[Fever of Unknown Origin in a Patient Administered With Bacillus Calmette-Guérin (BCG) to Treat Urothelial Vesical Carcinoma in Situ]

Paolo Ghiringhelli, Federica Macchi, Mariella Ciola, Girolamo Sala, Beatrice Valvo, Andrea Agostinelli, Lorenzo Bellintani, Gaetano Emanuele Rizzo, Michela Provisione, Michela Zaza, Alessandro Diana, Maurizio Ferrarese

DOI: https://doi.org/10.7175/cmi.v17i1.1543

Abstract

Koch’s Bacillus bovis (Mycobacterium bovis) was made avirulent by special culture conditions, i.e., 230 passages on medium containing potatoes treated with bile salts. It has been used mainly to prevent tuberculosis. The vaccine was named after the bacteriologist Albert Calmette and the veterinarian Camille Guérin, i.e., Bacillus Calmette-Guérin (BCG). These researchers worked at the Pasteur Institute in Lille and launched the vaccine in 1921.

Recently, BCG was used also for its non-specific immunostimulant action. Intravesical administration of BCG is an adjunctive therapy for the treatment of bladder cancer, which does not invade the muscle wall.

We will discuss the clinical case of a patient who had fever of unknown origin for about 2 months and was resistant to treatment with multiple lines of antibiotics.

