Infectious complications of intravesical BCG immunotherapy

Grubišić-Čabo F, Paić M, Bošnjak M, Mojsović A, Jajac-Bručić L, Reljić D, OB Šibenik

Intravesical application of bacillus Calmette- Guerin (BCG), a live attenuated strain of Mycobacterium bovis, is a mainstay of adjunctive therapy for superfitial bladder cancer. Symptoms of bladder irritation, such as dysuria and frequency, develop in the majority of patients within two to four hours of BCG instillation. Low-grade fever and malaise may also occur. Such manifestations generally resolve within 48 hours, without need for other therapy but analgetics. While generally well tolerated, in less then 5 percent of patients¹, severe side events, both local and systemic, can occur. The most common complications were: fever ( 2,9%), significant hematuria ( 1%), granulomatous prostatitis ( 0,9%), pneumonitis and/or hepatitis ( 0,7%), arthralgia ( 0,5% ), epididimytis ( 0,4%), sepsis ( 0,4%), ureteral obstruction ( 0,3%), contracted bladder ( 0,2%), renal abscess ( 0,1%), cytopenia ( 0,1%).

Fever higher than 39 °C may occasionally develop acutely, but does not necessarily signify BCG infection. Local symptoms from BCG infection cannot be distinguished from infection due to other organisms. This represents a problem while up to 20 percent of patients receiving intravesical BCG develop, during the treatment, conventional bacterial urinary tract infection. The cardinal sign of BGC infection is relapsing fever with drenching night sweats persisting beyond 48 hours. For patients with symptoms of moderate to severe cystitis persisting beyond 48 hours following instillation usually the treatment consists of fluoroquinolone or isoniazid. If the symptoms progress, or fail to resolve, within one to weeks isoniazid should be continued and rifampin may be added.

For disseminated BCG infection mostly triple antituberculotic therapy in indicated , with or without glucocorticoids. BCG infection can present herself early or late ( > 1 year) after the intravesical application of therapy, and could manifest herself localy or distant (systemic). Once BCG has been administered intravesicaly the possibility of BCG infection has to be considered, even years after instillation.

1) Lamm DL. Efficacy and safety of bacille Calmette-Guerin immunotherapy in superfitial bladder cancer. Clin Infect Dis 2000; 31 Suppl 3: S86.