淋球菌耐药现状及耐药机制研究进展

淋球菌对青霉素、四环素、氟喹诺酮和阿奇霉素等耐药严重,对头孢菌素敏感性降低的淋球菌株正在增加中,偶有大观霉素耐药的淋球菌株。淋球菌对青霉素和四环素耐药机制包括染色体介导的低度耐药和质粒介导的高度耐药。氟喹诺酮耐药主要是gyrA和parC基因发生突变引起。大环内酯类药物耐药与ermF、ermB、ermC基因及mtrR基因突变有关。淋球菌对头孢曲松敏感性降低主要由于penA、mtr等基因突变相关。淋球菌spe位点单步突变导致对大观霉素高度耐药。多重耐药主要与mtrR编码区内的基因突变或多位点突变相关。     

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。     

In vitro activity of gemifloxacin against clinical isolates of Neisseria gonorrhoeae with and without mutations in the gyrA gene

The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neisseria gonorrhoeae; strains were analyzed for the presence of mutations in both the gyrA and parC genes. Only seven strains were resistant to nalidixic acid due to a mutation in the gyrA gene but not in the parC gene, with six and two considered intermediate to ciprofloxacin and levofloxacin, respectively. The activity of gemifloxacin was similar to that of trovafloxacin and moxifloxacin, but was more active than nalidixic acid, ciprofloxacin or levofloxacin against the gyrA mutant strains. Gemifloxacin is a valid therapeutic alternative to treat infections with N. gonorrhoeae, retaining its activity against strains already presenting a mutation in gyrA.     

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     

Trends in antimicrobial resistance in Neisseria gonorrhoeae and molecular characteristics of N. gonorrhoeae with decreased susceptibility to ceftriaxone in Shandong,China, 2007 to 2014

In this study, the trends of antimicrobial resistance in Neisseria gonorrhoeae were analysed in Shandong Province of China during 2007 to 2014. Furthermore, the ceftriaxone (CRO) genetic resistance determinants, including penA, mtrR, penB, ponA, and pilQ genes, were sequenced and the molecular mechanisms of decreased susceptibility or resistance to CRO in N. gonorrhoeae were elucidated. Overall, the increasing trends of resistance to penicillin (PEN), tetracycline (TET), and ciprofloxacin (CIP), and decreasing trends of susceptibility to CRO and azithromycin (AZM) were observed in Shandong Province between 2007 and 2014. The proportions of PPNG, TRNG, PP/TRNG, and MDR isolates increased sharply in this district. PenA mosaic structure, the substitution of A501V, and an insertion of aspartate in amino acid position 345 were identified in the N. gonorrhoeae isolates with decreased susceptibility or resistance to CRO. All the 28 N. gonorrhoeae isolates had substitutions at Gly-120 and Ala-121 of porin encoded by penB, substitution of L421P in PBP1, and a single nucleotide (A) deletion in the 13?bp inverted repeat located between the ?10 and ?35 sequences in the mtrR promoter. Additionally, 21 N.gonorrhoeae isolates had substitutions of A39T/G45D in MtrR, and three new substitutions of R44G, L47R, and/or H105F in MtrR were observed. Therefore, PenA mosaic structure in N. gonorrhoeae and the substitutions of Ala-501 in PBP2 may considerably increase CRO MICs. A close association between the genetic polymorphisms in mtrR, penB, and ponA and the development of decreased susceptibility to CRO might be confirmed.     

