Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes.

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1ß, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1ß, and other known IL-1ß-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1ß, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1ß and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

[Evidence-based implant choice in infections of the spine : Is it a gut thing, after all?] / Evidenzbasierte Implantatwahl bei Infektionen der Wirbelsäule : Ist es doch eine Bauchsache?

The choice of implant in an infection of the spine depends on what type of infection it is: discitis, spondylodiscitis, early infection after spinal surgery, or a late infection. The appropriate treatment strategies vary. In spondylodiscitis, a titanium implant may be necessary. In implant-associated early infections, surgical sanitization is often sufficient without changing the implant. In late infections, implant exchange is necessary because of biofilm.

A review of microscopy-based evidence for the association of Propionibacterium acnes biofilms in degenerative disc disease and other diseased human tissue.

PURPOSE: Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin. A ubiquitous slow-growing organism with the capacity to form biofilm, P. acnes, recognized for its role in acne vulgaris and medical device-related infections, is now also linked to a number of other human diseases. While bacterial culture and molecular techniques are used to investigate the involvement of P. acnes in such diseases, definitive demonstration of P. acnes infection requires a technique (or techniques) sensitive to the presence of biofilms and insensitive to the presence of potential contamination. Fortunately, there are imaging techniques meeting these criteria, in particular, fluorescence in situ hybridization and immunofluorescence coupled with confocal laser scanning microscopy, as well as immunohistochemistry. METHODS: Our literature review considers a range of microscopy-based studies that provides definitive evidence of P. acnes colonization within tissue from a number of human diseases (acne vulgaris, degenerative disc and prostate disease and atherosclerosis), some of which are currently not considered to have an infectious etiology. RESULTS/CONCLUSION: We conclude that P. acnes is an opportunistic pathogen with a likely underestimated role in the development of various human diseases associated with significant morbidity and, in some cases, mortality. As such, these findings offer the potential for new studies aimed at understanding the pathological mechanisms driving the observed disease associations, as well as novel diagnostic strategies and treatment strategies, particularly for degenerative disc disease. These slides can be retrieved under Electronic Supplementary Material.

The bacteria-positive proportion in the disc tissue samples from surgery: a systematic review and meta-analysis.

PURPOSE: The role of bacteria, especially Propionibacterium acnes (P. acnes), in human intervertebral disc diseases has raised attention in recent years. However, limited sample size of these studies and diverse bacteria-positive proportion made this topic still controversial. We aimed to review related articles and summarize the bacteria-positive proportion in these studies. METHODS: We searched the PubMed, Cochrane Library, Embase for related literature from January 2001 to May 2018, and the reference articles were also searched. The random effects or fixed effects meta-analysis was used to pool the overall positive proportion or odds ratio of these studies. RESULTS: We found 16 relevant articles and 2084 cases of the bacteria culture from surgery. Within the 16 included studies, 12 studies' results supported the infection in the discs. The pooled bacterial infection rate was 25.3%. The pooled P. acnes infection rate was 15.5%. The overall pooled P. acnes proportion in bacteria-positive discs was 56.4%. We also found that the presence of bacteria may contribute to the development of Modic change with the odds ratio as 1.27 (95% CI: 0.44-3.64), but this result is not significant due to heterogeneity, so further study is needed. CONCLUSION: The existence of bacteria in the intervertebral discs was proved by many studies. However, the variety in sample collecting and culture methods is still obvious and the positive rate also fluctuated within the studies. Standardized and reliable methods should be taken to promote the study in the future. These slides can be retrieved under Electronic Supplementary Material.

Association between chronic inflammation and latent infection of Propionibacterium acnes in non-pyogenic degenerated intervertebral discs: a pilot study.

