Synergy between induction heating, antibiotics, and N-acetylcysteine eradicates Staphylococcus aureus from biofilm

Synergy between induction heating, antibiotics, and N-acetylcysteine eradicates Staphylococcus aureus from biofilm
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DOI:
10.1080/02656736.2019.1710269
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发表时间:
2020-01-01
影响因子:
3.1
通讯作者:
Nelissen, Rob G. H. H.
Nelissen, Rob G. H. H.
中科院分区:
医学2区
文献类型:
--
作者:
Pijls, Bart G.;Sanders, Ingrid M. J. G.;Nelissen, Rob G. H. H.

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背景资料:非接触式感应加热(NCIH)是一种非侵入性治疗方式,可用于在人工关节感染的情况下对金属植入物表面上的细菌生物膜造成热损伤。本研究的目的是(1)确定NCIH对从生物膜杀死金黄色葡萄球菌的有效性和(2)确定NCIH与抗生素和N-乙酰半胱氨酸(NAC)的混合物的可能协同作用。方法:在钛合金(Ti6 Al 4V)试块上生长金黄色葡萄球菌生物膜。将这些试样加热至50 ° C、60 ° C、70 ° C、80 ° C和90 ° C持续3.5分钟,随后暴露于临床相关浓度的万古霉素、利福平和NAC的混合物中24小时。结果:在未进行感应加热的对照组中,观察到2.2 × 10(7)个菌落形成单位(CFU)/cm(2)。在50 ° C、60 ° C、70 ° C、80 ° C和90 ° C下,分别观察到0.3-log、3.9-log、4.2-log、4.3-log和6.6-log CFU/cm(2)的减少。抗生素和感应加热之间存在协同作用,导致在60摄氏度下3.5分钟后残留的小于100 CFU/cm(2),并暴露于万古霉素和利福平。在80 ℃下观察到完全根除。在60 ℃和抗生素与NAC的混合物下也观察到完全根除。结论:感应加热钛合金片可有效降低S。金黄色葡萄球菌生物膜感应加热以及抗生素和NAC的混合物具有协同效应,其导致在60 ° C和更高的临床相关浓度的万古霉素、利福平和NAC下完全根除生物膜。
Background: Non-contact induction heating (NCIH) is a noninvasive treatment modality that can be used to cause thermal damage to bacterial biofilms on a metal implant surface in the context of a prosthetic joint infection. The purpose of this study was (1) to determine the effectiveness of NCIH on killing Staphylococcus aureus from biofilm and (2) to determine the possible synergistic effect of NCIH and cocktails of antibiotics and N-acetylcysteine (NAC). Methods: Staphylococcus aureus biofilms were grown on titanium alloy (Ti6Al4V) coupons. These coupons were heated to 50 degrees C, 60 degrees C, 70 degrees C, 80 degrees C, and 90 degrees C for 3.5 min and subsequently exposed to cocktails of vancomycin, rifampicin and NAC at clinically relevant concentrations over 24 h. Results: In the control group without induction heating, 2.2*10(7) colony forming units (CFU)/cm(2) were observed. At 50 degrees C, 60 degrees C, 70 degrees C, 80 degrees C, and 90 degrees C, a reduction of 0.3-log, 3.9-log, 4.2-log, 4.3-log, and 6.6-log CFU/cm(2) were observed, respectively. There was synergy between antibiotics and induction heating that resulted in less than 100 CFU/cm(2) remaining after 3.5 min at 60 degrees C, and exposure to vancomycin and rifampicin. Total eradication was observed at 80 degrees C. Total eradication was also observed at 60 degrees C and a cocktail of antibiotics with NAC. Conclusion: Induction heating of titanium alloy coupons is effective for the reduction of bacterial load in vitro in S. aureus biofilms. Induction heating and cocktails of antibiotics and NAC have a synergistic effect that results in the total eradication of the biofilm at 60 degrees C and higher for clinically relevant concentrations of vancomycin, rifampicin and NAC.