Mycobacterium bovis Vertebral Osteomyelitis as a Complication of Intravesical BCG Use

Abu-Nader, Rima; Terrell, Christine L.

doi:10.4065/77.4.393

Cited by 53 publications

(23 citation statements)

References 40 publications

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“…In most cases the thoracolumbar vertebrae are involved. The time between BCG-immunotherapy and presentation of BCG-spondylodiscitis differs from 3 months to 12 years 25 26. Back pain is the most frequent symptom of BCG-spondylodiscitis which was also present in our patient and was initially mistaken for osteoporosis.…”

Section: Discussionmentioning

confidence: 63%

Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment

Santbergen¹,

Vriens

Lange

et al. 2013

BMJ Case Reports

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We report a 58-year-old man with spondylodiscitis by Mycobacterium bovis-BCG 3 years after intravesical BCG treatment, and shortly after a vertebroplasty. Further examination showed a psoas abscess and oedema around an endovascular aortic graft, which had been placed 1 year earlier. Puncture of the psoas abscess also grew M bovis-BCG. The patient recovered with a combination of antituberculous treatment and surgery. With hindsight a mycotic aneurysm had been present at the time of aortic graft placement and spondylodiscitis at the time of vertebroplasty. This case shows that low grade and longstanding infections may occur following intravesical BCG installation.

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Section: Discussionmentioning

confidence: 63%

Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment

Santbergen¹,

Vriens

Lange

et al. 2013

BMJ Case Reports

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“…To identify the molecules associated with bone remodeling, we performed the subtraction method using BCG-infected and uninfected osteoblastic cell line MC3T3-E1, because M. tuberculosis and BCG infection showed significant alteration of bone metabolism (3,4). From the results of the subtraction experiments, one of the TNF-␣ receptor family proteins, 4-1BB, was identified as an up-regulated gene in the BCG-infected cells.…”

Section: -1bb Induction In Osteoblasts and Osteoclastogenesismentioning

confidence: 99%

“…Mycobacterium infection in bones and joints presents ϳ10% of the extra-pulmonary cases (2). Vertebral osteomyelitis and osteitis also occur as a complication of vaccination with bacillus Calmette-Guérin (BCG) 1 or intravesical use of BCG (3,4). Osteomyelitis and osteitis caused by M. tuberculosis or BCG infection sometimes lead to vertebral caries in some patients as a result of increased bone resorption.…”

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confidence: 99%

Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro Osteoclastogenesis

Saito

Ohara

Hotokezaka

et al. 2004

Journal of Biological Chemistry

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Bacterial infection sometimes impairs bone metabolism. In this study, we infected the osteoblastic cell line MC3T3-E1 with Mycobacterium bovis bacillus CalmetteGué rin (BCG) and identified genes that were up-regulated in the BCG-infected cells by the suppression subtractive hybridization method. A gene encoding 4-1BB (CD137), a member of the tumor necrosis factor-␣ receptor family, was found to be one of the up-regulated genes. Up-regulation of 4-1BB was also observed by infection with Escherichia coli, Salmonella typhimurium, and Tuberculosis is an ancient disease but still ranks as one of the foremost killers of the 21st century. About one-third of the world's population is infected with Mycobacterium tuberculosis and more than two million people die annually from tuberculosis (1). Most tuberculosis cases are pulmonary, but the microorganism sometimes invades the central nervous system, the lymphatic system, and the musculoskeletal system, or is sometimes disseminated throughout the whole body. Mycobacterium infection in bones and joints presents ϳ10% of the extra-pulmonary cases (2). Vertebral osteomyelitis and osteitis also occur as a complication of vaccination with bacillus Calmette-Guérin (BCG) 1 or intravesical use of BCG (3, 4). Osteomyelitis and osteitis caused by M. tuberculosis or BCG infection sometimes lead to vertebral caries in some patients as a result of increased bone resorption.Bone is maintained by dynamic equilibrium between osteoblasts and osteoclasts in bone marrow cells. M. tuberculosis and BCG infection of bone alters this equilibrium, resulting in the loss of extracellular matrix and collapse of bone, especially vertebrae. Whether this bone resorption is attributable to direct effects of the bacteria on bone cells or infection-induced activation of inflammatory cells has not been clarified. However, a few studies have shown that mycobacterial antigens interfere with bone metabolism. Wax D, a mycobacterial cell wall peptidoglycan fragment-arabinogalactan-mycolic acid complex, induced reactive bone formation accompanied with osteomyelitis in Buffalo rats (5). Heat shock protein 10 of M. tuberculosis stimulates bone resorption in bone explanting cultures and induces osteoclast recruitment but inhibits proliferation of an osteoblast bone-forming cell line (6). The secreted protein MPB70 of BCG has significant homology with four repeat domains of osteoblast-specific factor 2/periostin (7). Epidemiological study suggests that MPB70-overproducing strains of BCG seem to be associated with an increased incidence of osteitis after BCG vaccination of neonates (7).Osteoblasts express various enzymatic markers such as alkaline phosphatase (ALP) and produce collagenous and noncol-

