Identification of Quinolones/Fluoroquinolones Resistance Genes from Staphylococci Strains Isolated at the University Hospital of Brazzaville, Republic of the Congo

Staphylococci strains, like the majority of bacterial strains, have developed the resistance to several antibiotics, including Quinolones and Fluoroquin-olones In the Republic of the Congo, cases of resistance leading to treat-ment failures have been observed during the treatment of staphylococcal infections with antibiotics in hospitals. The objective of this study was to identify the Quinolone/Fluoroquinolone resistance genes from staphylo-cocci strains isolated in hospitals. A total of 51 strains of Staphylococci were isolated, including 16 (31.37%) community strains, and 35 (68.62%) clinical strains. 46 strains of Staphylococcus aureus (S. aureus) and 5 SCNs were identified. A total of 34 DNA fragments from different strains resistant to Quinolones/Fluoroquinolones, including 21 (61.67%) DNA fragments from clinical S. aureus and 13 (38.23%) from community SCN strains were analyzed by the molecular method (genotypic detection) by PCR. The genotypic results made it possible to identify the gyrA, grLA and norA genes and to show that these genes are involved in the resistance of the strains to the various antibiotics used. The grLA gene was the most identified gene with a frequency of 75%. The gyrA and grLA genes have been identified in Staphylococcus aureus and Coagulase Negative Staphy-lococci. The norA gene, on the other hand, has only been identified in Staphylococcus aureus. Two mechanisms are essentially involved in the resistance of Staphylococci to quinolones/Fluoroquinolones, the mecha-nism of resistance by efflux, which takes place thanks to a transmembrane protein coded by the norA gene and by point mutations (substitution and deletion of acids or nucleotides) observed within the protein and nucleic sequences of the chromosomal gyrA and grLA genes.

Detection of Shigella gyrA mutations and correlations between gyrA mutations and quinolones resistance

118 clinical strains of Shigella were serotyped, in which 116 strains were tested to be S. flexneri. The susceptibilities of the S .flexneri strains to quinolones were measured by the disk-diffusion method. It was found that most S .flexneri strains were susceptible to norfloxacin and ciprofloxacin, but resistant to nalidixic acid. To study the correlation between gyrA mutations and quinolones resistance, a fragment within the gyrA gene was amplified by PCR. The SSCP （Single-Strand Conformation Polymorphism） analysis was applied to detect mutations in PCR products of different strains. The mutations were then confirmed by DNA sequencing. Altogether, two types of mutation were revealed, in which one type was single mutation （ C42-T）, and the other was double mutations （ C42-T and A54- G）. By statistical analysis, C42-T （encoding Ser83-keu substitution） was shown to have correlation with nalidixic-acid resistance in the clinical strains of Shigella, while A54-G （encoding Asp87-Gly substitution） was shown to have correlations with both norfloxacin resistance and ciprofloxacin resistance.

Molecular Detection of Mutations within the Quinolone Resistance-Determining Regions in Non Typhoidal Salmonella Isolates from Malaysia

Introduction: The efficacy of chemotherapy in bacteraemia caused by non-typhoidal Salmonella (NTS) is compromised by antibiotic resistance. Objective: This study was undertaken to describe the mechanism of resistance among clinical NTS isolates. Materials & Methodology: Thirty of NTS were isolated from blood (n = 19), stool (n = 10) and bronchioalveolar lavage (BAL;n = 1) respectively. These isolates were tested for susceptibility testing by disc diffusion method against ampicillin, gentamicin, tetracycline, co-trimoxazole, nalidixic acid, ciprofloxacin and ceftriaxone. Epsilometer tests (E-test) for nalidixic acid and ciprofloxacin were performed for nalidixic acid resistant isolates by disc diffusion method. DNA sequencing was carried out on six of the nalidixic acid resistant Salmonella Enteritidis isolates to identify mutations within quinolones resistance determining regions (QRDR) of gyrA, gyrB, parC and parE genes. Results: Resistance rates of NTS isolates from blood, stool, and BAL were respectively 37%, 20% and 0% for ampicillin, 79%, 40% and 0% for tetracycline, 32%, 40% and 0% for co-trimoxazole, 37%, 10% and 100% for nalidixic acid. Eight isolates were resistant to nalidixic acid and had exhibited reduced susceptibility towards ciprofloxacin by E-test. Mutation within QRDR was detected in gyrA gene (n = 6;Asp 47 → His [3], Asp 51 → Asn [1], Asp 73 → Gly [1], and Gly 48 → Asp [1]) and double mutation was detected in parE gene (n = 3;Gly 48 → Asp [3], Glu 82 → Ser [3]). Out of six isolates, three isolates were found to have both gyrA and parE gene mutations. Conclusions: There was no mutation observed in gyrB and parC gene. Mutation in gyrA gene was sufficient to induce decreased susceptibility to ciprofloxacin. Variation in amino acid sequences are novel, while detection of other gene mutation was uncommon.

