Microbial biofilm correlates with an increased antibiotic tolerance and poor therapeutic outcome in infective endocarditis

Microbial biofilm correlates with an increased antibiotic tolerance and poor therapeutic outcome in infective endocarditis
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DOI:
10.1186/s12866-019-1596-2
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发表时间:
2019-10-21
期刊:
影响因子:
4.2
通讯作者:
Ensoli, Fabrizio
Ensoli, Fabrizio
中科院分区:
生物学3区
文献类型:
--
作者:
Di Domenico, Enea Gino;Rimoldi, Sara Giordana;Ensoli, Fabrizio

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感染性心内膜炎(IE)与高死亡率相关。使用大剂量静脉注射抗生素的长期治疗通常无法根除感染,经常导致高风险的手术干预。通过提供抗生素耐受性机制,其逃避常规抗生素敏感性分析,微生物生物膜代表了临床医生的关键诊断和治疗挑战。本研究旨在评估快速生物膜鉴定试验和生物膜生长细菌的靶向抗菌药物敏感性特征,这些细菌对抗生素治疗无反应。结果金黄色葡萄球菌最常见(50%),其次为粪肠球菌(25%)和解没食子酸链球菌(25%)。发现所有微生物分离株都能够在体外产生大的结构化生物膜。正如预期的那样,抗生素治疗,无论是基于抗生素的基础上,或经验性地选择那些被认为是一线抗生素的IE,包括头孢曲松,达托霉素,替加环素和万古霉素,是不能有效地消除生物膜生长的细菌。相反,生物膜生长细菌的抗菌药物敏感性特征表明替考拉宁、苯唑西林和夫西地酸对沙门氏菌最有效。金黄色葡萄球菌生物膜,而氨苄青霉素对金黄色葡萄球菌生物膜最有效。gallolyticus和E.粪便生物膜。结论本研究表明,从手术治疗的IE中产生生物膜的细菌显示出对抗生素的高耐受性,这是常规细菌耐药性图无法检测到的。IE中生物膜生长细菌的快速鉴定和抗菌药物耐受性分析可以为抗菌治疗和预防策略提供关键信息。
Background Infective endocarditis (IE) is associated with high rates of mortality. Prolonged treatments with high-dose intravenous antibiotics often fail to eradicate the infection, frequently leading to high-risk surgical intervention. By providing a mechanism of antibiotic tolerance, which escapes conventional antibiotic susceptibility profiling, microbial biofilm represents a key diagnostic and therapeutic challenge for clinicians. This study aims at assessing a rapid biofilm identification assay and a targeted antimicrobial susceptibility profile of biofilm-growing bacteria in patients with IE, which were unresponsive to antibiotic therapy. Results Staphylococcus aureus was the most common isolate (50%), followed by Enterococcus faecalis (25%) and Streptococcus gallolyticus (25%). All microbial isolates were found to be capable of producing large, structured biofilms in vitro. As expected, antibiotic treatment either administered on the basis of antibiogram or chosen empirically among those considered first-line antibiotics for IE, including ceftriaxone, daptomycin, tigecycline and vancomycin, was not effective at eradicating biofilm-growing bacteria. Conversely, antimicrobial susceptibility profile of biofilm-growing bacteria indicated that teicoplanin, oxacillin and fusidic acid were most effective against S. aureus biofilm, while ampicillin was the most active against S. gallolyticus and E. faecalis biofilm, respectively. Conclusions This study indicates that biofilm-producing bacteria, from surgically treated IE, display a high tolerance to antibiotics, which is undetected by conventional antibiograms. The rapid identification and antimicrobial tolerance profiling of biofilm-growing bacteria in IE can provide key information for both antimicrobial therapy and prevention strategies.