Direct-from-blood RNA sequencing identifies the cause of post-bronchoscopy fever

Abstract

BackgroundAntibiotic resistance is rising at disturbing rates and contributes to the deaths of millions of people yearly. Antibiotic resistant infections disproportionately affect those with immunocompromising conditions, chronic colonization, and frequent antibiotic use such as transplant patients or those with cystic fibrosis. However, clinicians lack the diagnostic tools to confidently diagnose and treat infections, leading to widespread use of empiric broad spectrum antimicrobials, often for prolonged duration.Case presentationA 22 year-old Caucasian female with cystic fibrosis received a bilateral orthotopic lung transplantation 5 months prior to the index hospitalization. She underwent routine surveillance bronchoscopy and was admitted for post-procedure fever. A clear cause of infection was not identified by routine methods. Imaging and bronchoscopic lung biopsy did not identify an infectious agent or rejection. She was treated with a prolonged course of antimicrobials targeting known colonizing organisms from prior bronchoalveolar lavage cultures (Pseudomonas, Staphylococcus aureus, and Aspergillus). However, we identified Stenotrophomonas maltophilia in two independent whole blood samples using direct-pathogen sequencing, which was not identified by other methods.ConclusionsThis case represents a common clinical conundrum: identification of infection in a high-risk, complex patient. Here, direct-pathogen sequencing identified a pathogen that would not otherwise have been identified by common techniques. Had results been clinically available, treatment could have been customized, avoiding a prolonged course of broad spectrum antimicrobials that would only exacerbate resistance. Direct-pathogen sequencing is poised to fill a diagnostic gap for pathogen identification, allowing early identification and customization of treatment in a culture-independent, pathogen-agnostic manner.

Precision Medicine in Control of Visceral Leishmaniasis Caused by L. donovani

“…It also provides information on subspecies and antimicrobial susceptibility. Disadvantages include contamination and lower sensitivity for organisms with small genomes or present in low quantities ( Ko et al., 2019 ; Li et al., 2021 ). While this technology has the advantage of diagnosing co-infections, the significance of finding a second microbe should be carefully assessed as to its clinical relevance.…”

An Observational Study of Sepsis in Takeo Province Cambodia: An in-depth examination of pathogens causing severe infections

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Surveillance for acute cellular rejection after lung transplantation

“…Risk of fever, pneumonia and sepsis as a result of bronchoscopy within the LTx populations are often included in the argument against surveillance, but very little published data exists. In non-LTx populations, post-procedural fever has been reported in up to 16% of immunocompetent adults (90,91), with transient bacteremia (92) and cytokine release from alveolar macrophages (93) being postulated causes. Novel use of RNA sequencing in peripheral blood has recently been shown to augment investigation in affected patients, to identify bacteria in culture negative or even colonized patients (90).…”