大肠埃希菌gyrA、parC和marOR基因突变与喹诺酮耐药的相关性

目的:研究大肠埃希菌gyrA、parC和marOR基因突变与喹诺酮类耐药的相关性。方法:采用微量稀释法进行常规药敏试验,筛选3株萘啶酸敏感大肠埃希菌和37株萘啶酸耐药大肠埃希菌株;PCR扩增大肠埃希菌喹诺酮耐药决定区(QRDR)相关gyrA、parC基因,进行聚合酶链反应-单链构象多态性(PCR-SSCP)分析,同时PCR扩增marOR基因;在耐药株选取部分菌株对gyrA、parC及marOR基因进行测序,检测其突变情况,其结果与体外药敏试验结果进行比较,研究其相关性。结果:37株耐药株均出现gyrA基因突变,但对环丙沙星低耐株最低抑菌浓度(MIC)=2mg/L只出现gyrA单位点突变,而parC基因未发生突变;环丙沙星高耐株(MIC=64mg/L)gyrA基因出现3个位点突变,parC基因出现单位点突变;在环丙沙星高耐株(MIC=256mg/L),并伴有其他类抗菌药物的多重耐药时,除了出现gyrA和parC基因双位点突变,同时检测到marOR基因的多位点突变。结论:gyrA和parC基因突变在大肠埃希菌对喹诺酮耐药中起着重要作用,gyrA和parC基因突变的程度与大肠埃希菌耐药水平有关,marOR基因多位点突变在多重耐药机制中具有一定的作用。     

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     

淋病奈瑟菌的耐药性与喹诺酮耐药基因突变的相关性分析

目的 分析本地区淋病奈瑟菌临床菌株gyrA基因突变与喹诺酮类药物耐药的相关性.方法 采用琼脂稀释法检测37株淋病奈瑟菌临床菌株对6种抗生素的最小抑菌浓度(MIC),PCR法扩增淋病奈瑟菌临床菌株gyrA基因片段并测序.结果37株淋病奈瑟菌临床菌株对大砚霉素、头孢曲松、四环素、青霉素、氧氟沙星和环丙沙星的耐药率分别为0、...     

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。     

In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).     

Levofloxacin treatment failure in a patient with fluoroquinolone-resistant Streptococcus pneumoniae pneumonia

The frequency of fluoroquinolone-resistant Streptococcus pneumoniae has increased as fluoroquinolone administration for treatment of respiratory tract infections has increased. Levofloxacin treatment failed in a patient who had pneumococcal pneumonia and had received three previous courses of levofloxacin therapy. Susceptibility testing revealed high-level resistance to levofloxacin (minimum inhibitory concentration [MIC] > 32 microg/ml), and cross-resistance to moxifloxacin (MIC 4 microg/ml), trovafloxacin (6 microg/ml), and gatifloxacin (12 microg/ml). Sequencing of the quinolone-resistance determining region revealed a mutation of serine-81 to phenylalanine (Ser81-->Phe) in the gyrA region of DNA gyrase and a Ser79-->Phe mutation in the parC region of topoisomerase IV The patient was treated successfully with intravenous ceftriaxone followed by oral cefprozil. Clinicians must be aware of local resistance patterns and the potential for fluoroquinolone treatment failures in patients with infections caused by S. pneumoniae.     

Selection of a gyrA mutation and treatment failure with gatifloxacin in a patient with Streptococcus pneumoniae with a preexisting parC mutation

An 81-year-old woman had pneumonia caused by Streptococcus pneumoniae (levofloxacin Etest minimum inhibitory concentration [MIC] 1.5 microg/ml) and was treated with intravenous gatifloxacin 200 mg/day. After 3 days of therapy, repeat sputum cultures were positive for S. pneumoniae, which was resistant to levofloxacin (Etest MIC > 32 microg/ml). The isolate obtained before therapy showed a preexisting parC mutation of aspartic acid-83 to asparagine (Asp83-->Asn), and the isolate obtained during therapy showed an acquired gyrA mutation from serine-81 to phenylalanine (Ser81-->Phe) and a second parC mutation from lysine-137 to Asn (Lys137-->Asn). Both isolates were the same strain, as determined with pulsed-field gel electrophoresis. This case demonstrates the potential for resistance to emerge during 8-methoxy fluoroquinolone therapy for fluoroquinolone-susceptible S. pneumoniae with a preexisting parC mutation. Additional clinical failures with a fluoroquinolone may occur unless these first-step parC mutants can be identified to assist clinicians in selecting appropriate antimicrobial therapy.     

