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PubMed1998

Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.

BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.

AIDS-Related Opportunistic Infections↗

PubMed2003

Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid.

Pyrazinamide is an important sterilizing drug that shortens tuberculosis (TB) therapy. However, the mechanism of action of pyrazinamide is poorly understood because of its unusual properties. Here we show that pyrazinoic acid, the active moiety of pyrazinamide, disrupted membrane energetics and inhibited membrane transport function in Mycobacterium tuberculosis. The preferential activity of pyrazinamide against old non-replicating bacilli correlated with their low membrane potential and the disruption of membrane potential by pyrazinoic acid and acid pH. Inhibitors of membrane energetics increased the antituberculous activity of pyrazinamide. These findings shed new light on the mode of action of pyrazinamide and may help in the design of new drugs that shorten therapy.

Antitubercular Agents↗

PubMed2006

pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates from the southeast region of Brazil.

OBJECTIVES: To investigate the presence of mutations in the pncA gene in 31 pyrazinamide-resistant Mycobacterium tuberculosis and 5 susceptible strains. MICs and pyrazinamidase (PZase) activity were also determined. METHODS: All 36 M. tuberculosis clinical isolates were genotyped by mycobacterial interspersed repetitive units (MIRUs) and most were also typed by spoligotyping. The MIC value necessary to inhibit 99% of the resistant mycobacterial isolates was determined by microplate Alamar Blue assay (MABA) and by Löwenstein-Jensen assay (LJA). The PZase activity was measured by pyrazinamide deamination to pyrazinoic acid and ammonia, and the entire pncA sequence including the 410 bp upstream from the start codon was determined by DNA sequencing of purified PCR products. RESULTS: Of the 31 isolates resistant to pyrazinamide, 26 (83.9%) showed at least one mutation in the pncA gene or in its putative regulatory region. Among the 22 different mutations detected in the pncA gene and in its regulatory region, 9 (40.9%) mutations (consisting of six substitutions, two insertions and one deletion) have not been described in previous studies. Three pyrazinamide-resistant isolates, confirmed by MIC varying from 800 to 1600 mg/L, carried the wild-type pncA sequence and retained PZase activity. CONCLUSIONS: These results contribute to the knowledge of the molecular mechanism of pyrazinamide resistance in Brazil and also expand the profile of pncA mutations worldwide. The MABA was successfully used to determine the MICs of pyrazinamide.

Amidohydrolases↗

PubMed2002

Population pharmacokinetic modeling of pyrazinamide in children and adults with tuberculosis.

STUDY OBJECTIVE: To determine population pharmacokinetic parameters of pyrazinamide after multiple oral doses given to children and adults with tuberculosis. DESIGN: Prospective, multiple-dose population pharmacokinetic study. SETTING: Five hospitals in the United States. PATIENTS: Sixty-seven adults and 23 children with active tuberculosis. INTERVENTION: The 90 patients received multiple oral doses of pyrazinamide as part of their treatment, based on the best clinical judgment of the attending physicians and in keeping with standard clinical practices at each institution. The patients also received other antituberculosis drugs empirically or based on in vitro susceptibility data. MEASUREMENTS AND MAIN RESULTS: Serum samples were collected over 12 hours after dosing and were assayed with a validated gas chromatography assay with mass selective detection. Concentration-time data were analyzed by using population methods. Pyrazinamide concentrations increased linearly with increasing oral doses (185-3550 mg). Median maximum serum concentration values were 41.0 microg/ml with daily dosing and 66.1 microg/ml with larger, twice-weekly dosing. Incomplete (18%) or delayed (30%) absorption was more common in children than in adults (1% for each). Pharmacokinetic parameters of pyrazinamide were independent of human immunodeficiency virus status and patient demographics, except for body weight. Population elimination half-life values in pediatric and adult patients were 3.5 and 6.0 hours, respectively. Median volume of distribution (L/kg) was 32% larger in children, and median clearance (L/hr/kg) was 106% larger in children, with a resultant median half-life 43% shorter in children. CONCLUSION: Pyrazinamide concentrations and most pharmacokinetic parameters were comparable to those previously published. Apparent half-life was somewhat shorter than that in previous reports. Compared with adults, absorption of pyrazinamide in children appeared more likely to be incomplete or delayed.