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“…31 Vertebral osteomyelitis after intravesical BCG instillation for bladder cancer has only been described in 10 prior cases worldwide. 30,[32][33][34][35][36][37][38][39][40] All of the 10 cases described and our patient were men aged 66 to 94 years, with a mean age of 77 years. Diagnosis of osteomyelitis ranged from 2 weeks to 12 years after BCG bladder instillation, with most diagnoses occurring within 2 years of therapy.…”

Section: Discussionmentioning

confidence: 98%

“…Differentiation of wild-type M bovis and M bovis BCG based on morphology and biochemical criteria is difficult because both species demonstrate susceptibility to thiophene-2-carboxylic acid hydrazide inhibition and resistance to pyrazinamide; however, M bovis BCG strains are more rapidly growing and eugonic, requiring 3 to 4 weeks to grow on Lowenstein-Jensen medium; have a rough, buff-colored appearance; and, in some cases, accumulate niacin as opposed to M bovis, which has a very slow growth rate, producing dysgonic-appearing colonies on Lowenstein-Jensen medium, frequently requiring 6 to 8 weeks to become observable. 36 The 4 validated methods for the definitive identification of M bovis BCG are phage typing, high-pressure liquid chromatography, restriction fragment length polymorphism analysis with the use of insertion element IS1081 as a probe, and amplification of a specific region containing the major polymorphic tandem repeat through polymerase chain reaction (PCR), followed by restriction enzyme analysis. 36 There are no guidelines for antimicrobial regimens for the treatment of vertebral osteomyelitis caused by BCG.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium bovis Bacillus Calmette-Guérin Vertebral Osteomyelitis After Intravesical Bacillus Calmette-Guérin Used for Bladder Cancer

Vindenes¹,

McGowan²,

Woo-Roderick³

et al. 2015

Infectious Diseases in Clinical Practice

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Background: Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis and has been used for intravesical treatment of superficial bladder cancer since 1976. Systemic complications of intravesical BCG are rare, and vertebral osteomyelitis has only been described in 10 prior cases worldwide.Case: A 64-year-old white man with benign prostatic hyperplasia was diagnosed with transitional cell bladder cancer and underwent transurethral resection of bladder tumor. He received perioperative mitomycin C followed by a 6-week course of intravesical BCG. Recurrent bladder cancer was noted on follow-up cystoscopy and he was started on a second 6-week course of BCG. Before the second intravesical BCG, he developed night sweats and severe progressive back pain with bilateral lower extremity weakness. Magnetic resonance imaging of the spine revealed a T11 to T12 vertebral body destruction with discitis, and biopsy revealed M bovis BCG. He received therapy with isoniazid, rifampin, capreomycin, as well as ethambutol and, later, additional drugs (cycloserine, moxifloxacin) secondary to clinical and radiographic progression of disease. He underwent a T11 to T12 vertebrectomy and continued on isoniazid, rifampin, cycloserine, and moxifloxacin for a total of 12 months postoperatively.Conclusions: Mycobacterium bovis BCG osteomyelitis is a rare complication of intravesical BCG therapy for bladder cancer and may occur as a solitary site of infection. A high degree of suspicion is important in patients with osteomyelitis with a history of transitional cell cancer managed with immunotherapy using BCG instillations.

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Mycobacterium bovis Vertebral Osteomyelitis as a Complication of Intravesical BCG Use

Cited by 53 publications

References 40 publications

Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment

Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment

Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro Osteoclastogenesis

Mycobacterium bovis Bacillus Calmette-Guérin Vertebral Osteomyelitis After Intravesical Bacillus Calmette-Guérin Used for Bladder Cancer

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