Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control program, Virginia, USA

Abstract

Therapeutic drug monitoring may be useful in tuberculosis management, but programmatic implementation is understudied. We performed a retrospective cohort study to determine prevalence of lower than expected levels of isoniazid, rifampin, ethambutol, and pyrazinamide measured at time of estimated peak serum concentration. Patients were tested for serum concentration at 2 hours after medication administration. When patients were tested, 22 had concentrations lower than expected range for rifampin, 23 of 39 patients had low levels of isoniazid, and 8 of 26 patients had low levels of ethambutol; all 20 patients tested for pyrazinamide were within expected range. Over 26 months, 42 patients met criteria for slow response. Diabetes was associated with slow response (p<0.001), and persons with diabetes were more likely than persons without diabetes to have low rifampin levels (p = 0.03). Dosage adjustment of rifampin was more likely to elevate serum concentration to the target range than adjustment of isoniazid given in daily doses (p = 0.01).

Figure 1

Results of serum concentration 2 hours after medication administration levels (C_2hr) of first-line antituberculosis medications among patients with a slow response to tuberculosis therapy. Frequencies are reported for low, within target, and high C_2hr levels corresponding to levels below, within, or above the expected range for each medication.

Figure 2

Results in patients with initial serum concentrations 2 h after medication below the expected range with follow-up levels after dose adjustment for rifampin daily or biweekly (A), isoniazid daily (B), and isoniazid biweekly (C). The median initial and follow-up doses of rifampin daily or biweekly were 600 mg and 900 mg, respectively; for isoniazid daily, 300 mg and 450 mg, respectively; and for isoniazid biweekly, 900 mg and 1,200 mg, respectively. Brackets represent expected ranges for each dose of medication.