TY - JOUR
T1 - Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in indonesian pulmonary tuberculosis patients
AU - Burhan, Erlina
AU - Ruesen, Carolien
AU - Ruslami, Rovina
AU - Ginanjar, Arum
AU - Mangunnegoro, Hadiarto
AU - Ascobat, Purwantyastuti
AU - Donders, Rogier
AU - Van Crevel, Reinout
AU - Aarnoutse, Rob
PY - 2013/8
Y1 - 2013/8
N2 - Numerous studies have reported low concentrations of antituberculosis drugs in tuberculosis (TB) patients, but few studies have examined whether low drug concentrations affect TB treatment response. We examined steady-state plasma concentrations of isoniazid, rifampin, and pyrazinamide at 2 h after the administration of drugs (C2 h) among 181 patients with pulmonary tuberculosis in Indonesia and related these to bacteriological response during treatment. C2 h values below reference values for either isoniazid, rifampin, or pyrazinamide were found in 91% of patients; 60% had at least two low C2 h concentrations. The isoniazid C2 h was noticeably lower in fast versus slow acetylators (0.9 mg/liter versus 2.2 mg/liter, P<0.001). At the end of treatment, 82% of the patients were cured, whereas 30 patients (17%) had dropped out during the study, and 2 patients (1%) failed treatment. No association was found between C2 h concentrations and sputum culture results at 8 weeks of treatment. Post hoc analysis showed that patients with low pyrazinamide C2 h (P0.01) and patients with large extensive lung lesions (P0.01) were at risk of at least one positive culture at week 4, 8, or 24/32. Antituberculosis drug concentrations were often low, but treatment response was nevertheless good. No association was found between drug concentrations and 8 weeks culture conversion, but low pyrazinamide drug concentrations may be associated with a less favorable bacteriological response. The use of higher doses of pyrazinamide may warrant further investigation.
AB - Numerous studies have reported low concentrations of antituberculosis drugs in tuberculosis (TB) patients, but few studies have examined whether low drug concentrations affect TB treatment response. We examined steady-state plasma concentrations of isoniazid, rifampin, and pyrazinamide at 2 h after the administration of drugs (C2 h) among 181 patients with pulmonary tuberculosis in Indonesia and related these to bacteriological response during treatment. C2 h values below reference values for either isoniazid, rifampin, or pyrazinamide were found in 91% of patients; 60% had at least two low C2 h concentrations. The isoniazid C2 h was noticeably lower in fast versus slow acetylators (0.9 mg/liter versus 2.2 mg/liter, P<0.001). At the end of treatment, 82% of the patients were cured, whereas 30 patients (17%) had dropped out during the study, and 2 patients (1%) failed treatment. No association was found between C2 h concentrations and sputum culture results at 8 weeks of treatment. Post hoc analysis showed that patients with low pyrazinamide C2 h (P0.01) and patients with large extensive lung lesions (P0.01) were at risk of at least one positive culture at week 4, 8, or 24/32. Antituberculosis drug concentrations were often low, but treatment response was nevertheless good. No association was found between drug concentrations and 8 weeks culture conversion, but low pyrazinamide drug concentrations may be associated with a less favorable bacteriological response. The use of higher doses of pyrazinamide may warrant further investigation.
UR - http://www.scopus.com/inward/record.url?scp=84880278465&partnerID=8YFLogxK
U2 - 10.1128/AAC.02468-12
DO - 10.1128/AAC.02468-12
M3 - Article
C2 - 23689725
AN - SCOPUS:84880278465
VL - 57
SP - 3614
EP - 3619
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 8
ER -