Aim. Pyogenic spondylodiscitis remains a therapeutic challenge, as demonstrated by divergent treatment guidelines. The combination of moxifloxacin and rifampicin may be an attractive treatment option for cases caused by staphylococci; however, previous studies have reported a reduction in plasma concentrations of moxifloxacin when co-administered with rifampicin. The magnitude of this reduction in spinal tissues is not known. We aimed to investigate the interaction of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue in steady-state conditions using microdialysis in a porcine model. Method. Twenty female pigs were randomized into two groups of ten pigs: Group A received moxifloxacin 400 mg orally once daily for three days preoperatively. Group B received moxifloxacin 400 mg orally for three days preoperatively combined with rifampicin 450 mg twice daily for seven days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues. Results. Co-administration of moxifloxacin and rifampicin demonstrated a reduction of free moxifloxacin concentrations in spinal tissues. The peak drug concentration (C. max. ) and the area under the concentration-time curve (AUC. 0–24. ) in all tissue compartments decreased in the range of 66–79% and 65–76%, respectively. Conclusions. Using microdialysis, we demonstrated a significant reduction of moxifloxacin C. max. and AUC. 0–24. in the spinal tissues when co-administered with rifampicin. Further studies are warranted to understand the clinical implications of this finding for the treatment of pyogenic spondylodiscitis

Aim. Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis. Method. We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months. Results. A total of 155 patients (male: N=88; female: N=67; mean age 66.1 ± 12.4 years) with SD were identified. In n= 74 (47.7%) cases, the infections were associated with the healthcare system (HA). N=34 (21.9%) patients suffered from sepsis. The lumbar spine was involved in 47.1% of the cases, the thoracic spine in 37.3%, and the cervical spine in 7.8%. In 7.8% of the cases, SD occurred in multiple spinal segments. N=96 (62.0%) patients were treated surgically. The mean hospital stay was 36.4 ± 36.3 days. Antibiograms of n=45 patients (HA: N=22; CA: N=23) could be retrospectively evaluated: The most frequently identified pathogens were Staphylococcus aureus (46.7%), Coagulase-negative Staphylococci (17.8%), Enterobacteriaceae (15.6%) and Streptococcus species (15.6%). Overall, 82.2% (HA: 68.2%; CA: 95.5%) of the isolated pathogens were sensitive to piperacillin/tazobactam, 77.8% (HA: 81.8%; CA: 72.2%) to vancomycin, 64.4% (HA: 68.2%; CA: 59.1%) to clindamycin, and 55.6% (HA: 36.4%; CA: 72.7%) to ceftriaxone. To a combination of vancomycin plus meropenem 97.8% of pathogens were sensitive (HA: 95.5%; CA: 100.0%), to vancomycin plus ciprofloxacin 91.1% (HA: 86.4%; CA: 95.7%), and to vancomycin plus cefotaxime 93.3% (HA: 90.9%; CA: 95.7%). In 14 cases, empiric antibiosis was adjusted based on the results of the antibiogram. Conclusions. Antibiotic resistance of CA SD pathogens differed significantly from HA SD. The identification of the pathogen and the analysis of its susceptibility guides the antibiotic therapy. Vancomycin in combination with a carbapenem, broad-spectrum cephalosporin, or fluoroquinolone may be appropriate for empiric treatment of HA SD

To investigate clinical outcome scores in surgically treated patients with either spontaneous or postoperative pyogenic spondylodiscitis after 3, 12 and 24 month. 70 consecutive patients (mean age 64y; male n=33 female n=27) underwent surgical treatment due to pyogenic spondylodiscitis with or without epidural abscess at our department from 2011 to 2013. We performed either microsurgical debridement or debridement in combination with ventral support employing dorsally instrumented spondylodesis followed by bracing and antibiotic therapy up to 12 weeks. European life quality score (EQ-5D), Oswestry disability index (ODI) and visual analogue scale for pain (VAS) were recorded 3, 12 and 24 month after surgery. Length of hospital stay (LOS) was 25,3 days. The Mean time to presentation at our spine center and diagnosis was 3,8 weeks. Distribution of inflammation was lumbar in 66 (94%) and thoracic in 4 (6%) patients. Thirtyfour patients (49%) had isolated spondylodiscitis (SD). Epidural abscess (ED) was found in 26 patients (37%). Ten patients (14%) showed a combination of SD and ED. SD or ED were predominantly found after previous surgery at the same or contiguous level 38 (54%). Nine patients (13%) suffered from ED or SD after previous lumbar epidural steroid injections (LESI). Spontaneous idiopathic inflammation was found only in 13 cases (19%). Standardized follow-up (FU) protocol was scheduled at 3, 12, and 24 month. FU rate was 60%. Healing of the inflammation was the rule. In our study cumulative EQ-5D increased from 0.47 to 0,80. ODI decreased from 41.1 to 24.3 and VAS concerning back pain decreased from 58.4 to 22.6 VAS according sciatica decreased from 46.8 to 20.5. Due to an increasing number of spine surgeries and spinal interventions as well as the increasing age and morbidity of patients, spinal surgeons have to deal more often with the diagnosis pyogenic spondylodiscitis. Standardized conservative or radical surgical treatment strategies in order to achieve good results according to patients life quality are gaining more importance

Aim. Cefuroxime is a time-dependent antibiotic widely used as intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2–3 hours. Due to the fact that postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates, we aimed to evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4-hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval. Method. This is preliminary data for 8 out of 16 female pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2×1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography. Results. The time with concentrations above the minimal inhibitory concentration (T>MIC) for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml, was superior in all compartments when administering cefuroxime as two single doses with 4-hours intervals. For the target MIC of 4 μg/ml, the mean T>MIC in all compartments ranged between 53–73% and 85–95% for Group A and B, respectively. For both groups the area under the concentration-curve (AUC) was higher for plasma compared to the remaining compartments, and the lowest AUCs were found in the vertebral cancellous bone and the IVD. There were no differences in AUC between the two groups. Furthermore, the maximal concentrations were lower for both vertebral cancellous bone and IVD compared to both SCT and plasma. When comparing the two groups, higher maximal concentrations were found in all compartments for Group A. Tissue penetration was incomplete and delayed for all compartments and comparable between the two groups. Conclusions. Despite comparable pharmacokinetic results between the two groups, Group B exhibited superior T>MIC in all compartments for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml. As such administration of cefuroxime as two single doses with 4-hours intervals provided sufficient cefuroxime spine tissue concentrations for a minimum of 85% of an 8-hour dosing interval, which may be acceptable for most spine procedures

Aim. Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. The objective of this study was therefore to assess the concentration of cefuroxime in intervertebral disc (IVD), vertebral body cancellous bone, subcutaneous adipose tissue (SCT) and plasma pharmacokinetics after single dose administration by use of microdialysis (MD) in a large animal model. Method. Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 min. Measurements of cefuroxime were obtained from plasma, SCT, the vertebral cancellous bone and the IVD for 8 hours thereafter. MD was applied for sampling in solid tissues. The cefuroxime concentration in both the MD and plasma samples was determined using ultra-high performance liquid chromatography. Results. For both the IVD and the vertebral cancellous bone, the area under the concentration-curve from zero to the last measured value was significantly lower than that of free plasma. Tissue penetration of cefuroxime was incomplete for the IVD, whereas for vertebral cancellous bone and SCT it was not. Furthermore, the penetration of cefuroxime from plasma to IVD was delayed. Additionally, a noticeable prolonged elimination rate of cefuroxime in the IVD was found. The maximal concentration and the elimination of cefuroxime were reduced in IVD compared to both SCT and vertebral cancellous bone. Due to this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T>MIC) was significantly higher in IVD than in SCT, vertebral cancellous bone and free plasma for MICs up to 6 μg/ml. Conclusions. MD was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but due to a prolonged elimination, the best results regarding T>MIC was found in IVD

