Systematic Review of Case Reports of Bacillus Calmette-Guerin Vascular Infections

Published:March 03, 2022DOI:


      Bacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used as immunotherapy against several malignancies. In particular, intravesical instillation of BCG has become a well-accepted adjuvant treatment for bladder cancer. BCG vascular infections are a rare complication of BCG therapy. Many aspects of these infections, including the presentations, risk factors, and treatment strategies, are poorly understood. Through a systematic review of the existing literature, we aimed to identify potential associations between this condition and patient characteristics, presentations, its treatments, and outcomes.


      We searched the PubMed, MEDLINE, and Embase databases for cases of BCG vascular infections from inception to June 2021. English-language reports of BCG vascular infections were included.


      A total of 74 cases of BCG vascular infections were included. Seventy-three (99%) cases were male patients, all of whom were exposed to BCG through bladder instillation. Fifty (68%) cases were diagnosed more than 12 months after exposure to BCG. Twenty-six (35%) cases presented with arterial rupture at the time of diagnosis. Concurrent BCG infections in nonvascular locations were present in 37 (50%) cases. The most common locations of BCG vascular infection were the abdominal aorta (57%), prosthetic grafts (15%), and thoracic aorta (12%). The most common treatment for BCG infection was open repair with synthetic graft in situ replacement for the abdominal aorta and endovascular repair for the thoracic aorta. The 30-day mortality, among the 59 cases where these data were reported, was 10%.


      We observed that many aspects of BCG vascular infections are similar to other forms of vascular infections. The high incidence of rupture or fistulation and the propensity toward abdominal aortic involvement and its prognosis are similar to those described in other vascular infections. However, our study also highlights 2 idiosyncratic features of BCG vascular infections: association with male sex and concurrent musculoskeletal infections.
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        • Hanekom W.A.
        • Hawn T.R.
        • Ginsberg A.M.
        Tuberculosis vaccines.
        in: Plotkin SAMD Orenstein WAMDD Offit PAMD Edwards KMMD Plotkin's Vaccines. 2018: 1095-1113.e9
        • Lobo N.
        • Brooks N.A.
        • Zlotta A.R.
        • et al.
        100 years of Bacillus Calmette–Guérin immunotherapy: from cattle to COVID-19.
        Nat Rev Urol. 2021; 18: 611-622
        • Liu Y.
        • Lu J.
        • Huang Y.
        • et al.
        Clinical spectrum of complications induced by intravesical immunotherapy of Bacillus Calmette-Guérin for bladder cancer.
        J Oncol. 2019; 2019: 1-11
        • Brausi M.
        • Oddens J.
        • Sylvester R.
        • et al.
        Side effects of Bacillus Calmette-Guérin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG.
        Eur Urol. 2014; 65: 69-76
        • Pérez-Jacoiste Asín M.A.
        • 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 (Baltimore). 2014; 93: 236-254
        • Larsen E.S.
        • Nordholm A.C.
        • Lillebaek T.
        • et al.
        The epidemiology of bacille Calmette-Guérin infections after bladder instillation from 2002 through 2017: a nationwide retrospective cohort study.
        BJU Int. 2019; 124: 910-916
        • Woods J.M.t.
        • Schellack J.
        • Stewart M.T.
        • et al.
        Mycotic abdominal aortic aneurysm induced by immunotherapy with bacille Calmette-Guérin vaccine for malignancy.
        J Vasc Surg. Jun 1988; 7: 808-810
        • Bornet P.
        • Pujade B.
        • Lacaine F.
        • et al.
        Tuberculous aneurysm of the femoral artery: a complication of bacille Calmette-Guerin vaccine immunotherapy--a case report.
        J Vasc Surg. 1989; 10: 688-692
        • Deresiewicz R.L.
        • Stone R.M.
        • Aster J.C.
        Fatal disseminated mycobacterial infection following intravesical bacillus Calmette-Guerin.