Keywords

BCG; Urothelial Carcinoma; Fever; Mycobacterium bovis

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References

  • Green DB, Kawashima A, Menias CO, et al. Complications of Intravesical BCG Immunotherapy for Bladder Cancer. RadioGraphics 2019; 39: 80-94; https://doi.org/10.1148/rg.2019180014
  • Marques M, Vazquez D, Sousa S, et al. Disseminated Bacillus Calmette-Guérin (BCG) infection with pulmonary and renal involvement: A rare complication of BCG immunotherapy. A case report and narrative review. Pulmonology 2020; 26: 346-52; https://doi.org/10.1016/j.pulmoe.2019.10.001
  • Gandhi NM, Morales A, Lamm DL. Bacillus Calmette-Guérin immunotherapy for genitourinary cancer: Bacillus Calmette-Guérin immunotherapy for genitourinary cancer. BJU Int 2013; 112: 288-97; https://doi.org/10.1111/j.1464-410X.2012.11754.x
  • Larsen ES, Nordholm AC, Lillebaek T, et al. The epidemiology of bacille Calmette-Guérin infections after bladder instillation from 2002 through 2017: a nationwide retrospective cohort study: BCG infections after bladder instillation. BJU Int 2019; 124: 910-6; https://doi.org/10.1111/bju.14793
  • Pearl R. Cancer and tuberculosis. Am J Epidemiol 1929; 9: 97-159; https://doi.org/10.1093/oxfordjournals.aje.a121646
  • Barza MJ, Blum JH, Graeme-Cook FM. Case 29-1998: A 57-Year-Old Man with Fever and Jaundice after Intravesical Instillation of Bacille Calmette-Guerin for Bladder Cancer. Cabot RC, Scully RE, Mark EJ, et al., eds. N Engl J Med 1998; 339: 831-7; https://doi.org/10.1056/NEJM199809173391209
  • Westhovens IM, Vanden Abeele ME, Messiaen PE, et al. Systemic BCG infection in a patient with pancytopaenia and fever 9 years after intravesical BCG administration for bladder cancer. BMJ Case Rep 2016; 2016: bcr2016215599; https://doi.org/10.1136/bcr-2016-215599
  • Pérez-Jacoiste Asín MA, Fernández-Ruiz M, López-Medrano F, et al. Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer: Incidence, Risk Factors, and Outcome in a Single-Institution Series and Review of the Literature. Medicine 2014; 93: 236-54; https://doi.org/10.1097/MD.0000000000000119
  • European Association of Urology. EAU Guidelines on Non-muscle-invasive Bladder Cancer (TAT1 and CIS). Disponibile all’indirizzo https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer (ultimo accesso luglio 2023)
  • Elkabani M, Greene JN, Vincent AL, et al. Disseminated Mycobacterium Bovis after Intravesicular Bacillus Calmette-Guérin Treatments for Bladder Cancer. Cancer Control 2000; 7: 476-81; https://doi.org/10.1177/107327480000700512
  • Mcparland C, Cotton DJ, Gowda KS, et al. Miliary Mycobacterium bovis Induced by Intravesical Bacille Calmette-Guérin Immunotherapy. Am Rev Respir Dis 1992; 146: 1330-3; https://doi.org/10.1164/ajrccm/146.5_Pt_1.1330
  • Kristjansson M, Green P, Manning HL, et al. Molecular Confirmation of Bacillus Calmette-Guerin as the Cause of Pulmonary Infection Following Urinary Tract Instillation. Clin Infect Dis 1993; 17: 228-30; https://doi.org/10.1093/clinids/17.2.228
  • Soylu A, Ince AT, Polat H, et al. Peritoneal tuberculosis and granulomatous hepatitis secondary to treatment of bladder cancer with Bacillus Calmette-Guérin. Ann Clin Microbiol Antimicrob 2009; 8: 12; https://doi.org/10.1186/1476-0711-8-12
  • Fradet V, Gaudreau C, Perrotte P, et al. Management of hepatic granulomatous tuberculosis complicating intravesical BCG for superficial bladder cancer. Can Urol Assoc J 2007; 1: 269-72; https://doi.org/10.5489/cuaj.83
  • Álvarez-Múgica M, Gómez JM, Vázquez VB, et al. Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature. J Med Case Rep 2009; 3: 7323; https://doi.org/10.4076/1752-1947-3-7323
  • Hakim S, Heaney JA, Heinz T, et al. Psoas abscess following intravesical bacillus Calmette-Guerin for bladder cancer: a case report. J Urol 1993; 150: 188-9; https://doi.org/10.1016/S0022-5347(17)35432-0
  • Hellinger WC, Oldenburg WA, Alvarez S. Vascular and other serious infections with Mycobacterium bovis after bacillus of Calmette-Guérin therapy for bladder cancer. South Med J 1995; 88: 1212-6; https://doi.org/10.1097/00007611-199512000-00005
  • Rohailla S, Kitchlu A, Wheatcroft M, et al. Mycotic aneurysm formation after bacillus Calmette-Guérin instillation for recurrent bladder cancer. CMAJ 2018; 190: E467-E471; https://doi.org/10.1503/cmaj.171214
