Intravesicular Bacillus Calmette-Guerin (BCG) treatment is a common treatment for superficial bladder cancer and is typically not associated with significant systemic side effects. Rarely, systemic dissemination and sepsis have been reported. Here we present a fatal case of dissemination following treatment with intravesicular BCG.
This is an 84 year old male with bladder cancer receiving treatment with intravesicualar BCG infusions. He recalled that his last treatment two months prior to admission was traumatic and he developed fever and chills at home later. One month prior to admission he developed fatigue, night sweats, decreased appetite, and a 10 pound weight loss. A CT scan of the chest revealed diffuse nodularity concerning for miliary tuberculosis. Rifampin, INH, pyridoxime, and levofloxacin were prescribed as outpatient therapy. He continued to have progression of his symptoms with an increasingly productive cough with associated dyspnea and was admitted for the same about four weeks later. The patient developed rapidly worsening hypoxemia with bilateral infiltrates requiring subsequent intubation and institution of mechanical ventilation for acute respiratory distress syndrome (ARDS). Transthoracic echocardiogram revealed absence of cardiac dysfunction. Vancomycin and piperacillin/tazobactam were added to treat a superimposed pneumonia. He was continued on treatment of disseminated M. bovis infection and given intravenous methylprednisolone for a presumed hypersensitivity reaction. The patient underwent a wedge resection of the lung that showed granulomas with central necrosis and diffuse alveolar damage. This was consistent with acute lung injury pattern, likely secondary to BCG dissemination. Cultures, including AFB were negative for an infectious etiology. Autoimmune and vasculitis serology was also negative. Due to his age and his expressed advanced directives of not wanting prolonged mechanical ventilation, his family elected to withdraw care after 48 hours of mechanical ventilation. The patient subsequently expired.
The intavesicular infusion of BCG contains a live attenuated strain of Mycobacterium bovis. It is generally well-tolerated with few complications and the rare cases involving dissemination were associated with cystitis, or, as in our patient a traumatic catheterization. The overall incidence is estimated to be one in 15,000 patients treated with intravesical BCG. Systemic disease can present with hepatitis, pneumonitis, and osteomyelitis. In pneumonitis, there is typically a nodular interstitial or miliary pattern with progressive respiratory compromise. Signs of BCG infection include recurrent fever and night sweats persisting beyond two days. Tissue samples typically do not grow M. bovis and PCR analysis for M. Bovis is also often negative. If there is clinical suspicion for systemic involvement, empiric therapy with rifampin, INH, and pyridoxime for three to six months should be administered. A fluoroquinolone is also usually added if there is concern for concomitant cystitis. Adjunctive glucocorticoids are added with the assumption of a hypersensitivity component.
Disseminated BCG sepsis is a rare, but potentially fatal complication of treatment for superficial bladder cancer. The occurrence of this side effect can be minimized by avoiding BCG instillation in the presence of known cystitis or with traumatic catheterization.
Juan Zeballos Chavez, No Financial Disclosure Information; No Product/Research Disclosure Information