        J Urol. 1990; 144 (discussion 1333-4): 1331-1333
        • Izes J.K.
        • Bihrle 3rd, W.
        • Thomas C.B.
        Corticosteroid-associated fatal mycobacterial sepsis occurring 3 years after instillation of intravesical bacillus Calmette-Guerin.
        J Urol. 1993; 150: 1498-1500
        • Hellinger W.C.
        • Oldenburg W.A.
        • Alvarez S.
        Vascular and other serious infections with Mycobacterium bovis after bacillus of Calmette-Guérin therapy for bladder cancer.
        South Med J. 1995; 88: 1212-1216
        • Wolf Y.G.
        • Wolf D.G.
        • Higginbottom P.A.
        • 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: 80-84
        • Rozenblit A.
        • Wasserman E.
        • Marin M.L.
        • et al.
        Infected aortic aneurysm and vertebral osteomyelitis after intravesical bacillus Calmette-Guérin therapy.
        AJR Am J Roentgenol. 1996; 167: 711-713
        • Damm O.
        • Briheim G.
        • Hagstrom T.
        • et al.
        Ruptured mycotic aneurysm of the abdominal aorta: a serious complication of intravesical instillation bacillus Calmette-Guerin therapy.
        J Urol. 1998; 159: 984
        • LaBerge J.M.
        • Kerlan Jr., R.K.
        • Reilly L.M.
        • et al.
        Diagnosis please. Case 9: mycotic pseudoaneurysm of the abdominal aorta in association with mycobacterial psoas abscess--a complication of BCG therapy.
        Radiology. 1999; 211: 81-85
        • Seelig M.H.
        • Oldenburg W.A.
        • Klingler P.J.
        • et al.
        Mycotic vascular infections of large arteries with Mycobacterium bovis after intravesical bacillus Calmette-Guérin therapy: case report.
        J Vasc Surg. 1999; 29: 377-381
        • Farber A.
        • Grigoryants V.
        • Palac D.M.
        • et al.
        Primary aortoduodenal fistula in a patient with a history of intravesical therapy for bladder cancer with bacillus Calmette-Guérin: review of primary aortoduodenal fistula without abdominal aortic aneurysm.
        J Vasc Surg. 2001; 33: 868-873
        • Geldmacher H.
        • Taube C.
        • Markert U.
        • et al.
        Nearly fatal complications of cervical lymphadenitis following BCG immunotherapy for superficial bladder cancer.
        Respiration. 2001; 68: 420-421
        • Kamphuis J.T.
        • Buiting A.G.
        • Miseré J.F.
        • 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: 71-75
        • Wada S.
        • Watanabe Y.
        • Shiono N.
        • et al.
        Tuberculous abdominal aortic pseudoaneurysm penetrating the left psoas muscle after BCG therapy for bladder cancer.
        Cardiovasc Surg. 2003; 11: 231-235
        • Witjes J.A.
        • Vriesema J.L.J.
        • Brinkman K.
        • et al.
        Mycotic aneurysm of the popliteal artery as a complication of intravesical BCG therapy for superficial bladder cancer.
        Urol Int. 2003; 71: 430-432
        • Dahl T.
        • Lange C.
        • Odegard A.
        • et al.
        Ruptured abdominal aortic aneurysm secondary to tuberculous spondylitis.
        Int Angiol. 2005; 24: 98-101
        • Harding G.E.
        • Lawlor D.K.
        Ruptured mycotic abdominal aortic aneurysm secondary to Mycobacterium bovis after intravesical treatment with bacillus Calmette-Guérin.
        J Vasc Surg. 2007; 46: 131-134
        • Safdar N.
        • Abad C.L.
        • Kaul D.R.
        • et al.
        Clinical problem-solving. An unintended consequence--a 79-year-old man with a 5-month history of fatigue and 20-lb (9-kg) weight loss presented to his local physician.
