喹诺酮类药物对老年患者神经系统影响的观察与护理对策

目的：由于老年患者使用喹诺酮类药物后神经系统反应率高且严重,为了提高老年患者喹诺酮类药物用药后的生活安全展开研究。方法：通过3年时间对135例使用喹诺酮类药的70岁以上老年患者,观察药物对其神经系统产生的影响,对不同神经系统症状出现的比例进行分析。结果：发现70岁以上老年患者神经系统反应的发生率高达13.51%,而且存在多种反应同时出现的问题,对患者的生活安全造成非常大的影响,有跌倒、坠床、意外伤害等风险暴露。结论：护理人员通过细致全面的护理观察、护理人员培训、强化安全宣教、提供个性化的安全护理措施,最大程度的及早发现安全隐患,不但保障了老年患者住院期间的安全而且对患者出院后的安全也起到了一定的警示作用。     

Characteristics of antibiotic resistance and sequence type of Acinetobacter baumannii clinical isolates in Japan and the antibacterial activity of DS-8587

DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the antibacterial activity and mechanism of DS-8587 in 31 quinolone-resistant Acinetobacter baumannii clinical isolates. Efflux pump and qnr genes, mutations in quinolone resistance-determining regions of target enzymes, and sequence types determined by multilocus sequence typing were analyzed. Forty-two quinolone-susceptible clinical isolates were analyzed for comparison. For susceptibility testing, DS-8587 exhibited more effective antibacterial activity when compared with ciprofloxacin and levofloxacin. When combined with the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, the MIC of DS-8587 was less affected when compared with the MIC exhibited by combined ciprofloxacin and 1-(1-napthylmethyl)-piperazine. The efflux pump genes adeA/adeB/adeC and regulatory elements adeR/adeS were detected in 23 of 31 quinolone-resistant isolates. The qnrA/qnrB/qnrS genes were not detected in any A. baumannii isolates analyzed. Mutations in quinolone resistance-determining regions were observed in all 31 quinolone-resistant isolates. Multilocus sequence typing analyses revealed that 22 of 31 quinolone-resistant isolates belonged to ST-2, corresponding to international clonal lineage II. In conclusion, DS-8587 exhibits potent antibacterial activity against quinolone-resistant A. baumannii isolates that harbor mutations in quinolone resistance-determining regions. In the presence of the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, no significant changes were observed in the MIC for DS-8587. DS-8587 should be considered as a treatment option for A. baumannii including ST-2 strains that are predominant among the quinolone-resistant A. baumannii isolates found in Japan.     

A successful antimicrobial therapeutic strategy for the discitis caused by Aggregatibacter actinomycetemcomitans under unknown drug susceptibility: A case report

Aggregatibacter actinomycetemcomitans is well-known as the pathogen of gingivitis or periodontitis, and discitis or vertebral osteomyelitis cases caused by this organism have rarely been reported. Ampicillin or amoxicillin has been used in the previously reported discitis cases; however, no cases have been reported that is treated with levofloxacin. We report the first published case we chose levofloxacin to treat. We failed to perform the susceptibility testing because of the poor growth and fastidious nature of the organism, and the result of susceptibility of amoxicillin was unclear. Levofloxacin, which A. actinomycetemcomitans is usually susceptible to, can be an effective alternative oral antimicrobial agent in such cases.     

加替沙星和司帕沙星的光动力抗菌研究

目的 喹诺酮作为抗菌药物在临床上具有一定的光敏毒副作用,那么喹诺酮化合物是否可以作为光敏抗菌药物应用呢？ 基于上述目的我们研究了加替沙星 (GFLX)、司帕沙星 (SPFX) 的光动力抗菌活性。方法 本文报道了 GFLX、SPFX 在 650、450 和 365nm 及白光不同光照波长及激光能量密度与暗反应条件下对耐药菌株金黄色葡萄球菌 (MRSA)、铜绿假单胞菌 (P. aeruginosa)、大 肠埃希菌 (E. coli) 的抗菌活性。结果 GFLX、SPFX 对 MRSA、P. aeruginosa、E. coli 暗毒性最低抑菌浓度 (MIC) ≤ 2.5μg/mL; 最低杀菌浓度 (MBC) ≤ 20μg/mL。GFLX 在 450nm 光照条件下对 MRSA、P. aeruginosa、E. coli 的 MIC 分别为 0.15、0.31 和 0.07μg/ mL;MBC 分别为 0.62、1.25 和 0.15μg/mL。相应的 SPFX 在 650nm 光照条件下抗菌活性分别为 0.31、0.31 和 0.07μg/mL;MBC 分 别为 20、5 和 0.15μg/mL。进一步研究表明 GFLX、SPFX 光动力灭菌活性及细胞毒性具有光波长及能量依赖性。结论 光照可以 一定程度上增加 GFLX 和 SPFX 的抗菌活性,但提升能力有限,在此区间其光敏毒副作用有限,这类药物不会伤及细胞,因而喹 诺酮类药物在临床上不足以作为光敏抗菌药物使用,相对安全。     

