In vitro synergism and anti-biofilm activity of ampicillin, gentamicin, ceftaroline and ceftriaxone against Enterococcus faecalis
In vitro synergism and anti-biofilm activity of ampicillin, gentamicin, ceftaroline and ceftriaxone against Enterococcus faecalis
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DOI：
10.1093/jac/dky051
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发表时间：
2018-06-01
影响因子：
5.2
通讯作者：
Pletz, Mathias W.
中科院分区：
文献类型：
--
作者：
Thieme, Lara;Klinger-Strobel, Mareike;Pletz, Mathias W.
背景：肠球菌经常引起严重的生物膜相关感染，如心内膜炎。最近临床评价认为，氨苄西林/头孢曲松联合治疗粪肠球菌心内膜炎的疗效非劣效于氨苄西林/庆大霉素标准治疗。目的：比较头孢洛林/氨苄青霉素与庆大霉素/氨苄青霉素、头孢曲松/氨苄青霉素联合应用对临床大肠杆菌的体外抗菌效果。方法：采用棋盘格法分析20株粪肠球菌的协同增效作用。粪杆菌分离株。生物膜根除和生物膜预防抗生素及其组合的活动进行了测定，通过激光共聚焦扫描显微镜定量生物膜分析（qBA）算法和cfu/mL determination.Results：在大多数菌株中，观察到的β-内酰胺类药物的组合相比，庆大霉素/氨苄青霉素具有可比的协同效应。然而，没有一种抗生素组合成功地根除了成熟的生物膜。庆大霉素显示出有希望的生物膜预防活性，但浓度高于临床耐受的浓度。β-内酰胺类抗生素对生物被膜的抑制作用呈U型剂量-反应关系。仅暴露于头孢菌素引起细胞形态学改变，这导致细胞以浓度依赖性方式伸长和重新聚集。重新聚类与高发生率的小菌落变异体（SCVs），特别是在高ceftriaxone concentration.Conclusions：这项研究表明，头孢菌素类药物或庆大霉素与氨苄青霉素的组合可能是有利的，只有当菌血症持续存在，而组合没有优势，超过单一治疗成熟的生物膜。在高浓度头孢曲松钠下SCV的选择值得进一步研究。
Background: Enterococci frequently cause severe biofilm-associated infections such as endocarditis. The combination of ampicillin/ceftriaxone has recently been clinically evaluated as non-inferior compared with the standard therapy of ampicillin/gentamicin for treatment of Enterococcus faecalis endocarditis. Ceftaroline is a novel cephalosporin with enhanced activity against Gram-positive bacteria.Objectives: To compare the in vitro effectiveness of the ceftaroline/ampicillin combination with those of gentamicin/ampicillin and ceftriaxone/ampicillin in planktonic and biofilm cultures of clinical E. faecalis isolates.Methods: Synergistic effects at the planktonic level were analysed by chequerboard assays in 20 E. faecalis isolates. Biofilm-eradicating and biofilm-preventing activities of the antibiotics and their combinations were determined by confocal laser scanning microscopy with quantification by quantitative biofilm analysis (qBA) algorithm and cfu/mL determination.Results: Comparable synergistic effects were observed for both beta-lactam combinations in most isolates, in contrast to gentamicin/ampicillin. However, none of the antibiotic combinations succeeded in eradicating mature biofilms. Gentamicin showed promising biofilm-preventing activity, but at concentrations above those clinically tolerable. The beta-lactams showed a U-shape dose-response relationship in biofilm prevention. Only exposure to cephalosporins caused alterations in cell morphology, which resulted in cell elongation and reclustering in a concentration-dependent manner. Reclustering was associated with high occurrences of small colony variants ( SCVs), especially at high ceftriaxone concentrations.Conclusions: This study suggests that combinations of cephalosporins or gentamicin with ampicillin may be advantageous only while bacteraemia persists, whereas combinations have no advantage over monotherapy regarding the treatment of mature biofilms. The selection of SCVs at high ceftriaxone concentrations is worth further study.