金黄色葡萄球菌异质性耐药机制及实验室检测技术

 异质性耐药是一种特殊的细菌耐药类型，常表现为同一克隆来源的不同细菌亚群对某种抗菌药物表现出不一致的耐药特征，大多数亚群对某种抗菌药物敏感，而少部分亚群对其耐药或高度耐药。异质性耐药分离株常会导致特定抗菌药物抗感染治疗失败。针对异质性耐药菌较为深入的研究主要集中于革兰阴性菌，革兰阳性球菌的相关报道较少。近年有研究报道万古霉素、利奈唑胺、苯唑西林等多种类型抗菌药物异质性耐药金黄色葡萄球菌分离株出现，但其实际临床意义尚待进一步评估。此文对金黄色葡萄球菌异质性耐药机制和检测技术最新进展进行综述，为细菌异质性耐药机制研究和新型检测技术研发提供新的思路。     

反复粪便培养金黄色葡萄球菌阳性老年患者口服万古霉素效果评价

目的 通过探讨肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者口服万古霉素的效果，为此类患者提供一种潜在的治疗方案。方法 前瞻性分析吉林大学第一医院干部病房2015 年9 月～2018 年12 月收治的186 例肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者。根据是否口服万古霉素治疗分为万古组和对照组。收集两组患者的一般临床资料，比较两组患者试验前后万古霉素血药浓度、血常规、降钙素原（PCT）、C 反应蛋白（CRP），试验期间粪便培养结果、体温、抗生素使用情况。结果 试验治疗期间，万古组便培养转阴率高于对照组，差异有统计学意义（P＜0.05）；万古组发热率（29.75%）低于对照组的34.77%，差异有高度统计学意义（P＜0.01）；万古组抗生素使用率（4.49%）低于对照组的19.23%，差异有高度统计学意义（P＜0.01）。试验前两组白细胞、中性粒细胞计数、中性粒细胞比例、PCT、CRP 比较，差异无统计学意义（P＞0.05）；试验后万古组白细胞、中性粒细胞计数、中性粒细胞比例、CRP 低于对照组，差异有高度统计学意义（P＜0.01）。试验后万古组白细胞、中性粒细胞计数、中性粒细胞比例、CRP 低于试验前，差异有高度统计学意义（P＜0.01）。结论 口服万古霉素可能提高肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者粪便转阴率，减少发热及抗生素的应用，降低炎症细胞水平，可能是此类患者一种潜在的临床治疗方案。     

A new aspect of in vitro antimicrobial leukocyte- and platelet-rich plasma activity based on flow cytometry assessment

The current literature suggests that the antibacterial effect of leukocyte- and platelet-rich plasma (L-PRP) is directly related to platelet and leukocyte concentrations. The aim of this study was twofold: first, to evaluate the antimicrobial effect of L-PRP against selected bacterial strains in vitro, and second, to correlate this effect with leukocyte and platelet content in the final concentration. Blood was collected from 20 healthy males, and L-PRP, acellular plasma (AP), and autologous thrombin were consecutively prepared. Flow cytometry analysis of the blood, L-PRP, and AP was performed. The L-PRP gel, liquid L-PRP, and thrombin samples were tested in vitro for their antibacterial properties against seven selected bacterial strains using the Kirby–Bauer disk-diffusion method. There was notable antimicrobial activity against selected bacterial strains. No statistically significant correlations between antimicrobial activities and the platelet concentration in L-PRP were observed. Statistically significant positive correlations between selected leukocyte subtypes and antimicrobial activity were noted. A negative correlation was found between elevated monocyte count and antimicrobial activity of L-PRP against one bacterial strain studied. L-PRP possesses antimicrobial activity and can be potentially useful in the fight against certain postoperative infections. The bactericidal effect of L-PRP is caused by leukocytes, and there exists a relationship among selected leukocyte subtypes and L-PRP antimicrobial activity.     

Kampo medicines suppress the production of exfoliative toxins causing impetigo in Staphylococcus aureus

An alternative approach, such as antivirulence therapy that modulates the production of bacterial toxins or virulence factors, is necessary to tackle the emergence of antimicrobial-resistant strains. Here, we investigated the potential antivirulence effects of seven Kampo medicines (Jumihaidokuto, Eppikajutsuto, Jizusoippo, Shomakakkonto, Sammotsuogonto, Hainosankyuto and Inchinkoto) against exfoliative toxin (ET)-positive Staphylococcus aureus, which is the major causative agent of impetigo. A growth inhibition assay showed that all of the selected Kampo medicines inhibited the growth of S. aureus at 1/5 (2.5 mg/mL) or less of the conventionally used concentrations. Among these, Jizusoippo and Inchinkoto (0.25–1 mg/mL) suppressed the production of ET without inhibiting the bacterial growth. Furthermore, Jizusoippo and Inchinkoto significantly suppressed the expression of ET genes in a concentration-dependent manner. Our findings strongly suggest, for the first time, that Kampo medicines, especially Jizusoippo and Inchinkoto, have the potential to serve as antivirulence agents against skin infections caused by S. aureus by suppressing the production of ET.     

Corynebacterium species as one of the major causative pathogens of bacterial pneumonia

Recent advances using molecular methods, matrix-assisted laser desorption ionization time of flightmass spectrometry, and next-generation sequencers enable rapid and precise detection of bacterial species in the clinical samples, revealing bacterial diversities in the human body. Corynebacterium species are Gram-positive bacilli, which can cause pneumonia and have been reported as causative pathogens of lower respiratory tract infections since the 1970's. However, Corynebacterium spp. may be recognized and sorted as part of normal respiratory flora on Gram staining and culture, resulting in clinical under-recognition as pathogenic bacteria.The results of the clone library method using bacterial 16S ribosomal RNA gene sequence analysis in Japanese patients with hospital-acquired pneumonia revealed that bronchoalveolar lavage fluid obtained from the lung lesions contained 11.8% Corynebacterium spp., which was the second most predominant bacterial phylotype. Additionally, among patients in whom Corynebacterium spp. were detected, C. simulans was most commonly detected followed by C. striatum. In addition, almost half of the patients in whom C. simulans was detected was monophylotypic infection and/or co-detection of C. simulansand C. striatum. Further clinical information is expected on corynebacteria as pathogens of lower respiratory tract infection.