Increase in the prevalence of Panton–Valentine leukocidin and clonal shift in community-onset methicillin-resistant Staphylococcus aureus causing skin and soft-tissue infections in the Rhine-Neckar Region,Germany, 2012–2016

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge for patient care. Community-associated (CA)-MRSA often have a fitness and virulence advantage compared with their nosocomial counterparts. Increased mobility, travel activities and migration accelerate the intercontinental spread of virulent CA-MRSA strains. Outpatient clinics are the most important route of entry for CA-MRSA into hospitals. However, systematic data on CA-MRSA in Germany are limited. In this study, community-onset (CO)-MRSA skin and soft-tissue infection (SSTI) isolates in the Rhine-Neckar Region from 2012–2016 were characterised to gain an insight into their molecular epidemiology and to monitor potential introduction of virulent and dominant MRSA strains into our hospital. A total of 2475 patients with S. aureus SSTI were identified in the outpatient departments of our hospital, of which 94 (3.8%) were MRSA. In addition, 40.4% of the CO-MRSA harboured the virulence factor Panton–Valentine leukocidin (PVL). ST8-t008-MRSA-IVa/c (23.7%; 9/39) and ST80-t044-MRSA-IVc (15.8%; 6/38) were the predominant PVL-positive MRSA. Molecular typing and epidemiological data revealed that 42.6% (40/94) of strains could be traced back to a local origin and 44.7% (42/94) were endemic outside of Europe. Resistance to quinolones, clindamycin and macrolides was common, whilst resistance to trimethoprim/sulfamethoxazole, tetracycline, mupirocin, chlorhexidine and fusidic acid was low. No resistance to rifampicin, fosfomycin or linezolid was observed. This study provides insight into the clonal composition of CO-MRSA in the Rhine-Neckar Region. The increase of PVL-positive MRSA and the introduction of imported strains may affect the local MRSA landscape in the near future and should be monitored closely.     

Silver oxide‐containing hydroxyapatite coating has in vivo antibacterial activity in the rat tibia

Bacterial infection is a serious postoperative complication of joint replacement. To prevent infections related to implantation, we have developed a novel antibacterial coating with Ag‐containing hydroxyapatite (Ag‐HA). In the present study, we examined the antibacterial activity of Ag‐HA implant coatings in the medullary cavity of rat tibiae. Forty 10‐week‐old rats received implantation of Ag‐HA‐ or HA‐coated titanium rods, then were inoculated with ～1.0 × 10² colony‐forming units of methicillin‐resistant Staphylococcus aureus. Bacterial counts were calculated for rats euthanized at 24, 48, and 72 h postoperatively. Serum levels of Ag (in the Ag‐HA group only) were calculated for rats euthanized at 24, 48, 72 h and 4 weeks. Radiographic evaluations of bone infection were also performed at 4 weeks. Tibiae from both groups showing infection were evaluated histologically. Significant differences in bacterial counts were seen at 24, 48, and 72 h. Mean concentrations of Ag in serum peaked about 48 h after implantation, then gradually decreased. Mean radiographic scores for infection were significantly lower with Ag‐HA implants than with HA implants. Histological examination showed better results for abscesses, bone resorption, and destruction of cortical bone around Ag‐HA‐coated implants. These results indicate that Ag‐HA coatings may help prevent surgical‐site infections associated with joint replacement. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1195–1200, 2013     

qPCR快速检测金黄色葡萄球菌及MRSA方法的建立及评价

目的建立q PCR法快速检测金黄色葡萄球菌及其mec A基因,以期快速精准诊断金黄色葡萄球菌感染及初步判断耐药情况。方法从NCBI数据库下载金黄色葡萄球菌nuc、atl、ica B、fnb A、hla、srap基因序列用于鉴定标志筛选,mec A基因序列用于MRSA标志筛选;经DNA MAN比对后,选择各基因保守区分别设计1~2套引物、探针,建立单重及双重q PCR,用临床分离株及标准菌株筛选出检测性能最好的基因片段作为检测标志物,建立金黄色葡萄球菌鉴定和耐药双重q PCR检测方法,并进行性能评价。结果经筛选,金黄色葡萄球菌atl基因(CP009361.1:1010217~1010341)、mec A基因(KF058908.1:1715~1843)两片段检测性能最优,将其作为标志物建立双重q PCR法。该方法的检测下限均低至4 copies/反应;扩增线性范围均达2.0×102~8copies/m L。335份金黄色葡萄球菌(含94份MRSA)培养阳性的患者样本中,q PCR法分别检出SA 335份,MRSA 94份;95份金黄色葡萄球菌培养阴性的患者样本中,q PCR法分别检出SA 17份,MRSA 4份,经PCR产物测序,与标准菌株同源性均≥90%。双重q PCR法从样品处理到报告结果≤2.0 h。结论 q PCR法方法简便、快速、灵敏度高、特异性好,可望提高金黄色葡萄球菌感染的诊断能力并实现快速检测,为尽早精准治疗赢得时间。     

Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n?=?2000), Gram-positives (n?=?403) and yeasts (n?=?132) had inhibition zone diameters for nitroxoline ≥18?mm. Except for Pseudomonas aeruginosa, nitroxoline MIC₉₀ values were ≤16?mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC₉₀ values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time–kill curves in Mueller–Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.     

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.     

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

相似文献