Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections.

BACKGROUND: Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment. The objective of the study was to assess the diagnostic value of next-generation sequencing (NGS) for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections. METHODS: This was a retrospective study. Between January and August 2020, 47 adult immunocompromised patients underwent NGS testing under the following clinical conditions: 1) prolonged fever and negative conventional cultures; 2) new-onset fever despite empiric antimicrobial treatment; and 3) afebrile with suspected infections on imaging. Clinical data, including conventional microbial test results and antimicrobial treatment before and after NGS, were collected. Data were analyzed according to documented changes in antimicrobial treatment (escalated, no change, or de-escalated) after the NGS results. RESULTS: The median time from hospitalization to NGS sampling was 19 d. Clinically relevant pathogens were detected via NGS in 61.7% of patients (29/47), more than half of whom suffered from fungemia (n=17), resulting in an antimicrobial escalation in 53.2% of patients (25/47) and antimicrobial de-escalation in 0.2% of patients (1/47). Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella, Pneumocystis jirovecii, and Candida. In the remaining three cases, NGS detected clinically relevant pathogens also detected by conventional cultures a few days later. The antimicrobial treatment was subsequently adjusted according to the susceptibility test results. Overall, NGS changed antimicrobial management in 55.3% (26/47) of patientst, and conventional culture detected clinically relevant pathogens in only 14.9% of patients (7/47). CONCLUSION: With its rapid identification and high sensitivity, NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

An Integrated Transcriptomics and Lipidomics Analysis Reveals That Ergosterol Is Required for Host Defense Against Bacterial Infection in Drosophila.

Animals adjust their lipid metabolism states in response to pathogens infection. However, the underlying molecular mechanisms for how lipid metabolism responds to infection remain to be elusive. In this study, we assessed the temporal changes of lipid metabolism profiles during infection by an integrated transcriptomics and lipidomics analysis. Ergosterol is identified to be required for proper host defense to pathogens. Notably, ergosterol level is increased in the hemolymph upon bacterial infection. We show that the increase of ergosterol level by food supplement or genetic depletion of Acsl, a long-chain fatty acid-CoA synthetase, promotes host survival against bacterial challenges. Together, our results suggest a critical role of lipid metabolism adaption in the process of host defense against invading pathogens.

Single-Component Bismuth Nanoparticles as a Theranostic Agent for Multimodal Imaging-Guided Glioma Therapy.

Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo. In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.