Pyogenic spondylodiscitis is an uncommon but clinically relevant infection that represents 3 to 5% of all cases or osteomyelitis. In Europe, it has an estimated incidence of 0.4 to 2.4/100.000 people/year. Mortality is less than 5%, increasing with a delay in diagnosis greater than 2 month. Patients with renal failure have greater predisposition to infections, consequence of the chronic uremic state. Infection rates in Polytetrafluoroethylene (PTFE) hemodialysis grafts in end-stage renal disease (ESRD) range from 3 to 35%. We present a rare case of concurrent spondylodiscitis and PTFE graft infection in a patient with ESRD and recurrent urinary tract infections (RUTI). The authors present a case of an 80-year-old man with past medical history significant for abdominal aortic aneurysm, bilateral ureter-hydronephrosis, Pseudomonas aeruginosa RUTI and ESRD. Three months after a dialysis PTFE graft hemoaccess was performed a Pseudomonas graft infection was diagnosed and the PTFE graft was removed. One week later, the patient was observed in the author's Department due to an insidious dorsal-lumbar mechanic back pain without neurologic deficits, with progressive deterioration over the past 6 months. A T12-L1 and L1-L2 spondylodiscitis with dural compression was diagnosed and vertebral instability was documented on MRI and TC, demanding surgical treatment. Instrumented fusion with a screw and rod construct was performed from T9 to L5, along with somatic L1 and L2 debridement, and T12-L1 interbody fusion with autograft. Microbiology results were positive for Pseudomonas aeruginosa. Antibotic therapy with ceftazidime (6 weeks) and ciprofloxacin (12 weeks) was performed. Symptomatic relieve was achieved and C-reactive protein and white blood cell count returned to normal values. No complications were documented. Four months post-surgery, the patient was asymptomatic (Visual Analogue Scale=0), with no significant limitation in his daily life activity (Disability Rating Index=85) and the vertebral body height was sustained, with imagiological signs of spinal fusion. ESRD patients are more susceptive to infections. Failure in early diagnosis and treatment may lead to disease progression and subsequent functional limitations, deformity and increase in mortality. An aggressive approach, despite delay on diagnosis, is the key factor for a worthy outcome. Despite the good results, recrudescence of spondylodiscitis is known to occur even years after the original offense is treated

The goal of this work is to evaluate the epidemiology and treatment employed in the treatment of pyogenic spondylodiscitis. Diagnosis was based on clinical and imaging, it does not include cases of postoperative infection and lesions contiguous with decubitus ulcers. The clinical records were used to obtain demography, comorbidities, presenting symptoms, physical examination, laboratorial values, diagnostic procedures, microbiological profile as well as medical and surgical treatment. Statistical analysis was performed using SPSS 20. After reviewing 22 patients met the inclusion criteria. The mean age was 60.82(range 22–86), 82 % were men(n=18). Most prevalent comorbidities were diabetes mellitus 41%(n=9), chronic alcoholism 18% (n=4), CKD 14%(n=3) and HIV in 9%(n=2). Approximately 40.1% had a septic focus in another location, the most common UTI 30%(n=3) and 20% sepsis(n=2). The most common symptoms were LBP 51%(n=21), weight loss 15%(n=6) and fever 12%(n=5). Laboratory evaluation revealed an average leukocytosis 11.8(range 4.3–21.8), ESR averaged 83.9 mm/h (range 10–128), mean CRP 11.6 mg/dl(range 0.4–38.7). The lumbar spine was the most affected segment 55%(n=12), then the dorsal 36%(n=8) and cervical 9%(n=2). The microbiological diagnosis was established in 55% of cases (n=12), 8(66.7%) cases were identified in blood cultures and 3(25%) in bone biopsy. The most common agents identified were MSSA in 18% of cases (n=4) and cogulase negative staphylococci 18%(n=4). A surgical procedure was performed in 86.4% (n=19), 7 for fusion and in 4 a transpedicular biopsy. The indications for surgery were crop material, abscess drainage and instability each with 32%(n=6). In terms of neurological sequelae 23%(n=5) had changes. The average length of stay was 57.4 days(range 19–190), mortality was 9%(n=2). We found no statistically significant differences regarding the identification of microorganisms using age (p=0.644), ESR(p=0.233), CRP(p=0.166) and leukocytosis(p=0.147) as variables. Our series has characteristics common to literature, predominantly male, risk factors as Diabetes, CKD and HIV are common. Alcoholism is linked with some immunosuppression and appears as a new risk factor. Obtaining microbiological diagnosis is crucial to avoid the need for prolonged antibiotic therapy and the potential increased costs and toxicity of broad spectrum. The low number of positive biopsy (25%) is explained by the early empirical antibiotic therapy before sampling. Surgery plays an important role in crop products for microbiological analysis and treatment of instability or neurological deficits. A high index of suspicion in patients with known risk factors and back pain is crucial since delay in diagnosis leads to worse outcomes