  • Viallard JF, Denis D, Texier-Maugein J, et al. Disseminated infection after bacille Calmette-Guérin instillation for treatment of bladder carcinoma. Clin Infect Dis 1999; 29: 451-2; https://doi.org/10.1086/520238
  • Han DP, Simons KB, Tarkanian CN, et al. Endophthalmitis from Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for bladder carcinoma. Am J Ophthalmol 1999; 128: 648-50; https://doi.org/10.1016/S0002-9394(99)00206-8
  • Gerbrandy SJ, Schreuders LC, de Smet MD. Mycobacterium bovis endophthalmitis from BCG immunotherapy for bladder cancer. Ocul Immunol Inflamm 2008; 16: 95-7; https://doi.org/10.1080/09273940802056273
  • Golub V, Malhotra P, Patel S. Mycobacterial brain tuberculomas due to Bacille Calmette-Guérin intravesical chemotherapy for bladder cancer: A case report and literature review. Can J Infect Dis Med Microbiol 2011; 22: 104-6; https://doi.org/10.1155/2011/869286
  • Wolf YG, Wolf DG, Higginbottom PA, et al. Infection of a ruptured aortic aneurysm and an aortic graft with bacille Calmette-Guérin after intravesical administration for bladder cancer. J Vasc Surg 1995; 22: 80-4; https://doi.org/10.1016/S0741-5214(95)70092-7
  • Wansaula Z, Wortham JM, Mindra G, et al. Bacillus Calmette-Guérin Cases Reported to the National Tuberculosis Surveillance System, United States, 2004-2015. Emerg Infect Dis 2019; 25: 451-6; https://doi.org/10.3201/eid2503.180686
  • Lamm DL, van der Meijden PM, Morales A, et al. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol 1992; 147: 596-600; https://doi.org/10.1016/S0022-5347(17)37316-0
  • Izes JK, Bihrle W 3rd, Thomas CB. Corticosteroid-associated fatal mycobacterial sepsis occurring 3 years after instillation of intravesical bacillus Calmette-Guerin. J Urol 1993; 150: 1498-500; https://doi.org/10.1016/S0022-5347(17)35824-X
  • Heiner JG, Terris MK. Effect of advanced age on the development of complications from intravesical bacillus Calmette-Guérin therapy. Urol Oncol 2008; 26: 137-40; https://doi.org/10.1016/j.urolonc.2007.04.005
  • Catalona WJ, Ratliff TL. Bacillus Calmette-Guérin and superficial bladder cancer. Clinical experience and mechanism of action. Surg Annu 1990; 22: 363-78
  • Ströck V, Dotevall L, Sandberg T, et al. Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment. BJU Int 2011; 107: 1592-7; https://doi.org/10.1111/j.1464-410X.2010.09923.x
  • Mavrogenis AF, Sakellariou VI, Tsiodras S, et al. Late Mycobacterium bovis spondylitis after intravesical BCG therapy. Joint Bone Spine 2009; 76: 296-300; https://doi.org/10.1016/j.jbspin.2008.10.011
  • Gonzalez OY, Musher DM, Brar I, et al. Spectrum of bacille Calmette-Guérin (BCG) infection after intravesical BCG immunotherapy. Clin Infect Dis 2003; 36: 140-4; https://doi.org/10.1086/344908
  • Yong C, Steinberg RL, O’Donnell MA. Severe Infectious Complications of Intravesical Bacillus Calmette-Guérin: A Case Series of 10 Patients. Urology 2020; 137: 79-83; https://doi.org/10.1016/j.urology.2019.10.013
  • Dammert P, Boujaoude Z, Rafferty W, et al. Fever of unknown origin and pancytopenia caused by culture-proven delayed onset disseminated bacillus Calmette-Guérin (BCG) infection after intravesical instillation. BMJ Case Rep 2013; 2013: bcr2013008949; https://doi.org/10.1136/bcr-2013-008949
  • Mehta AR, Mehta PR, Mehta RL. A cough conundrum in a patient with a previous history of BCG immunotherapy for bladder cancer. BMJ Case Rep 2012; 2012; bcr2012007327; https://doi.org/10.1136/bcr-2012-007327
  • Lamm DL, Stogdill VD, Stogdill BJ, et al. Complications of bacillus Calmette-Guerin immunotherapy in 1,278 patients with bladder cancer. J Urol 1986; 135: 272-4; https://doi.org/10.1016/S0022-5347(17)45606-0
  • Lamm DL. Complications of bacillus Calmette-Guérin immunotherapy. Urol Clin North Am 1992; 19: 565-72; https://doi.org/10.1016/S0094-0143(21)00423-7
  • French CG, Hickey L, Bell DG. Caseating granulomas on the glans penis as a complication of Bacille Calmette-Guérin intravesical therapy. Rev Urol 2001; 3: 36-8
  • Menke JJ, Heins JR. Epididymo-orchitis following intravesical bacillus Calmette-Guérin therapy. Ann Pharmacother 2000; 34: 479; https://doi.org/10.1345/aph.19212