Genotypic Diversity and Characterization of Quinolone Resistant Determinants from Enterobacteriaceae in Yaoundé, Cameroon

Background: Enterobacteriaceae causes many types of infections which are often treated with quinolones and fluoroquinolone (Q/FQ). The resistance mechanisms to Q/FQ are usually associated with mutations in the quinolone resistance determining region which alter the conformation of target amino acid residues within the protein and in the qnr genes. This study aimed at determining the antimicrobial resistant profile of a sample of Enterobacteriaceae from Cameroon and the genetic diversity in quinolone-resistant isolates in view of implementing a better management, treatment, control and prevention of the transmission of these resistant strains. Methods: Identification and antimicrobial susceptibility testing was done using VITEK 2. The detection of plamid-mediated quinolone resistance (PMQR) genes was carried out using the conventional PCR method. Sequencing was done using the Applied Biosystem 3500 genetic analyser. DNA fingerprint was obtained using Pulsed-Field Gel electrophoresis. Results: Among 440 Enterobacteriaceae, the most prevalent genera were: Escherichia 178/440 (39.5%);Klebsiella 148/440 (33.6%);Enterobacter 35/440 (8%);Pantoea 28/440 (6.4%);Proteus 14/440 (3.2%) Salmonella 13/440 (3%). Ampicillin resistance showed the highest prevalence with 371/440 (81%) and Imipenem the lowest resistance 9/440 (2.1%). The ciprofloxacin resistance rate was 161/440 (36.6%). The detected plasmid mediated quinolone resistance (PMQR) genes were: qnrA, 2/161 (1.2%);qnrB, 31/161 (19.3%);qnrS, 13/161 (8.1%): Aac (6')Ib-cr, 84/161 (52.2%) and qepA, 3/161 (1.9%). There were several mutations in the parC gene of Klebsiella leading to S80D and S80N substitutions. Two pairs of Klebsiella peumoniae strains were phenotypically and genotypically identical with 100% similarity in the dendrogramme. Conclusion: This study showed that quinolone resistance was high. The PMQR genes contributing to this resistance were diverse. This high PMQR indicates that there has been an unknown circulation of these genes in our community. To avoid the rapid dissemination of these PMQR genes continuous surveillance of antimicrobial resistance should be carried out not only in humans but also in animals to monitor the evolution of these genes.

Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains

AIM:To investigate the resistance of Helicobacter pylori(H.pylori) to ciprofloxacin(CIP),levofloxacin(LVX) and moxifloxacin(MOX) in the Beijing area and to elucidate the resistance mechanisms.METHODS:Seventy-nine H.pylori clinical strains,isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009,were tested for their susceptibility to CIP,LVX and MOX using the E-test method.H.pylori strain 26695 was included in the susceptibility testing as a control strain.According to the minimal inhibitory concentration(MIC) values,a strain was classified as resistant to CIP,LVX or MOX when the MIC was > 1 μg/mL.We amplified by polymerase chain reaction(PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H.pylori strains selected at random.RESULTS:In this study,the resistance rates of H.pylori to CIP,LVX or MOX were 55.7%(44/79),and the primary resistance rates were 26.6%(21/79).Patients with secondary resistance had received LVX in previous eradication treatments,but not MOX or CIP.Forty-five strains,including 29 CIP,LVX or MOX-resistant strains(MIC:1.5-32 μg/mL) and 16 susceptible strains,were selected randomly from the 79 strains and used in PCR analysis.Among these 45 strains,27 resistant strains had mutations in the gyrA gene,including 11 strains with mutations corresponding to Asp-91(MIC:2-32 μg/mL),one of which also had a mutation corresponding to Val-150,and 16 strains had mutations at Asn-87(MIC:4-32 μg/mL),three of which also had mutations corresponding to Arg-140 or Val-150.In addition,Arg-140,Val-150 or Ala-97 mutations were separately detected in three susceptible strains.Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation.There was a significant difference in the occurrence of mutations in the gyrA gene between CIP,LVX and MOX-resistant and-susceptible strains(P < 0.05),but 2 resistant strains were found to possess no quinolone resistance-determining region mutations.CONCLUSION:Resistance is primarily mediated through point mutations in gyrA.Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.

