International Journal of Infectious Diseases 35 (2015) 27–28

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International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Short Communication

A case of infectious endocarditis due to BCG

Alice Fournier a, Frédérique Gouriet a,b, Pierre-Edouard Fournier a,b, Jean-Paul Casalta a,
Ludivine Saby c, Gilbert Habib c, Michel Drancourt a,b, Didier Raoult a,b,*
a
Pôle de Maladies Infectieuses, Hôpital de la Timone, Marseille, France
b
Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, UMR CNRS 7278, IRD 198, Inserm 1095, Aix-Marseille Université,
Faculté de Médecine, 27 Boulevard Jean Moulin, 13385 Marseille cedex 05, France
c
Département de Cardiologie, Hôpital de La Timone, AP-HM, Marseille, France

A R T I C L E I N F O S U M M A R Y

Article history: The occurrence of bacillus Calmette–Guérin (BCG) disease following instillation for bladder cancer is
Received 14 January 2015 commonly documented. The intravesical administration of BCG is generally safe, but may present severe
Received in revised form 31 March 2015 complications. A fatal case of native aortic valve infectious endocarditis with septicemia due to BCG in a
Accepted 3 April 2015
patient treated with intravesical instillation is reported herein.
ß 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Keywords: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
Endocarditis nc-nd/4.0/).
BCG
Mycobacterium bovis

1. Introduction intravesical instillations of BCG TICE strain from April 2013 to

Bacillus Calmette–Guérin (BCG) is a live attenuated strain of
Mycobacterium bovis. The intravesical instillation of BCG has been
used as an alternative to chemotherapy in superficial bladder
cancer. The most frequently reported adverse reactions are fever,
nausea, hematuria, and dysuria, which can occur 8–10 weeks after
the first instillation. More severe complications include prostatic
infection, testicular tissue infection, miliary pneumonitis, granu-
lomatous hepatitis, bone marrow infection, and sepsis. Complica-
tions can occur 1 year after the initiation of treatment.1 A case of
native aortic valve infectious endocarditis with septicemia due to
BCG in a patient treated with intravesical instillation is reported
herein.
2. Case report
In January 2014, an 85-year-old man was admitted to the
Infectious Disease Department for the assessment of fever,
asthenia, anorexia, and weight loss. The patient, who had never
been vaccinated with BCG, had a history of bladder cancer treated
with transurethral resection of polyps in March 2013 and
* Corresponding author. Tel.: +33 491 38 55 17; fax: +33 491 87 77 72.
E-mail address: didier.raoult@gmail.com (D. Raoult).
December 2013. An early recurrence of the cancer had been
detected by cystoscopy in January 2014. On admission, transeso-
phageal echocardiography (TEE) revealed a bicuspid aortic valve
with a small mobile element. All clinical signs were considered
non-specific side effects of intravesical BCG therapy.
In April 2014, the patient was transferred to our department for
further assessment of prolonged fever and the onset of heart
failure. A second TEE showed a vegetation on the bicuspid aortic
valve, suggesting infectious endocarditis. Blood tests revealed
negative blood cultures, negative microbial serology, and a positive
rheumatoid factor at 37 UR/ml. Other routine laboratory tests were
within the normal range and showed an absence of leukocytosis
(white blood cells 6.38  109/l) and anemia (hemoglobin 118 g/l),
and a platelet count at 153  109/l. The patient had normal renal
and hepatic function and moderately elevated C-reactive protein
(68 mg/l). 18F-fluorodeoxyglucose positron emission tomography
(18F-FDG PET) coupled with computed tomography (CT) showed
no hypermetabolic activity around the cardiac valves. A total body
CT showed a cerebral occipital embolism, bilateral pleural effusion,
and a thickening of the bladder. Acid-fast bacilli were found in
blood, sputum, and stool samples. Cultures of these three types of
sample were negative for common bacteria, but were positive for
BCG.
Amplification and sequencing of the gene rpoB MycoB was
performed directly on the strain isolated and in the samples with

