[Experimental investigations of the optimal therapy of systemic BCG infection in vivo].
OBJECTIVE
Hematogenous spread of BCG after intravesical instillation against bladder cancer is rare, but may result in systemic infection and hypersensitivity reaction. We investigated fluoroquinolones and steroids in an animal model to improve the therapeutic options in local and systemic BCG infection. Furthermore, we tested the antitumor effectiveness of intravesical BCG with simultaneous application of fluoroquinolones and/or steroids.


METHODS
After systemic BCG infection, experiments were performed with quinolones as antimicrobial agent. Trimethoprim/sulfamethoxazole (TMS) was also tested in comparison to quinolones as a non-specific antimicrobial agent. To evaluate the hyperergic reaction after repeated BCG infection (hypersensitivity model), re-infection was performed seven days after primary infection with accompanying oral antimicrobial therapy with and without steroids. Intravesical tumor therapy was carried out with BCG in orthotopic murine bladder tumor model MB 49 together with simultaneous antimicrobial therapy.


RESULTS
After primary infection, quinolones led to a significant prolonged survival independent of steroid administration. Steroids alone after primary BCG infection reduced the survival. In contrast to these experiments, only steroid-treated mice had a significant improvement in survival after a second challenge with BCG. Therapeutic efficacy of BCG was not affected by antibacterial therapy with quinolones. Steroids alone induced a significantly increased death rate during intravesical BCG therapy.


CONCLUSIONS
Quinolones have a positive effect on survival in acute systemic BCG infection in mice. Re-infection with BCG led to severe hyperergic reaction that can only be influenced by steroids. Thus, quinolones can be used in primary systemic BCG infection after topical application as a sufficient alternative to common tuberculostatics. Repeated BCG instillation may lead to hyperergic reaction, making additional administration of steroids essential. In this animal model, therapeutic efficacy of BCG obviously was not affected by additional administration of antimicrobials.
Jurczok
A
A
Universitätsklinik und Poliklinik für Urologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, 06112 Halle/Saale, Germany. andreas.jurczok@medizin.uni-halle.de
Zacharias
M
M
Böhle
A
A
Fornara
P
P
Jocham
D
D
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000209:etiology; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D015363:Quinolones / Q000627:therapeutic use; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy / Q000662:veterinary; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001500:BCG Vaccine; D015363:Quinolones
Experimentelle Untersuchungen zur optimalen Therapie der systemischen BCG-Infektion in vivo.