Low rifampicin levels in plasma associated with a poor clinical response in patients with abdominal TB

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Low rifampicin levels in plasma associated with a poor clinical response in patients with abdominal TB Dear Editor, Extrapulmonary TB (EPTB) may require prolonged treatment due to delayed or incomplete response, possibly due to poor drug penetration at the site of pathology.The treatment recommendation for rifampicin (RIF, R) and isoniazid (INH, H) susceptible TB is the 6-month RIF-containing regimen including INH, RIF, pyrazinamide (PZA, Z) and ethambutol (EMB, E) (except for neurological and osteo-articular TB). 1 In the absence of an acceptable treatment end-point marker and poor yield of culture for EPTB, treatment completion decisions are based on an improvement in symptoms, weight gain and clinical evaluation, along with imaging. 2 Here we present the results of a prospective study on plasma drug concentrations of HRZE serially measured in patients with abdominal TB (ATB) to find any correlation with treatment outcomes.Patients diagnosed with ATB at the All India Institute of Medical Sciences (AIIMS), New Delhi, India, from 2017 to 2019 using microbiological reference standards (culture for Mycobacterium tuberculosis, Xpert V R MTB/RIF [Xpert; Cepheid, Sunnyvale, CA, USA] testing or acid-fast bacilli from abdominal sample) or exudative ascitic fluid pattern or biopsy (colonoscopic/surgical/needle-aided) suggestive of TB were included in the study.We excluded patients with only pulmonary TB (PTB), chronic kidney disease, TB resistant to RIF on Xpert, those resistant to anti-TB treatment (ATT) drugs on TB culture and drug susceptibility testing, patients who refused consent and patients aged <18 years.Baseline clinical history and treatment response during follow-up were obtained from all 45 patients enrolled (of 78 patients with ATB screened).Blood samples for the study were first drawn at 2 weeks after ATT initiation (initial few days required for reaching steady-state due to metabolism and auto-induction), 3 and then at months 2 and 3 for each time point: 0 h (C 0h ), 1 h (C 1h ), 2 h (C 2h ) and 4 h (C 4h ).Plasma was separated and stored at -80 C until analysis.Samples were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/ MS) assay, as reported previously.4 Pharmacokinetic (PK) parameters, time to peak plasma concentration (T max ) and peak plasma concentration (C max , defined as the highest concentration achieved in the 1, 2 and 4 h blood samples) were calculated manually.Area under the concentration-time curve (AUC 0-4 ) was

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