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Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study
  1. Tania A Thomas1,
  2. Saning'o Lukumay2,
  3. Sijia Yu3,
  4. Prakruti Rao1,
  5. Anna Siemiątkowska3,4,
  6. Leonid Kagan3,
  7. Domitila Augustino2,
  8. Paulo Mejan2,
  9. Restituta Mosha2,
  10. Deborah Handler5,
  11. Kristen Petros de Guex1,
  12. Blandina Mmbaga6,
  13. Herman Pfaeffle7,
  14. Robert Reiss5,
  15. Charles A Peloquin8,
  16. Christopher Vinnard5,
  17. Estomih Mduma2,
  18. Yingda L Xie5,
  19. Scott K Heysell1
  1. 1 Department of Medicine, Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
  2. 2 Department of Global Health Research, Haydom Lutheran Hospital, Mbulu, Tanzania, United Republic of
  3. 3 Pharmacy, Rutgers The State University of New Jersey, New Brunswick, New Jersey, USA
  4. 4 Pharmacy, Poznań University, Poznan, Poland
  5. 5 Department of Medicine, Infectious Diseases, Rutgers New Jersey Medical School, Newark, New Jersey, USA
  6. 6 Department of Pediatrics, Kilimanjaro Christian Medical College, Moshi, Tanzania, United Republic of
  7. 7 Department of Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia, USA
  8. 8 Pharmacy, University of Florida, Gainesville, Florida, USA
  1. Correspondence to Dr Scott K Heysell, University of Virginia, Charlottesville, VA 22908, USA; skh8r{at}


Objective Pharmacokinetic variability drives tuberculosis (TB) treatment outcomes but measurement of serum drug concentrations for personalised dosing is inaccessible for children in TB-endemic settings. We compared rifampin urine excretion for prediction of a serum target associated with treatment outcome.

Design Prospective diagnostic accuracy study.

Setting Inpatient wards and outpatient clinics, northern Tanzania.

Patients Children aged 4–17 years were consecutively recruited on initiation of WHO-approved treatment regimens.

Interventions Samples were collected after directly observed therapy at least 2 weeks after initiation in the intensive phase: serum at pre-dose and 1, 2 and 6 hours post-dose, later analysed by liquid chromatography-tandem mass spectrometry for calculation of rifampin total exposure or area under the concentration time curve (AUC0-24); urine at post-dose intervals of 0–4, 4–8 and 8–24 hours, with rifampin excretion amount measured onsite by spectrophotometry.

Main outcome measures Receiver operating characteristic (ROC) curve for percentage of rifampin dose excreted in urine measured by spectrophotometry to predict serum rifampin AUC0–24 target of 31.7 mg*hour/L.

Results 89 children, 52 (58%) female, with median age of 9.1 years, had both serum and urine collection. Only 59 (66%) reached the serum AUC0–24 target, reflected by a range of urine excretion patterns. Area under the ROC curve for percentage of rifampin dose excreted in urine over 24 hours predicting serum AUC0–24 target was 69.3% (95% CI 56.7% to 81.8%), p=0.007.

Conclusions Urine spectrophotometry correlated with a clinically relevant serum target for rifampin, representing a step toward personalised dosing for children in TB-endemic settings.

  • Child Health
  • Communicable Diseases
  • Global Health
  • Infectious Disease Medicine
  • Paediatrics

Data availability statement

Data are available upon reasonable request. Data not included in supplementary material and standard operating procedures are available on request to the corresponding author.

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Data availability statement

Data are available upon reasonable request. Data not included in supplementary material and standard operating procedures are available on request to the corresponding author.

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  • Correction notice This paper has been amended since it was first published. We have corrected the spelling of author Yingda L Xie.

  • Contributors SH, TT, CV and EM conceptualised and designed the study. PR, SS, TT and SH verified the source data. SS, PM, EM and BM managed patient recruitment and oversaw the study sites. CAP analysed pharmacokinetic data. PR and RM performed urinary assays. SS, DA, HP, BM, KPdG and DH contributed to data collection. TT, LK, CV, YX and SH interpreted the data. SY, AS, LK and RR performed statistical analysis. SY, AS, LK and RR produced figures. TT, PR and SH wrote the first draft of the manuscript. SH was the author responsible for overall content guarantee. All authors revised and edited the final version of the manuscript. All authors had final responsibility for the decision to submit for publication.

  • Funding This study was funded by National Institutes of Health grant R01 AI137080.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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