J Med Cases
Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
Journal website http://www.journalmc.org

Case Report

Volume 1, Number 3, December 2010, pages 81-83


Fatal Outcome Due to Sepsis by Mycobacterium Bovis Six Years After BCG Intravesical Instillations

Miguel Alvarez-Mugicaa, e, Jesus Ma Fernandez Gomezb, Veronica Bulnes Vazquezc, Antonio Jalon Monzonb, Jorge Garcia Rodriguezb, Jose Ma Fernandez Rodriguezd, Victor Asensid, Jose Antonio Cartond

aDepartment of Urology, Hospital Valle del Nalon, Langreo, Asturias, Spain
bDepartment of Radiology, Hospital Alvarez Buylla, Mieres, Asturias, Spain
cDepartment of Urology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
dDepartment of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
eCorresponding author: Urology department, Valle del Nalon Hospital, Poligono de Riano s/n, Langreo, Asturias, Spain

Manuscript accepted for publication September 9, 2010
Short title: Septicaemia Due to BCG
doi: https://doi.org/10.4021/jmc42w

Abstract▴Top 

Bacillus Calmette-Guerin (BCG) in intravesical instillations is the reference treatment for urothelial carcinoma with a high risk of progression. Morbidity secondary to intravesical BCG may present both locally and systemically. Most patients suffer a self-limited irritative voiding syndrome. Prevention of these complications requires implementing rules of good practice for the instillations. The undesirable side effects should be recognized early. Their treatment should be rapid and adapted to the patient. Besides the commonly seen side effects of intravesical BCG instillations, very rare complications have been reported. In some patients, infection appears early (within 3 months after instillation) and is characterized by generalized symptoms, with pneumonitis and hepatitis. Late-presentation disease occurs more than 1 year after the first BCG treatment and usually involves focal infection of the genitourinary tract (the site at which bacteria were introduced) and/or other sites that are typical for reactivation of mycobacterial disease, such as the vertebral spine or the retroperitoneal tissues. Non caseating granulomas are found in the majority of cases, whether early or late. Most patients respond to treatment with antituberculous drugs; in early-presentation disease, when features of hypersensitivity predominate, glucocorticosteroids are sometimes added. Late localized infection often requires surgical resection.

Keywords: Bacillus Calmette-Guerin; Instillations; Transitional cell carcinoma; Septicaemia

Introduction▴Top 

Bacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used to treat transitional-cell carcinoma since 1976 [1] and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease [2]. Intravesical therapy with BCG is generally considered safe, however, serious complications including hematuria, granulomatous pneumonitis, suppurative lymphadenitis, distant intramuscular and bone abscesses, hepatitis, and life-threatening BCG sepsis are well known [3], although late bacteriuria and sepsis due to BCG instillations, have not been described yet. The reported incidence of other than minor complications is under 5% [4]. Recommended treatment for disseminated BCG disease includes a combination of antituberculous medications (with the exception of pyrazinamide, to which BCG is typically resistant) and a tapering course of steroids [5].

These complications are an absolute contraindication for further BCG instillations. Despite its toxicity, the risk-benefit ratio favors the use of BCG in patients who have moderate and high risk tumors [2]. There are not differences of toxicity between Connaught and Pasteur strain in intravesical BCG-therapy of superficial bladder tumors [6].

Compliance with this treatment is altered by its potentially serious locoregional or general side effects. Prevention of these complications requires implementing rules of good practice for the instillations. The undesirable side effects should be recognized early. Their treatment should be rapid and adapted to the patient. In order to prevent complications from BCG immunotherapy, a French study showed that side effects were significantly reduced by administration of ofloxacin after each instillation of BCG. The number of side effects requiring antitubercular treatment was also reduced in the patients in this study who had received ofloxacin [7]. Puigvert Foundation in Spain developed a practical guideline for the management of the complications followed BCG instillations [8].