Molecular characterization of antimicrobial multi-drug resistance in non-typhoidal Salmonellae from chicken and clam in Mangalore, India

Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood（clams） were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden（8 from poultry and 12 from seafood） and 16 were S. Typhimurium（from seafood）. All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation,Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones（viz., qnrA, qnrB and qnrS） in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.

Molecular mechanism of the qnrA genemediated quionlone resistance in Gram-negative bacteria

To explore the prevalence of the plasmid-mediated quinolone resistance gene qnrA in Gramnegative bacteria and to investigate its molecular genetic background and resistance profile in isolates harboring this gene, a total of 629 nalidixic acid-resistant isolates of non-repetitive Gram-negative bacteria were collected from clinical specimens between April 2004 and April 2006 and these isolates were screened for qnrA gene by PCR using specific primers combined with DNA sequencing. The extended spectrum β-1actamase （ESBL） or AmpC-producing isolates were distinguished by the phenotypic confirmatory test combined with DNA sequencing, and the antibiotics susceptibility test for qnrA-positive isolates was carried out by Kirby-Bauer and E-test method. To detect the location of the qnrA gene, plasmid conjugation and Southern hybridization were performed and the integron structure containing the qnrA gene was cloned by PCR strategy and sequenced by primer walking. It was demonstrated that the incidence of the qnrA-positive strains in nalidixic acid-resistant bacteria was 1.9% （12/629）, in which the detection rates for Klebiesiella pneumoniae. Enterobacter cloacae, Enterobacter aerogenes, Citrobacterfreundii and Salmonella choeraesuis were 2.2% （3/138）, 17. 1% （6/35）, 9. 1% （1/11）, 12.5% （1/8）, and 14.3% （1/7）, respectively. The qnrA gene was found to be embedded in the complex sull-type integron located on plasmids with varied size （80-180 kb）. Among them, 4 qnrA-positive isolates carried integron In37 and 8 isolates carried a novel integron, temporarily desig- nated as InX. All the qnrA-positive isolates were ESBL-producing and transferable for the multi-drug resistance. It is concluded that the plasmid-mediated drug-resistance mechanism exists in the quinolone resistant strains of isolates from hospitals in Guangdong area, but the incidence was rather low. Nevertheless, it is still possible that the horizontal transfer of the resistant qnrA gene might lead to the spreading of drug-resistance.

2014-2018年江苏省人源喹诺酮耐药1,4,[5],12:i:-沙门氏菌的基因组学初步分析

目的分析江苏省喹诺酮耐药1,4,[5],12:i:-沙门氏菌分子流行病学特征。方法用cgMLST分析江苏省及欧美来源菌株的分子流行病学特征,并初步分析喹诺酮耐药1,4,[5],12:i:-沙门氏菌可能的传播特征。结果13株喹诺酮耐药1,4,[5],12:i:-沙门氏菌共注释11大类抗性基因(Antibiotic resistance genes,ARGs)。其中氨基糖苷类ARGs检出率最高(100%);12株喹诺酮耐药菌株(92.3%)均携带IncHI2/IncHI2A质粒类型;不同国家/地区来源菌株质粒介导喹诺酮耐药(PMQR)基因携带分析显示美国及欧洲来源菌株携带6类PMQR基因,qnrB19检出率最高。江苏省来源菌株携带3类PMQR基因类型,aac(6′)-Ib-cr检出率最高(11.84%);不同国家/地区来源菌株cgMLST位点差异分析显示形成3个主要流行谱系。结论江苏省人源喹诺酮耐药1,4,[5],12:i:-沙门氏菌分离株与欧美菌株可能具有共同进化来源,PMQR基因携带水平存在国家/地区差异。

