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    Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae? Albert Hanne B,Lambert Peter,Rollason Jess,Sorensen Joan Solgaard,Worthington Tony,Pedersen Mogens Bach,Nørgaard Hanne Schack,Vernallis Ann,Busch Frederik,Manniche Claus,Elliott Tom European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society PURPOSE:To investigate the prevalence of infected herniated nucleus material in lumbar disc herniations and to determine if patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone oedema) in the adjacent vertebrae after the disc herniation. MCs (bone oedema) in vertebrae are observed in 6 % of the general population and in 35-40 % of people with low back pain. These changes are strongly associated with low back pain. There are probably a mechanical cause and an infective cause that causes MC. Several studies on nuclear tissue from herniated discs have demonstrated the presence of low virulent anaerobic microorganisms, predominantly Propionibacterium acnes, in 7-53 % of patients. At the time of a herniation these low virulent anaerobic bacteria may enter the disc and give rise to an insidious infection. Local inflammation in the adjacent bone may be a secondary effect due to cytokine and propionic acid production. METHODS:Patients undergoing primary surgery at a single spinal level for lumbar disc herniation with an MRI-confirmed lumbar disc herniation, where the annular fibres were penetrated by visible nuclear tissue, had the nucleus material removed. Stringent antiseptic sterile protocols were followed. RESULTS:Sixty-one patients were included, mean age 46.4 years (SD 9.7), 27 % female. All patients were immunocompetent. No patient had received a previous epidural steroid injection or undergone previous back surgery. In total, microbiological cultures were positive in 28 (46 %) patients. Anaerobic cultures were positive in 26 (43 %) patients, and of these 4 (7 %) had dual microbial infections, containing both one aerobic and one anaerobic culture. No tissue specimens had more than two types of bacteria identified. Two (3 %) cultures only had aerobic bacteria isolated. In the discs with a nucleus with anaerobic bacteria, 80 % developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of those with aerobic bacteria and only 44 % of patients with negative cultures developed new MC. The association between an anaerobic culture and new MCs is highly statistically significant (P = 0.0038), with an odds ratio of 5.60 (95 % CI 1.51-21.95). CONCLUSION:These findings support the theory that the occurrence of MCs Type 1 in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc. The discs infected with anaerobic bacteria were more likely (P < 0.0038) to develop MCs in the adjacent vertebrae than those in which no bacteria were found or those in which aerobic bacteria were found. 10.1007/s00586-013-2674-z
    Prospective study using anterior approach did not show association between Modic 1 changes and low grade infection in lumbar spine. Rigal Julien,Thelen Thomas,Byrne Fergus,Cogniet Arnaud,Boissière Louis,Aunoble Stephane,Le Huec Jean-Charles European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 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. 10.1007/s00586-016-4396-5
    Bacteriology of degenerated lumbar intervertebral disks. Arndt Joseph,Charles Yann Philippe,Koebel Christelle,Bogorin Ioan,Steib Jean-Paul Journal of spinal disorders & techniques 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. 10.1097/BSD.0b013e318269851a
    Bacteriologic culture of excised intervertebral disc from immunocompetent patients undergoing single level primary lumbar microdiscectomy. Agarwal Vijay,Golish S Raymond,Alamin Todd F Journal of spinal disorders & techniques STUDY DESIGN:A consecutive case series from a single center of patients undergoing primary microdiscectomy for lumbar herniated nucleus pulposus (HNP) who received microbiologic laboratory culture of excised disc material. OBJECTIVE:To determine the prevalence of positive bacterial cultures in the disc material of immunocompetent patients without diabetes mellitus or other immune compromise. SUMMARY OF BACKGROUND DATA:The intradiscal space is a physiologically tenuous environment in terms of oxygen tension, pH, and vascularity. This space may be susceptible to indolent infections with an unknown effect on the pathogenesis of HNP. METHODS:This case series included 52 patients with radiculopathy and magnetic resonance imaging positive for HNP who elected for lumbar microdiscectomy after failure of conservative management. All patients received primary surgery at a single spinal level in the absence of diabetes mellitus, systemic steroid use, chemotherapy, other immune compromise, or prior lumbar surgery. Excised disc material was sent for routine bacterial culture. No special culture techniques were used to improve the yield of positive cultures. RESULTS:Cultures were positive in 10 patients (19.2%). Propionibacterium acnes was the sole organism isolated in 7 (13.5%), with Peptostreptococcus and Staphylococcus species accounting for the remainder. There were 24 women (46.2%) and 28 men (53.8%) with a mean age of 43.9 years (SE 1.8). Duration of symptoms was greater than 12 weeks in 35 patients (67.3%). Onset of symptoms was insidious in 22 patients (42.3%), sudden in 16 (30.8%), and the history was unclear in the remainder. Prior epidural steroid injection was received by 17 patients (32.7%), and 11 patients had a history of smoking (21.2%). None of these variables was significantly different in patients with positive and negative cultures (P >0.05). CONCLUSIONS:P. acnes was isolated by routine laboratory culture of excised disc material in 13.5% of immunocompetent patients undergoing primary single level discectomy for radiculopathy with lumbar HNP; other organisms were isolated in 6% of patients. LEVEL OF EVIDENCE:Diagnostic level of evidence III. 10.1097/BSD.0b013e3182019f3a
    [Spondylodiscitis due to Propionibacterium acnes. Case report and review of the literature]. Hammann C,Dudler J,Gaumann U,Landry M,Gerster J C Schweizerische medizinische Wochenschrift Propionibacterium acnes, a gram positive anaerobic organism, is a component of normal skin flora. It can exceptionally be a source of osteoarticular infection (osteitis, arthritis, spondylodiscitis). We report a case of Propionibacterium acnes spondylodiscitis following lumbar puncture. This observation should alert the clinician to the fact that Propionibacterium acnes may rarely cause spondylodiscitis and lumbar pain, and should be considered a causative agent of bone infections after local procedures.