        N Engl J. 2008; 358: 1496-1501
        • Coscas R.
        • Arlet J.B.
        • Belhomme D.
        • et al.
        Multiple mycotic aneurysms due to Mycobacterium bovis after intravesical bacillus Calmette-Guérin therapy.
        J Vasc Surg. 2009; 50: 1185-1190
        • Costiniuk C.T.
        • Sharapov A.A.
        • Rose G.W.
        • et al.
        Mycobacterium bovis abdominal aortic and femoral artery aneurysms following intravesical bacillus Calmette-Guerin therapy for bladder cancer.
        Cardiovasc Pathol. 2010; 19: e29-e32
        • Gao C.Q.
        • Mithani R.
        • Leya J.
        • et al.
        Granulomatous hepatitis, choroiditis and aortoduodenal fistula complicating intravesical Bacillus Calmette-Guérin therapy: case report.
        BMC Infect Dis. 2011; 11: 260
        • Maundrell J.
        • Fletcher S.
        • Roberts P.
        • et al.
        Mycotic aneurysm of the aorta as a complication of Bacillus Calmette-Guérin instillation.
        J R Coll Physicians Edinb. 2011; 41: 114-116
        • Khandelwal A.
        • Gupta A.
        • Virmani V.
        • et al.
        Ruptured aortic aneurysm secondary to psoas abscess after intravesical bacilli Calmette-Guérin.
        Med J Malaysia. 2012; 67: 534-535
        • Pittman M.
        • Sakai L.
        • Craig R.
        • et al.
        Primary aortoenteric fistula following disseminated bacillus Calmette-Guérin infection: a case report.
        Vascular. 2012; 20: 221-224
        • Denkinger C.
        • Aroesty J.
        • Weinberg A.
        • et al.
        The pieces of the puzzle—disseminated BCG infection with mycotic abdominal aneurysm identified on a blood culture.
        Infect Dis Clin Pract. 2013; 21: 17-20
        • Kuy S.
        • Dua A.
        • Desai S.S.
        • et al.
        Ruptured mycobacterial aneurysm of the carotid artery.
        Perspect Vasc Surg Endovasc Ther. 2013; 25: 53-56
        • Mizoguchi H.
        • Iida O.
        • Dohi T.
        • et al.
        Abdominal aortic aneurysmal and endovascular device infection with iliopsoas abscess caused by Mycobacterium bovis as a complication of intravesical bacillus Calmette-Guérin therapy.
        Ann Vasc Surg. 2013; 27: 1186.e1-e5
        • Psoinos C.M.
        • Simons J.P.
        • Baril D.T.
        • et al.
        A Mycobacterium bovis mycotic abdominal aortic aneurysm resulting from bladder cancer treatment, resection, and reconstruction with a cryopreserved aortic graft.
        Vasc Endovascular Surg. 2013; 47: 61-64
        • Roylance A.
        • Mosley J.
        • Jameel M.
        • et al.
        Aorto-enteric fistula development secondary to mycotic abdominal aortic aneurysm following intravesical bacillus Calmette-Guerin (BCG) treatment for transitional cell carcinoma of the bladder.
        Int J Surg Case Rep. 2013; 4: 88-90
        • Samadian S.
        • Phillips F.M.
        • Deeab D.
        Mycobacterium bovis vertebral osteomyelitis and discitis with adjacent mycotic abdominal aortic aneurysm caused by intravesical BCG therapy: a case report in an elderly gentleman.
        Age Ageing. 2013; 42: 129-131
        • Santbergen B.
        • Vriens P.H.
        • de Lange W.C.
        • et al.
        Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment.
        BMJ Case Rep. 2013; 2013 (bcr2012008161)
        • Watson K.
        • Ganapathi A.
        • Schechter M.
        • et al.
        Repair of mycotic thoracoabdominal aortic aneurysm following BCG treatment.