荧光PCR熔解曲线法检测幽门螺杆菌克拉霉素、喹诺酮耐药基因的性能验证

目的探讨采用荧光PCR熔解曲线法检测粪便样本中的幽门螺杆菌(Helicobacter pylori,Hp)克拉霉素(23S rRNA)及喹诺酮(gyrA)耐药相关基因突变在临床诊断中的应用价值。方法纳入胃镜检查Hp快速尿素酶阳性且未经治疗的1176例患者,收集患者胃黏膜组织及粪便样本用于对比研究,针对同一阳性病例,采用E-test法分析胃黏膜组织中Hp克拉霉素、喹诺酮耐药表型,荧光PCR熔解曲线法检测粪便样本中Hp克拉霉素、喹诺酮耐药基因型,Kappa检验分析两种方法检测结果的一致性;对于阳性病例的粪便样本提取2份核酸,分别采用荧光PCR熔解曲线法及一代测序法检测Hp 23S rRNA、gyrA耐药突变基因,并比较两种方法检测结果的一致性。结果在克拉霉素耐药研究中,最终获得有效样本934例,其中耐药阳性表型453例,耐药阳性基因型481例,阳性符合率为93.38%(95%CI:90.70%~95.32%);在喹诺酮耐药研究中,最终获得有效样本909例,其中表型耐药阳性426例,基因型耐药阳性413例,阳性符合率为86.85%(95%CI:83.31%~89.74%)。在对比研究中,23S rRNA基因检测有效样本986例,其中荧光PCR熔解曲线法检测耐药阳性514例,测序检测耐药阳性509例,阳性符合率为96.27%(95%CI:94.24%~97.60%),gyrA基因检测有效样本895例,其中荧光PCR熔解曲线法检测耐药阳性422例,测序检测耐药阳性405例,阳性符合率为95.80%(95%CI:93.38%~97.36%)。结论基于粪便样本的荧光PCR熔解曲线法检测Hp 23S rRNA、gyrA对预测Hp的耐药性具有一定的临床应用价值。

无锡地区2021—2023年肺炎支原体药敏分析

目的回顾性分析无锡地区2021年1月—2023年11月成人感染肺炎支原体对抗菌药物的敏感性,为临床用药提供参考依据。方法回顾性分析2021年1月—2023年11月来上海交通大学医学院附属瑞金医院无锡分院就诊患者呼吸道感染的104株肺炎支原体,对14种常见抗菌药物的耐药性。结果104株肺炎支原体中,耐乙酰螺旋霉素57株(54.8%),耐莫西沙星45株(43.3%),耐强力霉素34株(32.7%),耐美满霉素26株(25.0%),耐环丙沙星16株(15.4%),耐克林霉素14株(13.5%);耐依托红霉素、加替沙星、交沙霉素、左氧氟沙星、阿奇霉素、克拉霉素、红霉素及罗红霉素均在9株以下。结论对成人呼吸道感染的肺炎支原体,临床应以大环内酯类和喹诺酮类抗菌药物进行治疗,但应避免使用大环内酯类中的乙酰螺旋霉素和喹诺酮类中的莫西沙星和环丙沙星。

辅酶Q0增强氨基糖苷类和喹诺酮类抗生素杀灭大肠杆菌的效果分析

寻找新型的抗生素佐剂以提高现有抗生素的杀菌效率,实现快速高效杀灭病原菌是降低细菌耐药风险的重要手段。通过外源添加辅酶Q0(CoQ0)联合氨基糖苷类或喹诺酮类抗生素对大肠杆菌进行杀灭效果测试。结果表明:辅酶Q0能够显著增强氨基糖苷类和喹诺酮类抗生素对大肠杆菌BW25113及8株临床耐药大肠杆菌的杀灭效果。浓度梯度测试和时间依赖性试验结果显示辅酶Q0增强氨基糖苷、喹诺酮类抗生素杀菌具有浓度依赖性和时间依赖性。辅酶Q0最适浓度为30µg·mL-1,其中辅酶Q0辅助庆大霉素的最佳作用时间为5 h、辅助氧氟沙星的最佳作用时间为8 h。研究结果为开发辅酶Q0作为新型氨基糖苷类或喹诺酮类抗生素佐剂提供了数据支撑。

