Early Therapeutic Drug Monitoring for Isoniazid and Rifampin among Diabetics with Newly Diagnosed Tuberculosis in Virginia, USA

Abstract

Slow responders to tuberculosis (TB) treatment in Virginia have prolonged treatment duration and consume more programmatic resources. Diabetes is an independent risk factor for slow response and low serum anti-TB drug concentrations. Thus, a statewide initiative of early therapeutic drug monitoring (TDM) for isoniazid and rifampin at 2 weeks after TB treatment was piloted for all diabetics with newly diagnosed TB. During the period of early TDM, 12/01/2011–12/31/2012, 21 diabetics had C 2 hr concentrations performed and 16 (76%) had a value below the expected range for isoniazid, rifampin, or both. Fifteen had follow-up concentrations after dose adjustment and 12 (80%) increased to within the expected range (including all for rifampin). Of 16 diabetic patients with pulmonary TB that had early TDM, 14 (88%) converted their sputum culture to negative in <2 months. Early TDM for diabetics was operationally feasible, may speed response to TB therapy, and can be considered for TB programs with high diabetes prevalence.

Effect of Diabetes Mellitus on Rifampicin Peak Serum Concentration

“…A near inverse correlation was obtained in diabetic patients (Pearson's correlation=-0.402, P value=0.001); however such a correlation was not observed in non-diabetic pulmonary tuberculosis patients suggesting that the drug absorption is disfavoured only under hyperglycemic conditions and linear relationship does not exist between blood glucose and rifampicin Cmax (Pearson's correlation=0.006, P Value=0.962). This is similar to the study reported by Nijland et al (2006), Heysell et al (2010) and Heysell et al (2013) [12,[16][17]. The RBS vs Cmax correlation plot of non-diabetic and diabetic PTB patients is shown in fig.…”

“…Being highly pH dependent for solubility and well absorbed from an acidic pH, a shift in the gastric pH due to hyperglycemia delays rifampicin absorption and thereby tend to prolong the tmax and decrease the Cmax [15]. In addition, gastrointestinal ailments such as gastroparesis which are common in chronic diabetics may either delay or impair absorption of rifampicin leading to decreased systemic availability [17]. Univariate analyses were performed to determine the relationship between random blood glucose and rifampicin Cmax.…”

Limited Sampling Strategy and Target Attainment Analysis for Levofloxacin in Patients with Tuberculosis

“…TDM has been shown to be beneficial in the treatment of TB (14)(15)(16)(17)(18)(19). Additionally, several studies have shown that TB drug concentrations lower than the expected range are a risk factor for treatment failure (20)(21)(22)(23).…”

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

“…A standard low-fat diet was provided 3, 6, and 12 h after medication intake; the patients were allowed to ingest water ad libitum (17,18). After the drugs were administered, blood samples were collected 0.33, 0.66, 1, 1.5, 2, 2.5, 3,4,6,8,12, and 24 h postdose. Plasma was immediately separated and frozen at Ϫ80°C prior to analysis.…”

“…T2DM was associated with more-severe clinical manifestations (adjusted odds ratio [OR] ϭ 1.80), delayed sputum conversion (OR ϭ 1.51), and a higher probability of treatment failure (OR ϭ 2.93) (9). Differences in the pharmacokinetics (PK) of rifampin (RIF), the most important anti-TB concentration-dependent drug, may contribute to an increased risk of TB treatment failure for diabetic patients (10)(11)(12)(13)(14). Additionally, the study by Jiménez-Corona et al showed that TB recurrence in diabetic individuals compared with nondiabetic individuals was caused by MTC of the same genotype in 81% of cases, indicating a predominance of relapse over exogenous reinfection (9).…”