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。     

淋球菌对头孢曲松的敏感性及淋球菌多抗原测序分型研究

目的了解中国广东地区2010—2016年淋球菌对头孢曲松的敏感性以及相应菌株的淋球菌多抗原测序分型(NGMAST)基因型别。方法 2010—2016年在广东省疾病预防控制中心收集的285株淋球菌,经分离纯化及鉴定后,采用美国临床实验室标准化委员会(CLSI)推荐的琼脂稀释法测定其对头孢曲松的最小抑菌浓度(minimal inhibitory concentration,MIC);菌株培养后利用试剂盒提取DNA,并进行淋球菌多抗原测序分型(NG-MAST)。结果本次测试的285株淋球菌除1株MIC>0.25μg/mL外,其他都属于敏感菌株(CLSI敏感标准为≤0.25μg/mL),MIC≥0.06μg/mL的菌株比例为63.2%,其中2016年度MIC≥0.06μg/mL菌株比例为44.4%,2010年MIC≥0.06μg/mL菌株比例为70.6%。NG-MAST分型研究显示,285株淋球菌共有166个型别,菌株多样性较高,其中73种为已知型别,93种为新型别。测定的所有菌株中主要包括ST568(n=13),ST270(n=9),ST421(n=7),ST2288(n=5),ST1731(n=4),ST1766(n=4),ST1866(n=4),ST1870(n=4),ST1053(n=4),ST2318(n=4),ST5990(n=4),ST1614(n=4),ST1866(n=3)等。相同NG-MAST型别的菌株具有相同或相近的MIC值。结论广东地区淋球菌对头孢曲松MIC≥0.06μg/mL菌株比例较高,需要对此进行长期监测。7年间菌株的优势型别有较大变化,显示该地区性网络可能发生较大波动。NG-MAST分型可以作为分子生物学标记用于淋球菌耐药监测。     

Antimicrobial resistance of Neisseria gonorrhoeae in Japan, 1993-2002: continuous increasing of ciprofloxacin-resistant isolates

Susceptibility testing was conducted on 1357 isolates of Neisseria gonorrhoeae isolated from 1993 through 2002 in Japan to assess the antimicrobial resistance. Selected isolates were characterised by auxotype and analysis was done for mutations within the quinolone resistance-determining region (QRDR) in the gyrA and parC genes, which confer fluoroquinolone resistance to the organism. Isolates with ciprofloxacin resistance increased significantly from 6.6% (1993-1994) to 73.5% (2002). The proportion of plasmid-mediated penicillin-resistant isolates (PPNG) decreased significantly from 7.9% (1993-1994) to 0.9% (2002). The percentage of chromosomal-mediated resistance to penicillin decreased from 27.4% in 2000 to 12.0% in 2001 but increased to 28.9% in 2002. The proportion of isolates with any type of resistance to tetracycline decreased from 24.7% in 2000 to 13.9% in 2001 and then increased to 22.3% in 2002. The proportion of prototrophic isolates significantly decreased from 84.4% in 1992-1993 to 7.7% in 2001, while that of the proline-requiring isolates significantly increased from 4.4% in 1992-1993 and 80.8% in 1998. The proline-requiring isolates were less susceptible to ciprofloxacin than the prototrophic or arginine-requiring isolates. Of 87 isolates resistant to ciprofloxacin, 2 (2.3%) contained five amino acid substitutions within the GyrA and ParC proteins, 76 (87.4%) contained three or four amino acid substitutions and 9 (10.3%) contained one or two amino acid substitutions.     

Antimicrobial susceptibilities and molecular typing of neisseria gonorrhoeae isolates at a medical centre in Taiwan, 2001–2013 with an emphasis on high rate of azithromycin resistance among the isolates

A high prevalence of gonococcal resistance to various antimicrobials and Neisseria gonorrhoeae isolates exhibiting resistance to extended-spectrum cephalosporins have been reported in the past few decades. A total of 226 N. gonorrhoeae isolates obtained from the National Taiwan University Hospital from 2001 to 2013 were evaluated. The minimum inhibitory concentrations (MICs) of the isolates to antimicrobials were determined by the agar dilution method and interpreted using the 2017 clinical breakpoints or epidemiological cut-off values recommended by the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). The genetic relatedness of these isolates was determined by multilocus sequence typing. None of the isolates was resistant to ceftriaxone and cefotaxime, and the resistance rates to cefixime, spectinomycin, cefpodoxime, ciprofloxacin, and penicillin were 0.4%, 0.4%, 13.3%, 91.6%, and 87.6%, respectively. The rate of isolates resistant to azithromycin was 14.6% (EUCAST criteria), which is higher than in previous surveillance studies. A total of 57 sequence types (ST) were identified, and ST1901, ST7365, and ST1927 prevailed. Isolates of ST8143 emerged after 2011. ST1901 isolates had relatively higher MIC values for ceftriaxone and azithromycin than those of the other STs. In conclusion, ceftriaxone remains an effective drug of choice for gonorrhoeal management in Taiwan. High rates of azithromycin resistance among N. gonorrhoeae isolates were found. The circulating ST1901 strains with high MIC values for ceftriaxone and azithromycin and the emerging ST8143 strains were alarming.     

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.     

In vitro activity of moxifloxacin against recent community-acquired respiratory tract pathogens isolated in France: a national survey

Between February and June 2000, 2345 consecutive strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae were isolated from 2088 adult patients suffering from community-acquired respiratory tract infections, in 97 hospital laboratories. Of the 1037 S. pneumoniae isolates, 48.3% were intermediately or highly penicillin resistant. For invasive isolates, the MIC90s of penicillin G, amoxycillin, cefuroxime, ceftriaxone, erythromycin, ofloxacin, ciprofloxacin and moxifloxacin were 2, 2, 4, 0.5, 1024, 2, 2 and 0.25 mg/l, respectively. All but one invasive strain were susceptible to moxifloxacin whereas 97.5% were susceptible to levofloxacin. The MIC90s of clinical isolates with intermediate susceptibility or high resistance to penicillin G, were 2, 2, 4, 1, 1024, 2, 2 and 0.25 mg/l. About 98.1, 97.0, and 83.1% of strains were inhibited by concentrations < or = 1 mg/l of moxifloxacin, levofloxacin and ciprofloxacin, respectively (E-test). Eight of the 1037 S. pneumoniae strains were not susceptible to moxifloxacin and had mutations in gyrA (eight strains), parC (four strains) or parE (three strains). Against H. influenzae (32.7% were beta-lactamase producers) and M. catarrhalis (96.3% were beta-lactamase producers), the MIC90s of moxifloxacin, amoxycillin and co-amoxiclav were 0.094 and 0.125 mg/l, 64 and 8 mg/l, and 1.5 and 0.25 mg/l, respectively. Against oxacillin-susceptible S. aureus and K. pneumoniae, the MIC90s of moxifloxacin were 0.125 and 0.84 mg/l respectively. Moxifloxacin had the highest in vitro activity of all antibiotics tested.     

耐氟喹诺酮类铜绿假单胞菌gyrA及parC基因突变研究

目的　研究临床分离的耐氟喹诺酮类铜绿假单胞菌gyrA及parC基因突变情况。方法　测定临床分离的 5 5株铜绿假单胞菌MIC值 ,从中筛选出 1株敏感菌和 8株耐药菌 ,以标准敏感菌株ATCC2 785 3作为质控菌株。用聚合酶链反应 (PCR)扩增gyrA及parC基因的喹诺酮耐药决定区 (QR DR) ,扩增产物片段长度分别为 35 1bp、397bp。用限制性内切酶SacⅡ消化gyrAPCR产物 ,同时对上述 10株菌的gyrA及parC基因的喹诺酮决定区 (QRDR)进行PCR DNA直接测序分析。结果　有 8株耐菌株的gyrA基因在 83位 (ACC→ATC)有突变 ,导致氨基酸Thr→Ile的改变 ;有 3株高度耐药菌gyrA基因同时在 87位 (GAC→GGC)有突变 ,导致氨基酸Asp→Gly的改变 ;有 4株耐药菌株的parC基因在 87位有TCG→TTG突变 ,导致氨基酸由Ser→Leu的改变。同时具gy rA和parC突变MIC值是仅具gyrA突变菌株MIC值的 2～ 16倍。未发现parC突变单独存在。另外 ,有 6株耐药菌gyrA的 132位有CAC→CAT的突变 ;所有耐药菌株parC基因 115位有GCT→GCG的突变 ,该突变未引起氨基酸的改变。结论　gyrA83、87位突变及parC基因 87位突变都可引起铜绿假单胞菌对氟喹诺酮类药物产生耐药 ,但以gyrA基因 83位突变为主 ,合并gyrA基因 87位及parC基因 87位突变可增加耐药程度。