PURPOSE: Propionibacterium acnes may be considered a new pathogeny for disc degeneration, but its pathological role has remained unclear. This study was designed to determine whether the latent infection of P. acnes was associated with chronic inflammation in degenerated intervertebral discs via quantification of the levels of a series of cytokines and neutrophils. METHODS: Here, 76 degenerated intervertebral discs were harvested from patients with lower back pain and/or sciatica. Discs with and without P. acnes infection were distinguished and identified using anaerobic culture combined with 16S rDNA PCR and histological examination. Then, cytokines of TNF-α, IL-1ß, IL-6, IL-8, MCP-1, MIP-1α, and IP-10, and the numbers of neutrophils were quantified and compared. The severity of disc degeneration and the prevalence of Modic changes were also evaluated between discs with and without P. acnes. RESULTS: After anaerobic culture and PCR examination, 15 intervertebral discs were placed in the P. acnes-positive group. Another 15 discs were selected from the remaining bacteria-free samples and formed a matched P. acnes-negative group. IL-8, MIP-1α, MCP-1, IP-10, TNF-α, and neutrophils were much higher in P. acnes-positive group than that in the matched P. acnes-negative group. However, only IL-8, MIP-1α, and neutrophils were statistically significant. Furthermore, 7 of 15 P. acnes-positive samples were histologically positive and a subgroup analysis suggested that both histological and PCR-positive samples had the highest concentrations of cytokines of IL-8, MIP-1α, TNF-α, and MCP-1 and the greatest numbers of neutrophils. PCR-positive but histologically negative samples showed the second-greatest, and matched P. acnes-negative samples showed the fewest. However, the difference was only statistically significant between samples found positive under both histology and PCR and samples found negative for P. acnes. Finally, P. acnes-positive group had significantly lower height of intervertebral discs and there was a trend with higher proportion of Modic changes in P. acnes-positive group, but without statistical results. CONCLUSIONS: Latent P. acnes infection was associated with chronic inflammation in degenerated intervertebral discs, especially in the samples with visible bacteria in histology, which manifested as increased numbers of cytokines and neutrophils. Discs with P. acnes infection had much severer disc degeneration and P. acnes-associated chronic inflammation may be the reason.

Low virulence bacterial infections in cervical intervertebral discs: a prospective case series.

STUDY DESIGN: A prospective cross-sectional case series study. OBJECTIVE: To investigate the prevalence of low virulence disc infection and its associations with characteristics of patients or discs in the cervical spine. BACKGROUND: Low virulence bacterial infections could be a possible cause of intervertebral disc degeneration and/or back pain. Controversies are continuing over whether these bacteria, predominantly Propionibacterium acnes (P. acnes), represent infection or contamination. However, the current studies mainly focus on the lumbar spine, with very limited data on the cervical spine. METHODS: Thirty-two patients (20 men and 12 women) who underwent anterior cervical fusion for degenerative cervical spondylosis or traumatic cervical cord injury were enrolled. Radiological assessments included X-ray, CT, and MRI of the cervical spine. Endplate Modic changes, intervertebral range of motion, and disc herniation type were evaluated. Disc and muscle tissues were collected under strict sterile conditions. Samples were enriched in tryptone soy broth and subcultured under anaerobic conditions, followed by identification of the resulting colonies by the PCR method. RESULTS: Sixty-six intervertebral discs were excised from thirty-two patients. Positive disc cultures were noted in eight patients (25%) and in nine discs (13.6%). The muscle biopsy (control) cultures were negative in 28 patients and positive in 4 patients (12.5%); three of whom had a negative disc culture. Seven discs (10.6%) were positive for coagulase-negative Staphylococci (CNS) and two discs were positive for P. acnes (3.0%). A younger patient age and the extrusion or sequestration type of disc herniation, which represented a complete annulus fibrous failure, were associated with positive disc culture. CONCLUSIONS: Our data show that CNS is more prevalent than P. acnes in degenerative cervical discs. The infection route in cervical discs may be predominantly through an annulus fissure. Correlation between these infections and clinical symptoms is uncertain; therefore, their clinical significance needs to be investigated in the future. These slides can be retrieved under Electronic Supplementary Material.

Latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs.