  • Ceylan OM, Durukan AH, Uysal Y, et al. Ocular Complications of Intravesicular BCG Treatment for Bladder Carcinoma. Ocul Immunol Inflamm 2022; 30: 111-4; https://doi.org/10.1080/09273948.2020.1783323
  • Wittes R, Klotz L, Kosecka U. Severe bacillus Calmette-Guerin cystitis responds to systemic steroids when antituberculous drugs and local steroids fail. J Urol 1999; 161: 1568-9; https://doi.org/10.1016/S0022-5347(05)68961-6; https://doi.org/10.1097/00005392-199905000-00046
  • LaFontaine PD, Middleman BR, Graham SD Jr, et al. Incidence of granulomatous prostatitis and acid-fast bacilli after intravesical BCG therapy. Urology 1997; 49: 363-6; https://doi.org/10.1016/S0090-4295(96)00507-9
  • Rival G, Garot D, Mercier E, et al. [Acute respiratory failure and septic shock induced by Mycobacterium bovis. A rare side effect of intravesical BCG therapy]. Presse Med 2006; 35: 980-2; https://doi.org/10.1016/S0755-4982(06)74732-7
  • Ziegler J, Ho J, Gibson IW, et al. Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer. Transpl Infect Dis 2018; 20: e12931; https://doi.org/10.1111/tid.12931
  • Choi CH, Lee SO, Smith G. Subclinical miliary Mycobacterium bovis following BCG immunotherapy for transitional cell carcinoma of the bladder. BMJ Case Rep 2014; 2014: bcr2013201202; https://doi.org/10.1136/bcr-2013-201202
  • Mignon F, Chevrière A, Mesurolle B, et al. [Miliary induced by intravesical BCG immunotherapy for carcinoma of the bladder: CT Findings]. J Radiol 2002; 83: 368-71
  • Rachakonda T, Kendall B, Spivak AM, et al. Pleural Effusion Caused by Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer. Open Forum Infect Dis 2017; 4: ofx126; https://doi.org/10.1093/ofid/ofx126
  • Proctor DD, Chopra S, Rubenstein SC, et al. Mycobacteremia and granulomatous hepatitis following initial intravesical bacillus Calmette-Guerin instillation for bladder carcinoma. Am J Gastroenterol 1993; 88: 1112-5
  • Thompson D, Cumming J. Granulomatous hepatitis following intravesical BCG therapy. Br J Urol 1990; 66: 432-3; https://doi.org/10.1111/j.1464-410X.1990.tb14971.x
  • Modesto A, Marty L, Suc JM, et al. Renal complications of intravesical bacillus Calmette-Guérin therapy. Am J Nephrol 1991; 11: 501-4; https://doi.org/10.1159/000168368
  • Kamphuis JT, Buiting AG, Miseré JF, et al. BCG immunotherapy: be cautious of granulomas. Disseminated BCG infection and mycotic aneurysm as late complications of intravesical BCG instillations. Neth J Med 2001; 58: 71-5; https://doi.org/10.1016/S0300-2977(00)00098-X
  • Katz DS, Wogalter H, D’Esposito RF, et al. Mycobacterium bovis vertebral osteomyelitis and psoas abscess after intravesical BCG therapy for bladder carcinoma. Urology 1992; 40: 63-6; https://doi.org/10.1016/0090-4295(92)90439-4
  • Fishman JR, Walton DT, Flynn NM, et al. Tuberculous spondylitis as a complication of intravesical bacillus Calmette-Guerin therapy. J Urol 1993; 149: 584-7; https://doi.org/10.1016/S0022-5347(17)36155-4
  • Aljada IS, Crane JK, Corriere N, et al. Mycobacterium bovis BCG causing vertebral osteomyelitis (Pott's disease) following intravesical BCG therapy. J Clin Microbiol 1999; 37: 2106-8; https://doi.org/10.1128/JCM.37.6.2106-2108.1999
  • Kusakabe T, Endo K, Nakamura I, et al. Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review. BMC Infect Dis 2018; 18: 290; https://doi.org/10.1186/s12879-018-3205-7
  • Clavel G, Grados F, Lefauveau P, et al. Osteoarticular side effects of BCG therapy. Joint Bone Spine 2006; 73: 24-8; https://doi.org/10.1016/j.jbspin.2004.12.003
  • Tinazzi E, Ficarra V, Simeoni S, et al. Reactive arthritis following BCG immunotherapy for urinary bladder carcinoma: a systematic review. Rheumatol Int 2006; 26: 481-8; https://doi.org/10.1007/s00296-005-0059-2
  • Miranda S, Verdet M, Héron F, et al. [Acute reactive arthritis after intravesical instillation of bacillus Calmette-Guérin. Two case reports and literature review]. Rev Med Interne 2010; 31: 558-61; https://doi.org/10.1016/j.revmed.2010.01.010
  • Ng KL, Chua CB. Reiter’s syndrome postintravesical Bacillus Calmette-Guérin instillations. Asian J Surg 2017; 40: 163-5; https://doi.org/10.1016/j.asjsur.2014.01.016