Adult↗

PubMed1990

Alteration in the levels of pyrazinamide in pleural fluid following simultaneous administration of prednisoline in patients of tubercular pleural effusion.

20 Patients of tuberculous pleural effusion were administered a combination of pyrazinamide (30 mg/kg) + isoniazid (300 mg) orally for 7 consecutive days and pyrazinamide was estimated by spectrophotometric method in serum and pleural fluid. Prednisolone was added to the above regimen for next 7 consecutive days and pyrazinamide was again estimated. The level of pyrazinamide in pleural fluid was 23.4 +/- 1.2 (micrograms/ml). Following addition of prednisolone the level increased (27.6 +/- 1.3) significantly (P less than 0.001). The serum pyrazinamide level was not influenced by simultaneous administration of prednisolone. The pleural fluid/serum pyrazinamide ratio was increased from 0.465 to 0.542 by the addition of prednisolone to therapeutic regimen.

Adolescent↗

PubMed1995

Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid.

Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation.

Adolescent↗

PubMed1998

[Eruption after the 1st dose of standard antitubercular chemotherapy. Thoughts on pyrazinamide].

UNLABELLED: We report 3 cases of rash after the first dose of antituberculosis polytherapy, thus raising questions concerning the procedures to be followed. CASE REPORT: Three patients developed a pruritic rash 1 hour after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol given simultaneously. The eruption did not recur after readministration of isoniazide and rifampicine successively. Pyrazinamide, which was readministered last (at the full dose in one case and at progressive doses in the two others), induced a recurrence in two of them. Pyrazinamide was definitively withdrawn in one patient with recurrence and slower pyrazinamide readministration allowed continuation of treatment in the other two patients. CONCLUSION: Since pyrazinamide appeared to be responsible for rash following the first administration of antituberculosis polytherapy, a protocol for readministration of the 4 drugs is suggested. If the responsibility of pyrazinamide is confirmed it should be readministered very slowly.

Aged↗

PubMed1976

Adverse reactions to short-course regimens containing streptomycin, isoniazid, pyrazinamide and rifampicin in Hong Kong.

Three studies of drug toxicity were made in Chinese adults with pulmonary tuberculosis admitted concurrently to short-course antituberculosis regimens. The first was of streptomycin plus isoniazid plus pyrazinamide given daily (SHZ regimen), three times a week (S3H3Z3 regimen) or twice a week (S2H2Z2 regimen). The second was of pyrazinamide in the SHZ regimen and PAS in the standard daily combination of streptomycin plus isoniazid plus PAS (SPH regimen). The third was of the SHZ regimen and these 3 drugs plus rifampicin daily (SHRZ regimen). In study 1 (174 SHZ, 185 S3H3Z3, 182 S2H2Z2 patients), the incidence of arthralgia was associated with the number of doses per week (P less than 0.001). The incidence of other reactions, most of which were cutaneous or vestibular, or symptomless increases in the serum alanine transaminase (AIT) concentration, was similar on all 3 regimens. In study 2 (142 SHZ, 137 SPH patients), hepatic reactions occurred on the SHZ but not on the SPH regimen (P less than 0.002), serum AIT concentrations were distributed over a higher range on the SHZ regimen, and 2 patients had jaundice. Gastrointestinal reactions were more frequent on the SPH regimen (P = 0.06). Arthralgia was commoner on the SHZ regimen (P less than 0.05). In study 3 (38 SHZ, 41 SHRZ patients), the incidence of hepatic reactions, jaundice and arthralgia was similar in the 2 regimens. On the pyrazinamide regimens combined, hepatic reactions were marginally more frequent in patients with Australia antigen or antibody either before or during chemotherapy (P = 0.09). Serum uric acid concentrations were higher in patients on daily than on intermittent pyrazinamide (P less than 0.005), and in patients with arthralgia on the daily pyrazinamide regimen than in matched controls (P = 0.07).

Aminosalicylic Acids↗

PubMed2003

Evaluation of bioequivalence of isoniazid and pyrazinamide in three and four drugs fixed dose combinations using WHO simplified protocol.

