Severe Infectious Complications of Intravesical Bacillus Calmette-Guérin: A Case Series of 10 Patients

Yong, Courtney; Steinberg, Ryan L.; O’Donnell, Michael A.

doi:10.1016/j.urology.2019.10.013

Cited by 12 publications

(18 citation statements)

References 20 publications

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“…Multiple-dose BCG vaccine was used for reversing type-1 diabetes & for treating bladder cancer [4][5]. While intravesical multiple doses of BCG for bladder cancer showed many complications [6][7], intradermal multiple doses of BCG for diabetes showed high safety profile [4].…”

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confidence: 99%

COVID-19 vaccination clinical trials should consider multiple doses of BCG

Ayoub¹

2020

Preprint

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Vaccine repositioning is a hot research topic as an alternative to the traditional vaccine approach, which is a costly and time-consuming process due to the availability of previous safety and toxicology data. Multiple-dose BCG vaccine repurposing for COVID-19 will be an uprising breakthrough of vaccine discovery with safer outcomes. BCG induces cross-protection that might not be related to the target disease as innate immune cells, including monocytes and natural killer cells, contribute to this immune protection as known as “trained immunity” [1]. BCG had multifaceted protection against TB, Leprosy & heterogeneous pathogens [2]. Moreover, it was repositioned as a treatment for type-1 diabetes, many types of cancer & multiple sclerosis [2]. BCG vaccine accelerates the “resetting” of the immune system [3] or “turn on” immunity mechanism that agrees with its pleiotropic repurposing for many diseases. Multiple-dose BCG vaccine was used for reversing type-1 diabetes & for treating bladder cancer [4-5]. While intravesical multiple doses of BCG for bladder cancer showed many complications [6-7], intradermal multiple doses of BCG for diabetes showed high safety profile [4]. As recent studies have shown that upon certain vaccinations, human innate immune cells can undergo extensive metabolic and epigenetic reprogramming, which results in enhanced immune responses upon heterologous re-infection, a process termed trained immunity [8]; The author recommends that COVID-19 vaccination clinical trials should consider multiple doses of BCG. After reviewing the recent COVID-19 literature, although some preliminary studies suggested BCG to fight COVID-19 [9-12], they did not consider the use of multiple intradermal BCG vaccination (at least 2 doses, 4 weeks apart [4]) for the prophylaxis of COVID-19 outbreak. I do recommend that diabetic patients should participate in clinical trials to benefit from the reported BCG anti-hyperglycemic effect [4]. What if safe multiple doses of BCG turned on the immunity and protected people from COVID-19 more efficiently than a single dose?

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confidence: 99%

COVID-19 vaccination clinical trials should consider multiple doses of BCG

Ayoub¹

2020

Preprint

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“…Among comorbidities, none of them was particularly prevalent a part of hypertension that affected almost the 60% of patients. Even though previous case reports had identified the traumatic use of urinary catheter as a possible risk factor to develop BCGitis after intravesical instillations, we did not confirm this finding since only 10% of our participants were using this device [6][7][8][9][10][11][12]. On the other hand, since our small cohort is retrospective, we are not able to recall if any traumatic catheterization occurred in the rest of the population who did not permanently wear a urinary catheter.…”

Section: N Resultsmentioning

confidence: 62%

“…[5] Among the systemic complications described in the Literature, we may list active tuberculosis (typically associated with a miliary pattern), BCG sepsis, hepatitis, nephritis, meningitis, arthritis, osteomyelitis and also the hypothesis that BCGitis might be due to a systemic immune reaction in place of a direct mycobacterial pathogenic effect has been proposed. There are several case reports describing complications after BCG instillation and a few case series, the last one published in 2021 in Italy [3,[6][7][8][9][10][11][12]. In addition to the broad range of clinical presentations, the difficulty in obtaining direct microbiological demonstration of the mycobacterium and the lack of indirect diagnostic tests lead to diagnostic uncertainty and under reporting.…”

Section: N Introductionmentioning

confidence: 99%

BCGitis after Bacille CalmetteGuerin intravesical administration from two referral centers: clinical characteristics and risk factors

et al. 2022

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Bacillus Calmette-Guerin (BCG) is commonly and safely used as intravesical instillation to treat bladder cancer. Adverse effects are widely described in case report and series with a broad range of clinical presentations known as "BCGitis". Moreover, microbiological identification is often inconclusive leading to diagnostic uncertainty and no standardisation of definitions is available. We retrospectively collected all cases of BCGitis (n=19) after BCG intravesical administration occurred in 2 major Italian hospitals in the last 10 years. Median age was 71.8 years and among comorbidities hypertension affected 60% of patients. The SUMMARY delay in the onset of symptoms was < one week and an inverse correlation was observed between the number of instillations and the time to the onset of symptoms. Moreover, a febrile presentation was the commonest clinical symptom (85%) and an interstitial or micronodular pattern at chest X-ray or CT scan was found positive in about 70% and 90% of cases, respectively. Larger cohorts are needed in order to inform clinically relevant algorythms for this uncommon disease.

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“…The rate of BCG sepsis has been quoted at 0.4% in the largest published series [15,16]. A recent case series of BCG cystitis and disseminated infection identified delayed onset of symptoms (>3 months after last BCG dose) in 70% of patients [17]. In a series of 22 patients with infectious complications during induction BCG, patients developed symptoms after a median of five instillations [18].…”

Section: Discussionmentioning

confidence: 99%

Time interval from transurethral resection of bladder tumour to bacille Calmette–Guérin induction does not impact therapeutic response

et al. 2021

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To investigate bacille Calmette-Gu erin (BCG) tolerability and response with respect to the timing of BCG administration after transurethral resection of bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC). Patients and MethodsA review of patients with NMIBC at our institution managed with at least 'adequate BCG' (defined by the United States Food and Drug Administration as at least five of six induction instillations, with two additional instillations comprising either maintenance or repeat induction) at our institution from 2000 to 2018 was performed. Time from TURBT to first instillation of induction BCG was stratified by quartile and analysed as a continuous variable. Kaplan-Meier and log-rank tests analysed differences in recurrence-free (RFS) and progression-free survival (PFS). Cox proportional hazards regression models identified associations between risk factors and survival outcomes. ResultsA total of 518 patients received adequate BCG at a median (range) of 26 (6-188) days from TURBT. Overall, 45 patients (9%) developed BCG intolerance at a median (range) 12 (7-33) instillations. When time from TURBT to BCG was stratified into quartiles, there was no difference with respect BCG intolerance (P = 0.966), RFS (P = 0.632) or PFS (P = 0.789). On both uni-and multivariate regression analysis for RFS and PFS, time from TURBT to BCG was not a significant predictor when analysed by quartile or as a continuous variable (the hazard ratio for RFS was 1.00, 95% confidence interval [CI] 0.99-1.00, P = 0.449; and for PFS was 0.99, 95% CI 0.98-1.00, P = 0.074). ConclusionThe rates of tolerability and response to adequate BCG are not predicated by the timing of induction BCG instillation after TURBT. Early administration in properly selected patients is safe and delays do not affect therapeutic response.

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Severe Infectious Complications of Intravesical Bacillus Calmette-Guérin: A Case Series of 10 Patients

Cited by 12 publications

References 20 publications

COVID-19 vaccination clinical trials should consider multiple doses of BCG

COVID-19 vaccination clinical trials should consider multiple doses of BCG

BCGitis after Bacille CalmetteGuerin intravesical administration from two referral centers: clinical characteristics and risk factors

Time interval from transurethral resection of bladder tumour to bacille Calmette–Guérin induction does not impact therapeutic response

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