Sensitivity of BCG to modern antibiotics

The viability of bacillus Calmette-Guérin (BCG) in intravesical instillation therapy has been demonstrated to be crucial for the prevention of bladder tumour recurrence. The aim of the present study was to determine the effects of modern antibacterial chemotherapeutics on BCG viability, particularly cycloserine, which has been recommended in the treatment of BCG-induced sepsis. The minimal inhibitory concentrations (MICs) of 32 antibacterial drugs potentially effective against the Connaught BCG strain were measured in vitro by the radiometric BACTEC 460TB method. The MICs were compared with the drug concentrations achievable in blood and urine. Susceptibility testing of cycloserine was performed with three different strains (Connaught, Tice and RIVM), using the modified proportion method, as defined in the German guidelines for anti-tuberculosis drug testing. The Connaught BCG strain was highly susceptible to fluoroquinolones, but was resistant to beta-lactams, macrolides (except clarithromycin), and some aminoglycosides. It was also sensitive to doxycycline and gentamicin at dosages that typically occur in the urine of patients after a normal dose. Connaught BCG was susceptible to all the tuberculostatic drugs tested, except for pyrazinamide. All the BCG strains analysed were resistant to cycloserine. During intravesical BCG instillation therapy, simultaneous administration of fluoroquinolones, doxycycline or gentamicin should be avoided. In cases of severe systemic complications, or if one of the antituberculosis drugs is not tolerated, fluoroquinolones may be used. Cycloserine is no longer recommended for the early treatment of BCG sepsis.