http://dx.doi.org/10.1016/j.ijid.2015.04.003
1201-9712/ß 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
28 A. Fournier et al. / International Journal of Infectious Diseases 35 (2015) 27–28
99.9% similarity with M. bovis BCG (GenBank cp003900). When the
microbiological diagnosis was made, the 3-week treatment for
blood culture-negative endocarditis with vancomycin and genta-
micin was switched to rifampicin combined with isoniazid,
ethambutol, and pyrazinamide. The patient was not able to
undergo heart surgery because of his unstable general condition
and he died 2 weeks later.
3. Discussion
Disseminated M. bovis infection is commonly documented after
bladder infusion.1 In the present case, infectious endocarditis was
suspected using the modified Duke criteria incorporating TEE
findings (vegetation) as a major criterion and valvulopathy,
rheumatoid factor, and fever as three minor criteria. Endocarditis
was firmly diagnosed by isolation of M. bovis BCG from blood.
One reported case was found in the literature of a patient with
BCG infection of an implantable defibrillator in the abdominal
position associated with spondylodiscitis, after intravesical
instillation of BCG for bladder cancer 5 months earlier.2 In that
patient, BCG was isolated in defibrillator pocket, pericardium, and
lumbar tissue cultures. The patient was cured after 4 months of
antimicrobial therapy.
BCG treatment has been evaluated in a cohort of 1045 patients
with non-muscle invasive bladder cancer, including 143 patients
with a pacemaker, artificial heart valve, or orthopedic device.
Patients with a prosthetic device were found not to have an
increased risk of fever, infection, or treatment interruption because
of side effects compared with the general population.3
BCG is susceptible to most of the anti-tuberculosis drugs, with
the exception of pyrazinamide. The recommended treatment for
disseminated BCG disease includes a combination of anti-
tuberculosis drugs. Our patient was of advanced age and had a
recurrence of bladder cancer. A significant association between
older age (>70 years) in those receiving BCG therapy and a poorer
prognosis of the bladder cancer has been noted,4 and the
occurrence of complications is more common. Our patient was
not vaccinated during his childhood and received BCG TICE. This
particular strain has been associated with a lack of efficacy
compared to the Connaught BCG strains.5
This case shows that the generally safe intravesical adminis-
tration of BCG may present severe complications such as this
deadly infectious endocarditis.
Acknowledgements
We thank Dr Djamel Thiberville, Dr Jean-Philippe Mouret, and
Pr Franck Thuny who managed the patient at the beginning of this
case history.
Conflict of interest: .
References
1. Gonzalez OY, Musher DM, Brar I, Furgeson S, Boktour MR, Septimus EJ, et al.
Spectrum of bacille Calmette–Guérin (BCG) infection after intravesical BCG
immunotherapy. Clin Infect Dis 2003;36:140–8.
2. Stone DR, Estes III NA, Klempner MS. Mycobacterium bovis infection of an
implantable defibrillator following intravesical therapy with bacille Calmette–
Guérin. Clin Infect Dis 1993;16:825–6.
3. Rosevear HM, Lightfoot AJ, Nepple KG, O’Donnell MA. Safety and efficacy of
intravesical bacillus Calmette–Guérin plus interferon alpha-2b therapy for non-
muscle invasive bladder cancer in patients with prosthetic devices. J Urol
2010;184:1920–4.
4. Takashi M, Murase T, Mizuno S, Hamajima N, Ohno Y. Multivariate evaluation of
prognostic determinants in bladder cancer patients. Urol Int 1987;42:368–74.
5. Rentsch CA, Birkhauser FD, Biot C, Gsponer JR, Bisiaux A, Wetterauer C, et al.
Bacillus Calmette–Guérin strain differences have an impact on clinical outcome
in bladder cancer immunotherapy. Eur Urol 2014;66:677–88.
Alice Fournier is a fellow in the Division of Infectious Diseases at Aix-Marseille
University School of Medicine. Her primary research interest is infectious endocarditis.