Analysis on first- and second-line drug resistant patterns in 518 Mycobarterium tuberculosis strains in Shanghai / 中华传染病杂志

Objective To investigate the resistant patterns of Mycobacterium tuberculosis (MTB) strains against first- and second-line anti-tuberculosis drugs. Methods Drug susceptibility tests of 518 MTB strains collected from January 2008 to March 2009 were performed using BactecMGIT 960. The data were analyzed by chi square test. ResultsIn 518 strains, 168 (32.44％) were all sensitive to all seven drugs, 350 (67.56％) were resistant to at least one drug. Among all strains, 72 (13.90％) were resistant to one drug, 24 (4.63％) were resistant to two drugs, 254 (49.03％) were resistant to three or more drugs. A total of 217 strains (41.89 ％) were classified as multi-drug resistant tuberculosis (MDR-TB)strains and 65(12.55％)were extensively drug resistant tuberculosis (XDR-TB) strains which accounted for 29.95 ％ of MDR-TB strains. The drug resistant rate of isoniazid which belonged to first-line drugs was 53.67％ (278 strains) and that of ofloxacin which belonged to second-line drugs was 39.77 ％ (206 strains). In 433 retreated patients, the drug resistant rate against any drugs, MDR rate and XDR rate were 72.05％, 46.42％ and 13.86％,respectively, which were all higher than those in treatment naive patients (44.70％, 18. 82％ and 5.88％, respectively; x2 = 24. 253, x2 ＝ 22. 229 and x2 ＝ 4. 117, respectively; all P ＜ 0.01).ConclusionsThe resistant rate of MTB is high in a tuberculosis specialized hospital in Shanghai, and MDR-TB also shares a high resistant rate as well as XDR-TB. Furthermore, drug resistance is more common in retreated patients.

Effect of Combination Therapy of Isoniazid, Rifampicin, Ethambutol, and Pyazinamide on Theophylline Pharmacokinetics / 결핵

BACKGROUND: Since up to 90% of a theophylline dose is biotransformed, probably by interaction with one or more the variants of the cytochrome P-450 drug metabolism system, anti-tuberculosis agents including drugs influencing microsomal enzyme systems, such as isoniazid and rifampicin, may be affect the elimination of theophylline. METHODS: The effect of combination therapy with isoniazid(INH), rifampicin(RFP), ethambutol(EMB) and pyrazinamide(PZA) on the pharmacokinetics of theophylline was evaluated by a computer program using Bayesian method. Three group were divided as follows. Group lis control, Group II is treated with INH, RFP, EMB and PZA and Group lll is treated with INH, RFP and EMB. All of them were non-smoker who were normal in liver and renal functions, and not administered drugs affecting on the clearance of theophylline with exception of anti-tuberculous agents. RESULTS: When it compared control with test groups, the clearance of theophylline in Group ll and Group lll was significantly decreased(p<0.001), and half life in Group ll and Group lll showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group ll and Group lll. CONCLUSION: These results suggest that theophylline dose may be need of readjustment in concurrent medica fion of anti-tuberculous agents including INH, RFP, and EMB.

CYP1A2 activity as a risk factor for bladder cancer

CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p< 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3-demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer.