Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature.
Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.
Unit of Infectious Diseases (MAPJA, MFR, FLM, CL, RSJ, ML, JMA), Department of Urology (AT, AAP), and Department of Internal Medicine (SP), Hospital Universitario "12 de Octubre," Instituto de Investigación Hospital "12 de Octubre" (i+12), Madrid, Spain.
María Asunción
MA
Pérez-Jacoiste Asín
Mario
M
Fernández-Ruiz
Francisco
F
López-Medrano
Carlos
C
Lumbreras
Ángel
Á
Tejido
Rafael
R
San Juan
Ana
A
Arrebola-Pajares
Manuel
M
Lizasoain
Santiago
S
Prieto
José María
JM
Aguado
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000283:Administration, Intravesical; D000368:Aged; D000995:Antitubercular Agents; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000453:epidemiology* / Q000209:etiology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D000995:Antitubercular Agents; D001500:BCG Vaccine