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糖尿病足感染中金黄色葡萄球菌生物膜的药敏模式

Susceptibility patterns of Staphylococcus aureus biofilms in diabetic foot infections.

作者信息

Mottola Carla, Matias Carina S, Mendes João J, Melo-Cristino José, Tavares Luís, Cavaco-Silva Patrícia, Oliveira Manuela

机构信息

Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA), Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, 1300-477, Lisbon, Portugal.

Departamento de Medicina Interna, Hospital de Santa Marta/Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal.

出版信息

BMC Microbiol. 2016 Jun 23;16(1):119. doi: 10.1186/s12866-016-0737-0.

Abstract

BACKGROUND

Foot infections are a major cause of morbidity in people with diabetes and the most common cause of diabetes-related hospitalization and lower extremity amputation. Staphylococcus aureus is by far the most frequent species isolated from these infections. In particular, methicillin-resistant S. aureus (MRSA) has emerged as a major clinical and epidemiological problem in hospitals. MRSA strains have the ability to be resistant to most β-lactam antibiotics, but also to a wide range of other antimicrobials, making infections difficult to manage and very costly to treat. To date, there are two fifth-generation cephalosporins generally efficacious against MRSA, ceftaroline and ceftobripole, sharing a similar spectrum. Biofilm formation is one of the most important virulence traits of S. aureus. Biofilm growth plays an important role during infection by providing defence against several antagonistic mechanisms. In this study, we analysed the antimicrobial susceptibility patterns of biofilm-producing S. aureus strains isolated from diabetic foot infections. The antibiotic minimum inhibitory concentration (MIC) was determined for ten antimicrobial compounds, along with the minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC), followed by PCR identification of genetic determinants of biofilm production and antimicrobial resistance.

RESULTS

Results demonstrate that very high concentrations of the most used antibiotics in treating diabetic foot infections (DFI) are required to inhibit S. aureus biofilms in vitro, which may explain why monotherapy with these agents frequently fails to eradicate biofilm infections. In fact, biofilms were resistant to antibiotics at concentrations 10-1000 times greater than the ones required to kill free-living or planktonic cells. The only antibiotics able to inhibit biofilm eradication on 50 % of isolates were ceftaroline and gentamicin.

CONCLUSIONS

The results suggest that the antibiotic susceptibility patterns cannot be applied to biofilm established infections. Selection of antimicrobial therapy is a critical step in DFI and should aim at overcoming biofilm disease in order to optimize the outcomes of this complex pathology.

摘要

背景

足部感染是糖尿病患者发病的主要原因,也是糖尿病相关住院和下肢截肢的最常见原因。金黄色葡萄球菌是目前从这些感染中分离出的最常见菌种。特别是耐甲氧西林金黄色葡萄球菌(MRSA)已成为医院中的一个主要临床和流行病学问题。MRSA菌株不仅对大多数β-内酰胺类抗生素具有耐药性,而且对多种其他抗菌药物也有耐药性,这使得感染难以控制且治疗成本非常高。迄今为止,有两种对MRSA普遍有效的第五代头孢菌素,头孢洛林和头孢托罗,它们具有相似的抗菌谱。生物膜形成是金黄色葡萄球菌最重要的毒力特征之一。生物膜生长在感染过程中通过提供对多种拮抗机制的防御发挥重要作用。在本研究中,我们分析了从糖尿病足感染中分离出的产生物膜金黄色葡萄球菌菌株的抗菌药敏模式。测定了十种抗菌化合物的抗生素最低抑菌浓度(MIC),以及最低生物膜抑菌浓度(MBIC)和最低生物膜清除浓度(MBEC),随后通过PCR鉴定生物膜产生和抗菌耐药性的遗传决定因素。

结果

结果表明,在体外抑制金黄色葡萄球菌生物膜需要非常高浓度的治疗糖尿病足感染(DFI)最常用的抗生素,这可能解释了为什么用这些药物进行单一疗法常常无法根除生物膜感染。事实上,生物膜对抗生素的耐药浓度比杀死游离或浮游细胞所需浓度高10 - 1000倍。唯一能够在50%的分离株上抑制生物膜清除的抗生素是头孢洛林和庆大霉素。

结论

结果表明抗生素药敏模式不适用于已形成生物膜的感染。抗菌治疗的选择是DFI中的关键步骤,应旨在克服生物膜疾病,以优化这种复杂病理的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2227/4918071/58508f1cec14/12866_2016_737_Fig1_HTML.jpg

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