Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, 2200 Copenhagen, Denmark.
Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, 2200 Copenhagen, Denmark; Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark.
J Cyst Fibros. 2019 Sep;18(5):657-664. doi: 10.1016/j.jcf.2019.01.005. Epub 2019 Jan 31.
Pseudomonas aeruginosa is a major pathogen of the chronic lung infections in cystic fibrosis (CF) patients. These persistent bacterial infections are characterized by bacterial aggregates with biofilm-like properties and are treated with nebulized or intravenous tobramycin in combination with other antibiotics. However, the chronic infections are close to impossible to eradicate due to reasons that are far from fully understood. Recent work has shown that re‑oxygenation of hypoxic aggregates by hyperbaric oxygen (O) treatment (HBOT: 100% O at 2.8 bar) will increase killing of aggregating bacteria by antibiotics. This is relevant for treatment of infected CF patients where bacterial aggregates are found in the endobronchial secretions that are depleted of O by the metabolism of polymorphonuclear leukocytes (PMNs). The main objective of this study was to investigate the effect of HBOT as an adjuvant to tobramycin treatment of aggregates formed by P. aeruginosa isolates from CF patients.
The effect was tested using a model with bacterial aggregates embedded in agarose. O profiling was used to confirm re‑oxygenation of aggregates.
We found that HBOT was able to significantly enhance the effect of tobramycin against aggregates of all the P. aeruginosa isolates in vitro. The effect was attributed to increased O levels leading to increased growth and thus increased uptake of and killing by tobramycin.
Re‑oxygenation may in the future be a clinical possibility as adjuvant to enhance killing by antibiotics in cystic fibrosis lung infections.
铜绿假单胞菌是囊性纤维化 (CF) 患者慢性肺部感染的主要病原体。这些持续性细菌感染的特征是具有生物膜样特性的细菌聚集物,并通过雾化或静脉注射妥布霉素与其他抗生素联合治疗。然而,由于远未完全了解的原因,慢性感染几乎不可能根除。最近的研究表明,通过高压氧 (O) 治疗(2.8 巴时 100% O)使缺氧聚集物再氧化,将增加抗生素对聚集细菌的杀伤作用。这对于治疗感染 CF 的患者非常重要,因为在这些患者的支气管分泌物中,由于多形核白细胞 (PMN) 的代谢作用,O 被耗尽,会发现细菌聚集物。本研究的主要目的是研究高压氧作为妥布霉素辅助治疗 CF 患者分离的铜绿假单胞菌形成的聚集物的效果。
使用琼脂糖中嵌入细菌聚集物的模型来测试效果。O 分布测试用于确认聚集物的再氧化。
我们发现高压氧能够显著增强妥布霉素对所有体外铜绿假单胞菌分离株聚集物的作用。这种作用归因于 O 水平的增加导致生长增加,从而增加妥布霉素的摄取和杀伤。
再氧化将来可能成为一种临床可能性,作为增强囊性纤维化肺部感染中抗生素杀菌作用的辅助手段。