        J Vasc Surg. 2013; 58: 1733
        • Holmes B.J.
        • LaRue R.W.
        • Black 3rd, J.H.
        • et al.
        Mycotic aortic aneurysm due to intravesical BCG immunotherapy: clinical manifestations and diagnostic challenges.
        Int J Mycobacteriol. 2014; 3: 60-65
        • Yildiz H.
        • Colin G.
        • Lambert M.
        An unexpected complication of bacillus Calmette-Guérin therapy.
        Acta Clin Belg. 2014; 69: 312
        • Akita H.
        • Okamura T.
        • Nakane A.
        • et al.
        Infectious aortic aneurysms occurring 1 year after bacillus Calmette-Guerin bladder instillation therapy.
        Int J Urol. 2015; 22: 234-235
        • Davis F.M.
        • Miller D.J.
        • Newton D.
        • et al.
        Successful treatment of a mycotic multifocal thoracoabdominal aortic aneurysm as a late sequelae of intravesical bacillus Calmette-Guerin therapy: case report and literature review.
        Ann Vasc Surg. 2015; 29: 840.e9-13
        • Leo E.
        • Molinari A.L.
        • Rossi G.
        • et al.
        Mycotic abdominal aortic aneurysm after adjuvant therapy with bacillus Calmette-Guérin in patients with urothelial bladder cancer: a rare but misinterpreted complication.
        Ann Vasc Surg. 2015; 29: 1318.e1-e6
        • Nam E.Y.
        • Na S.H.
        • Kim S.Y.
        • et al.
        Infected aortic aneurysm caused by Mycobacterium bovis after intravesical Bacillus Calmette-Guérin treatment for bladder cancer.
        Infect Chemother. 2015; 47: 256-260
        • Seastedt K.P.
        • Ahmad U.
        • Lau C.
        • et al.
        Mycotic thoracic aortic aneurysm after intravesical Bacillus Calmette–Guérin treatment.
        Ann Thorac Surg. 2015; 99: 2210-2212
        • Ventosa-Fernandez G.
        • Milisenda J.C.
        • Pereda D.
        • et al.
        Infected false aneurysm of the aortic arch after endoscopic transurethral instillation of Bacillus Calmette-Guérin.
        Ann Thorac Surg. 2015; 100: 717-720
        • Duvnjak P.
        • Laguna M.
        Left anterior descending coronary artery and multiple peripheral mycotic aneurysms due to Mycobacterium bovis following intravesical Bacillus Calmette-Guerin therapy: a case report.
        J Radiol Case Rep. 2016; 10: 12-27
        • Hui D.S.
        • Stoeckel D.A.
        • Kaufman E.E.
        • et al.
        Massive hemoptysis from an aortobronchial fistula secondary to BCG-related mycotic thoracic aortic aneurysm.
        Ann Thorac Surg. 2016; 101: 350-352
        • Nandavaram S.
        • Al Twal A.
        • Jacoby H.
        • et al.
        Mycobacterium bovis Aneurysm.
        Infect Dis Clin Pract. 2016; 24: 1
        • van Moorselaar R.J.A.
        • Wisselink W.
        Case presentation: mycotic aortic aneurysm and psoas abscess as a complication of Bacillus Calmette-Guérin instillations.
        Eur Urol Focus. 2016; 2: 351-353
        • Coddington N.D.
        • Sandberg J.K.
        • Yang C.
        • et al.
        Mycotic aneurysm after Bacillus Calmette-Guerin treatment: case report and review of the literature.
        Case Rep Urol. 2017; 2017: 4508583
        • Lee C.J.
        • Davila D.
        • Dua A.
        • et al.
        Disseminated mycotic aneurysms following intravesical Bacillus Calmette-Guérin therapy for bladder cancer: case discussion and systematic treatment algorithm.
        Ann Vasc Surg. 2017; 39: 284.e5-e10
        • Leeman M.
        • Burgers P.
        • Brehm V.
