Case Presentation: A 69 year-old man with history of high-grade invasive urothelial bladder cancer post tumor resection on Bacillus Calmette-Guérin (BCG) treatment and renal cell carcinoma post left partial nephrectomy presented with high-grade fever, night sweats, rigors, and lower abdominal pain for 2 weeks. The last BCG instillation, of 11 total, was 17 days prior to admission. After the 9th treatment and routine cystoscopy, the patient developed urinary retention that resolved with a course of Levofloxacin. 3 days after the final instillation, he developed symptoms and presented to the emergency department. Physical exam was significant for mild suprapubic tenderness and absent costovertebral angle tenderness. Urinalysis was negative except small leukocyte esterase and few bacteria. He was treated with Levofloxacin and Cefepime for 7 days during which he continued to spike daily high-grade fevers with maximum of 40°C. A CT scan showed heterogeneous left renal enhancement with enlargement and edema, plus diffuse thickening and enhancement of the left ureter indicating ureteropyelonephritis. All blood and urine culture were negative. A working diagnosis of disseminated BCG infection was made and patient was started on empiric BCG-osis treatment with Ethambutol (ETH), Isoniazid (INH), and Rifampin. Fever defervesced after 2 days, and the patient was discharged with close outpatient follow up. The patient remained afebrile and asymptomatic. 4 weeks into BCG-osis treatment, another screening eye exam found choroidal lesions and mild retinal vasculitis consistent systemic blood-borne tuberculosis. The patient had a repeat CT 10 weeks into treatment which showed resolution of the ureteropyelonephritis. He completed an 8-week course of ETH, and due to ocular involvement INH and Rifampin were extended to 6 months.
Discussion: BCG is a live attenuated strain of Mycobacterium bovis which has become a mainstay of adjuvant therapy for superficial bladder cancer. Treatment with BCG exposes the patient to possible serious infections. The most serious infection is a disseminated BCG infection which could cause sepsis and involve different organs such as lung, bone, liver etc. In one patient, a delayed endophthalmitis was diagnosed. Our patient has 3 weeks of high-grade fevers, rigors, and night sweats which did not respond to Levofloxacin and Cefepime. Work up showed a sterile ureteropyelonephritis and later choroidal lesions/mild vasculitis on fundoscopic exam consistent with systemic blood-borne tuberculosis. He defervesced shortly after initiation of three drugs. Repeat imaging study 10 weeks later showed a resolution of his pyelonephritis. Our patient has negative urine and blood cultures for Mycobacterium, possibly a false negative due to prior treatment with Levofloxacin. Ocular BCG was found incidentally 6 weeks later despite absence of ocular symptoms and a normal baseline exam, suggesting patients treated for BCG infection might benefit from repeat eye exam during treatment to rule out ocular dissemination.
Conclusions: In a patient on intravesical BCG treatment for bladder cancer presenting with unremitting high-grade fever, rigors, and night sweats, disseminated BCG infection should be suspected and treated promptly. Negative urine and blood cultures for Mycobacterium should not hinder the empiric treatment with anti-tuberculosis drugs to ensure a positive clinical outcome.