    Lumbar spondylodiscitis caused by Propionibacterium acnes after epidural obstetric analgesia. Hernández-Palazón Joaquín,Puertas-García J Pablo,Martínez-Lage Juan F,Tortosa José A Anesthesia and analgesia IMPLICATIONS:We report a case of Propionibacterium acnes spondylodiscitis after the placement of an epidural catheter for obstetric analgesia. This observation should alert the anesthesiologist to the fact that infection, although rare, may occur after uneventful epidural analgesia in the healthy parturient and reinforces the importance of aseptic technique during epidural catheter insertion. 10.1213/01.ane.0000055819.35383.d3
    Late implant infections caused by Propionibacterium acnes in scoliosis surgery. Hahn Frederik,Zbinden Reinhard,Min Kan European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society One hundred and one consecutive adolescent scoliosis patients instrumented from the posterior between 1995 and 2002, with a minimum follow-up of 24 months (maximum 106 months), were reviewed for incidence of infection. Stainless steel implants with pedicle screws were used in the thoracic and lumbar spine of all patients. All were operated on by a single surgeon. There were no early infections. Incidence of late infection was 6.9% (seven patients). Clinical indicators for infection were the sudden onset of local pain and swelling without fever after an initial pain-free interval. There were no reliable laboratory parameters. Normal CRP and ESR did not rule out a late infection. Extended cultures were done from intraoperative swabs. Propionibacterium acnes was found in six patients. There were no other organisms identified. No causative organism could be identified in one patient, despite extended cultures. All patients were successfully treated with implant removal and antibiotic therapy for 4-9 weeks. No pseudarthrosis was seen on implant removal. Despite bony fusion, loss of correction between 10 degrees and 26 degrees was observed in three patients after implant removal. 10.1007/s00586-004-0854-6
    Postoperative discitis due to Propionibacterium acnes: a case report and review of the literature. Harris Anthony E,Hennicke Chrisanne,Byers Karin,Welch William C Surgical neurology BACKGROUND:No previous report has described a progressive, destructive postoperative discitis requiring operative stabilization due to Propionibacterium acnes. The clinical and radiographic features and treatment options associated with discitis due to P acnes are presented in a retrospective case study, as well as a review of the current literature. CASE DESCRIPTION:Seven weeks after a routine lumbar discectomy, the patient presented with clinical findings and radiographic imaging consistent with discitis. Intraoperative cultures obtained from irrigation and debridement of the disc space revealed P acnes, and appropriate intravenous antibiotic treatment was instituted. Approximately 2 months later, the patient showed progression to a destructive osteomyelitis requiring operative stabilization. Nine weeks after stabilization, the patient continued to have lower back pain without radiculopathy. Laboratory values had normalized. Radiographic imaging revealed good instrumentation positioning and adequate fusion. The patient was ambulatory with bilateral articulating ankle foot orthoses and a walker. CONCLUSION:The reported case adds to the literature on postoperative discitis due to P acnes and demonstrates that this organism can occasionally be the cause of progressive, destructive osteomyelitis. In addition, we review the incidence, risk factors, and clinical course of discitis due to P acnes. 10.1016/j.surneu.2004.06.012
    [Postoperative discitis due to Propionibacterium acnes]. Pers Yves-Marie,Chekroun Johana,Lukas Cédric,Combe Bernard,Morel Jacques Presse medicale (Paris, France : 1983) 10.1016/j.lpm.2010.04.003
    Propionibacterium acnes induces discogenic low back pain via stimulating nucleus pulposus cells to secrete pro-algesic factor of IL-8/CINC-1 through TLR2-NF-κB p65 pathway. Jiao Yucheng,Yuan Ye,Lin Yazhou,Zhou Zezhu,Zheng Yuehuan,Wu Wenjian,Tang Guoqing,Chen Yong,Xiao Jiaqi,Li Changwei,Chen Zhe,Cao Peng Journal of molecular medicine (Berlin, Germany) Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical. KEY MESSAGES: Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions. P. acnes can induce LBP via IL-8/CINC-1 in IVDs. P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. 10.1007/s00109-018-1712-z