mcr-1基因阳性禽源性大肠埃希菌耐药基因研究

目的调查鲁中地区禽源性大肠埃希菌mcr-1基因的携带情况,了解mcr-1基因阳性禽源性大肠埃希菌对常用β-内酰胺类药物、氨基糖苷类药物、喹诺酮类药物耐药基因的携带情况,掌握其耐药性。方法收集2020年4月至2021年10月鲁中地区3家大规模养殖场302份健康活鸡、鸭肛拭子新鲜粪便,对分离的大肠埃希菌用聚合酶链反应(PCR)检测mcr-1基因的携带率。对mcr-1阳性大肠埃希菌,采用BD凤凰hoenix TM 100 NMIC/ID-4复合板鉴定菌种及进行药敏试验,采用PCR检测各种β-内酰胺类药物耐药基因、氨基糖苷类修饰酶耐药基因、16S rRNA甲基化酶耐药基因和质粒介导的喹诺酮类药物耐药基因。结果302份样品中共分离出291株禽源性大肠埃希菌,其中27株携带mcr-1基因,mcr-1基因携带率为9.3%。27株mcr-1基因阳性禽源性大肠埃希菌中:超广谱β-内酰胺酶(ESBL)基因CTX-M-14、CTX-M-15、TEM-1携带率分别为100.00%(27/27)、70.37%(19/27)、74.07%(20/27);质粒介导AmpC酶耐药基因CMY-2携带率为14.81%(4/27);未检出bla SHV、bla DHA、OXA等β-内酰胺类药物相关耐药基因;未检出碳青霉烯酶基因;16S rRNA甲基化酶耐药基因rmtB及氨基糖苷类修饰酶耐药基因aac(6′)-Ⅰb-cr、ant(3″)-Ⅰ的携带率分别为25.93%(7/27)及25.93%(7/27)、92.59%(25/27);喹诺酮类药物耐药基因qnrS的携带率为81.48%(22/27),未检出qnrA、qnrB基因。对多黏菌素B、头孢噻肟、头孢西丁、左氧氟沙星、复方磺胺甲噁唑表现出了100.00%耐药,对头孢吡肟、头孢他啶、氨曲南、哌拉西林/他唑巴坦、阿米卡星和庆大霉素的耐药率分别为85.19%、33.33%、62.96%、14.81%、25.93%和77.78%,未出现对碳青霉烯类药物耐药的菌株。结论禽源性大肠埃希菌mcr-1基因的携带率为9.3%,是引起多黏菌素耐药的主要耐药机制。mcr-1基因阳性禽源性大肠埃希菌同时携带多种耐药基因,表现出多重耐药的特征。

碳青霉烯类耐药肺炎克雷伯菌对喹诺酮类的高度耐药性及其耐药机制

目的了解碳青霉烯类耐药肺炎克雷伯菌(CRKP)对喹诺酮类的耐药性及其耐药机制,包括可移动喹诺酮类耐药(TMQR)基因分布。方法对2019年我国7所医院临床分离的CRKP菌株采用肉汤微量稀释法进行抗菌药物敏感性试验。采用Illumina HiseqX测序平台进行基因组测序,并分析CRKP携带的毒力基因、MLST分型、染色体喹诺酮类耐药决定区(QRDR)的变异情况,以及TMQR基因分布。结果481株CRKP对左氧氟沙星和环丙沙星不敏感率分别为98.4%和99.2%,ST11型和ST15型为优势克隆。303株携带毒力基因的CRKP(CV-CRKP)中,ST11型和ST15型菌株分别为92.1%和5.0%。178株不携带毒力基因的CRKP(non-CV-CRKP)中,ST11型和ST15型菌株分别为53.4%和34.3%。全部ST11和ST15型菌株对喹诺酮类耐药并伴有gyrA和parC基因变异,对喹诺酮类敏感菌株均为非ST11和非ST15型菌株。可移动元件介导的喹诺酮耐药基因中,qnrS1(294株,61.1%)、qnrB4(48株,10.0%)及aac(6)-Ib-cr(90株,18.7%)的检出率高,其他基因的检出较低,包括有qnrB1(4株)、qnrB2(2株)、qnrD1(2株)、qnrB6(1株)。其中,qnrB4主要分布在左氧氟沙星高度耐药(MIC≥8 mg/L)菌株中。aac(6)-Ib-cr主要分布在环丙沙星耐药(MIC>8 mg/L)菌株中。结论临床分离的CRKP菌株对喹诺酮类耐药率高。喹诺酮类耐药的CRKP菌株中QRDR变异率高,TMQR基因携带率高。

