1886. N1,N12-Diacetylspermine as Potential Urinary Biomarker to Monitor Treatment Response and Bacterial Load in Pulmonary Tuberculosis

Abstract

BackgroundAdequate control of the global tuberculosis (TB) burden is limited by a lack of accurate measures of treatment efficacy. Current gold standard relies on sputum cultures, which often lag weeks behind time of sample collection. Previous studies have identified urinary N1,N12-diacetylspermine (DiAcSpm) as a potential biomarker of active pulmonary TB (ATB). We aimed to quantify urinary DiAcSpm in participants being treated for ATB and identify its relationship to treatment response.MethodsLongitudinal urine samples were obtained from two separate cohorts of participants treated for ATB. Cohort one consisted of 34 successfully treated ATB cases with urine collected at weeks 0, 2, 4, 8, 17, 26, and 52. Cohort two consisted of 35 ATB cases under two treatment arms: one arm was successfully treated with the standard therapy of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE), and the other arm received an experimental drug, which was later found to be ineffective against ATB. Urine from cohort two was collected at days 0, 2, 4, and 14. All samples were blinded, randomized, normalized to osmolality and urinary creatinine, and analyzed using high-performance liquid chromatography-mass spectrometry. DiAcSpm concentrations were further tested using ELISA.ResultsUsing linear-mixed modeling that adjusted for age, sex, and participant weight, we found that urinary DiAcSpm significantly decreased by week 2 of successful treatment in both cohorts (P < 0.0001). DiAcSpm levels remained unchanged in the ineffective experimental drug group (cohort two), significantly differentiating treatment success and failure by day 14 (P < 0.0001). Additionally, concentrations of urinary DiAcSpm positively correlate with sputum mycobacterial burden (P = 0.0002).These findings were consistent across both methods of detection.ConclusionOur results suggest that urinary concentrations of DiAcSpm correlate with TB treatment outcome and mycobacterial disease burden, and have the potential to serve as an early biomarker of TB treatment efficacy. Disclosures All Authors: No reported Disclosures.