    Propionibacterium acnes Incubation in the Discs Can Result in Time-Dependent Modic Changes: A Long-Term Rabbit Model. Shan Zhi,Zhang Xuyang,Li Shengyun,Yu Tianming,Liu Junhui,Zhao Fengdong Spine STUDY DESIGN:A case-control study of animal model of Modic changes (MCs) on rabbits. OBJECTIVE:To evaluate the feasibility of inducing of MCs by injection of Propionibacterium acne (P. acnes) into the lumbar intervertebral discs of rabbits. SUMMARY OF BACKGROUND DATA:MCs have been widely observed, and assume to be closely associated with low back pain and P. acnes, but there are few animal models showing the progression of MCs. METHODS:Ten rabbits were used for the study. The L3-4 and L4-5 discs of all rabbits were injected with 100 μL P. acnes (1.6 × 10 CFU/mL) as P. acnes group, L2-3 disc were injected with 100 μL normal saline as vehicle, and L5-6 disc was untreated (blank). MCs were investigated by magnetic resonance imaging before operation and at 2 weeks, 1, 3, 4.5, 6, and 9 months postoperatively. Following sacrifice, histological analysis, blood test and micro-computed tomography were performed. Cytokine expression in nucleus and endplate tissues was quantified using real-time polymerase chain reaction. RESULTS:From 3 months postoperatively, the P. acnes group showed significantly decreased T1-weighted signal intensity, whereas the T2-weighted signal was significantly higher at 3 and 4.5 months, and then decreased remarkably at 6 and 9 months. Eleven of 20 inferior endplates were identified as type I MCs at 4.5 months, and 9 of 20 were identified as type II MCs at 9 months. Real-time polymerase chain reaction showed that expression of interleukin-1β, tumor necrosis factor α, interferon-γ, matrix metalloproteinase-9, and thrombospondin motifs-5 in the nucleus pulposus, and interleukin-1β, tumor necrosis factor α, and thrombospondin motifs-5 in the endplates, were significantly upregulated after injection of P. acnes. Histological slices of discs injected with P. acnes showed disc degeneration, endplate abnormalities, and inflammatory response, with micro-computed tomography confirming bone resorption. CONCLUSION:P. acnes infection of the disc can induce degeneration of the disc and an inflammatory response in the endplate region, presenting as MCs type I and II time dependently. LEVEL OF EVIDENCE:N/A. 10.1097/BRS.0000000000002192
    Relationship between annular tear and presence of Propionibacterium acnes in lumbar intervertebral disc. Zhou Zezhu,Chen Zhe,Zheng Yuehuan,Cao Peng,Liang Yu,Zhang Xingkai,Wu Wenjian,Xiao Jiaqi,Qiu Shijing European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society PURPOSE:Propionibacterium acnes (P. acnes) in the intervertebral disc may result in low back pain. The purpose of this study was to determine how P. acnes accesses the disc. METHODS:Patients with low back pain and/or sciatica were examined using X-ray and MRI before surgery. The intervertebral disc space height was measured on X-ray image. Disc and muscle samples were obtained from 46 patients undergoing discectomy at the lumbar spine. The tear of annulus was inspected before discectomy. In the disc and muscle tissue cultures, 16S rDNA gene specific for P. acnes was examined using PCR. RESULTS:The discs from 11 (23.9 %) patients were identified as 16S rDNA positive, in which two patients also had 16S rDNA in their muscles. 16S rDNA gene was significantly more likely to appear in the discs with annular tear than those without tear (P < 0.05). The disc space height was significantly decreased when the disc contained P. acnes. CONCLUSION:P. acnes is significantly more likely to be present in herniated discs with an annular tear than in herniated discs without such a tear. Since in the vast majority of these cases, no P. acnes was found in control muscle samples, a true infection with P. acnes is far more likely than a contamination. 10.1007/s00586-015-4180-y
    Genotypic and antimicrobial characterisation of Propionibacterium acnes isolates from surgically excised lumbar disc herniations. Rollason Jess,McDowell Andrew,Albert Hanne B,Barnard Emma,Worthington Tony,Hilton Anthony C,Vernallis Ann,Patrick Sheila,Elliott Tom,Lambert Peter BioMed research international The anaerobic skin commensal Propionibacterium acnes is an underestimated cause of human infections and clinical conditions. Previous studies have suggested a role for the bacterium in lumbar disc herniation and infection. To further investigate this, five biopsy samples were surgically excised from each of 64 patients with lumbar disc herniation. P. acnes and other bacteria were detected by anaerobic culture, followed by biochemical and PCR-based identification. In total, 24/64 (38%) patients had evidence of P. acnes in their excised herniated disc tissue. Using recA and mAb typing methods, 52% of the isolates were type II (50% of culture-positive patients), while type IA strains accounted for 28% of isolates (42% patients). Type III (11% isolates; 21% patients) and type IB strains (9% isolates; 17% patients) were detected less frequently. The MIC values for all isolates were lowest for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, and vancomycin (≤1 mg/L). The MIC for fusidic acid was 1-2 mg/L. The MIC for trimethoprim and gentamicin was 2 to ≥4  mg/L. The demonstration that type II and III strains, which are not frequently recovered from skin, predominated within our isolate collection (63%) suggests that the role of P. acnes in lumbar disc herniation should not be readily dismissed. 10.1155/2013/530382
    Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes. Dudli Stefan,Miller S,Demir-Deviren S,Lotz J C European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society PURPOSE:Intervertebral disc with Propionibacterium acnes (P. acnes) is suggested to be an etiology of Modic type I changes in the adjacent bone marrow. However it is unknown if disc cells can respond to P. acnes and if bone marrow cells respond to bacterial and disc metabolites draining from infected discs. METHODS:Human disc cells (n = 10) were co-cultured with 10- and 100-fold excess of P. acnes over disc cells for 3 h and 24 h. Lipopolysaccharide was used as positive control. Expression of IL1, IL6, IL8, and CCL2 by disc cells was quantified by quantitative PCR. Lipase activity was measured in culture supernatants (n = 6). Human vertebral bone marrow mononuclear cells (BMNCs) (n = 2) were cultured in conditioned media from disc cell/P. acnes co-cultures and expression of IL1, IL6, IL8, and CCL2 was measured after 24 h. RESULTS:All disc cells responded to lipopolysaccharide but only 6/10 responded to P. acnes with increased cytokine expression. Cytokine increase was time- but not P. acnes concentration-dependent. Disc cell responsiveness was associated with the presence of lumbar Modic changes in the donor. Lipase activity was increased independent of disc cell responsiveness. BMNCs responded with inflammatory activity only when cultured in supernatants from responsive disc cell lines. CONCLUSION:Disc cell responsiveness to P. acnes associates with the presence of lumbar Modic changes. Furthermore, bone marrow cells had an inflammatory response to the cocktail of disc cytokines and P. acnes metabolites. These data indicate that low virulent P. acnes infection of the disc is a potential exacerbating factor to Modic changes. 10.1007/s00586-017-5291-4
    Risk factors for surgical site infections among 1,772 patients operated on for lumbar disc herniation: a multicentre observational registry-based study. Habiba Samer,Nygaard Øystein P,Brox Jens I,Hellum Christian,Austevoll Ivar M,Solberg Tore K Acta neurochirurgica BACKGROUND:There are no previous studies evaluating risk factors for surgical site infections (SSIs) and the effectiveness of prophylactic antibiotic treatment (PAT), specifically for patients operated on for lumbar disc herniation. METHOD:This observational multicentre study comprises a cohort of 1,772 consecutive patients operated on for lumbar disc herniation without laminectomy or fusion at 23 different surgical units in Norway. The patients were interviewed about SSIs according to a standardised questionnaire at 3 months' follow-up. RESULTS:Three months after surgery, 2.3% of the patients had an SSI. Only no PAT (OR = 5.3, 95% CI = 2.2-12.7, p< 0.001) and longer duration of surgery than the mean time (68 min) (OR = 2.8, 95% CI = 1.2-6.6, p = 0.02) were identified as independent risk factors for SSI. Numbers needed to have PAT to avoid one SSI was 43. CONCLUSIONS:In summary, this study clearly lends support to the use of PAT in surgery for lumbar disc herniation. Senior surgeons assisting inexperienced colleagues to avoid prolonged duration of surgery could also reduce the occurrence of SSI. 10.1007/s00701-017-3184-2
    Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial. Bråten Lars Christian Haugli,Rolfsen Mads Peder,Espeland Ansgar,Wigemyr Monica,Aßmus Jörg,Froholdt Anne,Haugen Anne Julsrud,Marchand Gunn Hege,Kristoffersen Per Martin,Lutro Olav,Randen Sigrun,Wilhelmsen Maja,Winsvold Bendik Slagsvold,Kadar Thomas Istvan,Holmgard Thor Einar,Vigeland Maria Dehli,Vetti Nils,Nygaard Øystein Petter,Lie Benedicte Alexandra,Hellum Christian,Anke Audny,Grotle Margreth,Schistad Elina Iordanova,Skouen Jan Sture,Grøvle Lars,Brox Jens Ivar,Zwart John-Anker,Storheim Kjersti, BMJ (Clinical research ed.) OBJECTIVE:To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). DESIGN:Double blind, parallel group, placebo controlled, multicentre trial. SETTING:Hospital outpatient clinics at six hospitals in Norway. PARTICIPANTS:180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. INTERVENTIONS:Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. MAIN OUTCOME MEASURES:The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. RESULTS:In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was -1.6 (95% confidence interval -3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was -2.3 (-4.2 to-0.4, P=0.02) for patients with type 1 Modic changes and -0.1 (-2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. CONCLUSIONS:In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. TRIAL REGISTRATION:ClinicalTrials.gov NCT02323412. 10.1136/bmj.l5654
    Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial. Storheim Kjersti,Espeland Ansgar,Grøvle Lars,Skouen Jan Sture,Aßmus Jörg,Anke Audny,Froholdt Anne,Pedersen Linda M,Haugen Anne Julsrud,Fors Terese,Schistad Elina,Lutro Olav,Marchand Gunn Hege,Kadar Thomas,Vetti Nils,Randen Sigrun,Nygaard Øystein Petter,Brox Jens Ivar,Grotle Margreth,Zwart John-Anker Trials BACKGROUND:A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months' follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers. METHODS/DESIGN:A double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (β = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group. DISCUSSION:To ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT02323412 . Registered on 21 November 2014. 10.1186/s13063-017-2306-8
