Purification and characterisation of a novel antistaphylococcal peptide (ASP-1) from Bacillus sp. URID 12.1

A strong antistaphylococcal peptide (ASP-1) from Bacillus subtilis URID 12.1 strain that is active against cefoxitin- and methicillin-resistant Staphylococcus aureus clinical isolates was purified to homogeneity by solvent extraction, silica gel-based adsorption chromatography and reversed-phase high-performance liquid chromatography. The peptide sequence of ASP-1 as determined by MALDI-TOF/MS and ESI-FTICR-MS was acetylated Phe-Thr-Ala-Val-Dhb-Phe-Ile/Leu. The peptide was further analysed by alkaline hydrolysis, ESI-Q-TOF-MS and an ion mobility assay, which detected the presence of a lactone ring in the intact peptide and a cyclic nature, subsequently revealing the linearised peptide sequence as acPhe-Leu-Phe-Thr-Val-Ala-Dhb. Based on the molecular mass (804.5 Da), peptide sequence and amino acid composition, ASP-1 was identified as a lactone ring-containing peptide similar to TL-119, a poorly studied cyclic depsipeptide. Circular dichroism spectroscopy revealed its predominantly random structure in aqueous solution and its β-sheet conformation in methanol. Minimum inhibitory concentrations (MICs) of the purified peptide against S. aureus and methicillin-resistant S. aureus (MRSA) ranged from 2?µg/mL to 64?µg/mL. At sub-MICs and 1× MIC, ASP-1 showed a strong antibiofilm characteristic. ASP-1 at a concentration of 128?µg/mL did not show haemolytic activity, and no cytotoxicity was observed against hepatic carcinoma and breast carcinoma cell lines at the same concentration. Peptide ASP-1 with anti-MRSA and antibiofilm abilities and non-haemolytic and non-cytotoxic properties has not been reported previously. These findings suggest that it may serve as a lead molecule for developing alternative topical antibacterial agents.     

2015-2017年黄石市妇幼保健院住院患者感染MRSA的用药调查

目的 了解黄石市妇幼保健院住院患者感染耐甲氧西林金黄色葡萄球菌（MRSA）的用药情况。方法 选取2015-2017年该院院内感染MRSA的住院病历410份,对标本来源、抗菌药名称、用法用量、疗程、联合用药及特殊级抗菌药物临床应用管理等进行调查,计算抗菌药物用药频度（DDDs）和药物利用度指数（DUI）,并对不适宜用药进行总结。结果 410株MRSA标本主要来自于痰液（51.46%）、脓性分泌物（22.44%）和血液（12.44%）。410份病历中,共涉及6种抗菌药,其中替考拉宁使用最多（32.81%）,其次为万古霉素（25.79%）和利奈唑胺（23.08%）;替考拉宁的DDDs最大（1 512.35）,其次为利奈唑胺（922.83）和万古霉素（907.20）,所有药物的DUI ≤ 1.0;用药不适宜病历57份（13.90%）,主要为用法用量不适宜（25份,43.86%）和溶媒不适宜（16份,28.07%）;所有特殊级抗菌药物均未越级使用,但只有38份（9.27%）经专家会诊后使用。结论 万古霉素、替考拉宁和利奈唑胺是该院治疗MRSA感染的主要药物,且临床使用较好,不存在滥用倾向,但也有必要进一步规范合理用药,延缓细菌耐药。     

Dosing strategies to optimize currently available anti-MRSA treatment options (Part 2: PO options)

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen in both outpatient and inpatient settings. Research to optimize the dosing of these agents is needed to slow the development of antimicrobial resistance and to decrease the likelihood of clinical failure.

Areas covered: This review summarizes the available data for orally administered antimicrobials routinely used as monotherapy for MRSA infections. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 – Present) search was performed to identify relevant literature for this review.

Expert commentary: There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to guide dosing decisions for older MRSA agents compared with the oxazolidenones.

Five-year view: Additional retrospective data will become available for the older MRSA agents in severe MRSA infections.     

Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin,linezolid or vancomycin,and strains with defined SCCmec types

Ceftobiprole is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative pathogens including Pseudomonas aeruginosa. The aim of this study was to evaluate the activity of ceftobiprole against MRSA isolates with decreased susceptibility to daptomycin, linezolid or vancomycin as well as isolates from staphylococcal chromosome cassette mec (SCCmec) types I, II, III and IV. Overall, ceftobiprole demonstrated high potency against the 216 isolates tested, with MIC₅₀ and MIC₉₀ values (minimum inhibitory concentrations required to inhibit 50% and 90% of the isolates, respectively) of 1 mg/L and 2 mg/L (97.2% susceptible). The MIC₉₀ for ceftobiprole was 2 mg/L against the linezolid-non-susceptible, daptomycin-non-susceptible and vancomycin-intermediate (VISA and hVISA) subsets and was 1 mg/L against the vancomycin-resistant (VRSA) strains. The MIC_50/90 values for ceftobiprole were 2/4, 1/2, 2/2 and 1/1 mg/L against SCCmec types I, II, III and IV, respectively. SCCmec type I strains had the highest MICs, with six strains exhibiting a ceftobiprole MIC of 4 mg/L and 15 strains at 2 mg/L. Ceftobiprole demonstrated potent activity against MRSA, including subsets of isolates with reduced susceptibility to daptomycin, linezolid and vancomycin. The activity of ceftobiprole against these resistant phenotypes indicates that it may have clinical utility in the treatment of infections caused by multidrug-resistant S. aureus and across strains from prevalent SCCmec types.     

1例MRSA全身严重感染病例抗菌治疗的临床分析

1例颅脑外伤后MRSA（耐甲氧西林金黄色葡萄球菌）所致吸入性肺炎、胸膜炎、败血症合并血小板减少患者抢救中,临床药师发挥专业特长,针对患者的病情,根据患者的感染程度、病理生理状况,结合药物的药动药效学特点进行分析,适时调整抗感染治疗方案,取得了满意的疗效。临床药师在具备良好的临床药学专业知识和正确的临床思维后,可以优化药物治疗方案,为临床解决实际问题,成为治疗团队中的一员,发挥提供临床药学服务的作用。     

Triazole-Linked Glycolipids Enhance the Susceptibility of MRSA to β-Lactam Antibiotics

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Staphylococcus aureus: A pathogen with still unresolved issues

Staphylococcus aureus is a major human pathogen, and considerable research efforts have been put forward to improve our understanding of its complex pathogenesis. In spite of these efforts, the burden of staphylococcal infections is still on the rise. This review focuses on a selected set of crucial unresolved questions regarding this pathogen, namely: (i) the nature of the driving forces behind the rise and decline of methicillin-resistant S. aureus (MRSA) clones; (ii) the mechanisms by which a commensal becomes a pathogen; (iii) the molecular underpinnings of toxin overexpression in hypervirulent MRSA clones such as USA300; and (iv) the repeated failures of anti-S. aureus vaccine approaches.     

感染创面相关环境标本分离葡萄球菌的同源性分析

目的对某医疗机构葡萄球菌感染情况进行持续监测,对创面感染患者相关医源性环境检出的葡萄球菌进行分子溯源分析。方法采用实时荧光聚合酶链反应（PCR）和分类培养鉴定相结合的方法,对该医疗机构5例创面感染患者相关的医源性环境进行采样检测,并进行金黄色葡萄球菌多位点序列分析和MecA基因的分型分析。结果采集医源性环境标本71份,葡萄球菌阳性26份（36.62%）,其中23份检出甲氧西林耐药（MecA+）株（88.46%,23/26）。金黄色葡萄球菌甲氧西林耐药株占77.78%（7/9）,凝固酶阴性葡萄球菌甲氧西林耐药株占95.00%（19/20）。多位点序列分析结果显示,分离的金黄色葡萄球菌以ST239为主（6株）;SCCMec分析,金黄色葡萄球菌以Ⅲ型为主,凝固酶阴性葡萄球菌以Ⅲ、Ⅳ型较多。结论医源性感染中葡萄球菌污染较多,且多为耐药株,应加强对耐药性葡萄球菌的持续监测,关注其变异对医疗机构医院感染的风险。     

整形外科患者创面感染MRSA的感染率及对应治疗观察

目的:探讨整形外科创面感染的特点及复方新诺明对创面耐甲氧西林金黄色葡萄球菌感染的治疗作用。方法:2013年1月~12月,共收治70例慢性创面患者,其中12例MRSA感染,创面大小1.5cm×1.5cm~20cm×15cm,通过每日复方新诺明悬浮液进行治疗,观察临床疗效、细菌清除情况及不良反应。结果:治疗创面1周后MRSA转阴率83.3%,治疗2周后MRSA转阴率91.67%,未出现明显的不良反应。结论:整形外科慢性局部创面MRSA感染不能忽视,复方新诺明可作为治疗局部创面MRSA感染的首选局部用药。