Prevalence of plasmid-mediated quinolone resistance determinants in ESBL Enterobacteriaceae clinical isolates over a 1-year period in a French hospital

The prevalence of plasmid-mediated quinolone resistance (PMQR) determinants (qnrA, qnrB, qnrS, aac(6′)-Ib-cr, and qepA) was investigated in a collection of 47 extended-spectrum β-lactamase (ESBL) producing enterobacterial isolates with reduced susceptibility to fluoroquinolones, recovered at Nantes University hospital, in 2006. qnr, aac(6′)-Ib-cr, and qepA genes were screened by PCR, and positive results were subsequently confirmed by sequencing. The epidemiological relationship between positive isolates was studied by pulsed-field gel electrophoresis (PFGE). qnr-positive isolates were analyzed for antimicrobial susceptibility and presence of mutations in the quinolone resistance-determining region (QRDR) of gyrA and parC genes. ESBL genes were characterized by PCR and sequencing. Conjugation experiments were performed to determine whether the qnr-carrying plasmids were self-transferable. Two Klebsiella pneumoniae isolates (4.3%), not clonally related, harboured a qnrS1 gene, whereas no qnrA- or qnrB-positive isolate was detected. The aac(6′)-Ib-cr gene was detected in 11 Escherichia coli and one K. pneumoniae isolates. None of the 47 isolates carried the qepA gene. ESBLs associated with QnrS1 were CTX-M-14 and CTX-M-15. The CTX-M-15 producing isolate was highly resistant to fluoroquinolones and harboured three mutations in the QRDR and two PMQR determinants (qnrS1 and aac(6′)-Ib-cr). The CTX-M-14-producing isolate exhibited reduced susceptibility or resistance to fluoroquinolones without resistance to nalidixic acid. This strain harboured only a qnr gene on a single 170 kb transferable plasmid, without any mutation in the QRDR. In conclusion, our study showed that aac(6′)-Ib-cr gene had occurred in multiclonal ESBL-producing enterobacterial isolates collected at Nantes University hospital in 2006, with a higher prevalence than qnr genes.     

Relation between induction of the mar operon and cyclohexane tolerance and reduction in fluoroquinolone susceptibility in Salmonella spp.

The relationship between cyclohexane tolerance and induction of the mar operon and a decrease in susceptibility to ciprofloxacin and moxifloxacin in isolates of Salmonella spp. from food and clinical isolates of Salmonella spp. was studied. We studied the influence of the mar operon using an inductor (acetylsalicylic acid) and we also studied the cyclohexane resistance. Induction was seen to produce an increase in the minimum inhibitory concentration (MIC) of these quinolones, which suggested that there was overexpression of the AcrAB type active efflux systems due to induction of the mar operon. Cyclohexane susceptibility was not shown to be a very sensitive method for studying this process, as only 3% (5/176) of the clinical isolates studied were cyclohexane-resistant; most of these belonged to the Hadar serotype. This study confirmed the participation of active efflux systems in the decrease in fluoroquinolone susceptibility in Salmonella spp. Furthermore, the study has indicated that these mechanisms (i.e., active efflux systems) are present in strains that are susceptible to the fluoroquinolone compounds, so their stimulation may be one of the mechanisms involved in the reduction in fluoroquinolone susceptibility. This suggests that the exposure of Salmonella spp. to antibiotics should be limited in order to prevent these active efflux systems from being activated. Consequently, the use of fluoroquinolones, both in the treatment of humans and in veterinary practice, should be controlled and rationalized in an attempt to curb the increase in the number of strains that are resistant to these compounds.     

