An 85–year–old man received the last of twelve treatments of intravesical Bacillus Calmette–Guérin (BCG) for transitional cell carcinoma of the bladder. Urinary catheter placement was difficult and complicated by hematuria. Over the next week, he developed fever, malaise and anorexia. His primary physician admitted him to a local hospital, where he was noted to be febrile and hypoxic. A CXR showed diffuse interstitial infiltrates. Admission labs revealed hyponatremia, acute kidney injury and transaminitis. Blood and urine cultures were obtained but grew no organisms. Despite empiric levofloxacin and ceftriaxone, his status worsened; febrile episodes continued and were accompanied by runs of SVT. He was transferred to our hospital for further evaluation and treatment. Upon presentation, he was afebrile and breathing comfortably on 6 L/min supplemental O2. Twelve hours later he was delirious, febrile, tachycardic, and required 100% O2. He was moved to the ICU for NIPPV, where rifampin and isoniazid were empirically initiated for Mycobacterium bovis sepsis. Other bacterial, viral and fungal etiologies were exhaustively ruled out. After 48 hours, he remained critically ill. Methylprednisolone was added to treat hypersensitivity pneumonitis. Subsequently, his oxygenation improved and his hepatic enzymes normalized. His renal function, however, did not fully recover. He was discharged to a rehabilitation facility with plans for 6 months of anti–tuberculous therapy and a steroid taper. At 1 month, he was doing well but has subsequently been lost to follow up.
Disseminated M. bovis is an uncommon complication of intravesical BCG therapy, affecting less than 1% of patients. BCG sepsis occurs in less than 0.5% and carries a high mortality rate. Dissemination can also manifest as pneumonitis, hepatitis, nephritis, osteomyelitis or cytopenias. Pathophysiology is believed to be related to either hematogenous spread of organisms, hypersensitivity reactions to M. bovis proteins, or both. Risk factors include cystitis and urologic trauma, which allow for hematogenous spread of mycobacteria. Diagnosis is based on clinical, laboratory and radiographic findings. Blood and urine cultures should be performed but may be negative. Biopsy of affected organs may reveal granulomata. Early treatment with rifampin, isoniazid and corticosteroids is essential and BCG immunotherapy should be discontinued.
Hospitalists often manage patients receiving treatment for malignancy. In patients receiving intravesical BCG, fever with hypoxia and hepatic or renal dysfunction may be signs of disseminated M. bovis with sepsis and/or hypersensitivity reaction. Anti–tuberculous agents with systemic corticosteroids are the treatments of choice.
Figure 1Interstitial infiltrates.