Synthesis and antibacterial activity of N-[5-chlorobenzylthio-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives

A series ofN-[5-(chlorobenzylthio)-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives (4a-1) have been synthesized by reaction of piperazinyl quinolones with 5-chloro-2-(chloroben-zylthio)-1,3,4-thiadiazoles. Their structures were confirmed by elemental analysis, IR and NMR spectra. The antibacterial activities of4a-1 against a variety of Gram-positive and Gram-negative bacteria were determined. Several compounds showed a good antibacterial activity against Gram-positive bacteria among which, compound 4e with a 2-chlorobenzylthio moiety in ciprofloxacin derivative, exhibited high activities againstStaphylococcus aureus andStaphylococcus epidermidis (MIC=0.06 μg/mL). The structure-activity relationship (SAR) study revealed that the position of chlorine atom on benzyl moiety would dramatically affect the antibacterial activities of the synthesized compounds.     

Excess mortality associated with antimicrobial drug-resistant Salmonella typhimurium

In a matched cohort study, we determined the death rates associated with drug resistance in Salmonella Typhimurium. We linked data from the Danish Surveillance Registry for Enteric Pathogens with the Civil Registration System and the Danish National Discharge Registry. By survival analysis, the 2-year death rates were compared with a matched sample of the general Danish population, after the data were adjusted for differences in comorbidity. In 2,047 patients with S. Typhimurium, 59 deaths were identified. Patients with pansusceptible strains of S. Typhimurium were 2.3 times more likely to die 2 years after infection than persons in the general Danish population. Patients infected with strains resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline were 4.8 times (95% CI 2.2 to 10.2) more likely to die, whereas quinolone resistance was associated with a mortality rate 10.3 times higher than the general population.     

2009～2010年蚌埠地区喹诺酮类抗菌药物不良反应分析

目的了解蚌埠地区喹诺酮类抗菌药物致药品不良反应（ADR）的发生情况。方法对2009年1月～2010年12月蚌埠地区上报的喹诺酮类抗菌药物致ADR报告,按性别、年龄、给药途径、药品类别、ADR涉及器官或系统及临床表现等进行统计、分析。结果 ADR涉及的喹诺酮类抗菌药物共11种,659例次,发生频次以左氧氟沙星（269例,占40.82%）居首位,其次为氧氟沙星和环丙沙星;主要的ADR类型为皮肤及其附件损害;有2例严重ADR。结论应规范喹诺酮类抗菌药物的临床应用,严格掌握其适应症、禁忌症及用法用量,以减少ADR的发生率。     

某教学医院2006~2009年喹诺酮类抗菌药物利用分析

目的了解喹诺酮类药物临床应用情况,促进该类药物合理使用。方法从采购金额、限定日剂量、日用药费用等方面对某教学医院2006~2009年喹诺酮类药物的使用情况进行统计分析。结果采购品种数变化不大;采购总金额逐年上升,其中注射剂型均占80%以上;左氧氟沙星的DDDs份额稳居首位,莫西沙星逐年增长,诺氟沙星和环丙沙星保持稳定,妥舒沙星异军突起。结论该院喹诺酮类药物使用状况与国内相关报道相似。多数临床使用变化趋势比较合理,个别品种的临床异动值得关注。     

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。     

Comparison of antibiotic use in the COVID-19 pandemic with the pre-pandemic period in a university hospital

IntroductionThe appropriate use of antibiotics is an important strategy in slowing the development of antimicrobial resistance. This study aimed to evaluate antibiotic consumption and antibiotic use during the coronavirus disease 2019 (COVID-19) pre-pandemic period and pandemic period.MethodsAntibiotic consumption was evaluated with the antibiotic consumption index (ACI).ResultsAntibiotics with the largest increase in ACI value during the pandemic period compared to the previous year increased from 0.4 to 1.8 DDI/100 bed days in moxifloxacin. Teicoplanin, linezolid, and clindamycin were not affected in terms of consumption.ConclusionsIt was observed that the use of many intravenous antibiotics in our hospital increased during the pandemic period.     

Investigation of plasmid‐mediated quinolone resistance genes among clinical isolates of Klebsiella pneumoniae in southwest Iran

BackgroundExtensive and inappropriate use of quinolones has led to growing resistance rates to these broad‐spectrum antibiotics. The present study purposed to investigate the prevalence of plasmid‐mediated quinolone resistance (PMQR) genes in Klebsiella pneumoniae clinical isolates.MethodNinety‐two non‐repetitive K. pneumoniae clinical isolates were confirmed by standard microbiological methods. Antibacterial susceptibility of isolates toward seven agents from the quinolone family was evaluated by the disc diffusion method. Ciprofloxacin minimum inhibitory concentrations (MICs) were determined using the standard agar dilution method. PCR amplification was used to detect the existence of PMQR genes in the studied isolates.ResultsIn the present study, significant quinolones'' resistance (40%) was observed in K. pneumoniae isolates, and most of the strains were resistant to nalidixic acid (94.6%) and ofloxacin (45.6%). MIC analysis showed 15 strains were resistant to 6–128 μg/ml of ciprofloxacin, and five were intermediately‐resistant. PMQR genes were detected in 88% of all isolates. Acc(6’)‐Ib‐cr was constituted half of the total PMQR genes detected among ciprofloxacin non‐susceptible isolates. Of 20 ciprofloxacin non‐susceptible isolates, 65% (n = 13) harbored multiple PMQR determinants, and 15 strains were determined as integron carriage.ConclusionThe findings of this study indicated considerable resistance against quinolones, which could be correlated with the extensive and inappropriate use of this class of antibiotics as empirical treatment.     

Novel anti-staphylococcal targets and compounds

Many antimicrobial drugs have become less effective at combating infectious diseases, and experts in the field are concerned about the possibility of a ‘post-antibiotic era’ for some clinically important pathogens, particularly staphylococci. In our hospitals, nosocomial infections due to vancomycin-resistant enterococci have emerged, and there are concerns that the same resistance pattern may evolve in methicillin-resistant Staphylococcus aureus (MRSA). Examples from three main areas addressed to prevent this scenario are discussed: (i) screening of isolated biochemical targets and intact bacteria using high-throughput screening technologies, (ii) modifying existing compound classes like quinolones and glycopeptides to create more powerful compounds overcoming pathogen resistance and (iii) introduction of completely new classes of antibiotics.     

AcrAB外排泵ramA对肺炎克雷伯菌耐喹诺酮类药物的影响

目的 探讨AcrAB外排泵调控基因ramA对肺炎克雷伯菌耐喹诺酮类药物的影响。方法 用喹诺酮类药敏纸片扩散法、MIC及其逆转实验和有机溶剂耐受实验测定细菌耐药表型,用PCR扩增外排泵结构基因acrA、acrB、tolC及调控基因acrR,ramA,marA,用半定量PCR 检测调控基因的转录水平。结果 泵的结构基因和调控基因均存在43株KP菌中。仅喹诺酮类耐药株与敏感株ramA转录水平存在统计学差异(P<0.05)。和对照组相比,高表达ramA的 AC-1株,其泵结构基因的转录水平增高,耐药表型也有明显改变,用泵抑制剂后,其喹诺酮类的MIC恢复对照水平。结论 ramA是KP菌耐喹诺酮类抗生素的一个重要因素。抑制ramA的表达,有助于治疗多重耐药肺炎克雷伯菌的感染。