We evaluated the in vivo therapeutic activities of benzoxazinorifamycin KRM-1648, clarithromycin (CAM) and levofloxacin (LVFX) against Mycobacterium avium infectioninduced in mice. Mice infected intravenously with M. avium (1.4×107) were given KRM-1648 (20mg/kg), CAM (10mg/kg), or LVFX (5 mg/kg) alone, or combination of KRM-1648 with diclofenac sodium (1.25mg/kg) by gavage, once daily, five times per week, from day 1 for up to 8 weeks. The bacterial loads in the lungs and spleens were determinedby counting colony forming units of the organisms in the tissue homogenates of the visceral organs using 7H11 agar plates. Both KRM-1648 and CAM caused significantlevels of bacteriological response in mice treated with these drugs, while LVFX exertedno appreciable therapeutic effect. The therapeutic efficacies of test antimicrobials were intheorder, KRM-1648>CAM>>LVFX. The combined use of diclofenac sodium with KRM-1648 did not affect the expression of therapeutic activity of KRM-1648. This excludes thepossibility that cyclooxygenase-dependent inflammatory reactions may beinvolved in theestablishment of persistent bacterial growth of M. avium organisms at the sites of infectionin mice. Furthermore, the present study showed that the parameters of in vitroantimicrobial activities of drugs such as MIC and MBC values are not useful in predictingtheir therapeutic outcome in M. avium-infected mice.

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We evaluated the cause of death in patients with pulmonary tuberculosis who diedwithin one year after diagnosing as tuberculosis. Of 325 bacillary patients during thepast seven years, 43 (13.2%) died within one year.
Twenty-three patients (53.5%) died directly of tuberculosis. In this group, 13 patientsdied in emaciation state. Most of them were aged and under a poor nutritional condition. Some patients died in spite of improvement of tuberculosis. The fact indicates the needto detect tuberculosis as early as possible in elderly persons, and treatment should be initiatedimmediately. Eight patients died of respiratory failure and their chest X-ray filmshowed wide-spread tuberculosis. Seven of the patients died in spite of initiating treatmentwithin one month after the onset of symptoms. This fact suggests the importanceof regular check up by chest X-ray. to detect tuberculosis early. Two patients diedof massive hemoptysis. They had an episode of bloody sputum and the laboratory examinationshowed anemia.
On the other hand, 20 patients died due to coexisting diseases unrelated to tuberculosis.
Ten patients died of malignant diseases and most of them were lung cancer. Two patientsdied of hepatic failure possibly caused by the adverse reaction of TB chemotherapy. Theinterval between the onset of the treatment and death was less than a month, and thefact suggests the need to observe carefully for adverse reactions especially in the earlystage of treatment.

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