Korean J Lab Med.  2011 Jul;31(3):197-200. 10.3343/kjlm.2011.31.3.197.

Mycobacterial Infection after Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: A Case Report

  • 1Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. mrmicro@skku.edu


Bacillus Calmette-Guerin (BCG) has been traditionally used as a vaccine against tuberculosis. Further, intravesical administration of BCG has been shown to be effective in treating bladder cancer. Although BCG contains a live attenuated strain of Mycobacterium bovis, complications such as M. bovis BCG infection caused by BCG administration are extremely rare. Here, we report a case of BCG infection occurring after intravesical BCG therapy. A 67-yr-old man presented with azotemia and weight loss. He had been diagnosed with bladder cancer 4 yr back, and had undergone transurethral resection of the bladder tumor and intravesical BCG (Tice strain) therapy at that time. An acid-fast bacterial strain was isolated from his urine sample. We did not detect Mycobacterium tuberculosis protein 64 (MPT-64) antigen in the isolates obtained from his sample, and multiplex PCR and PCR-reverse blot hybridization assay indicated that the isolate was a member of the M. tuberculosis complex, but was not M. tuberculosis. Finally, sequence analysis of 16S ribosomal RNA and DNA gyrase, subunit B (gyrB) suggested that the organism was M. bovis or M. bovis BCG. Although we could not confirm that M. bovis BCG was the causative agent, the results of the 3 molecular methods and the MPT-64 antigen assay suggest this finding. This is an important finding, especially because M. bovis BCG cannot be identified using common commercial molecular genetics tools.


BCG; Mycobacterium bovis; Bladder cancer; Multiplex-PCR; Sequence analysis

MeSH Terms

Administration, Intravesical
BCG Vaccine/administration & dosage/*adverse effects
DNA Gyrase/genetics
Mycobacterium Infections/*diagnosis/etiology
Mycobacterium bovis/genetics/*isolation & purification
Polymerase Chain Reaction
RNA, Ribosomal, 16S/genetics
Urinary Bladder Neoplasms/*therapy


  • Fig. 1 Colony morphology on solid medium (A) and cord formation by acid-fast bacillus (B) (Ziehl-Neelsen stain, ×1,000). The presence of cords is known to be a criterion for presumptive identification of the Mycobacterium tuberculosis complex.

  • Fig. 2 Multiplex-PCR to identify the isolate. Products of the multiplex-PCR performed using DNA from the isolates were separated on a 2.0% agarose gel using electrophoresis, and the gel was stained with ethidium bromide. The bands for the isolates (S1-S3 and L1-L3) corresponded to that for NTM. IC, internal control (660 bp); NC, negative control; NTM, control non-tuberculous mycobacteria; MTB, control Mycobacterium tuberculosis; S1-S3, isolates from solid media; L1-L3, isolates from liquid media; M, molecular markers.


1. Bellmunt J, Orsola A, Maldonado X, Kataja V. Bladder cancer: ESMO practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010; 21(S5):S134–S136.
2. Lamm DL, van der Meijden PM, Morales A, Brosman SA, Catalona WJ, Herr HW, et al. Incidence and treatment of complications of bacillus Calmette-Guérin intravesical therapy in superficial bladder cancer. J Urol. 1992; 147:596–600. PMID: 1538436.
3. Harving SS, Asmussen L, Roosen JU, Hermann G. Granulomatous epididymo-orchitis, a rare complication of intravesical bacillus Calmette-Guérin therapy for urothelial cancer. Scand J Urol Nephrol. 2009; 43:331–333. PMID: 19396724.
4. Ilgan S, Koca G, Gundogdu S. Incidental detection of granulomatous prostatitis by F-18 FDG PET/CT in a patient with bladder cancer: a rare complication of BCG instillation therapy. Clin Nucl Med. 2009; 34:613–614. PMID: 19692827.
5. Korac M, Milosevic B, Lavadinovic L, Janjic A, Brmbolic B. Disseminated BCG infection in patients with urinary bladder carcinoma. Med Pregl. 2009; 62:592–595. PMID: 20491388.
6. CLSI. CLSI document MM18-A. Interpretive criteria for identification of bacteria and fungi by DNA target sequencing; approved guideline. 2008. Wayne, PA: Clinical and Laboratory Standards Institute.
7. Nakajima C, Rahim Z, Fukushima Y, Sugawara I, van der Zanden AG, Tamaru A, et al. Identification of mycobacterium tuberculosis clinical isolates in Bangladesh by a species distinguishable multiplex PCR. BMC Infect Dis. 2010; 10:118. PMID: 20470432.
8. Nam SB, Park JS, Kim JJ, Park JT, Nam SK. Ureteral obstruction caused by periureteral tuberculous granuloma after intravesical BCG therapy for superficial bladder tumors. Korean J Urol. 2006; 47:436–439.
9. Jeon HJ, Ham WS, Lee SH, Kim WY, Kim JH, Cho SY, et al. Renal tuberculous granuloma after intravesical bacillus Calmette-Guérin instillation for bladder tumor. Korean J Urol. 2002; 43:1104–1106.
10. Lee GS, Lee GY, Yoon JC, Na DJ, Jeong SS, Sul CK, et al. Two cases of pulmonary complications following intravesical bacillus Calmette-Guérin immunotherapy in patients with superficial bladder cancer. Tuberc Respir Dis. 1999; 46:869–878.
11. Kim SH, Kim HW, Lee HJ, Bae WJ, Cho SY. Tuberculous prostatic abscess following intravesical bacillus Calmette-Guérin instillation. Korean J Urol. 2009; 50:186–187.
12. Son JI, Chung JP, Paek SS, Lee JI, Kim JH, Moon BS, et al. A case of granulomatous hepatitis developed after intravesical BCG instillation for bladder cancer. Korean J Gastroenterol. 2002; 39:375–378.
13. Kim SH, Kim SY, Eun BW, Yoo WJ, Park KU, Choi EH, et al. BCG osteomyelitis caused by the BCG Tokyo strain and confirmed by molecular method. Vaccine. 2008; 26:4379–4381. PMID: 18603342.
14. Nagai S, Wiker HG, Harboe M, Kinomoto M. Isolation and partial characterization of major protein antigens in the culture fluid of mycobacterium tuberculosis. Infect Immun. 1991; 59:372–382. PMID: 1898899.
15. Harboe M, Nagai S, Patarroyo ME, Torres ML, Ramirez C, Cruz N. Properties of proteins MPB64, MPB70, and MPB80 of mycobacterium bovis BCG. Infect Immun. 1986; 52:293–302. PMID: 3514457.
16. Li H, Ulstrup JC, Jonassen TO, Melby K, Nagai S, Harboe M. Evidence for absence of the MPB64 gene in some substrains of mycobacterium bovis BCG. Infect Immun. 1993; 61:1730–1734. PMID: 8478061.
17. Behr MA, Small PM. A historical and molecular phylogeny of BCG strains. Vaccine. 1999; 17:915–922. PMID: 10067698.
Full Text Links
  • KJLM
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr