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基于四氢卟啉四对甲苯磺酸盐(THPTS)的光动力灭活体外耐多药关键细菌。

Tetrahydroporphyrin-tetratosylate (THPTS)-based photodynamic inactivation of critical multidrug-resistant bacteria in vitro.

机构信息

Department of Anesthesiology and Intensive Care, University of Leipzig, Medical Faculty, Leipzig, Germany.

Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University of Leipzig, Medical Faculty, Leipzig, Germany.

出版信息

Int J Antimicrob Agents. 2020 Jun;55(6):105976. doi: 10.1016/j.ijantimicag.2020.105976. Epub 2020 Apr 20.

Abstract

BACKGROUND

Photodynamic inactivation (PDI) is a promising approach to treat multidrug-resistant infections. However, effectiveness of PDI is limited, particularly in Gram-negative bacteria. The use of photosensitizer (PS) 3,3',3'',3'''-(7,8,17,18-tetrahydro-21H,23H-porphyrine-5,10,15,20-tetrayl)tetrakis[1-methyl-pyridinium]tetratosylate (THPTS) and laser light has led to very promising results. This study focuses on the effects of THPTS in various critical multidrug-resistant bacterial strains and explores the possibility of light-emitting diode (LED)-based activation as a clinically more feasible alternative to laser light.

METHODS

THPTS was further chemically characterized and in vitro testing of PDI of different multidrug-resistant bacterial strains was performed under various experimental conditions, including varying drug concentration, incubation time, light source (laser and LED) and light intensity, by determination of viable bacteria after treatment. The effect of hyaluronic acid as an adjuvant for medical applications was also evaluated.

RESULTS

Bacterial density of all investigated bacterial strains was reduced by several orders of magnitude, irrespective of multidrug-resistance or hyaluronic acid addition. The effect was less intense in Gram-negative strains (disinfection), and more pronounced in Gram-positive strains (sterilization), even at reduced THPTS concentrations or decreased light treatment intensity. Controls without THPTS or without light treatment did not indicate reduced bacterial density.

CONCLUSIONS

PDI with THPTS and laser light was effective in all investigated bacterial strains. Gram-negative strains were less, but sufficiently, susceptible to PDI. Adding hyaluronic acid did not reduce the antibacterial treatment effect. LED-based PDI is equally effective when illumination duration is increased to compensate for reduced light intensity.

摘要

背景

光动力灭活(PDI)是治疗多药耐药感染的一种很有前途的方法。然而,PDI 的效果有限,特别是在革兰氏阴性菌中。使用光敏剂(PS)3,3',3'',3'''-(7,8,17,18-四氢-21H,23H-卟啉-5,10,15,20-四羧酸)四[1-甲基-吡啶]四硫酸盐(THPTS)和激光光已取得了非常有希望的结果。本研究专注于 THPTS 在各种关键多药耐药细菌菌株中的作用,并探讨了基于发光二极管(LED)的激活作为激光光更可行的临床替代方案的可能性。

方法

进一步对 THPTS 进行了化学表征,并在不同实验条件下对不同多药耐药细菌菌株进行了 PDI 体外检测,包括改变药物浓度、孵育时间、光源(激光和 LED)和光强度,通过处理后活菌的测定来进行。还评估了透明质酸作为医疗应用的佐剂的效果。

结果

所有研究的细菌菌株的细菌密度都降低了几个数量级,无论多药耐药性或透明质酸的添加与否。在革兰氏阴性菌株中(消毒)效果较弱,而在革兰氏阳性菌株中(灭菌)效果更明显,即使在降低 THPTS 浓度或降低光处理强度的情况下也是如此。没有 THPTS 或没有光处理的对照没有表明细菌密度降低。

结论

THPTS 和激光光的 PDI 对所有研究的细菌菌株都有效。革兰氏阴性菌株对 PDI 的敏感性较低,但足以敏感。添加透明质酸不会降低抗菌处理效果。当增加照明持续时间以补偿光强度降低时,基于 LED 的 PDI 同样有效。

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