Disseminated Mycobacterium Sepsis with Bone
Marrow, Liver, and Lung Involvement Following
Intravesical Bacillus Calmette-Guerin (BCG)
Therapy
Drew Hager, MD, Zeenib Kohja, MD, Terry Wuerz, MD, Arjuna Ponnampalam, MD
About the Authors:
Drew Hager is PGY-2 Internal Medicine at the University of Manitoba, Winnipeg, MB. Zeenib Kohja is with the Max Rady College
of Medicine at the University of Manitoba. Terry Wuerz is with the Department of Internal Medicine - Infectious Diseases at the
University of Manitoba. Arjuna Ponnampalam is with the Department of Internal Medicine Hematology at the University of
Manitoba
Submitted: April 24, 2018. Accepted: July 5, 2018. Published: May 21, 2019. DOI:10.22374/cjgim.v14i2.283
Abstract
Introduction
Bacillus Calmette-Guerin (BCG) therapy is first-line therapy for high grade non-muscle invasive
bladder cancer (NMIBC).
Case Presentation
A 54-year-old male presented with fevers, rigors, and hematuria one week following intravesical
BCG administration for treatment of NMIBC. He developed fever, pancytopenia, elevated liver
enzymes and pulmonary infiltrates with the progression of symptoms despite broad-spectrum
antimicrobial therapy. A bone marrow biopsy showed granulomatous infiltration; cultures of
urine demonstrated the growth of Mycobacterium bovis. A diagnosis of disseminated BCG
infection secondary to intravesical administration was made; rifampin, isoniazid, ethambutol,
and high dose prednisone were initiated.
Conclusion
Adverse events associated with BCG administration have been attributed to both the primary
mycobacterium infection and to hypersensitivity reactions. Timely collection of histopathology
can lead to early treatment of disseminated BCG with good outcomes. Internists should have
a high index of suspicion for patients presenting with organ dysfunction with an immediate or
remote history of intravesical BCG administration.
RESUME
Introduction
Le Bacillus Calmette-Guerin (BCG) est le traitement de première intention du cancer de la vessie
non invasif non musculaire (NMIBC) de haut grade.
Canadian Journal of General Internal Medicine
34 Volume 14, Issue 2, 2019
Case Study
Présentation de cas
Un homme de 54 ans a présenté des fièvres, des rigueurs et une hématurie une semaine après
ladministration intravésicale de BCG pour le traitement du NMIBC. Il a développé de la fièvre,
une pancytopénie, une élévation des enzymes hépatiques et des infiltrations pulmonaires avec la
progression des symptômes malgré un traitement antimicrobien à large spectre. Une biopsie de
moelle osseuse a révélé une infiltration granulomateuse ; des cultures d’urine ont démontré la
croissance de Mycobacterium bovis. Un diagnostic d’infection au BCG disséminée secondaire à
ladministration intravésicale a été posé ; la rifampicine, l’isoniazide, léthambutol et la prednisone
à dose élevée ont été amorcés.
Conclusion
Les effets indésirables associés à ladministration du BCG ont été attribués à la fois à l’infection
mycobactérienne primaire et aux réactions d’hypersensibilité. La collecte en temps opportun de
données histopathologiques peut mener à un traitement précoce du BCG disséminé avec de bons
résultats. Les internistes devraient avoir un indice élevé de suspicion chez les patients présentant
un dysfonctionnement organique et des antécédents immédiats ou à distance dadministration
intravésicale de BCG.
Intravesical Bacillus-Calmette-Guerin (BCG) therapy is the
standard of care as adjunctive therapy for non-muscle invasive
bladder cancer (NMIBC) in Canada.
1
Therapy is generally well
tolerated; however, serious adverse events can occur. We present
a case of disseminated BCG infection following intravesical BCG
therapy and discuss clinical, diagnostic and therapeutic aspects
of relevance to clinicians who care for patients receiving BCG
intravesical therapy.
Case Presentation
A 54-year-old male presented to the emergency department
with persistent fever, chills, and hematuria despite receiving
antimicrobials targeting a urinary tract infection as an outpatient.
One week prior, he received his first intravesical administration
of BCG following traumatic Foley catheter insertion for the
treatment of non-muscle invasive urothelial carcinoma. He was
diagnosed with urothelial carcinoma six-months prior and has
undergone two transurethral resections of the bladder tumour
procedures. His remaining past medical history included rectal
carcinoma treated with local radiation and resection, paroxysmal
atrial fibrillation, and hypertension.
On examination, his maximum temperature was 39.1°C and
his heart rate was 120 beats per minute and irregular. Remaining
vital signs were unremarkable. Rigors and diaphoresis were
noted. The remainder of his physical exam was unremarkable.
Laboratory investigations included a complete blood count,
electrolytes, and renal function which were unremarkable.
Liver enzymes including aspartate aminotransferase (AST),
alanine transaminase (ALT), alkaline phosphatase (ALP) and
gamma-glutamyltransferase (GGT) were elevated at 104 IU/L,
138 IU/L, 256 IU/L and 353 IU/L respectively. Urinalysis was
suggestive of cystitis. Urine and blood cultures were sent. His
initial chest radiography (CXR) was unremarkable.
The patient was initially admitted for sepsis with a
suspected urogenital source and was started on broad-spectrum
antimicrobials. Despite this therapy, his fevers and diaphoresis
persisted in hospital. Liver enzymes remained elevated; a
work-up for infectious, autoimmune, metabolic, and structural
causes of elevated liver enzymes was unremarkable. Computed
tomography of the abdomen showed benign cysts and magnetic
resonance imaging of the liver was normal. His condition
further deteriorated as he developed hypoxemia with new
bilateral infiltrates on CXR, as well as a relative pancytopenia
with WBC 2.0 cell/L, Hb 100 g/dL and platelets 90 x10
9
/L. A
presumptive diagnosis of disseminated BCG was made. Bone
marrow biopsy demonstrated non-caseating granulomas,
supporting this diagnosis (Figure 1). Bone marrow and cultures
for Mycobacteria were negative. Urine cultures demonstrated
the growth of Mycobacterium bovis after three weeks.
The patient was managed with rifampin 600 mg oral once
daily, isoniazid 300 mg oral once daily, ethambutol 1200 mg
oral once daily, and prednisone 40 mg oral once daily. Ten
days following the initiation of therapy, his fevers, hepatitis,
and hypoxemia resolved. The pancytopenia resolved following
two months of therapy. Glucocorticoids were tapered as an
outpatient as tolerated. He was evaluated in follow-up by the
outpatient infectious diseases specialist and was continued on
his anti-tuberculosis regimen for nine months. Unfortunately,
Canadian Journal of General Internal Medicine
Volume 14, Issue 2, 2019 35
H a g e r e t a l .
he later developed metastatic urothelial carcinoma and died
due to the progression of this illness within the following year.
Discussion
BCG is a live, attenuated strain of Mycobacterium bovis. The
intravesical administration of BCG has been approved as first
line therapy for non-muscle invasive urothelial carcinoma within
North America.
2
The Canadian
Urology Associations 2015
guidelines suggest high-grade NMIBC
should be treated with
intravesical BCG immunotherapy,
1
which has been shown to
reduce tumour recurrence, progression, and
mortality in this
population.
2
Trea