The reliable supply of quality drugs in the form of fixed dose combination (FDC) is an essential part of tuberculosis treatment. The objective of this investigation was to evaluate whether the World Health Organization (WHO) simplified screening protocol for the bioequivalence assessment of rifampicin can be used for the evaluation of other components of FDC so as to ensure the bioavailability of all drugs at tissue site. These bioequivalence studies were conducted on 20 and 22 healthy male volunteers for evaluation of three and four drugs FDC formulations, respectively. Both studies were conducted as randomized, open, crossover trials and sampling schedule was upto 8h according to WHO recommended protocol for evaluation of rifampicin bioequivalence. The bioequivalence of isoniazid and pyrazinamide were estimated using AUC(0-8), AUC(0-alpha), and C(max). FDC formulation was considered bioequivalent to separate formulations for isoniazid and pyrazinamide if bioequivalence limit fall in between 0.80 and 1.25. Bioequivalence estimates of AUC(0-8) and AUC(0-alpha) for isoniazid and all the three pharmacokinetic measures of pyrazinamide were within the acceptable limits, whereas C(max) of isoniazid from four drugs FDC was outside the limit when evaluated by two-way ANOVA. After evaluation of isoniazid and pyrazinamide based on their pharmacokinetics, it was found that C(max) is being affected by limited sampling time points of WHO protocol. Further, AUC was a robust parameter unaffected by sampling schedule adopted. The WHO simplified protocol for assessment of rifampicin is also suitable for evaluating bioequivalence of isoniazid and pyrazinamide from FDC formulations. However, for comparison of rate of absorption by means of C(max), careful evaluation of concentration-time profile along with pharmacokinetics is necessary before final judgment.

Administration, Oral↗

PubMed1956

The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug.

Populations of tubercle bacilli of human origin exposed in vivo to pyrazinamide and a companion drug, vanished from the tissues of the mouse in so far as could be determined by microscopy, culture, or guinea pig subinoculation. The vanishing did not represent a complete elimination of the tubercle bacilli from all the animals. 90 days after the completion of treatment, tubercle bacilli could be cultured from approximately one-third of the animals examined at that time. This complete disappearance of the tubercle bacilli thus meets the definition of a truly latent infection in that the infection is present but is hidden beyond the limits of diagnostic reach. All but one of the strains of tubercle bacilli which survived in the animals and were detectable in the posttreatment period, were susceptible to pyrazinamide when tested under appropriate conditions in vitro. Only two factors could be identified which were essential for the uniform occurrence of the disappearance of tubercle bacilli: the administration of the pyrazinamide in a high daily dosage for at least eight of a total of 12 weeks of antimicrobial therapy; and the concurrent or prior exposure of the microbial populations to isoniazid or in some cases to other antituberculous drugs. The observations suggest that the ability of pyrazinamide-containing chemotherapies to bring about the disappearance of a tubercle bacillus is closely related to the occurrence of some alteration in the bacillus, essential for maximal pyrazinamide action, in response to environmental influences, including other antituberculous drugs present in the environment.

Animals↗

PubMed2006

A new rapid and simple colorimetric method to detect pyrazinamide resistance in Mycobacterium tuberculosis using nicotinamide.

OBJECTIVES: The purpose of this study was to develop and assess a rapid method for pyrazinamide resistance detection in Mycobacterium tuberculosis using nicotinamide in a colorimetric resazurin assay. METHODS: We have tested M. tuberculosis isolates using nicotinamide in a 96-well format with the redox indicator resazurin (REMA) and compared results using the BACTEC 460-TB system with two concentrations of pyrazinamide (100 and 300 mg/L), as well as the Wayne method for detecting pyrazinamidase activity. Mutations in the pncA gene were detected by DNA sequencing of the pyrazinamide-resistant strains. RESULTS: Out of 95 clinical isolates of M. tuberculosis tested, 25 were determined to be resistant by the Wayne, BACTEC (300 mg/L), and the REMA nicotinamide methods. Using a nicotinamide MIC>250 mg/L as the cut-off for defining resistance, only one strain was falsely labelled as resistant. The REMA nicotinamide assay demonstrated a sensitivity of 100% and a specificity of 98%. The BACTEC (100 mg/L) falsely classified 8 strains as resistant. DNA sequencing detected mutations in 18/22 of the pncA genes from pyrazinamide-resistant strains. CONCLUSIONS: The REMA plate using nicotinamide to detect resistance to pyrazinamide is a simple and rapid method that could be useful in limited-resource countries.

