Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

Abstract

Intravesical Bacilli Calmette-Guérin (BCG) immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain) immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin), he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS) prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP) Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin) and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

The role of BCG in prevention of tuberculosis and the strategies to improve its immunogenicity

“…Similarly, systemic BCG infections were sporadically recorded in the course of treatment of the bladder cancer patients [27,28].…”

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer

“…It has been shown that during maintenance of BCG treatment, only 16 % of patients were able to receive all instillations of the 3 years treatment, mainly because of side effects (Lamm et al 2000). Side effects complications can occur as a result of live bacterial use, leading to the appearance of symptoms such as fever, cystitis, pneumonitis, hepatitis, sepsis by BCG, and even death (Brausi et al 2014;Lamm et al 1991;Lamm et al 2000;Lukacs et al 2013;Naudžiunas et al 2012). More than that, treatment-limiting cystitis is observed in approximately 20 % of patients treated with BCG, presumably caused by a combination of increased activation of the immune response and uncontrolled BCG replication.…”

“…More than that, treatment-limiting cystitis is observed in approximately 20 % of patients treated with BCG, presumably caused by a combination of increased activation of the immune response and uncontrolled BCG replication. The most serious complications of BCG immunotherapy for bladder cancer are widely disseminated infection (to the lungs, for example) referred to as BBCGosis^and localized genitourinary tract infection, especially in debilitated patients or those whose immune system is compromised (Gan et al 2013;Lukacs et al 2013;Naudžiunas et al 2012)…”

Screening the activity of anti-tuberculosis drugs against M. bovis BCG Connaught and M. bovis BCG Pasteur growing in J774A.1 cell line macrophages

“…It is attenuated strain derived from M. bovis (Russell et al, 2010). BCG has been known to safely prevent severe form of the disease like childhood pulmonary and meningeal tuberculosis (Roy et al, 2014) and to treat superficial bladder cancer as immunotherapy (Watts et al, 2011 andLukacs et al, 2013). But its administration is not recommended to individuals with impaired cellular immunity since 2007 because of its combined complications (FitzGerald, 2000;Paiman et al, 2006 andArend andvan Soolingen, 2011).…”

“…But its administration is not recommended to individuals with impaired cellular immunity since 2007 because of its combined complications (FitzGerald, 2000;Paiman et al, 2006 andArend andvan Soolingen, 2011). Which may involve lifethreatening side effects including BCG sepsis (Lukacs et al, 2013). These complications combating regime depends on using antituberculosis drugs; with assumption of BCG is fully responsive to these drugs (Kolibab et al, 2011 andFahimzad et al, 2015).…”