BACKGROUND: The existence of latent low-virulence anaerobic bacteria in degenerated intervertebral discs (IVDs) remains controversial. In this study, the prevalence of low-virulence anaerobic bacteria in degenerated IVDs was examined, and the correlation between bacterial infection and clinical symptoms was analysed. METHODS: Eighty patients with disc herniation who underwent discectomy were included in this study. Under a stringent protocol to ensure sterile conditions, 80 disc samples were intraoperatively retrieved and subjected to microbiological culture. Meanwhile, tissue samples from the surrounding muscle and ligaments were harvested and cultured as contamination markers. The severity of IVD degeneration and the prevalence of Modic changes (MCs) were assessed according to preoperative MRI analysis. RESULTS: Of the 80 cultured discs, 54 were sterile, and 26 showed the presence of bacteria: Propionibacterium acnes (21 cases) and coagulase-negative staphylococci (5 cases). MRI revealed that the presence of bacteria was significantly associated with MCs (P<0.001). However, there was no significant association between bacterial infection and the severity of IVD degeneration (P = 0.162). CONCLUSIONS: Our findings further validated the presence of low-virulence anaerobic bacteria in degenerated IVDs, and P. acnes was the most frequent bacterium. In addition, the latent infection of bacteria in IVDs was associated with Modic changes. Therefore, low-virulence anaerobic bacteria may play a crucial role in the pathophysiology of MCs and lumbar disc herniation.

ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis.

STUDY DESIGN: Proteomic and 16S rDNA analysis of disc tissues obtained in vivo. OBJECTIVE: To address the controversy of infection as an aetiology for disc disorders through protein profiling. There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection. METHODS: 22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA. RESULTS: LC-MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein-protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C. CONCLUSION: Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection as a possible initiator of disc disease. These results can lead to a paradigm shift in our understanding and management of disc disorders.

What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature.

This review presents a summary of the pathology and epidemiology of Modic changes and the possible role of Propionibacterium acnes. This information is followed by a synthesis of the most recent clinical research involved in culturing the discs of patients with degenerative disc disease for the presence of bacteria. We also discuss a randomized controlled trial that investigates the effects of antibiotics on patients with chronic low back pain and type 1 Modic changes. We conclude with a brief discussion of the difficulties involved in this research and the significance of the findings.

Prospective study using anterior approach did not show association between Modic 1 changes and low grade infection in lumbar spine.

INTRODUCTION: The modern literature is producing a rapidly growing number of articles which highlight the relationship between infection and lumbar disc degeneration. However, the means by which samples are collected is questionable. Posterior approach surgery is not free from skin contamination. The possibility of intraoperative contamination of disc biopsies cannot be excluded. OBJECTIVE: The objective of this study was to determine if an association existed between lumbar disc degeneration and chronic infection of the intervertebral disc. MATERIALS AND METHODS: 313 patients (186/127, F/M) with chronic low back pain secondary to degenerative disc disease which was resistant to medical treatment were included in a single-centre prospective study. All underwent a lumbar anterior video-assisted minimally invasive fusion or disc prosthesis in L4-L5 and/or L5-S1 via an anterior retroperitoneal approach. The patients MRI scans demonstrated in Pfirrmann's classification grade IV or V disc degeneration; 385 disc drives were taken. In terms of Modic changes, 303 Modic 1, 58 Modic II and 24 absence of Modic change, respectively. All underwent intraoperative biopsy, performed according to a strict aseptic protocol. The biopsies were then cultured for 4 weeks with specialised enrichment cultures and subjected to histopathological analysis. RESULTS: The mean age was 47 ± 8.6 years sterile cultures were obtained in 379 samples (98.4%) and 6 were positive (1.6%). The cultured bacteria were: Propionibacterium acnes (n:2), Staphylococcus epidermidis (n:2), Citrobacter freundii (n:1), and Saccharopolyspora hirsuta (n:1). Histopathological analysis did not demonstrate any evidence of a neutrophilia. There were no delayed or secondary infections. DISCUSSION AND CONCLUSION: Unlike the posterior approach where contamination is common, the anterior video-assisted approach allows a biopsy without skin contact. This approach to the spine is the most effective way to eliminate the risk of contamination. Our results confirm the absence of any relationship between infection and disc degeneration. We suggest that the 6 positive samples in our study may be related to contamination. The absence of infection at 1-year followup is an additional argument in favour of our results. In conclusion, our study shows no association between infection and disc degeneration. The pathophysiology of disc degeneration is complex, but the current literature opens new perspectives.