Although fatal sepsis has been described before [9-11], in a search of PubMed we did not find any fatal sepsis as late complication of BCG instillations. What we report, to our knowledge, is the first case of disseminated BCG infection causing septicemia and death 6 years after intravesical treatment with BCG therapy for bladder cancer.

Case Report▴Top 

An 83-year-old man was hospitalized with a 2-week history of fever, malaise, anorexia and bleeding from a back drainage. The patient had previously undergone two trans-urethral resections receiving 12 intravesical bacillus Calmette-Guerin instillations without any complications for a high grade transitional cell carcinoma of the bladder. Due to tumor progression he was performed a radical cystoprostatectomy 5 years earlier of this admission. He also had an endovascular stent-graft repair of an infrarenal abdominal aortic aneurysm. Six months before this new admission, he was diagnosed from multiple retroperitoneal abscesses in which mycobacterium bovis grew. Since then, the patient received a combination of antitubercular medication.

Physical examination revealed an ill-appearing man. Pulmonary and cardiac examinations were unremarkable. He complained of abdominal pain in the right flank. Laboratory tests revealed abnormal liver function tests, anemia, renal insufficiency, leukocytosis and signs of coagulation disorder. A computed tomography (CT) scan of the abdomen showed a diffused and enlarged left psoas muscle. High doses of corticosteroids were associated to the antitubercular treatment. The patient developed a severe sepsis. Blood cultures were positive for acid-fast bacilli stains. Despite partial improvement, the course was complicated with a multiple organ failure, and the patient died two weeks after admission.

Discussion▴Top 

Permanent increase in neoplasm incidence including bladder neoplasm makes physicians to search for new forms and methods of treatment that prevents either appearance and/or progression of the disease. Application of new preparations entails in many cases appearance of side effects which sometimes are difficult to manage and thus must be monitored constantly. To avoid complications which in case of BCG application are very burdensome and sometimes dangerous for patient, it is necessary to intervene in due time.

The BCG therapy has been effectively used in the management of superficial bladder cancers. It is especially useful as an adjuvant therapy following bladder surgery for cancer. For instance, Demkow et al [2], in a recent study, reported that nearly 66% of the patients who received intravesical BCG therapy following complete transurethral resection of a bladder tumor were cancer free after a median follow-up of 45 months.

Adverse events following intravesical BCG therapy are related to strain virulence, allergic reactions or to nosocomial urinary tract infections. BCG is a potent immunostimulator that exerts its urological effects by inducing a strong immune response and by causing cell cycle arrest at the G1/S transition phase [12, 13]. A multicenter reviewed and studied complications on 1,278 patients after bacillus Calmette-Guerin therapy for bladder cancer [14]. Cystitis occurred in 91% of the patients. Complications identified included fever in 50 patients (3.9%), granulomatous prostatitis in 17 (1.3%), bacillus Calmette-Guerin pneumonitis or hepatitis in 12 (0.9%), arthritis or arthralgia in 6 (0.5%), hematuria requiring catheterization or transfusion in 6 (0.5%), skin rash in 5 (0.4%), skin abscess in 5 (0.4%), ureteral obstruction in 4 (0.3%), epididymo-orchitis in 2 (0.2%), bladder contracture in 2 (0.2%), hypotension in 1 (0.1%), and cytopenia in 1 (0.1%). Deaths due to BCG sepsis and the high frequency of BCG-induced cystitis have compromised the use of BCG. However, with increased experience in applying BCG, the side-effects now appear to be less prominent. Serious side-effects are encountered in fewer than 5% [15]. Major complications can appear after systemic absorption of the drug, therefore BCG should not be administered during the first 2 weeks after transurethral resection, in patients with hematuria and after traumatic catheterization. Morbidity secondary to intravesical BCG may present both locally and systemically. Most patients suffer a self-limited irritative voiding syndrome. Prevention of these complications requires implementing rules of good practice for the instillations. The undesirable side effects should be recognized early. Their treatment should be rapid and adapted to the patient. Besides the commonly seen side effects of intravesical BCG instillations, very rare complications have been reported.