    Single-use instrumentation in posterior lumbar fusion could decrease incidence of surgical site infection: a prospective bi-centric study. Litrico Stéphane,Recanati Geoffrey,Gennari Antoine,Maillot Cédric,Saffarini Mo,Le Huec Jean-Charles European journal of orthopaedic surgery & traumatology : orthopedie traumatologie PURPOSE:Single-use surgical instruments were recently introduced to improve OR efficiency and reduce infection risks. This study aimed to investigate clinical results 1 year after instrumented lumbar fusion, with the aid of single-use surgical instruments, with particular attention to surgical site infection and Oswestry Disability Index (ODI). METHOD:This prospective bi-centric study included 21 men and 28 women, aged 61.6 ± 12.8 years, that underwent short instrumented lumbar fusion for degenerative disc disease, canal stenosis, or degenerative spondylolisthesis. All patients underwent posterior or transforaminal lumbar interbody fusion, using the SteriSpine™ PS Pedicle Screw System, available in multiple traceable sterile kits. RESULTS:Instrumented fusion was performed at one level in 31, two levels in 11, three levels in 5, and four levels in 2 patients. The mean follow-up was 16.4 ± 2.1 months, during which the ODI improved by 20 or more points in 28 patients (57 %), improved by less than 20 points in 17 patients (35 %), and remained unchanged or worsened in 4 patients (8 %). Only one infection (2 %) was observed in a 60-year-old man with previous spine surgery and two additional risk factors (diabetes mellitus and BMI 38). Compared to an older series, using reusable instrumentation, performed by the same team for the same indications, the clinical outcomes were similar but the infection rate was 6 %. DISCUSSION:Single-use instrumentation could reduce the incidence of surgical site infections following lumbar fusion to acceptable levels as in hip and knee arthroplasties. The preservation of screws and rods in sterile packs until ready for insertion reduces their exposure to air-borne bacteria in the OR and eliminates their contamination through repetitive hospital sterilization. The short operation time and minimal blood loss achieved could also contribute to the reduction in infection risks. LEVEL OF EVIDENCE:Level II, prospective randomized bi-centric study. 10.1007/s00590-015-1692-4
    Bacteria: back pain, leg pain and Modic sign-a surgical multicentre comparative study. Fritzell Peter,Welinder-Olsson Christina,Jönsson Bodil,Melhus Åsa,Andersson Siv G E,Bergström Tomas,Tropp Hans,Gerdhem Paul,Hägg Olle,Laestander Hans,Knutsson Björn,Lundin Anders,Ekman Per,Rydman Eric,Skorpil Mikael European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society PURPOSE:To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence. METHODS:Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33-49) and 20 control patients with scoliosis (median age 17, IQR 15-20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes. RESULTS:No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated. CONCLUSIONS:Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned. These slides can be retrieved under Electronic Supplementary Material. 10.1007/s00586-019-06164-1
    Bacterial biofilms: a possible mechanism for chronic infection in patients with lumbar disc herniation - a prospective proof-of-concept study using fluorescence in situ hybridization. Ohrt-Nissen Søren,Fritz Blaine G,Walbom Jonas,Kragh Kasper N,Bjarnsholt Thomas,Dahl Benny,Manniche Claus APMIS : acta pathologica, microbiologica, et immunologica Scandinavica A relationship has been suggested between lumbar disc herniation (LDH) and chronic bacterial infection frequently involving Propionibacterium acnes, which is known to cause chronic infection through the formation of biofilm aggregates. The objective of the study was to assess whether a disc infection involving biofilm formation is present in patients with LDH. A total of 51 LDH patients and 14 controls were included. Bacterial DNA was detected by real-time polymerase chain reaction (PCR) in 16/51 samples in the LDH group and 7/14 controls (p = 0.215). Sequencing identified bacteria in 9/16 and 6/7 PCR positive samples in the LDH and control groups, respectively. All samples were stained using fluorescence in situ hybridization (FISH) and examined by confocal laser scanning microscopy. Microscopy demonstrated tissue-embedded bacterial aggregates with host inflammatory cells in 7/51 LDH patients and no controls. The presence of both bacterial aggregates and inflammatory cells suggests a chronic infection in a subset of LDH patients. The finding of bacterial 16S rDNA in both LDH and control disc tissue highlights the importance of microscopic observation to discriminate infection vs contamination. Our findings may have therapeutic implications, as the treatment of biofilm infections is different and more challenging than traditional infections. 10.1111/apm.12841
