Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Autor: Xie YL; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Modi N; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Handler D; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Yu S; Department of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey , Piscataway, New Jersey, USA., Rao P; Division of Infectious Diseases and International Health, University of Virginia , Charlottesville, USA., Kagan L; Department of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey , Piscataway, New Jersey, USA., Petros de Guex K; Division of Infectious Diseases and International Health, University of Virginia , Charlottesville, USA., Reiss R; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Siemiątkowska A; Department of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey , Piscataway, New Jersey, USA.; Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences , Poznań, Poland., Narang A; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Narayanan N; Department of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey , Piscataway, New Jersey, USA., Hearn J; Virginia Department of Health , Richmond, USA., Khalil A; Virginia Department of Health , Richmond, USA., Woods P; New Jersey Department of Health , Trenton, USA., Young L; Virginia Department of Health , Richmond, USA., Lardizabal A; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Subbian S; Department of Medicine, Rutgers New Jersey Medical School , Newark, New Jersey, USA., Peloquin CA; College of Pharmacology, University of Florida , Gainesville, USA., Vinnard C; Rutgers New Jersey Medical School , Newark, USA., Thomas TA; Division of Infectious Diseases and International Health, University of Virginia , Charlottesville, USA., Heysell SK; Division of Infectious Diseases and International Health, University of Virginia , Charlottesville, USA.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 Nov 15; Vol. 67 (11), pp. e0093223. Date of Electronic Publication: 2023 Oct 25.
DOI: 10.1128/aac.00932-23
Abstrakt: Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled. Serum and urine samples were collected over 24 h. Rifampin serum concentrations were measured using validated liquid chromatography-tandem mass spectrometry, and total exposure (area under the concentration-time curve) over 24 h (AUC 0-24 ) was determined through noncompartmental analysis. The Sunahara method was used to extract total rifamycins, and rifampin urine excretion was measured by spectrophotometry. An analysis of 58 eligible participants, including 15 (26%) with type 2 diabetes mellitus, demonstrated that urine spectrophotometry accurately identified subtarget rifampin AUC 0-24 at 0-4, 0-8, and 0-24 h. The area under the receiver operator characteristic curve (AUC ROC) values were 0.80 (95% CI 0.67-0.90), 0.84 (95% CI 0.72-0.94), and 0.83 (95% CI 0.72-0.93), respectively. These values were comparable to the AUC ROC of 2 h serum concentrations commonly used for therapeutic monitoring (0.82 [95% CI 0.71-0.92], P = 0.6). Diabetes status did not significantly affect the AUC ROCs for urine in predicting subtarget rifampin serum exposure ( P = 0.67-0.92). Spectrophotometric measurement of urine rifampin excretion within the first 4 or 8 h after dosing is a simple and cost-effective test that accurately predicts rifampin underexposure. This test provides critical information for optimizing tuberculosis treatment outcomes by facilitating appropriate dose adjustments.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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