Amidohydrolases↗

PubMed1983

Susceptibility of Mycobacterium tuberculosis to pyrazinamide and its relationship to pyrazinamidase activity.

Pyrazinamidase activity has been associated with pyrazinamide-susceptible Mycobacterium tuberculosis strains. The detection of pyrazinamidase activity by the Wayne method was found to be of limited value when compared with the results of standard pyrazinamide susceptibility tests, especially when a high level of pyrazinamide resistance was found. When resistance to pyrazinamide reached a level of 150 to 200 micrograms/ml, there was too much variability in Wayne test results to accurately define pyrazinamide susceptibility.

Amidohydrolases↗

PubMed1977

Inhibition of probenecid uricosuria by pyrazinamide and para-aminohippurate.

Both para-aminohippurate (PAH) and pyrazinamide inhibited the uricosuric response to probenecid administration. The mechanism of this inhibition of probenecid uricosuria was assessed in 18 male subjects. The decrease in uricosuria was assessed in 18 male subjects. The decrease in uricosuric response to probenecid observed after pyrazinamide administration or PAH infusion occurs by different mechanisms. Administration of PAH and probenecid together resulted in reduced excretion of both drugs. PAH was weakly uricosuric and did not appear to inhibit urate secretion. PAH inhibition of probenecid uricosuria is accounted for by inhibition of probenecid secretion. Probenecid excretion was not affected by pyrazinamide administration. Inhibition of probenecid-induced uricosuria by pyrazinamide is most likely due to inhibition of urate secretion. The urate secretory carrier inhibited by pyrazinamide appears to be independent of that responsible for secretion of probenecid and PAH. Probenecid secretion appears to be required for its uricosuric effect.

Adolescent↗

PubMed1992

The combined effect of rifampin and pyrazinamide within the human macrophage.

A recent study in the murine model suggested that a combination of rifampin and pyrazinamide used as preventive therapy might shorten the duration of treatment time. Clinical trials using this combination have been initiated, but significant results will not be available for many years. The ex vivo human macrophage model has been instructive in expanding our knowledge of the activity of chemotherapeutic agents against intracellular virulent tubercle bacilli. Prior studies have shown rifampin to have a bactericidal effect in this model while even at clinically unachievable levels, pyrazinamide had only a bacteriostatic impact. This study finds an enhanced bacteriostatic effect when low, nonbactericidal levels of rifampin are combined with clinically achievable levels of pyrazinamide but not with higher bactericidal levels of rifampin. Adding pyrazinamide 2 days after the introduction of rifampin clearly enhanced the combined killing effect. However, reversing the order and adding rifampin 2 days after the introduction of pyrazinamide produced a result weaker than introducing the agents simultaneously. Our findings do not support the use of these agents as a potentially effective preventive therapy combination, but they suggest that the timing of the administration of these chemotherapeutic agents could be an important factor in their effectiveness.

Colony Count, Microbial↗

PubMed1996

Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis.

The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%). Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.

Adolescent↗

PubMed2001

Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of tryptophan to niacin and of tryptophan to serotonin in rats.

The effects of pyrazinamide on the metabolism of tryptophan to niacin and of tryptophan to serotonin were investigated to elucidate the mechanism for pyrazinamide action against tuberculosis. Weanling rats were fed with a diet with or without 0.25% pyrazinamide for 61 days. Urine samples were periodically collected for measuring the tryptophan metabolites. The administration of pyrazinamide significantly increased the metabolites, 3-hydroxyanthranilic acid and beyond, especially quinolinic acid, nicotinamide, N'-methylnicotinamide, and N1-methyl-4-pyridone-3-carboxamide, and therefore significantly increased the conversion ratio of tryptophan to niacin and the blood NAD level . However, no difference in the upper metabolites of the tryptophan to niacin pathway such as anthranilic acid, kynurenic acid and xanthurenic acid was apparent between the two groups. No difference in the concentrations of trytptophan and serotonin in the blood were apparent either. It is suggested from these results that the action of pyrazinamide against tuberculosis is linked to the increase in turnover of NAD and to the increased content of NAD in the host cells.