    Low virulence bacterial infections in cervical intervertebral discs: a prospective case series. Chen Yilei,Wang Xianjun,Zhang Xuyang,Ren Hong,Huang Bao,Chen Jian,Liu Junhui,Shan Zhi,Zhu Zhihai,Zhao Fengdong European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 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. 10.1007/s00586-018-5582-4
    Higher proportion of low-virulence anaerobic bacterial infection in young patients with intervertebral disc herniation. Tang Guoqing,Chen Yong,Chen Ji,Wang Zhuo,Jiang Weimin Experimental and therapeutic medicine Intervertebral disc (IVD) degeneration caused by the latent infection of low-virulence anaerobic bacteria (LVAB) is a hot research topic. The present study analyzed and compared the positive rate of LVAB within IVDs of patients of different ages. IVD samples were intraoperatively retrieved from 176zpatients with disc herniation and subjected to microbiological culture. Subsequently, all the patients were classified into 3 groups based on their ages as follows: Group A (age <30 years), group B (age from 30 to 50 years) and group C (age >50 years) and the positive rates of LVAB were compared among the three groups. The severity of IVD degeneration was also assessed by measuring intervertebral height. Of the 176 cultured discs, 39 samples had bacterial growth, while 6 of them were suspiciously contaminated. Follwoing the exclusion of the 6 suspicious samples, 31 samples were and 2 samples were coagulase-negative of the remaining 33 samples, The bacterial positive rates were significantly higher in younger patients, with 34.4% (11/32), 25.5% (13/51) and 10.3% (9/87) in group A, B and C, respectively. More importantly, the bacterial-positive samples had a significantly lower disc height compared with the negative samples in groups A and B. Therefore, it can be reasonably concluded that younger patients have a much higher prevalence of LVAB infection in herniated IVDs and a greater severity of IVD degeneration when infected by bacteria. The LVAB may have a strong association with IVD degeneration, particularly in young patients. 10.3892/etm.2019.7910
    ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis. Rajasekaran S,Tangavel Chitraa,Aiyer Siddharth N,Nayagam Sharon Miracle,Raveendran M,Demonte Naveen Luke,Subbaiah Pramela,Kanna Rishi,Shetty Ajoy Prasad,Dharmalingam K European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 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. 10.1007/s00586-017-4972-3
    Latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs. Tang Guoqing,Wang Zhuo,Chen Ji,Zhang Zhengshi,Qian Hongbin,Chen Yong BMC musculoskeletal disorders 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. 10.1186/s12891-018-2373-3
    Overview: the role of Propionibacterium acnes in nonpyogenic intervertebral discs. Chen Zhe,Cao Peng,Zhou Zezhu,Yuan Ye,Jiao Yucheng,Zheng Yuehuan International orthopaedics Propionibacterium acnes (P. acnes), an important opportunistic anaerobic Gram-positive bacterium, causes bone and joint infections, discitis and spondylodiscitis. Accumulated evidence suggested that this microbe can colonise inside intervertebral discs without causing symptoms of discitis. Epidemiological investigation shows that the prevalence ranges from 13 % to 44 %. Furthermore, colonisation by P. acnes inside nonpyogenic intervertebral discs is thought to be one pathogen causing sciatica, Modic changes and nonspecific low back pain. Specially, patients can attain significant relief of low back pain, amelioration of Modic changes and alleviation of sciatica after antibiotic therapy, indicating the role of P. acnes in these pathological changes. However, until now, there were hypotheses only to explain problems such as how P. acnes access intervertebral discs and what the exact pathological mechanism it employs during its latent infection period. In addition, research regarding diagnostic procedures and treatment strategies were also rare. Overall, the prevalence and possible pathological role that P. acnes plays inside nonpyogenic intervertebral discs is summarised in this paper. 10.1007/s00264-016-3115-5
    What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature. Georgy Mark,Stern Mark,Murphy Kieran Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes 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. 10.1016/j.carj.2017.07.004
    Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study. Capoor Manu N,Ruzicka Filip,Machackova Tana,Jancalek Radim,Smrcka Martin,Schmitz Jonathan E,Hermanova Marketa,Sana Jiri,Michu Elleni,Baird John C,Ahmed Fahad S,Maca Karel,Lipina Radim,Alamin Todd F,Coscia Michael F,Stonemetz Jerry L,Witham Timothy,Ehrlich Garth D,Gokaslan Ziya L,Mavrommatis Konstantinos,Birkenmaier Christof,Fischetti Vincent A,Slaby Ondrej PloS one BACKGROUND:The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes' ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy. METHODS AND FINDINGS:The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001). CONCLUSIONS:In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease. 10.1371/journal.pone.0161676
    Association Between Lumbar Disc Degeneration and Propionibacterium acnes Infection: Clinical Research and Preliminary Exploration of Animal Experiment. Li Bo,Dong Zhe,Wu Yongchao,Zeng Ji,Zheng Qixin,Xiao Baojun,Cai Xianyi,Xiao Zhiyong Spine STUDY DESIGN:Clinical research and animal experiment. OBJECTIVE:To investigate whether lumbar disc degeneration is associated with Propionibacterium acnes (P acnes) infection. SUMMARY OF BACKGROUND DATA:The hypothesis that herniated discs may be infected with P acnes by way of bacteremia is remarkable. This may bring a tremendous change in treatment of lumbar disc herniation (LDH). However, this hypothesis is still controversial. Since P acnes isolated may be related to contamination. METHODS:Nucleus pulposus from 22 patients (30 discs) with lumbar disc herniation was collected during discectomy, following aerobic and anaerobic cultures for 10 days.Twenty-four rabbits were divided into four groups. After L3-L6 being exposed, an incision was made into the three discs in groups A and B. While in groups C and D, two random segments were operated. Six weeks later, 0.05 mL of 5 × 10 CFU/mL P acnes was inoculated into operated discs in group A and sterile physiological saline in group B. In group C, 0.2 mL of 5 × 10 CFU/mL P acnes was injected through ear vein. Sterile saline was used in group D. Six weeks later, MRI was performed. Then, nucleus pulposus and paraspinal muscles were harvested for aerobic and anaerobic cultures. RESULTS:Clinical research: Anaerobic cultures were positive in three cases: two coagulase-negative staphylococci, one particles chain bacterium. No P acnes was found. Staphylococcus epidermidis was isolated in one aerobic culture.Animal experiment: P acnes was found in 11 out of 18 (61%) discs in group A. There was no P acnes found in the other three groups. CONCLUSION:Degenerated discs were suitable for P acnes growth. This research did not find the evidence of the symptomatic degenerated lumbar discs infected with P acnes or that P acnes could infect the degenerated lumbar discs by way of bacteremia. LEVEL OF EVIDENCE:N/A. 10.1097/BRS.0000000000001383
    Propionibacterium acnes, Coagulase-Negative Staphylococcus, and the "Biofilm-like" Intervertebral Disc. Coscia Michael F,Denys Gerald A,Wack Matthew F Spine STUDY DESIGN:Patients scheduled for spinal surgery were screened prospectively for a microbial presence associated with intervertebral disc specimens. Inclusion was limited to patients requiring surgery for any of five conditions: study patients with cervical spine intervertebral herniation (IVH), lumbar spine IVH, lumbar spine discogenic pain, and control patients with idiopathic scoliosis/Scheurermann's kyphosis or trauma/neuromuscular deformity. Exclusion criteria included ongoing systemic infection, abnormal pre-operative white cell counts, documented or suspected spinal infection, or previous surgery to the involved disc. OBJECTIVE:The aim of this study was to test for an association between the presence of a bacterial entity in operated discs and a diagnosis of pathologic disc disease. SUMMARY OF BACKGROUND DATA:An association has been described between microbial colonization and progressive intervertebral disc degeneration in 36 herniation patients undergoing microdiscectomies. A total of 19 patients had positive cultures on long-term incubation, with Propionibacterium acnes present in 84% of discs. MATERIALS AND METHODS:Discs were harvested during surgery, using strict sterile technique. Each disc was divided, with half the sample sealed in a sterile, commercially prepared anaerobic culture transport container, and half fixed in formalin. Live specimens were cultured for bacteria at a university-affiliated laboratory in a blinded fashion. Fixed pathologic specimens were gram-stained and read by a board-certified pathologist. RESULTS:A total of 169 intervertebral discs from 87 patients were evaluated (46 males, 41 females). Positive cultures were noted in 76 of 169 discs (45%), with 34 discs positive for P. acnes and 30 discs positive for Staphylococcus. No pathologic evidence was seen of microorganisms, acute or chronic inflammation, or infection. Pooling the IVH and discogenic pain patients and contrasting them with control patients showed a significant association of IVH with positive bacterial cultures (χ = 15.37; P = 0.000088). CONCLUSION:Endemic bacterial biofilms are significantly associated with IVH and discogenic pain. LEVEL OF EVIDENCE:N/A. 10.1097/BRS.0000000000001909
    Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy. Capoor Manu N,Ruzicka Filip,Schmitz Jonathan E,James Garth A,Machackova Tana,Jancalek Radim,Smrcka Martin,Lipina Radim,Ahmed Fahad S,Alamin Todd F,Anand Neel,Baird John C,Bhatia Nitin,Demir-Deviren Sibel,Eastlack Robert K,Fisher Steve,Garfin Steven R,Gogia Jaspaul S,Gokaslan Ziya L,Kuo Calvin C,Lee Yu-Po,Mavrommatis Konstantinos,Michu Elleni,Noskova Hana,Raz Assaf,Sana Jiri,Shamie A Nick,Stewart Philip S,Stonemetz Jerry L,Wang Jeffrey C,Witham Timothy F,Coscia Michael F,Birkenmaier Christof,Fischetti Vincent A,Slaby Ondrej PloS one BACKGROUND:In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. METHODS:Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. RESULTS:Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). CONCLUSIONS:This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination. 10.1371/journal.pone.0174518