References▴Top 
  1. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976;116(2):180-183.
    pubmed
  2. Demkow T, Alter A, Wiechno P. Intravesical bacillus Calmette-Guerin therapy for T1 superficial bladder cancer. Urol Int 2008;80(1):74-79.
    pubmed doi
  3. Rawls WH, Lamm DL, Lowe BA, Crawford ED, Sarosdy MF, Montie JE, Grossman HB, et al. Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer. J Urol 1990;144(6):1328-1330.
    pubmed
  4. Gonzalez OY, Musher DM, Brar I, Furgeson S, Boktour MR, Septimus EJ, Hamill RJ, et al. Spectrum of bacille Calmette-Guerin (BCG) infection after intravesical BCG immunotherapy. Clin Infect Dis 2003;36(2):140-148.
    pubmed doi
  5. Rischmann P, Desgrandchamps F, Malavaud B, Chopin DK. BCG intravesical instillations: recommendations for side-effects management. Eur Urol 2000;37 Suppl 1:33-36.
    pubmed
  6. Champetier D, Valignat C, Lopez JG, Ruffion A, Devonec M, Perrin P. [Intravesical BCG-therapy: comparison of side effects of Connaught (Toronto) and Pasteur (Paris) strains]. Prog Urol 2000;10(4):542-547.
    pubmed
  7. Colombel M, Picard A. [Prevention of Bacillus Calmette-Guerin immunotherapy complications]. Prog Urol 2008;18 Suppl 5:S105-110.
    pubmed
  8. Rodriguez F, Palou J, Martinez R, Rodriguez O, Rosales A, Huguet J, Villavicencio H. [Practical guideline for the management of adverse events associated with BCG installations]. Arch Esp Urol 2008;61(5):591-596.
    pubmed doi
  9. Nadasy KA, Patel RS, Emmett M, Murillo RA, Tribble MA, Black RD, Sutker WL. Four cases of disseminated Mycobacterium bovis infection following intravesical BCG instillation for treatment of bladder carcinoma. South Med J 2008;101(1):91-95.
    pubmed
  10. Borre S, Brustia D, Rosa F, Brondolo R, Rizzo G, Garavelli PL. [Calmette-Guerin bacillus disseminated infection after intravesical instillation]. Recenti Prog Med 2002;93(4):247-248.
    pubmed
  11. Elmer A, Bermes U, Drath L, Buscher E, Viertel A. [Sepsis and multiple organ failure after BCG-instillation for bladder cancer]. Internist (Berl) 2004;45(8):935-939.
    pubmed doi
  12. Chen F, Zhang G, Cao Y, Payne R, See WA. Bacillus Calmette-Guerin inhibits apoptosis in human urothelial carcinoma cell lines in response to cytotoxic injury. J Urol 2007;178(5):2166-2170.
    pubmed doi
  13. Shintani Y, Sawada Y, Inagaki T, Kohjimoto Y, Uekado Y, Shinka T. Intravesical instillation therapy with bacillus Calmette-Guerin for superficial bladder cancer: study of the mechanism of bacillus Calmette-Guerin immunotherapy. Int J Urol 2007;14(2):140-146.
    pubmed doi
  14. Lamm DL, Stogdill VD, Stogdill BJ, Crispen RG. Complications of bacillus Calmette-Guerin immunotherapy in 1,278 patients with bladder cancer. J Urol 1986;135(2):272-274.
    pubmed
  15. van der Meijden AP, Sylvester RJ, Oosterlinck W, Hoeltl W, Bono AV. Maintenance Bacillus Calmette-Guerin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial. Eur Urol 2003;44(4):429-434.
    pubmed doi


This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Journal of Medical Cases is published by Elmer Press Inc.

 

Browse  Journals  

     

Journal of clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 

 

 

 

Journal of Medical Cases, monthly, ISSN 1923-4155 (print), 1923-4163 (online), published by Elmer Press Inc.            
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.journalmc.org   editorial contact: editor@journalmc.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.