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耐甲氧西林金黄色葡萄球菌去定植失败——生物膜是其中的关键环节吗?

MRSA decolonization failure-are biofilms the missing link?

作者信息

Günther Frank, Blessing Brigitte, Tacconelli Evelina, Mutters Nico T

机构信息

Department of Infectious Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69126 Heidelberg, Germany.

Division of Infectious Diseases - Department of Internal Medicine I, Tübingen University Hospital, Tübingen, Germany.

出版信息

Antimicrob Resist Infect Control. 2017 Mar 28;6:32. doi: 10.1186/s13756-017-0192-1. eCollection 2017.

Abstract

BACKGROUND

Device-associated infections due to biofilm-producing methicillin-resistant (MRSA) have been recently associated with the failure of antibiotic treatment and decolonization measures. The goal of our study was to evaluate the extent to which the formation of biofilms influenced the efficacy of topical decolonization agents or disinfectants such as mupirocin (MUP), octenidine (OCT), chlorhexidine (CHG), polyhexanide (POL), and chloroxylenol (CLO).

METHODS

Bacterial killing in biofilms by the disinfectants and MUP was determined as the reduction [%] in metabolic activity determined by a biofilm viability assay that uses kinetic analysis of metabolic activity. The test substances were diluted in water with standardized hardness (WSH) at 25 °C at the standard concentration as well as half the standard concentration to demonstrate the dilution effects in a practical setting. The tested concentrations were: CHG 1%, 2%; OCT 0.1%, 0.05%; PH 0.04%, 0.02%; and CLO 0.12%, 0.24%. A test organism suspension, 1 mL containing ~1 × 10 bacterial cells/mL, and 1 mL of sterile WSH were mixed and incubated for six different exposure times (15 s, 1, 3, 5, 10 and 20 min) after the test substance was added. Additionally, the bactericidal effects of all substances were tested on planktonic bacteria and measured as the log10 reduction.

RESULTS

The disinfectants OCT and CHG showed good efficacy in inhibiting MRSA in biofilms with reduction rates of 94 ± 1% and 91 ± 1%, respectively. POL, on the other hand, had a maximum efficacy of only 81 ± 7%. Compared to the tested disinfectants, MUP showed a significantly lower efficacy with <20% inhibition ( < .05). Bactericidal effects were the greatest for CHG (log10 reduction of 9.0), followed by OCT (7.7), POL (5.1), and CLO (6.8). MUP, however, showed a very low bactericidal effect of only 2.1. Even when the exposure time was increased to 24 h, 2% MUP did not show sufficient bactericidal effect.

CONCLUSIONS

Our data provide evidence that OCT and CHG are effective components for disinfection of MRSA-biofilms. On the other hand, exposure to MUP at the standard concentrations in topical preparations did not effectively inhibit MRSA-biofilms and also did not show adequate bactericidal effects. Combining an MUP-based decolonization regimen with a disinfectant such as OCT or CHG could decrease decolonization failure.

摘要

背景

由产生物膜的耐甲氧西林金黄色葡萄球菌(MRSA)引起的与设备相关的感染,近来与抗生素治疗及去定植措施的失败有关。我们研究的目的是评估生物膜形成在多大程度上影响局部去定植剂或消毒剂(如莫匹罗星(MUP)、奥替尼啶(OCT)、氯己定(CHG)、聚己缩胍(POL)和对氯间二甲苯酚(CLO))的疗效。

方法

通过生物膜活力测定法(利用代谢活性的动力学分析)测定消毒剂和MUP对生物膜内细菌的杀灭情况,以代谢活性降低的百分比表示。将测试物质在25℃下用标准硬度的水(WSH)稀释至标准浓度以及标准浓度的一半,以展示实际情况下的稀释效果。测试浓度分别为:CHG 1%、2%;OCT 0.1%、0.05%;PH 0.04%、0.02%;CLO 0.12%、0.24%。将1mL含有约1×10⁸个细菌细胞/mL的测试生物体悬浮液与1mL无菌WSH混合,加入测试物质后,在六个不同的暴露时间(15秒、1、3、5、10和20分钟)下进行孵育。此外,测试了所有物质对浮游细菌的杀菌效果,并以log₁₀降低值来衡量。

结果

消毒剂OCT和CHG在抑制生物膜内MRSA方面显示出良好的效果,降低率分别为94±1%和91±1%。另一方面,POL的最大疗效仅为81±7%。与测试的消毒剂相比,MUP的疗效显著较低,抑制率<20%(P<0.05)。杀菌效果以CHG最大(log₁₀降低值为9.0),其次是OCT(7.7)、POL(5.1)和CLO(6.8)。然而,MUP的杀菌效果非常低,仅为2.1。即使将暴露时间延长至24小时,2%的MUP也未显示出足够的杀菌效果。

结论

我们的数据表明,OCT和CHG是用于消毒MRSA生物膜的有效成分。另一方面,局部制剂中标准浓度的MUP暴露并不能有效抑制MRSA生物膜,也未显示出足够的杀菌效果。将基于MUP的去定植方案与OCT或CHG等消毒剂联合使用,可能会降低去定植失败的发生率。

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