    Infection in Disc Material and Different Antibiotic Susceptibility in Patients With Lumbar Disc Herniation. Salehpour Firooz,Aghazadeh Javad,Mirzaei Farhad,Ziaeii Ehsan,Alavi Seyed Ahmad Naseri International journal of spine surgery Background:Low back pain is an important, worldwide clinical problem from which human populations are suffering. It has been suggested that is associated with low back pain. The objective of this clinical study is to evaluate the infection in the disc material and antibiotic susceptibility in patients with disc herniation. Methods:A total of 120 patients with disc herniation surgery were enrolled in the study. The samples were excited during discectomy and then cultured in both anaerobic and aerobic incubations. Minimum inhibitory concentration (MIC) was performed for determination of antibiotic susceptibility. Results:Of 120 samples, 60 (50%) samples were positive for microorganisms. Disc herniation was at the level of L4-L5 in 63 cases and L5-S1 in 57 cases. Conclusions:According to the results and presence of in more than 35% of the cultured samples, the presence of in lumbar disc herniation is a suspected element leading to this condition. After analysis of the antibiotics, the lowest MIC value was identified for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, vancomycin; the moderate MIC value was for fusidic acid; and the highest MIC value was for gentamicin and trimethoprim. 10.14444/6019
    Modic changes in the adjacent vertebrae due to disc material infection with Propionibacterium acnes in patients with lumbar disc herniation. Aghazadeh Javad,Salehpour Firooz,Ziaeii Ehsan,Javanshir Naghme,Samadi Afshin,Sadeghi Javid,Mirzaei Farhad,Naseri Alavi Seyed Ahmad European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society INTRODUCTION:Modic changes (MCs) in vertebral bones are induced by two mechanisms of mechanical factors and infection. As Propionibacterium acnes (P. acnes) have been reported to be associated with LBP. The aim of this study is to evaluate the MCs in patients with disc herniation and positive for P. acnes. METHODS AND MATERIAL:A total of 120 patients with disc herniation surgery were enrolled into the study. The samples were excised during discectomy and then cultured in both anaerobic and aerobic incubations. Gram staining was employed for investigation of all colonies. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction (PCR). MCs of baseline MRI were evaluated. RESULTS:In this study, 120 subjects (69 male and 51 female) with mean age of 43.15 ± 12.62 years were investigated. Sixty disc samples and eight muscle samples were positive for microorganisms. Moreover, 16S rDNA gene was identified in 46 (38.3%) disc samples. Moreover, 36/46 patients with P. acnes in their sample had MCs. CONCLUSION:According to the results and presence of 36/46 MCs in patients with lumbar disc herniation, positive for P. acnes suggests that P. acnes can lead to edema on the vertebrae endplates near to infected area. 10.1007/s00586-016-4887-4
    The distribution of infection with Propionibacterium acnes is equal in patients with cervical and lumbar disc herniation. Javanshir Naghmeh,Salehpour Firooz,Aghazadeh Javad,Mirzaei Farhad,Naseri Alavi Seyed Ahmad European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society BACKGROUND:Cervical and back pains are important clinical problems affecting human populations globally. It is suggested that Propionibacterium acnes (P. acnes) is associated with disc herniation. The aim of this study is to evaluate the distribution of P. acnes infection in the cervical and lumbar disc material obtained from patients with disc herniation. METHODS AND MATERIAL:A total of 145 patients with mean age of 45.21 ± 11.24 years who underwent micro-discectomy in cervical and lumbar regions were enrolled into the study. The samples were excited during the operation and then cultured in the anaerobic incubations. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction. RESULTS:In this study, 145 patients including 25 cases with cervical and 120 cases with lumbar disc herniation were enrolled to the study. There was no significant difference in the age of male and female patients (p = 0.123). P. acnes infection was detected in nine patients (36%) with cervical disc herniation and 46 patients (38.3%) with lumbar disc herniation and no significant differences were reported in P. acnes presence according to the disc regions (p = 0.508.). Moreover, there was a significant difference in the presence of P. acnes infection according to the level of lumbar disc herniation (p = 0.028). CONCLUSION:According to the results, the presence of P. acnes is equal in patients with cervical and lumbar disc herniation. There was a significant difference in the distribution of P. acnes infection according to level of lumbar disc herniation. LEVEL OF EVIDENCE:II. 10.1007/s00586-017-5219-z