Antibiotic Resistance Laboratory, Vall d'Hebron Research Institute, Infectious Diseases Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain.
Microbiol Spectr. 2023 Feb 14;11(1):e0280722. doi: 10.1128/spectrum.02807-22. Epub 2022 Dec 6.
There is currently an urgent need to find new strategies to tackle antimicrobial resistance and biofilm-related infections. This study has two aims. First, we evaluated the efficacy of hyperthermia in preventing biofilm formation on the surfaces of polyvinyl chloride discs. Second, we assessed the efficacy of hyperthermia in preventing biofilm formation in endotracheal tubes (ETTs) of a rabbit model. For the studies, nine clinical extensively drug-resistant/multidrug-resistant Gram-negative isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and three clinical methicillin-resistant Staphylococcus aureus strains were studied. For biofilm formation, an adhesion step of 30 or 90 min followed by a growth step of 24 h were performed with application of one, two, and three pulses at 42°C for 15 min each pulse after the adhesion step. For the studies, New Zealand rabbits were intubated with ETTs previously colonized with K. pneumoniae or P. aeruginosa strains, and three pulses at 42°C for 15 min were applied after the adhesion step. The application of three pulses at 42°C for 15 min each pulse was needed to achieve the prevention of the biofilm formation of 100% of the tested strains. The application of heat pulses in a rabbit intubation model led to biofilm prevention of 85% against two K. pneumoniae strains and 80% against two P. aeruginosa strains compared to the control group. Hyperthermia application through pulses at 42°C could be a new nonantibiotic strategy to prevent biofilm formation in ETTs. Biofilm-producing microorganisms are considered medically crucial since they cause 80% of the infections that occur in the human body. Medical devices such as endotracheal tubes (ETTs) can act as a reservoir for pathogens providing the surface to which microorganisms can adhere and cause biofilm-associated infections in critically ill patients. This biofilm has been related with the development of ventilator-associated pneumonia (VAP), with an incidence of 8 to 28%, a mortality rate up to 17% and its associated high extra costs. Although some VAP-preventive measures have been reported, they have not demonstrated a significant reduction of VAP incidence. Therefore, we present a new nonantibiotic strategy based on hyperthermia application to prevent biofilm formation inside ETTs. This technology could reduce VAP incidence, intubation duration, hospital and intensive care unit (ICU) length stays, and mortality rates. Consequently, this could decrease the antibiotics administered and influence the impact of antibiotic resistance in the ICU.
目前迫切需要寻找新的策略来应对抗微生物药物耐药性和生物膜相关感染。本研究有两个目的。首先,我们评估了高热在防止聚氯乙烯(PVC)圆盘表面生物膜形成方面的功效。其次,我们评估了高热在预防兔模型中气管内导管(ETT)生物膜形成方面的功效。在研究中,使用了 9 株临床广泛耐药/多药耐药革兰氏阴性菌(鲍曼不动杆菌、肺炎克雷伯菌和铜绿假单胞菌)和 3 株耐甲氧西林金黄色葡萄球菌临床分离株进行生物膜形成研究。生物膜形成采用 30 分钟或 90 分钟的黏附步骤,然后是 24 小时的生长步骤,在黏附步骤后应用 42°C 下的 15 分钟的 1、2 和 3 个脉冲。在研究中,将先前定植了肺炎克雷伯菌或铜绿假单胞菌的 ETT 插入新西兰兔中,并在黏附步骤后应用 42°C 下的 15 分钟 3 个脉冲。需要应用 42°C 下的 15 分钟 3 个脉冲才能实现对测试菌株 100%生物膜形成的预防。与对照组相比,在兔插管模型中应用热脉冲可预防 85%的两种肺炎克雷伯菌菌株和 80%的两种铜绿假单胞菌菌株的生物膜形成。通过 42°C 的脉冲应用热疗可能是一种新的非抗生素策略,可预防 ETT 中的生物膜形成。生物膜产生的微生物被认为具有医学重要性,因为它们导致人体中 80%的感染。医疗设备,如气管内导管(ETT)可以作为病原体的储存库,为微生物提供附着的表面,并导致危重病患者的生物膜相关感染。这种生物膜与呼吸机相关性肺炎(VAP)的发生有关,其发病率为 8%至 28%,死亡率高达 17%,相关的额外费用很高。尽管已经报道了一些预防 VAP 的措施,但它们并没有显示出 VAP 发病率的显著降低。因此,我们提出了一种基于热疗应用的新的非抗生素策略,以防止 ETT 内的生物膜形成。这项技术可以降低 VAP 的发生率、插管持续时间、住院和重症监护病房(ICU)停留时间以及死亡率。因此,可以减少抗生素的使用,并影响 ICU 中抗生素耐药性的影响。