Antibacterial activity of adriamycin against bacillus Calmette-Guerin

Although intravesical instillation of bacillus Calmette-Guerin (BCG) or adriamycin (ADR) is an established and effective therapy for superficial bladder cancer, the current major problems are BCG-resistant and ADR-resistant bladder cancer and recurrence after the instillation therapy. Combination therapy with BCG and ADR might overcome the drug-resistance of bladder cancer. However, before combined used of BCG and ADR, it should be clarified whether ADR has bactericidal and bacteriostatic effects on BCG or not, since only alive BCG has a potential antitumor effect. In the current study, the in vitro antibacterial activity of ADR was assessed on BCG by the standard serial two-fold dilution method. When BCG was treated with ADR at 0.13-125 mu g/ml for two hours, ADR had no effect on the viability and the growth of BCG. However, ADR at 250-1,000 mu g/ml had a bactericidal effect on BCG. Epirubicin (EPI) at 0.13-15.6 mu g/ml did not affect the viability and the growth of BCG, however, EPI at 31.3-1,000 mu g/ml had a bactericidal activity. Pirarubicin (THP) at 125-1,000 mu g/ml also had a bactericidal activity. The minimal inhibitory concentrations of ADR, EPI and THP were 250, 250 and 125 mu g/ml, respectively. This study demonstrates that ADR at high concentrations had bactericidal and bacteriostatic effects on BCG. These findings suggest that combination treatment with BCG and low dose ADR could be used and overcome the resistance of bladder cancer to BCG and ADR. The possible clinical implications of the combined use of BCG and ADR are discussed.