Oral malabsorption of anti-TB drugs is one possible cause for treatment failure, although rarely described. In patients receiving appropriate anti-TB therapy in DOT regime without clinical, radiological or microbiological improvement, malabsorption must be considered.1–6
Malabsorption of ≥1 drug may justify treatment failure, adverse clinical outcome, disease progression and even promotion of drug resistance.1 2 4 5 7 8
Most patients with TB absorb anti-TB drugs properly and do not require drug monitoring as long as they respond expectedly to therapy.1 9
Malabsorption of anti-TB drugs has been reported in a small subset of patients.1 2 4 8
Potential causes have been recognised, although they remain poorly characterised. Most reports have focussed on HIV infection as the most important risk factor for anti-TB drugs malabsorption.1–5 7–9
HIV patients may present lower serum concentrations of ≥1 anti-TB drugs, even in the absence of malabsorption symptoms.1 7
Malabsorption in non-HIV patients is not clearly explained and data in literature are lacking. Other comorbidities that can possibly impair drug absorption include hypoalbuminemia in malnourished, gastrointestinal or malabsorptive diseases, infectious gastroenteritis, gastric achlorydria, end-stage liver or renal diseases.1 3
Altered drug bioavailability with the use of combination INH/RIF compared with individual tablet forms has also been reported in the literature.2 3
It is also known the deleterious effects of high-fat food on the absorption of INH and RIF. So it is advisable that patients fasted before medication or restrict intake to a light snack.
Measurement of anti-TB drugs levels has been encouraged in patients infected with a sensitive MT, which remain AFB smear positive after 3 months of DOT regime with effective drugs according to DST.1–3 6
Maximum INH and RIF serum concentration are typically reached 2 h after oral administration and their normal half time is 2–4 h. Two separate measurements (2-h and 6-h postdose) are advocated to distinguish between delayed absorption (late peak close to normal) and malabsorption (low concentrations at all time).6
This clinical case refers to a patient presenting respiratory TB not responsive to standard therapy. Despite good compliance to DOT regime and DST 3 months apart confirming sensitivity to first-line drugs in use, treatment failure has occurred.
To face the possibility of surreptitious non-adherence to treatment, our usual DOT regime was reinforced by maintenance of patient in our department after taking medication under direct supervision for about 2 h to ensure that medication was not rejected nor vomited or expelled.
Measurement of anti-TB drugs blood levels before and after the beginning of parenteral TB drugs was performed during a few days period of hospitalisation which revealed that serum concentration of INH and RIF were undetected or much below expected range, which supported our hypothesis of oral malabsorption of anti-TB drugs.
Patient's HIV status was negative. Gastrointestinal or malabsorptive disease, as a cause of drug malabsorption, seemed unlikely. Patient presented a good nutritional status, albumin and protein blood levels were normal and blood analysis revealed no signs of deficient absorption. Patient was not taking any antiacid medication. Moreover, a detailed study to clarify a possible gastrointestinal malabsorption was conducted in collaboration with Gastroenterology Department which revealed no abnormalities.
Gastrointestinal TB was excluded. However, according to literature, blood concentration of anti-TB drugs is not impaired in patients with gastrointestinal TB.10
In the absence of comorbidities pointed earlier, possibility of isolated anti-TB drugs malabsorption was considered. To clarify this situation, patient was admitted to pulmonology ward and measurement of anti-TB drugs levels was performed with patient taking oral anti-TB medication under a tighter DOT regime during the period of hospitalisation. Under these conditions, undetected or low serum concentration of anti-TB drugs strongly supported this hypothesis. Introduction of intravenous regime, followed by good clinical, radiological and microbiological response, confirmed malabsorption as the most possible cause for treatment failure.
- For the vast majority of patients, standard drug regimes prescribed are adequate.
- Although rare, malabsorption of anti-TB drugs is an increasingly prevalent problem.
- There are few reports in the literature about TB treatment failure due to antimycobacterial drugs malabsorption and particularly in the absence of predisposing comorbidities.
- Nevertheless in patients who remain AFB smear positive after 3 months of adequate treatment under DOT regime and proven DST, drug blood levels monitoring must be considered.
- We believe that drug malabsorption as a cause for low drug blood concentrations and treatment failure applies to this clinical case, even if cause of malabsorption was not clear.