  • Guerra CE, Betts RF, O’Keefe RJ, et al. Mycobacterium bovis osteomyelitis involving a hip arthroplasty after intravesicular bacille Calmette-Guérin for bladder cancer. Clin Infect Dis 1998; 27: 639-40; https://doi.org/10.1086/514714
  • Segal A, Krauss ES. Infected total hip arthroplasty after intravesical bacillus Calmette-Guérin therapy. J Arthroplasty 2007; 22: 759-62; https://doi.org/10.1016/j.arth.2006.07.010
  • Reigstad O, Siewers P. A total hip replacement infected with mycobacterium bovis after intravesicular treatment with Bacille-Calmette-Guérin for bladder cancer. J Bone Joint Surg Br 2008; 90-B: 225-7; https://doi.org/10.1302/0301-620X.90B2.20038
  • Rosevear HM, Lightfoot AJ, Nepple KG, et al. Safety and efficacy of intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer in patients with prosthetic devices. J Urol 2010; 184: 1920-4; https://doi.org/10.1016/j.juro.2010.06.149
  • Coscas R, Arlet JB, Belhomme D, et al. Multiple mycotic aneurysms due to Mycobacterium bovis after intravesical bacillus Calmette-Guérin therapy. J Vasc Surg 2009; 50: 1185-90; https://doi.org/10.1016/j.jvs.2009.06.004
  • Granel B, Serratrice J, Morange PE, et al. Cryoglobulinemia vasculitis following intravesical instillations of bacillus Calmette-Guerin. Clin Exp Rheumatol 2004; 22: 481-2
  • Misra S, Gupta A, Symes A, et al. Haemophagocytic syndrome after intravesical bacille Calmette-Guérin instillation. Scand J Urol 2014; 48: 328-30; https://doi.org/10.3109/21681805.2013.836724
  • Sheron MW, Holt SL, Ingram CW. Mycobacterium bovis Cerebellar Abscess Following Treatment With Bacillus Calmette-Guérin. J Pharm Pract 2017; 30: 378-80; https://doi.org/10.1177/0897190016636533
  • Parent ME, Richer M, Liang P. The first case of bacillus Calmette-Guérin-induced small-vessel central nervous system vasculitis. Clin Rheumatol 2018; 37: 2297-302; https://doi.org/10.1007/s10067-018-4136-9
  • Rock RB, Olin M, Baker CA, et al. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev 2008; 21: 243-61; https://doi.org/10.1128/CMR.00042-07
  • Lowther C, Miedler JD, Cockerell CJ. Id-like reaction to BCG therapy for bladder cancer. Cutis 2013; 91: 145-6
  • Larsen ES, Joensen UN, Poulsen AM, et al. Bacillus Calmette-Guérin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections. APMIS 2020; 128: 92-103; https://doi.org/10.1111/apm.13011
  • Smith JA Jr, Labasky RF, Cockett AT, et al. Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association. J Urol 1999; 162: 1697; https://doi.org/10.1097/00005392-199911000-00040
  • Silverman MS, Reynolds D, Kavsak PA, et al. Use of an interferon-gamma based assay to assess bladder cancer patients treated with intravesical BCG and exposed to tuberculosis. Clin Biochem 2007; 40: 913-5; https://doi.org/10.1016/j.clinbiochem.2007.04.006
  • Durek C, Rüsch-Gerdes S, Jocham D, et al. Sensitivity of BCG to modern antibiotics. Eur Urol 2000; 37 Suppl 1: 21-5; https://doi.org/10.1159/000052378
  • Steg A, Leleu C, Debré B, et al. Systemic bacillus Calmette-Guerin infection in patients treated by intravesical BCG therapy for superficial bladder cancer. Prog Clin Biol Res 1989; 310: 325-34
  • Molina JM, Rabian C, D’Agay MF, et al. Hypersensitivity systemic reaction following intravesical bacillus Calmette-Guerin: successful treatment with steroids. J Urol 1992; 147: 695-7; https://doi.org/10.1016/S0022-5347(17)37354-8
  • Lamm DL. Efficacy and safety of bacille Calmette-Guérin immunotherapy in superficial bladder cancer. Clin Infect Dis 2000; 31 Suppl 3: S86-S90; https://doi.org/10.1086/314064
  • Zhao LC, Meeks JJ, Helfand BT, et al. Screening urine analysis before bacille Calmette-Guérin instillation does not reduce the rate of infectious complications. BJU Int 2012; 109: 1819-21; https://doi.org/10.1111/j.1464-410X.2011.10735.x
  • Herr HW. Outpatient urological procedures in antibiotic-naive patients with bladder cancer with asymptomatic bacteriuria. BJU Int 2012; 110: E658-E660; https://doi.org/10.1111/j.1464-410X.2012.11405.x
  • Van der Meijden AP, Brausi M, Zambon V, et al. Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Research and Treatment of Cancer genito-urinary group randomized phase III trial. J Urol 2001; 166: 476-81; https://doi.org/10.1016/S0022-5347(05)65966-6; https://doi.org/10.1097/00005392-200108000-00016

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