高压氧治疗对抗小鼠热创伤中铜绿假单胞菌生物膜微隔室现象

IF 5.9 Q1 MICROBIOLOGY Biofilm Pub Date : 2023-09-26 DOI:10.1016/j.bioflm.2023.100159
Anne Sofie Laulund , Franziska Angelika Schwartz , Niels Høiby , Kim Thomsen , Claus Moser
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引用次数: 0

摘要

背景生物膜抗生素耐受性的部分原因是生物膜作为一个独立的药代动力学微区室的行为。高压氧治疗已被证明可以增强生物膜中的抗生素作用。本研究在动物生物膜模型中研究了高压氧治疗(HBOT)对妥布霉素生物膜微药代动力学/药效学行为的影响。方法采用热损伤法在小鼠肩胛骨中段建立全层坏死模型。四天后,将三个含有铜绿假单胞菌PAO1的16小时海藻藻酸盐生物膜珠插入坏死处,并将三个珠插入相邻的未受影响皮肤下。将小鼠随机分为三组:I)在2.8大气压和0.8mg妥布霉素/小鼠皮下进行1.5小时的HBOT;II) 托布霉素单药治疗,相同剂量;III) 生理盐水对照组。处死第1组和第2组的一半小鼠,3小时后全部回收珠子,另一半和安慰剂小鼠在4.5小时后处死并收集珠子。结果与大气环境中的珠子相比,接受HBOT的烧伤组在3小时和4.5小时的CFU较低(p=0.043和p=0.0089),在未烧伤的皮肤中没有观察到CFU差异(HBOT与大气)。在4.5小时时,与相应的大气组相比,接受HBOT的组中未烧伤皮肤中的CFU较低(p=0.02)。在施用HBOT的3小时时,烧伤皮肤中CFU高于未烧伤皮肤(p=0.04),在4.5小时效果消失。在这两个时间点,烧伤皮肤下珠子中的妥布霉素含量在HBOT组中高于大气组(p=0.031和p=0.0078)。仅在4.5小时时,HBOT处理的烧伤皮肤下的珠子中的妥布霉素含量才高于相应的非烧伤皮肤下(p=0.006),通过增加可用的妥布霉素和增强细菌杀伤来对抗生物膜药代动力学的微区室化。
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Hyperbaric oxygen therapy counteracts Pseudomonas aeruginosa biofilm micro-compartment phenomenon in murine thermal wounds

Background

Biofilm antibiotic tolerance is partly explained by the behavior of a biofilm as an independent pharmacokinetic micro-compartment. Hyperbaric oxygen therapy has been shown to potentiate antibiotic effects in biofilms. The present study investigates the effect of hyperbaric oxygen therapy (HBOT) on the biofilm micro-pharmacokinetic/pharmacodynamic behavior of tobramycin in an animal biofilm model.

Methods

Full-thickness necroses were created mid-scapular on mice by means of a thermal lesion. After four days, three 16 h seaweed alginate biofilm beads containing Pseudomonas aeruginosa PAO1 were inserted under the necrosis, and three beads were inserted under the adjacent non-affected skin. The mice were randomized to three groups I) HBOT for 1.5 h at 2.8 atm and 0.8 mg tobramycin/mouse subcutaneously; II) Tobramycin as monotherapy, same dose; III) Saline control group. Half the number of mice from group 1 and 2 were sacrificed, and beads were recovered in toto after 3 h and the other half and the placebo mice were sacrificed and beads collected after 4.5 h.

Results

Lower CFUs were seen in the burned group receiving HBOT at 3 and 4.5 h compared to beads in the atmospheric environment (p = 0.043 and p = 0.0089). At 3 h, no CFU difference was observed in the non-burned skin (HBOT vs atmospheric). At 4.5 h, CFU in the non-burned skin had lower CFUs in the group receiving HBOT compared to the corresponding atmospheric group (p = 0.02). CFU was higher in the burned skin than in the non-burned skin at 3 h when HBOT was applied (p = 0.04), effect faded out at 4.5 h.

At both time points, the tobramycin content in the beads under burned skin were higher in the HBOT group than in the atmospheric groups (p = 0.031 and p = 0.0078). Only at 4.5 h a higher tobramycin content was seen in the beads under the HBOT-treated burned skin than the beads under the corresponding non-burned skin (p = 0.006).

Conclusion

HBOT, as an anti-biofilm adjuvant treatment of chronic wounds, counteracts biofilm pharmacokinetic micro-compartmentalization through increased available tobramycin and augmented bacterial killing.

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来源期刊
Biofilm
Biofilm MICROBIOLOGY-
CiteScore
7.50
自引率
1.50%
发文量
30
审稿时长
57 days
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