Institut Pasteur, Unité de Génétique des Biofilms, Département de Microbiologie, Paris, France.
Antimicrob Agents Chemother. 2012 Dec;56(12):6310-8. doi: 10.1128/AAC.01606-12. Epub 2012 Oct 1.
Biofilms that develop on indwelling devices are a major concern in clinical settings. While removal of colonized devices remains the most frequent strategy for avoiding device-related complications, antibiotic lock therapy constitutes an adjunct therapy for catheter-related infection. However, currently used antibiotic lock solutions are not fully effective against biofilms, thus warranting a search for new antibiotic locks. Metal-binding chelators have emerged as potential adjuvants due to their dual anticoagulant/antibiofilm activities, but studies investigating their efficiency were mainly in vitro or else focused on their effects in prevention of infection. To assess the ability of such chelators to eradicate mature biofilms, we used an in vivo model of a totally implantable venous access port inserted in rats and colonized by either Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, or Pseudomonas aeruginosa. We demonstrate that use of tetrasodium EDTA (30 mg/ml) as a supplement to the gentamicin (5 mg/ml) antibiotic lock solution associated with systemic antibiotics completely eradicated Gram-positive and Gram-negative bacterial biofilms developed in totally implantable venous access ports. Gentamicin-EDTA lock was able to eliminate biofilms with a single instillation, thus reducing length of treatment. Moreover, we show that this combination was effective for immunosuppressed rats. Lastly, we demonstrate that a gentamicin-EDTA lock is able to eradicate the biofilm formed by a gentamicin-resistant strain of methicillin-resistant S. aureus. This in vivo study demonstrates the potential of EDTA as an efficient antibiotic adjuvant to eradicate catheter-associated biofilms of major bacterial pathogens and thus provides a promising new lock solution.
生物膜在留置装置上的形成是临床环境中的一个主要关注点。虽然去除定植的装置仍然是避免与器械相关的并发症的最常见策略，但抗生素锁定治疗是导管相关感染的辅助治疗。然而，目前使用的抗生素锁定解决方案对于生物膜并不是完全有效的，因此需要寻找新的抗生素锁定解决方案。金属结合螯合剂由于其双重抗凝/抗生物膜活性而成为潜在的佐剂，但研究其效率的研究主要是在体外进行的，或者专注于它们在预防感染方面的作用。为了评估这些螯合剂根除成熟生物膜的能力，我们使用了一种在大鼠体内植入的完全可植入静脉接入端口模型，该模型被金黄色葡萄球菌、表皮葡萄球菌、大肠杆菌或铜绿假单胞菌定植。我们证明，使用四钠 EDTA（30mg/ml）作为抗生素锁定溶液（含 5mg/ml 庆大霉素）的补充，与全身抗生素联合使用，可以完全根除完全可植入静脉接入端口中形成的革兰氏阳性和革兰氏阴性细菌生物膜。庆大霉素-EDTA 锁定可以通过单次灌注消除生物膜，从而缩短治疗时间。此外，我们表明这种组合对免疫抑制大鼠有效。最后，我们证明庆大霉素-EDTA 锁定能够根除耐万古霉素金黄色葡萄球菌的耐庆大霉素菌株形成的生物膜。这项体内研究证明了 EDTA 作为一种有效的抗生素佐剂的潜力，可以根除主要细菌病原体的导管相关生物膜，从而提供了一种有前途的新锁定解决方案。
