Dataset Information

Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study.

ABSTRACT:

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 (AUC_0-24); 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 AUC_0-24 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 AUC_0-24 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 AUC_0-24 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.

SUBMITTER: Thomas TA

PROVIDER: S-EPMC10766442 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study.

Thomas Tania A TA Lukumay Saning'o S Yu Sijia S Rao Prakruti P Siemiątkowska Anna A Kagan Leonid L Augustino Domitila D Mejan Paulo P Mosha Restituta R Handler Deborah D Petros de Guex Kristen K Mmbaga Blandina B Pfaeffle Herman H Reiss Robert R Peloquin Charles A CA Vinnard Christopher C Mduma Estomih E Xie Yingda L YL Heysell Scott K SK

Archives of disease in childhood 20230425 8

<h4>Objective</h4>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.<h4>Design</h4>Prospective diagnostic accuracy study.<h4>Setting</h4>Inpatient wards and outpatient clinics, northern Tanzania.<h4>Patients</h4>Children aged 4-17 years were consecutiv ...[more]

PMID: 37171408

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Project description:ObjectivesTo assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people.DesignDiagnostic accuracy study.ParticipantsOlder people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis).Reference standard for hydration statusDirectly measured serum/plasma osmolality: current dehydration (serum osmolality>300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg).Index tests39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality.ResultsAcross 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality>300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve>0.8). The best equation was osmolarity=1.86×(Na++K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status.ConclusionsSome commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults.Trial registration numbersDRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012.

Dataset Information

Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study.

Objective

Design

Setting

Patients

Interventions

Main outcome measures

Results

Conclusions

Publications

Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study.

Similar Datasets

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