        • et al.
        Psoas abscess after bacille Calmette-Guérin instillations causing iliac artery contained rupture.
        J Vasc Surg. 2017; 66: 1236-1238
        • Okon E.
        • Stearns J.
        • Durgam A.K.
        Tuberculous psoas abscess and worsening vascular aneurysm; all from Bacillus Calmette-Guerin (BCG) therapy?.
        Am J Case Rep. 2017; 18: 810-812
        • Simar J.
        • Belkhir L.
        • Tombal B.
        • et al.
        Ruptured aortic aneurysm due to Mycobacterium bovis BCG with a delayed bacteriological diagnosis due to false negative result of the MPB 64 immunochromatographic assay.
        BMC Res Notes. 2017; 10: 64
        • Torres-Blanco Á
        • Gómez-Palonés F.
        • Edo-Fleta G.
        Arteriocutaneous fistula associated with bilateral femoral pseudoaneurysms caused by Bacillus Calmette-Guérin. Apropos of a case and review of literature.
        Ann Vasc Surg. 2017; 39: 291.e1-e6
        • Darriet F.
        • Bernioles P.
        • Loukil A.
        • et al.
        Fluorescence in situ hybridization microscopic detection of Bacilli Calmette Guerin mycobacteria in aortic lesions: a case report.
        Medicine (Baltimore). 2018; 97: e11321
        • Higashi Y.
        • Nakamura S.
        • Kidani K.
        • et al.
        Mycobacterium bovis-induced aneurysm after intravesical Bacillus Calmette-Guérin therapy: a case study and literature review.
        Intern Med. 2018; 57: 429-435
        • 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
        • Lim A.
        • Kaur G.
        • Poyck P.
        • et al.
        Bacillus Calmette-Guérin immunotherapy: a rare cause for a ruptured common femoral artery.
        ANZ J Surg. 2018; 88: 931-933
        • Roeke T.
        • Hovsibian S.
        • Schlejen P.M.
        • et al.
        A mycotic aneurysm of the abdominal aorta caused by Mycobacterium bovis after intravesical instillation with bacillus Calmette-Guérin.
        J Vasc Surg Cases Innov Tech. 2018; 4: 122-125
        • 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
        • Viviani E.
        • De Gregorio C.
        • De Capua A.
        • et al.
        Ruptured iliac pseudoaneurysm after intravesical Bacillus Calmette-Guérin: urgent endovascular treatment. Case report and literature review.
        Ann Vasc Surg. 2018; 53: 269.e1-e9
        • Wadhwani A.
        • Moore R.D.
        • Bakshi D.
        • et al.
        Mycotic aortic aneurysms post-Intravesical BCG treatment for early-stage bladder carcinoma.
        CVIR Endovasc. 2018; 1: 28
        • Jorgensen M.S.
        • Oldenburg W.A.
        • Murray P.M.
        Mycotic aneurysm of the ulnar artery secondary to Bacillus Calmette-Guérin therapy for bladder cancer: a rare presentation of hypothenar hammer syndrome.
        J Hand Surg Am. 2019; 44: 905.e1-e4
        • Lareyre F.
        • Reverso-Meinietti J.
        • Carboni J.
        • et al.
        Mycotic aortic aneurysm and infected aortic graft after intravesical Bacillus Calmette-Guérin treatment for bladder cancer.
        Vasc Endovascular Surg. 2019; 53: 86-91
        • Ribeiro L.
        • Rajendran S.
        • Stenson K.
        • et al.
        Rare case of a proximal descending thoracic aorta mycotic aneurysm following intravesical BCG injections for the treatment of bladder cancer.
        BMJ Case Rep. 2019; 12: e231595
        • Vudatha V.
        • Ranson M.
        • Blair L.
        • et al.
        Rapid detection of bacille Calmette-Guérin-associated mycotic aortic aneurysm using novel cell-free DNA assay.
