Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer

Abstract

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.

Tuberculosis Miliary in Patients Treated With Bacillus Calmette-Guerin Immunotherapy: Case Report

“…In addition, as it has been observed in our patient, the diagnosis is often delayed by the fact that the thorax radiography has a low sensitivity, not allowing the diagnosis in many cases with a disseminated miliary pattern later proven in CT [11]. Sometimes Batista et al J Med Cases.…”

“…A relevant feature in the present case is the isolation of M. bovis in urine, an aspect in favor of the hypothesis of hematogenous dissemination of mycobacteria as a mechanism to explain the systemic complication. The recommended treatment is triple antibiotic therapy (isoniazid, rifampicin and etambutol) for 2 months followed by double therapy (isoniazid and rifampicin) for 4 months [11]. It should be noted that although M. bovis is intrinsically resistant to pyrazinamide [15], several cases have been described in which it was included in the treatment of these patients with no apparent impact on therapeutic success [11].…”

“…The recommended treatment is triple antibiotic therapy (isoniazid, rifampicin and etambutol) for 2 months followed by double therapy (isoniazid and rifampicin) for 4 months [11]. It should be noted that although M. bovis is intrinsically resistant to pyrazinamide [15], several cases have been described in which it was included in the treatment of these patients with no apparent impact on therapeutic success [11]. Our patient showed a rapid improvement in his clinical symptoms right after the start of the quadruple antibacterial therapy.…”

“…In another study involving 2,602 patients, the following systemic complications were observed: high fever > 39.5 °C (2.9%), hematuria (1.0%), granulomatous prostatitis (0.9%), hepatitis or granulomatous pneumonitis (0.7%), arthralgia (0.5%), epididymitis (0.4%), sepsis (0.4%), rash (0.3%), ureteral obstruction (0.3%), bladder contracture (0.2%), renal abscess (0.1%) and cytopenia (0.1%) [10]. In a more recent review that included a total of 282 patients with complications, the authors found more frequent disseminated disease (34.4%), genitourinary infections (23.4%) and musculoskeletal infections (19.9%) [11].…”

Impacto de la ley uruguaya de seguridad vial en la mortalidad por siniestros de tránsito

“…En casos de insuficiencia multiorgánica, la administración de altas dosis de corticosteroides es una parte esencial del tratamiento (23,31,39,40) . En la figura 3 se muestra una propuesta de algoritmo de manejo de las infecciones por M. bovis siguiendo a la inyección intravesical (19) .…”