophilic agents such as tetracycline. Moreover, this strain contained gyrA and parC mutations that confer high-level resistance to ciprofloxacin. These results indicate the emergence of a N. gonorrhoeae strain with reduced susceptibility to ceftriaxone, which also showed a multidrug-resistant phenotype that can be explained by the presence of multiple loci mutations associated with antibiotic resistance.     

2006年陕西地区淋球菌对4种抗生素敏感性的检测结果分析

目的:了解陕西地区淋球菌对抗生素的耐药性及产β-内酰胺酶淋球菌(PPNG)的流行状况。方法:采用琼脂稀释法测定4种抗生素对102株淋球菌的最低抑菌浓度(MIC);采用纸片酸度定量法测定PPNG菌株。结果:淋球菌对青霉素、环丙沙星、大观霉素及头孢曲松的耐药率分别为85.29%、94.12%、3.92%、0%。检出25株(24.51%)PPNG菌株。结论:头孢三嗪、大观霉素仍可作为陕西地区治疗淋病的首选用药,但淋球菌对青霉素及环丙沙星耐药率较高。     

2018年成都地区淋病奈瑟菌对抗生素耐药性的结果分析

目的 了解2018年成都地区淋病奈瑟菌对5种抗生素的耐药性及产β-内酰胺酶淋病奈瑟菌(PPNG)和质粒介导的高度耐四环素淋病奈瑟菌(TRNG)的流行状况。方法 用琼脂稀释法测定5种抗生素的最小抑菌浓度(MIC)和用纸片酸度法检测β-内酰胺酶。结果 112株淋病奈瑟菌检测出PPNG 58株(51.79%)、TRNG 31株(27.68%)，青霉素和阿奇霉素的耐药率分别为76.79%和25.00%，检测出淋病奈瑟菌对环丙沙星全部耐药，同时发现一株耐大观霉素的菌株，未发现有对头孢曲松耐药的菌株。淋病奈瑟菌多重耐药41株(36.61%)，其中对环丙沙星、青霉素和四环素同时耐药24株比例(21.43%)最高，对环丙沙星、青霉素、四环素、阿奇霉素和大观霉素同时耐药1株比例(0.89%)最低。结论 头孢曲松和大观霉素可作为成都地区治疗淋病的首选药物，同时持续监测淋病奈瑟菌对抗生素的耐药性十分重要。     

2018年成都地区淋病奈瑟菌对抗生素耐药性的结果分析

目的 了解2018年成都地区淋病奈瑟菌对5种抗生素的耐药性及产β-内酰胺酶淋病奈瑟菌(PPNG)和质粒介导的高度耐四环素淋病奈瑟菌(TRNG)的流行状况。方法 用琼脂稀释法测定5种抗生素的最小抑菌浓度(MIC)和用纸片酸度法检测β-内酰胺酶。结果 112株淋病奈瑟菌检测出PPNG 58株(51.79%)、TRNG 31株(27.68%),青霉素和阿奇霉素的耐药率分别为76.79%和25.00%,检测出淋病奈瑟菌对环丙沙星全部耐药,同时发现一株耐大观霉素的菌株,未发现有对头孢曲松耐药的菌株。淋病奈瑟菌多重耐药41株(36.61%),其中对环丙沙星、青霉素和四环素同时耐药24株比例(21.43%)最高,对环丙沙星、青霉素、四环素、阿奇霉素和大观霉素同时耐药1株比例(0.89%)最低。结论     

82株淋病奈瑟菌的耐药性分析

目的了解本地区淋病奈瑟菌的耐药性,为临床治疗提供实验依据。方法细菌鉴定采用API鉴定条,药敏试验采用K-B法,并进行统计分析。结果82例淋病奈瑟菌中,产β-内酰胺酶菌株25株,阳性率为30．5％;淋病奈瑟菌对大观霉素、头孢曲松较敏感,对青霉素、环丙沙星有较高的耐药性。结论青霉素、四环素以及氟喹诺酮类药物已不宜作为本地区治疗淋病的常规药物;大观霉素、头孢曲松可作为治疗淋病的首选药物,同时应加强淋病奈瑟菌的耐药性监测。     

In vitro antibacterial effects of spectinomycin and penicillin G on Neisseria gonorrhoeae singly and in combination (author's transl)]

The antibacterial effects of spectinomycin and penicillin G on clinical isolates of Neisseria gonorrhoeae were studied. The concentrations of penicillin G at which the isolates showed drug sensitivity ranged widely from 0.011 to 6.25 mug/ml. Some of the isolates were resistant to penicillin G. Sensitivity to spectinomycin was observed at the drug concentrations ranging from 3.13 to 12.5 mug/ml. About 60% of the isolates were sensitive to 6.25 mug/ml of spectinomycin, and those isolates which were resistant to penicillin G showed good sensitivity to spectinomycin. No correlation in sensitivity was noted between the two drugs. Tests for their bactericidal activities on bouillon media revealed that the addition of spectinomycin at the concentration of 12.5 mug/ml or over produced a marked bactericidal effect in a short time while penicillin G exhibited a bactericidal or bacteriostatic effect depending upon the concentration used. A synergistic effect of a penicillin and an aminoglycoside antibiotic was observed in these isolates of N. gonorrhoea as was in the isolates of Pseudomonas aeruginosa. Where penicillin G and spectinomycin were used in combination, a simultaneous addition of both the drugs produced the most marked synergistic effect. Morphology of N. gonorrhoeae cells exposed to either of these drugs was examined under a scanning electron microscope. Exposure to spectinomycin at the level of 6.25 mug/ml resulted in almost no morphological change. At 6.25 mug/ml of the drug, however, a roughened cell surface, a bleb-like structure or a state suggesting the loosening of such a bleb-like structure was noted. The addition of penicillin G at 0.19 mug/ml led to an impairment of cell division at one hour of exposure and to cell swelling and lysis with further exposure. At 1.19 mug/ml of the drug, these processes of cell swelling and lysis took place early.