Animals↗

PubMed1995

Chemoprophylaxis of multidrug-resistant tuberculous infection in HIV-uninfected individuals using ciprofloxacin and pyrazinamide. A decision analysis.

STUDY OBJECTIVE: To evaluate the use of ciprofloxacin and pyrazinamide for the prophylaxis of individuals infected with multiply drug-resistant strains of Mycobacterium tuberculosis. DESIGN: Decision analysis, using software (SMLTREE). Probabilities based on published studies, with sensitivity analysis for each probability. SETTING: Health-care workers infected with multidrug-resistant strains of M tuberculosis. INTERVENTIONS: Prophylaxis with ciprofloxacin and pyrazinamide. MEASUREMENTS AND RESULTS: We calculated the utilities of taking or not taking prophylaxis with ciprofloxacin and pyrazinamide. The decision analysis favored the use of ciprofloxacin-pyrazinamide prophylaxis by a small margin. CONCLUSION: Ciprofloxacin-pyrazinamide prophylaxis should be considered for health-care workers infected with multiply drug-resistant M tuberculosis.

Adult↗

PubMed2000

[The effectiveness of pyrazinamide-containing six-month short course chemotherapy].

Incidence of tuberculosis worldwide will increase progressively unless the effective program is implemented immediately. In Japan, the decreasing of tuberculosis incidence has been very slow since 1977 and this trend has not been improved till now. Six-month regimens for the treatment of tuberculosis were recommended by IUATLD, ATS, CDC, and WHO and have been adopted in most developed countries since late 1980s, but not adopted in Japan till April, 1996. We studied effectiveness of 6-month regimen including pyrazinamide (2HRZS or E/4HRE) on newly diagnosed pulmonary tuberculosis who started the treatment in the Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA). From January 1991 to December 1997, 726 newly diagnosed pulmonary tuberculosis patients started treatment with 6-month regimen. Bacillary negative conversion rate among 424 patients whose bacilli were susceptible to both isoniazid and rifampicin, was 92.9% after 2 months of treatment and who completed treatment without change of treatment regimen. Among 726 cases, 593 (81.7%) succeeded, 48 (6.6%) defaulted, 53 (7.3%) were referred to other doctors, and 32 (4.4%) died. The relapse rate after completion of the treatment was 3.2 percent among 345 patients whose bacilli were susceptible to both isoniazid and rifampicin and who completed the treatment without change of regimen. The relapse rate among the patients complicated with diabetes mellitus (DM) was higher than that among non-DM patients (6.31/100 person-years vs 0.90/100 person-years) (P < 0.001). When drug-induced hepatitis was defined as the elevation of serum liver enzyme levels with the clinical symptoms of hepatitis or their elevation over 5 times of normal upper limit, the incidence of drug-induced hepatitis among the patients treated with pyrazinamide-containing 6-month regimen was not higher than that among the patients treated with 9-month regimen without pyrazinamide (6HRS or E/3HR) (7.9% vs 7.3%). The risk factors for drug-induced hepatitis included elderly, history of gastrectomy, hypoalbuminemia, the higher dose of isoniazid over than 7.5 mg/kg, higher than 30 mg/kg of pyrazinamide and positive HCV antibody. The effectiveness of 6-month regimen on the patients whose organisms were resistant to isoniazid and susceptible to rifampicin was studied. The average duration of the treatment for the patients started 6-month regimen was 3.2 months shorter than for the patients started 9-month regimen (10.2 months vs 13.4 months). I concluded that 6-month regimen containing-pyrazinamide was effective for the patients with isoniazid-rifampicin susceptible tuberculosis patients except the patients complicated with diabetes mellitus. But the frequency of drug-induced hepatitis was higher than that of previous reports, and further studies are needed to elucidate the cause of high frequency of hepatitis among Japanese patients.

Adult↗