集中带量采购政策对注射用喹诺酮类药物处方行为和细菌耐药性影响分析

目的 研究集中带量采购政策对注射用喹诺酮类药物使用情况的影响和细菌耐药情况的变化。方法 提取南京鼓楼医院2017年1月—2019年10月和2020年1月—2022年10月注射用喹诺酮类药物的使用数据,采用中断时间序列模型分析集采政策对其产生的影响;基于集采政策相关的调查问卷分析本院医务人员对政策的看法及产生相应行为的原因;利用相应时间段细菌耐药率、检出量进行相关性分析。结果 第三批集采政策实施后,莫西沙星使用量呈下降趋势;第五批集采政策实施后,莫西沙星和环丙沙星的使用量呈上升趋势,且相较于对照组变化存在显著性差异;左氧氟沙星使用量呈持续下降趋势。问卷调查显示,喹诺酮类药物作为替代药优先选择,与第五批集采后喹诺酮类药物使用量的上升一致。喹诺酮类药物耐药率受政策影响不明显,与喹诺酮类药物用量无高度相关性。结论 喹诺酮类药物在第三批集采政策实施后使用量下降,在第五批实施后也未出现异常增长现象。相关病原菌耐药率与药物使用量无高度相关性,政策对耐药率变化的影响还需长期监测。

喹诺酮类抗菌药物的研究进展

喹诺酮类药物在抗菌谱方面具有广泛的活性,可有效抑制多种细菌感染,被广泛用于上呼吸道感染、下呼吸道感染、尿路感染、皮肤和软组织感染以及消化道感染的治疗。然而,喹诺酮类药物也存在一些副作用和耐药性问题,需要引起注意。本文对喹诺酮类药物的化学结构、抗菌谱和作用机制进行了介绍。同时还对喹诺酮类药物的发展趋势包括新型喹诺酮类药物的研究与开发、喹诺酮类药物在抗菌联合治疗中的应用以及在临床治疗中的前景进行了展望。

Emerging bedaquiline resistance:A threat to the global fight against drug-resistant tuberculosis

Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis(TB),yet standardized regimens for managing bedaquiline-resistant TB are lacking.Studies indicate a high proportion of bedaquiline-resistant cases have previously been treated for TB,and often involve strains resistant to quinolones.Regular monitoring of the culture status in patients receiving bedaquiline resistance treatment is advised.Methods such as experimental evolution,protein modeling,genome sequencing,and phenotypic analysis have been instrumental in identifying the mechanisms of bedaquiline resistance.Specifically,variants in the Rv0678 transcriptional repressor of the MmpS5-MmpL5 efflux system are linked to this type of resistance.Bayesian probability estimates show promise in determining the genotypic–phenotypic association for bedaquiline resistance,suggesting potential utility in clinical practice.Future research should explore the practical application of Bayesian probabilities in managing bedaquiline resistance.Sequencing-based technologies are anticipated to play a vital role in the early detection and management of drug-resistant TB strains.

含贝达喹啉耐药结核治疗方案对患者心电图QT间期的影响

目的探索含贝达喹啉耐药结核治疗方案对患者心电图QT间期的影响。方法选取2018年8月-2022年12月在昆明市第三人民医院结核科接受耐药治疗结核病患者204例。治疗方案含贝达喹啉(观察组)84例,其中退出4例、死亡2例,最终78例。治疗方案不含贝达喹啉(对照组)120例,死亡1例、退出4例,最终115例。收集并记录两组治疗不同阶段心电图QT间期和临床资料。结果与基线比较,观察组治疗的第2、4、8、12、16、20、24周心电图QT间期均较高,差异有统计学意义(P<0.05)。观察组治疗第16、20、24周较对照组QT期间长,差异均有统计学意义(P<0.05)。观察组QT间期大于500 ms有15例(19.2%,15/78),其中7例背景方案含氯法齐明和莫西沙星。结论含贝达喹啉的治疗方案会引起患者心电图QT间期的延长,但背景方案含氯法齐明和喹诺酮类更会加重QT间期的延长,因此使用贝达喹啉联合氯法齐明和喹诺酮类时更应加强心电图监测及心脏检查。

喹诺酮类药物及细菌对其耐药性机制研究进展

本文从喹诺酮类抗菌药物的结构、进入细菌体内的方式及喹诺酮类药物的作用机理进行简明阐述。针对喹诺酮类药物的广泛使用而导致的细菌对喹诺酮类药物的耐药性逐渐增加的原因入手,阐述了细菌对喹诺酮类药物耐药性——从染色体突变到质粒介导的喹诺酮类耐药性的几种分子机制及研究进展,为研究新型喹诺酮类抗菌药物提供依据。

1993-2008年禽源大肠杆菌和沙门菌对喹诺酮类药物耐药性分析

目的了解上世纪90年代以来我国部分地区禽源大肠杆菌和沙门菌分离株对1-4代喹诺酮类药物耐药情况。方法血清型采用常规的凝集试验进行测定;药敏纸片试验采用CLSI(clinical and laboratory standards institute)推荐的K-B药敏纸片法。结果344株禽源大肠杆菌分离株覆盖了27个血清型,其中O78、O2、O1和O18血清型菌株分别有141、47、27和22株,共237株,占定型菌株的68.90%;224株禽源沙门菌经血清型鉴定均为鸡白痢沙门菌。1993-1999年禽源大肠杆菌分离株仅对萘啶酸的耐药率超过60%(62.43%,113/181);2000-2008年禽源大肠杆菌分离株对1-3代9种喹诺酮类药物的耐药率均超过60%;禽源沙门菌从2000年起开始出现喹诺酮类耐药菌株,2000-2008年分离到的沙门菌对萘啶酸的耐药率达到了83.74%,但对其它喹诺酮类抗生素的耐药率相对较低。结论近20年来,我国禽源大肠杆菌和沙门菌对喹诺酮类药物的耐药性不断上升,10种喹诺酮类药物之间存在着不同程度的交叉耐药性,且禽源大肠杆菌比沙门菌对喹诺酮类药物的耐药性更为严重,交叉耐药情况亦更为复杂。

养殖龟鳖源气单胞菌耐药性与质粒介导喹诺酮类耐药基因分析

为了解养殖龟鳖源气单胞菌的耐药情况及质粒介导的喹诺酮类耐药（PMQR）、喹诺酮类耐药决定区（QRDR）与耐药表型之间的关系；实验采用K—B纸片法测定了1996--2013年从广东地区患病龟鳖分离的67株气单胞菌对23种常见抗菌药物的耐药性，并检测5种PMQR基因qnrA、qnrB、qnrS、qepA和aac（6’）-Ib—cr，同时分析PMQR基因阳性菌株染色体上gyrA、parC基因QRDR的突变情况。结果显示，67株气单胞菌对氨苄西林、头孢噻吩和磺胺复合物的耐药率分别高达100％、92．54％和83．58％，对喹诺酮类药物呈现中等耐药，耐药率介于19．40％-64．18％，而对亚胺培南、呋喃妥因、阿米卡星、头孢噻肟敏感性较高，耐药率低于10％；79．10％（53／67）的菌株对3类或以上抗菌药物具有耐药性。19．40％（13／67）的菌株携带PMQR基因，其中，8．96％（6／67）携带qnrSl基因、5．97％（4／67）携带qnrS2基因、7．46％（5／67）携带aac（6’）-Ib—CF基因[其中2株同时携带qnrS2和aac（6’）-Ib．CF基因]。13株PMQR基因阳性菌株均分别携带1—4个质粒，大小介于0．8-15kb；其中6株在gyrA基因及parC基因上均发生变异，3株仅在删rA基因上发生变异，另外4株未发现QRDR的基因突变。研究表明，广东地区龟鳖源气单胞菌对多种抗菌药物耐药并存在多重耐药现象；而且PMQR机制的存在预示着喹诺酮类耐药性很可能会在水产临床上更加快速而广泛地传播，应引起重视。