Lumbar discitis caused by Clostridium perfringens.

We report here a rare case of chronic lumbar discitis caused by Clostridium perfringens in an elderly patient that was treated with a combination of ß-lactams and clindamycin. Molecular analysis performed on the strain revealed an unusual toxin gene pattern.

Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.

The Effect of Gut Microbiota on the Progression of Intervertebral Disc Degeneration.

OBJECTIVE: Intervertebral disc degeneration (IDD) is the main cause of back pain, and its treatment is a serious socio-economic burden. The safety and treatment of fecal microbiota transplantation (FMT) has been established. However, the relationship between FMT and IDD still unclear. We aimed to explore whether FMT plays a role in IDD to provide a reference for the treatment of IDD. METHODS: An experimental model of IDD was established using 2-month-old male Sprague-Dawley rats. FMT was performed by intragastric gavage of IDD rats with a fecal bacterial solution. Rat serum, feces, and vertebral disc tissue were collected after surgery for 2 months. The levels of TNF-α, IL-1ß, IL-6, matrix metalloproteinase (MMP)-3, MMP-13, Collagen II, and aggrecan in the serum or vertebral disc tissue were measured by an enzyme-linked immunosorbent assay, immunohistochemistry, quantitative real-time polymerase chain reaction, or western blotting. We also examined the pathology of the vertebral disc tissue using hematoxylin and eosin (HE) and safranin O-fast green staining. Finally, we examined the gut microbiota in rat feces using 16 S rRNA gene sequencing. RESULTS: We found that the expression of TNF-α, IL-1ß, IL-6, MMP-3, MMP-13, NLRP3 and Caspase-1 increased in the IDD group rats. In contrast, Collagen II and aggrecan levels were downregulated. Additionally, vertebral disc tissue was severely damaged in the IDD group, with disordered cell arrangement and uneven safranin coloration. FMT reversed the effects of IDD modeling on these factors and alleviated cartilage tissue damage. In addition, FMT increased the gut microbiota diversity and microbial abundance in rats treated with IDD. CONCLUSION: Our findings suggest that FMT has a positive effect in maintaining cellular stability in the vertebral disc and alleviating histopathological damage. It affects the diversity and abundance of gut microbiota in rats with IDD. Therefore, FMT may serve as a promising target for amelioration of IDD.

Bacteriology of degenerated lumbar intervertebral disks.

STUDY DESIGN: A prospective microbiological analysis of intervertebral disk material in surgically treated patients presenting lumbar disk degeneration. OBJECTIVE: To determine the prevalence and species of bacteria in degenerated lumbar disks, their eventual role in the pathophysiology, and the possible influence of risk factors. SUMMARY OF BACKGROUND DATA: Intervertebral disk degeneration results from biochemical, mechanical, genetic, and toxic factors. The hypothesis of low-grade infection has been raised but not elucidated to date. METHODS: Eighty-three patients (34 males, 49 females, 41 y) were treated by lumbar disk replacement at L3-L4, L4-L5, or L5-S1. An intraoperative biopsy and microbiological culture were performed for each disk to determine if intradiskal bacteria were present. Magnetic resonance stages were Pfirrmann IV or V, with Modic I in 32, and Modic II in 25 cases. A preoperative discography was performed in 49 patients, 24 had previous nucleotomy. RESULTS: Bacteria were found in 40 disks, 43 cultures were sterile. The following bacteria were evidenced: Propionibacterium acnes 18, coagulase-negative staphylococci 16, gram-negative bacilli 3, Micrococcus 3, Corynebacterium 3, others 5. Ten biopsies presented 2 different species. Multinucleated cells were evidenced histologically in 33% of positive biopsies. Bacteria were predominantly found in males (P=0.012). The mostly positive level was L4-L5 (P=0.075). There was no significant relationship between bacterial evidence and Modic sign. A preoperative discography or previous nucleotomy did not represent significant contamination sources. None of the patients presented infectious symptoms. CONCLUSIONS: Although the hypothesis of biopsy contamination cannot be excluded, intradiskal bacteria might play a role in the pathophysiology of disk degeneration. However, the histologic presence of multinucleated cells may indicate an inflammatory process that could sustain the hypothesis of low-grade spondylodiscitis at 1 stage of the cascade of lumbar disk degeneration. These microbiological and histologic findings would need to be compared with nondegenerated disks. LEVEL OF EVIDENCE: : Diagnostic level III.