        J Vasc Surg Cases Innov Tech. 2019; 5: 143-148
        • Walkty A.
        • Koulack J.
        • Milligan B.
        • et al.
        An 81-year-old male with a pulsatile abdominal mass.
        Clin Infect Dis. 2019; 69: 1456-1459
        • Akabane K.
        • Uchida T.
        • Matsuo S.
        • et al.
        Hybrid operation for infectious thoracic and abdominal aortic aneurysms complicated with Bacillus Calmette-Guerin therapy for bladder cancer: a case report.
        Medicine (Baltimore). 2021; 100: e24796
        • Buerger M.
        • Kapahnke S.
        • Omran S.
        • et al.
        Aortic aneurysm and aortic graft infection related to Mycobacterium bovis after intravesical Bacille Calmette-Guerin therapy-a case series.
        BMC Surg. 2021; 21: 138
        • Dubert M.
        • Abihssira S.
        • Diamantis S.
        • et al.
        Mycobacterium bovis infection of an aortobifemoral bypass graft with Streptococcus intermedius superinfection after intravesical bacillus Calmette-Guerin immunotherapy for bladder cancer.
        Infection. 2021; 49: 345-348
        • Koterazawa S.
        • Watanabe J.
        • Uemura Y.
        • et al.
        A case of infectious thoracic aortic aneurysm after intravesical Bacillus Calmette-Guérin instillation therapy for a superficial bladder cancer.
        Urol Case Rep. 2021; 36: 101574
        • Pham S.T.D.
        • Lee A.
        • Struminger J.S.
        • et al.
        Mycotic infrarenal aortic aneurysm due to mycobacterium after intravesical treatment for bladder cancer.
        J Vasc Surg Cases Innov Tech. 2021; 7: 354-356
        • Manzur M.F.
        • Han S.M.
        • Weaver F.A.
        Infected arterial aneurysms.
        in: Sidawy Ap Perler B.A. Rutherford’s Vascular Surgery and Endovascular Therapy. Elsevier, Philadelphia2019: 1906-1917.e4
        • Chakfé N.
        • Diener H.
        • Lejay A.
        • et al.
        Editor's choice - European society for vascular surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.
        Eur J Vasc Endovasc Surg. 2020; 59: 339-384
        • Sörelius K.
        • Budtz-Lilly J.
        • Mani K.
        • et al.
        Systematic review of the management of mycotic aortic aneurysms.
        Eur J Vasc Endovasc Surg. 2019; 58: 426-435
        • Bray F.
        • Ferlay J.
        • Soerjomataram I.
        • et al.
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2018; 68: 394-424
        • Hannawa K.K.
        • Eliason J.L.
        • Upchurch Jr., G.R.
        Gender differences in abdominal aortic aneurysms.
        Vascular. 2009; 17 Suppl 1: S30-S39
        • Man J.J.
        • Beckman J.A.
        • Jaffe I.Z.
        Sex as a biological variable in atherosclerosis.
        Circ Res. 2020; 126: 1297-1319
        • Bennett D.E.
        • Cherry J.K.
        Bacterial infection of aortic aneurysms. A clinicopathologic study.
        Am J Surg. 1967; 113: 321-326
        • Wilson W.R.
        • Bower T.C.
        • Creager M.A.
        • et al.
        Vascular graft infections, mycotic aneurysms, and endovascular infections: a scientific statement from the American Heart Association.
        Circulation. 2016; 134: e412-e460
        • Lamm D.L.
        • van der Meijden P.M.
        • 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
        • Willette P.A.
        • Coffield S.
        Current trends in the management of difficult urinary catheterizations.
        West J Emerg Med. 2012; 13: 472-478
        • Bhatt N.R.
        • Davis N.F.
        • Addie D.
        • et al.
        Evaluating the cost of iatrogenic urethral catheterisation injuries.
        Ir J Med Sci. 2017; 186: 1051-1055