[Pyrazinamide-containing initial intensive short course chemotherapy of pulmonary tuberculosis]

Six-month short course regimen had been accepted all over the world since early 1980s. In Japan this short course regimen had not been accepted as a standard regimen for treatment of pulmonary tuberculosis until April 1996. The reason why this was not accepted is resumably due to hepatotoxicity of pyrazinamide. The situation around tuberculosis were changing in Japan especially in urban areas. Incidence of tuberculosis in younger generations is higher in urban areas than in rural areas. More effective and shorter course regimen were needed. Efficacy of pyrazinamide were briefly described first, then results of six-month regimen with pyrazinamide in Fukujuji Hospital since 1991 January were discussed. Pyrazinamide can kill tubercle bacilli in acidic environment. It works bacericidally during the early treatment phase. It can kill not only replicating bacilli but also semidormant ones. The results of many six-month regimens showed that only pyrazinamide containing regimens were acceptable for standard regimen in pulmonary tuberculosis with less than a few percent of relapse. Newly accepted standard chemotherapy included 2HRZ with or without S or E/4HRE, 6HRS or E/3HR, and 6HR. Among 429 tuberculosis patients treated at Fukujuji Hospital with pyrazinamide-containing regimens, the negative conversion rate after two months of chemotherapy was 95 percent and similar to those of Western, African and Asian tuberculosis trials. Six of 290 evaluable cases have relapsed. (relapse rate; 2%) Noticeably all relapsed cases were complicated with diabetes mellitus. The higher percent of patients, 8.2 had elevated serum transaminase levels 5 times of upper limit of normal level or more compared with that of patients without pyrazinamide, 6.6 percents, but this difference is not statistically significant. One patient whose pretreatment liver function was abnormal with unknown origin died from hetatoxicity of anti-tuberculous drugs. The risk factors of hepatotoxicity included HCV carrier, elderly more than 80 years old, but HB carrier, alcohol drinking and hepatic diseases were not risk factors. Less patients, 5.6% defaulted from regimen compared with that with 9-month regimen without pyrazinamide (8.6%), but this difference is not statistically significant. The efficacy of the regimen was 90.3% higher than that of 9-month regimen, 86.0% In summary, six-month regimen containing pyrazinamide is highly effective. The incidence and severity of hepatotoxicity must be further studied in Japan.