Red Light-Mediated Photoredox Catalysis Triggers Nitric Oxide Release for Treatment of Cutibacterium Acne Induced Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been known as a highly prevalent and disabling disease, which is one of the main causes of low back pain and disability. Unfortunately, there is no effective cure to treat this formidable disease, and surgical interventions are typically applied. Herein, we report that the local administration of nitric oxide (NO)-releasing micellar nanoparticles can efficiently treat IVDD associated with Modic changes in a rat model established by infection with Cutibacterium acnes (C. acnes). By covalent incorporation of palladium(II) meso-tetraphenyltetrabenzoporphyrin photocatalyst and coumarin-based NO donors into the core of micellar nanoparticles, we demonstrate that the activation of the UV-absorbing coumarin-based NO donors can be achieved under red light irradiation via photoredox catalysis, although it remains a great challenge to implement photoredox catalysis reactions in biological conditions due to the complex microenvironments. Notably, the local delivery of NO can not only efficiently eradicate C. acnes pathogens but also inhibit the inflammatory response and osteoclast differentiation in the intervertebral disc tissues, exerting antibacterial, anti-inflammatory, and antiosteoclastogenesis effects. This work provides a feasible means to efficiently treat IVDD by the local administration of NO signaling molecules without resorting to a surgical approach.

Propionibacterium acnes Accelerates Intervertebral Disc Degeneration by Inducing Pyroptosis of Nucleus Pulposus Cells via the ROS-NLRP3 Pathway.

Our previous study verified the occurrence of Propionibacterium acnes (P. acnes), a low-virulence anaerobic bacterium, latently residing in degenerated intervertebral discs (IVDs), and the infection had a strong association with IVD degeneration. We explored whether P. acnes induces nucleus pulposus cell (NPC) pyroptosis, a more dangerous cell death process than apoptosis, and accelerates IVD degeneration via the pyroptotic products interleukin- (IL-) 1ß and IL-18. After coculturing with P. acnes, human NPCs showed significant upregulation of NOD-like receptor 3 (NLRP3), cleaved IL-1ß, cleaved caspase-1, and cleaved gasdermin D in response to the overexpression of IL-1ß and IL-18 in a time- and dose-dependent manner. In addition, the gene expression of inflammatory factors and catabolic enzymes significantly increased in normal NPCs when cocultured with pyroptotic NPCs in a transwell system, and the adverse effects were inhibited when NPC pyroptosis was suppressed. Furthermore, inoculation of P. acnes into the IVDs of rats caused significant pyroptosis of NPCs and remarkable IVD degeneration. Finally, coculture of NPCs with P. acnes induced the overexpression of reactive oxygen species (ROS) and NLRP3, while inhibition of both factors reduced NPC pyroptosis. Therefore, P. acnes induces NPC pyroptosis via the ROS-NLRP3 signaling pathway, and the pyroptotic NPCs cause an IVD degeneration cascade. Targeting the P. acnes-induced pyroptosis of NPCs may become an alternative treatment strategy for IVD degeneration in the future.

The role of Propionibacterium acnes in and Modic type 1 changes†:†A literature review.

