LOW SERUM ANTIMYCOBACTERIAL DRUG LEVELS IN NON-HIV-INFECTED TUBERCULOSIS PATIENTS

Background: Despite the use of directly observed therapy (DOT) by tube rculosis control programs, patient treatment failure, relapse, and acq uired drug resistance remain problematic in a small number. We investi gated serum drug levels in non-HIV-infected tuberculosis patients who were receiving DOT by the health department and did not respond to tre atment as expected. Methods: The indications for checking levels were as follows: (1) slow clinical response or failure to convert the sputu m culture within 12 weeks; (2) treatment failure, early disease relaps e <13 1 months since being declared cured; (3) relapse, late disease r eactivation greater than or equal to 13 months since being declared cu red; and (4) acquired drug resistance while receiving DOT. Baseline ch aracteristics of control subjects who responded to therapy as expected were compared. Venous blood for analysis was obtained at 2 h after di rectly observed ingestion and measured by high-performance liquid chro matography. Results: Twenty-four patients receiving daily or twice-wee kly standard therapy with isoniazid (INH, 300 or 900 mg) and rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h, Fo r INH, 15 of 22 patients (68%) had levels less than the reported targe t range. For RMP, 14 of 22 patients (64%) had low levels. Among the 14 patients receiving INH, 900 mg, and RMP, 600 mg, 4 (29%) had very low levels of both. Use of a combination INH/RMP tablet was associated wi th lower INH levels (p=0.04); however, RMP levels were higher (p<0.02) . Alcohol use was associated with significantly higher RMP (p<0.01) se rum concentrations. Conclusions: Important questions remain concerning the utility and timing of serum drug measurements. However, if a pati ent is not responding to therapy as expected and one is assured that t he Mycobacterium tuberculosis organism is susceptible to the drugs giv en and that the patient is taking the medication as prescribed, drug l evel monitoring should be considered.