金黄色葡萄球菌MgrA蛋白对喹诺酮类药物耐药性影响研究

目的了解金黄色葡萄球菌MgrA蛋白对喹诺酮耐药性的影响,为临床治疗金黄色葡萄球菌感染提供实验室依据。方法以本实验室已经构建的MgrA高表达质粒为研究材料,采用琼脂平板倍比稀释法检测金黄色葡萄球菌耐药株和敏感株、转MgrA组的MIC、凝固酶活性、荧光定量PCR、半定量PCR。结果转MgrA的金黄色葡萄球菌对喹诺酮类药物的耐药性增高,其NorA的表达与MgrA的表达具有线性关系,即MgrA高表达组的NorA表达也增高。结论MgrA蛋白mRNA表达水平与金黄色葡萄球菌氟喹诺酮耐药性相关,其介导耐药的原因可能与NorA基因mRNA表达水平增高有关。     

Bloodstream infections caused by qnr-positive Enterobacteriaceae: clinical and microbiologic characteristics and outcomes

The clinical significance of plasmid-mediated quinolone resistance determinant qnr has not been well characterized. We investigated the clinical and microbiologic characteristics and outcomes of bloodstream infections (BSIs) caused by qnr-positive Enterobacteriaceae. We prospectively collected 351 nonduplicate consecutive blood isolates of Enterobacter spp. and Klebsiella pneumoniae. qnr genes were detected by polymerase chain reaction and confirmed by sequencing. The medical records of patients were retrospectively reviewed. qnr genes were detected in a total of 26 isolates. A comparison of these 26 qnr-positive and 297 qnr-negative Enterobacteriaceae BSIs in adult patients showed that the population characteristics and clinical features of BSIs were similar between the qnr-positive and qnr-negative groups. However, patients with hematologic malignancies, solid organ transplant recipients, and BSIs caused by strains with multiple antimicrobial resistance, including extended-spectrum β-lactamase (ESBL) resistance, were more common in the qnr-positive group. Previous antibiotic therapy and prior use of trimethoprim–sulfamethoxazole or aminoglycosides were significantly associated with BSIs caused by qnr-positive strains. In the multivariate analysis, prior use of trimethoprim–sulfamethoxazole (odds ratio [OR], 5.55; 95% confidence interval [CI], 1.47–20.94) and having an underlying disease other than solid tumor (OR, 4.06; 95% CI, 15.07) were independently associated with qnr-positive Enterobacteriaceae BSIs. There was no significant difference in 30-day mortality rates between the qnr-positive and qnr-negative groups (15.4% [4/26] versus 13.8% [41/297], P = 0.77). Although qnr determinants were significantly associated with multiple antimicrobial resistance including ESBL resistance, they did not affect clinical outcomes of BSIs.     

Simultaneous determination of (fluoro)quinolones antibacterials residues in bovine milk using ultra performance liquid chromatography–tandem mass spectrometry

The ultra performance liquid chromatography–tandem mass spectrometry (UPLC) method had been developed for 22 (fluoro)quinolone(QNs) antibacterials in milk with multiple reaction monitoring (MRM) as acquisition mode. The analytes were extracted from the sample using Mcllvaine buffer by ultrasonic bath, and purified by solid-phase extraction (SPE) cartridge. The residue were dried under nitrogen and dissolved in mobile phase before UPLC–MS/MS final analysis. The calibration curve of six concentrations for 22 QNs showed good linearity and the good correlation coefficients (r ≥ 0.9851) were achieved. The limit range of quantification was 0.008–0.339 μg/kg. The recovery range was 63.1–94.6% except flumequine, nalidixic acid and nadifloxacin. The method was precise: the relative standard deviations of the method for milk were not more than 13.12%. The accuracies and sensitivity of the method were good for simultaneous determination of 22 QNs.     

Safety profile of Tysabri: international risk management plan

An 83-year-old man was admitted for right lower lobe pneumonia which did not improve after a 5-day outpatient treatment with amoxicillin/clavulinate and clarithromycin. An empiric treatment with levofloxacin was started with a significant improvement after 24 h of this treatment. On the third day of hospitalization, delirium developed, while the patient was afebrile and with normal blood oxygenation. Treatment with levofloxacin was stopped, and a complete resolution of the patient’s delirium was observed 2 days later. To the best of our knowledge, this is the third case of levofloxacin-induced delirium described in the medical literature.