Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report

Schwartz, Noah G.; Hernández-Romieu, Alfonso C; Annambhotla, Pallavi; Filardo, Thomas D.; Althomsons, Sandy; Free, Rebecca J; Li, Ruoran; Wilson, Wendy; Deutsch-Feldman, Molly; Drees, Marci; Hanlin, Emily; White, Kelly; Lehman, Kimberly A; Thacker, Tyler C.; Brubaker, Scott A.; Clark, Brychan; Basavaraju, Sridhar V.; Benowitz, Isaac; Glowicz, Janet; Cowan, Lauren S.; Starks, Angela M.; Morris, Sapna Bamrah; LoBue, Philip; Stewart, Rebekah J; Wortham, Jonathan M.; Haddad, Maryam B.

doi:10.1016/s1473-3099(22)00425-x

Cited by 22 publications

(19 citation statements)

References 22 publications

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“…These diseases include HIV, syphilis, hepatitis B, and hepatitis C, but there are currently no guidelines to screen for TB. In this specific donor sample, the donor was found to have previously resided in and traveled to a country with a high incidence of TB, although they had negative tuberculin skin testing 10 . Regardless of donor history, after cells are obtained, they undergo sterilization and subsequent cryopreservation in 5% dimethyl sulfoxide.…”

Section: Discussionmentioning

confidence: 99%

“…After identification of commonalities between spinal fusion patients who contracted TB, FiberCel was identified as the likely source of infection and was recalled 9 . Within 5 months of CBM implantation, 8/113 (7.1%) patients died; with 3 deaths attributable to TB, 3 deaths unrelated, and 2 with insufficient evidence to attribute causality 10 . A report of 23 exposed patients in Delaware identified that 19 (83%) developed symptoms of TB, 16 (70%) required hospital readmission, and 12 (52%) required additional surgery to manage complications of TB infection 9 .…”

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confidence: 99%

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Cellular Bone Matrix Leading to Disseminated Tuberculosis After Spinal Fusion

Issa

Lambrechts

Toci

et al. 2023

JBJS Case Connector

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Case:Although implanted tuberculosis (TB) is rare, a single lot of cellular bone matrix was found to be infected with TB, leading to devastating outcomes. We present 2 cases referred to our institution because of instrumentation failure caused by TB inoculation of cellular bone matrix.Conclusion:Irrespective of spinal region of implanted TB infection, excision of infected bone, extensive irrigation and debridement, and instrumented stabilization are of primary importance to ensure TB eradication and adequate stabilization.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cellular Bone Matrix Leading to Disseminated Tuberculosis After Spinal Fusion

Issa

Lambrechts

Toci

et al. 2023

JBJS Case Connector

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“…1 Still, a risk of transmission of infectious disease remains as the example of a spectacular case in 2021 shows, whereby a viable bone allograft, that was tested for viruses, bacteria, and fungi, but not for mycobacteria, caused a nationwide tuberculosis outbreak in the US. 11 The second measure, besides discarding donor tissue with unacceptable bioburden, is preventing contamination by using aseptic handling techniques, since processing, shaping, and cutting prior to transplantation exposes the tissues to possible contamination from the environment or the equipment used. 12 However, despite these stringent measures, microbiological testing immediately prior to transplantation revealed contamination rates of 4% to 11% in previously negatively tested bone allografts.…”

Section: Introductionmentioning

confidence: 99%

Systematic enhancement of microbial decontamination efficiency in bone graft processing by means of high hydrostatic pressure using Escherichia coli as a model organism

Loeffler,

Waletzko‐Hellwig,

Fischer

et al. 2024

J Biomed Mater Res

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To obtain bone allografts that are safe for transplantation, several processing steps for decellularization and decontamination have to be applied. Currently available processing methods, although well‐established, may interfere with the biomechanical properties of the bone. High hydrostatic pressure (HHP) is known to devitalize tissues effectively while leaving the extracellular matrix intact. However, little is known about the inactivation of the contaminating microorganisms by HHP. This study aims to investigate the ability of high‐pressure decontamination and to establish a treatment protocol that is able to successfully inactivate microorganisms with the final goal to sterilize bone specimens. Using Escherichia coli (E. coli) as a model organism, HHP treatment parameters like temperature and duration, pressurization medium, and the number of treatment cycles were systematically adjusted to maximize the efficiency of inactivating logarithmic and stationary phase bacteria. Towards that we quantified colony‐forming units (cfu) after treatment and investigated morphological changes via Field Emission Scanning Electron Microscopy (FESEM). Additionally, we tested the decontamination efficiency of HHP in bovine cancellous bone blocks that were contaminated with bacteria. Finally, two further model organisms were evaluated, namely Pseudomonas fluorescens as a Gram‐negative microorganism and Micrococcus luteus as a Gram‐positive representative. A HHP protocol, using 350 MPa, was able to sterilize a suspension of stationary phase E. coli, leading to a logarithmic reduction factor (log RF) of at least −7.99 (±0.43). The decontamination of bone blocks was less successful, indicating a protective effect of the surrounding tissue. Sterilization of 100% of the samples was achieved when a protocol optimized in terms of treatment temperature, duration, pressurization medium, and number and/or interval of cycles, respectively, was applied to bone blocks artificially contaminated with a suspension containing 104 cfu/mL. Hence, we here successfully established protocols for inactivating Gram‐negative model microorganisms by HHP of up to 350 MPa, while pressure levels of 600 MPa were needed to inactivate the Gram‐positive model organism. Thus, this study provides a basis for further investigations on different pathogenic bacteria that could enable the use of HHP in the decontamination of bone grafts intended for transplantation.

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“…Bone allografts are mainly osteoconductive, with only demineralized bone matrix (DBM) preparations retaining lower osteoinductivity. Despite this, inferior recovery was detected compared with autologous grafts, and the risk of disease transmission and other infectious agents was also documented [ 9 ]. More critically, the typical amounts of naturally available bone graft substitutes are still insufficient to meet therapeutic demands, especially in light of the approaching aging and obesity situations worldwide [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Osteoimmunomodulatory Nanoparticles for Bone Regeneration

et al. 2023

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Treatment of large bone fractures remains a challenge for orthopedists. Bone regeneration is a complex process that includes skeletal cells such as osteoblasts, osteoclasts, and immune cells to regulate bone formation and resorption. Osteoimmunology, studying this complicated process, has recently been used to develop biomaterials for advanced bone regeneration. Ideally, a biomaterial shall enable a timely switch from early stage inflammatory (to recruit osteogenic progenitor cells) to later-stage anti-inflammatory (to promote differentiation and terminal osteogenic mineralization and model the microstructure of bone tissue) in immune cells, especially the M1-to-M2 phenotype switch in macrophage populations, for bone regeneration. Nanoparticle (NP)-based advanced drug delivery systems can enable the controlled release of therapeutic reagents and the delivery of therapeutics into specific cell types, thereby benefiting bone regeneration through osteoimmunomodulation. In this review, we briefly describe the significance of osteoimmunology in bone regeneration, the advancement of NP-based approaches for bone regeneration, and the application of NPs in macrophage-targeting drug delivery for advanced osteoimmunomodulation.

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Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report

Cited by 22 publications

References 22 publications

Cellular Bone Matrix Leading to Disseminated Tuberculosis After Spinal Fusion

Cellular Bone Matrix Leading to Disseminated Tuberculosis After Spinal Fusion

Systematic enhancement of microbial decontamination efficiency in bone graft processing by means of high hydrostatic pressure using Escherichia coli as a model organism

Osteoimmunomodulatory Nanoparticles for Bone Regeneration

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