A New Method for Rapid Detection of Intracranial Infection in Patients After Neurosurgery

Significance 

CNS infections are potentially life threatening if not diagnosed and treated fast. For instance after undergoing neurosurgical procedures, patients may be at risk of intracranial infections, which can be fatal. The key to diagnosis and treatment is early, reliable intracranial bacterial identification. It can be challenging to identify an intracranial infection during hospitalization with certainty. Biochemical and routine studies on cerebrospinal fluid typically produce rapid  answers. However, the diagnostic value has not come to a consensus due to the presence of intraoperative aseptic inflammatory reactions for several pathologies. It is still difficult to distinguish between intracranial infections and non-infectious conditions. Therefore, it is critical to create an efficient treatment for bacterial infection and a quick and reliable detection technique. More efficient bacterial detection and treatment using non-invasive techniques are in demand. The photothermal antibacterial therapy (PTAT) offers distinct advantages over other non-invasive antibacterial techniques since it causes only modest harm to healthy tissue and has a low risk of causing the emergence of antibiotic resistance.

In a new study published in Journal of Frontiers in Bioengineering and Biotechnology Dr. Long Zhang, Dr. Deyun Zhang, Dr. Hai Tang, Dr. Yufu Zhu, Dr. Hongmei Liu, and Dr. Rutong Yu from Xuzhou Medical University developed a new method for combining the photothermal therapy of bacteria with sensitive detection. They measured adenosine triphosphate (ATP) bioluminescence after targeted photothermal lysis. The new technique let bacteria wear ICG clothing in order to get fast ATP, fluoresces dual detection methods, and photothermal antibacterial therapy for bacterial infection.

According to the authors there is a need for quick, sensitive, precise, and fairly cost diagnostics for developing effective treatments for infectious disorders. The authors therefore created a quick and easy method for the precise detection of bacteria by detecting ATP bioluminescence after focused photothermal lysis. Mammalian cells were unable to incorporate it into their cell walls, but bacteria could, and the azide group can react with the molecularly changed dibenzocyclooctyne as a result of the biorthogonal reaction. D-amino acids were thus used by researchers as chemicals to target bacteria in a specific way. To test their method, the authors took CSF samples from patients who had fevers of unknown cause following neurosurgery as a standard procedure for biochemical detection and cultured to look for germs. Additionally, WBC, CRP levels, and glucose levels in the CSF are the conventional markers for early diagnosis of infectious and noninfectious disorders. However, a slow identification of cerebral infection following surgery is caused by the lengthy clinical microbiological culture process and the insensitivity of WBC to infection. The effectiveness of the sulfo-DBCOICG coating on d-AzAla-bacteria and the strong linear association between ATP levels and CFU are both confirmed by their testing results. Their investigations were done in sizable number of patients with five individuals undergoing craniotomies with clinically proven intracranial infections and 17 patients with suspected intracranial infections had CSF samples taken. The same procedure used in vitro was used to detect ATP in CSF. According to the authors, the ATP value was not contaminated between 0 and 60, but values above 60 likely to be affected. These results were combined with clinical biochemical signs and the ATP value.

In their studies with the MRSA-infection model the authors demonstrated using In vivo imaging the DBCO-ICG group’s ability to target the MRSA-infected model, and after 180 seconds of exposure to near-infrared light, the diseased skin on the mouse’s back could attain a temperature of 46 °C. Additionally, the in vivo imaging experiments confirmed that DBCO-ICG had an excellent antibacterial activity and was biocompatible in mouse wounds infected with MRSA.

In conclusion, Xuzhou Medical University scientists created an innovative platform for simultaneous bacterial illness detection and antibiotic treatment. This approach is quicker than clinical microbiological culture, doesn’t lead to drug resistance like antibiotics do, and doesn’t kill healthy cells. It might offer a useful suggestion for the quick clinical detection of germs.

About the author

Hongmei Liu is an Associate Professor of Department of Biomedical Engineering, Southern University of Science and Technology. She obtained Ph. D. degree from Institute of Process Engineering, Chinese Academy of Sciences in 2015. Liu is working in the field of biomaterials and nanomedicine. The primary goal of her research is to develop biomaterials to delivery drugs for tumor, brain trauma treatment, and diagnosis of disease. Hongmei has published more than 32 peer-reviewed manuscripts on journals such as Biomaterials, Theranostics, and Advanced Healthcare Materials.

About the author

Rutong Yu received his Ph.D. degree from the West China Hospital, Sichuan University in 1999. Now he is a Director of department of neurosurgery and the academic leader of the National key clinical specialty, the Affiliated Hospital of Xuzhou Medical University, China. His current research focuses on molecular mechanisms and targeted therapy of glioma. As the corresponding author, he has published many high-quality papers on journals including Biomaterials, Neuro-Oncol and Journal of Hematology & Oncology. He has acquired the first prize of the Advance Science and Technology Award in Jiangsu as the first completer. He has hosted 5 science projects of the National Natural Science Foundation of China.

Reference

Zhang L, Zhang D, Tang H, Zhu Y, Liu H, Yu R. Bacteria Wear ICG Clothes for Rapid Detection of Intracranial Infection in Patients After Neurosurgery and Photothermal Antibacterial Therapy Against Streptococcus Mutans. Frontiers in bioengineering and biotechnology. 2022 Jul 6;10:932915.

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