Propionibacterium acnes (P. acnes) is part of the normal flora of human skin, oral cavity, intestinal tract and external ear canal. However, breach in the mucosa as well as ruptured annulus fibrosus provide favorable pathway for P. acnes to nucleus pulposus where it can proliferate under anaerobic condition. In past two decades many authors have identified P. acnes in routine culture of discs. There studies showed that almost 50% of discs cultured were positive for various organism, and in vast majority of culture positive disc, P. acnes was the primary organism isolated. However, there are few studies that refute the hypothesis that P. acnes has a role in pathogenesis of Modic type 1 changes. Identification of P. acnes in culture indicates the infective patho-mechanism in the pathogenesis of Modic type 1 changes, which may be ameable to antibiotic treatment. However, it is still difficult to identify which subset of these patients (patients with low back pain with type 1 Modic change) are infective in nature. Further investigation and more clinical trails will be required for clear identification of the infective subgroup among low back patient in general. J. Med. Invest. 67 : 21-26, February, 2020.

Optimizing the safety of intradiscal platelet-rich plasma: an in vitro study with Cutibacterium acnes.

Aim: The most common risk associated with intradiscal injection of platelet-rich plasma (PRP) is discitis with Cutibacterium acnes. It is hypothesized that antimicrobial activity of PRP can be enhanced through inclusion of leukocytes or antibiotics in the injectate. Materials & methods: Multiple PRP preparations of varying platelet and leukocyte counts were co-cultured with C. acnes with or without cefazolin, with viable bacterial colony counts being recovered at 0, 4, 24 and 48 hours post-inoculation. Results: A direct correlation between C. acnes recovery and granulocyte counts were observed. Conclusion: We observed the greatest antimicrobial activity with the leukocyte-rich, high platelet PRP preparation combined with an antibiotic in the injectate. However, cefazolin did not completely clear the bacteria in this assay.

The Relationship Between Low-Grade Infection and Degenerative Disk Disease: A Review of Basic Science and Clinical Data.

Low back pain resulting from intervertebral disk degeneration is a cause of substantial disability and productivity loss. Over the past few years, growing evidence exists which suggests that low-grade bacterial infection, particularly infection with Cutibacterium acnes, may be associated with degenerative disk disease in the lumbar spine. Positive cultures are obtained in approximately 30% of intervertebral disk specimens removed at the time of surgery. In addition, one randomized trial has shown that antibiotic therapy for low back pain in patients with disk degeneration can slow the progression of degeneration and improve pain and disability levels. Although these results are encouraging, the link between infection and disk degeneration remains controversial. Investigators have attempted to address the limitations of clinical research by using translational methods and animal models. These methods have shown that seeding of the disk with bacteria can lead to increased local inflammation and an in vivo phenotype that is similar to human disk degeneration. This review seeks to provide an overview of the clinical, translational, and animal model data linking infection to disk degeneration. We review mechanisms for disk degeneration in the setting of infection and explore areas for future investigation.

Degenerate-disc infection study with contaminant control (DISC): Application of a proposed histological scoring system.

Recent evidence into an infectious etiology of discogenic back pain/leg pain are ongoing with contradictory data in literature. We sought to validate the clinical relevance of histopathological evidence of inflammation through a previously proposed histological grading system. In this prospective cohort study, 124 consecutive patients undergoing an elective spinal decompression and/or fusion procedure involving discectomy were selected with intraoperative tissue sampling of intervertebral disc and paraspinal tissue at a single institution. The histological domains were correlated with positive disc cultures to assist in identifying relevant positive infections. Inter-observer analysis of the scoring system was also performed. There were 124 samples (36 cervical and 88 lumbar) obtained. 29 (23.4%) disc specimens and 37 (29.8%) of ligament samples demonstrated growth of C. acnes. In total, 38/124 (30.6%) of disc specimens were positive for growth of any species. There was poor association between positive disc culture and the presence of neutrophilia (p = 0.123) or chronic inflammatory changes (p = 0.092) on histopathological assessment. There was no statistical significance noted across all histological domains examined within the finalised scoring system and positive culture across disc specimens. There was moderate agreement in between observers (kappa range: 0.41-0.60) in the assessment of inflammatory changes using the proposed scoring system. The current study suggests poor correlation between histopathological evidence of chronic or acute inflammation and positive disc cultures questioning the idea that disc infection is the root cause of acute or chronic back pain/leg pain.