Isoniazid resistance among Bacillus Calmette Guerin strains: implications on bladder cancer immunotherapy related infections.

Bacillus Calmette Guerin (BCG) immunotherapy is widely used for treatment of superficial bladder transitional cell carcinoma. Infectious complications while rare can be serious and severe disseminated infections as well as sepsis has been reported. There are no standard guidelines to direct therapy of these complications. Isoniazid is a commonly and widely used component of the various treatment regimens. Various strains of BCG are used for treatment of bladder cancer as well as vaccinations. These strains have evolved because of repeated subcultures in various laboratories in the world and have been shown to exhibit phenotypic differences in their immunogenicity as well as recently in susceptibility to various antimycobacterial agents. In this article, we review the resistance of BCG strains to various antimycobacterial agents. Some of these strains including the BCG Connaught strain, which is widely used in the United States, Canada and some other parts of the world for bladder cancer therapy exhibit intrinsic resistance to isoniazid. Although the clinical relevance of these differences is unclear, recent studies have questioned the role of isoniazid in treatment of infections after vaccination with these strains. Also, use of isoniazid in combination therapy for these infections may lead to the development of resistance to other antimycobacterial agents. We conclude that isoniazid may not be a suitable agent for empiric treatment of infections related to intravesical immunotherapy for bladder cancer with these strains and further studies are needed to clarify its role.