A Comprehensive Review of the Pathogenesis, Diagnosis, and Management of Diabetic Foot Infections.

GENERAL PURPOSE: To review an approach to diabetic foot infections (DFIs), including acute osteomyelitis, while also discussing current practices and the challenges in diagnosis and management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will1. Identify the risk factors for developing DFIs.2. Outline diagnostic techniques for assessing DFIs.3. Select the assessment techniques that support a diagnosis of osteomyelitis.4. Choose the appropriate pharmacologic and nonpharmacologic treatment options for patients who have DFIs. ABSTRACT: Diabetic foot ulcers result from a combination of peripheral neuropathy, vascular compromise, and repetitive trauma. Approximately 50% of individuals with diabetic foot ulcers will develop a diabetic foot infection (DFI), and 20% of individuals with a DFI will develop osteomyelitis. Herein, the authors review an approach to DFIs including acute osteomyelitis and discuss current practices and challenges in diagnosis and management.The diagnosis of a skin and soft tissue DFI is based on clinical criteria. A bone biopsy is considered the criterion standard for diagnosis of osteomyelitis; however, biopsy is not always feasible or available. Consequently, diagnosis can be made using a combination of clinical, biochemical, and radiographic findings. X-ray is the recommended imaging modality for initial evaluation; however, because of its lower relative sensitivity, advanced imaging may be used when clinical suspicion remains after negative initial testing.The microbiology of skin and soft tissue DFIs and osteomyelitis is similar. Staphylococcus aureus and other Gram-positive cocci are the most common pathogens identified. Deep cultures are preferred in both DFI and osteomyelitis to identify the etiologic pathogens implicated for targeted antimicrobial therapy. Management also requires a multidisciplinary approach. Surgical debridement in those with deep or severe infections is necessary, and surgical resection of infected bone is curative in cases of osteomyelitis. Finally, appropriate wound care is critical, and management of predisposing factors, such as peripheral neuropathy, peripheral arterial disease, tinea, and edema, aids in recovery and prevention.

Personalized three-dimensional printed polyether-ether-ketone prosthesis for reconstruction after subtotal removal of chronic clavicle osteomyelitis: A case report.

RATIONALE: Three-dimensional (3D) printing has attracted wide attention for its potential and abilities in the assistance of surgical planning and the development of personalized prostheses. We herewith report a unique case of chronic clavicle osteomyelitis treated with a two-stage subtotal clavicle reconstruction using a 3D printed polyether-ether-ketone (PEEK) prosthesis. PATIENT CONCERNS: A 23-year-old Chinese female presented to our clinic complaining about a progressive pain of her right clavicle for about 1 year. DIAGNOSES: Chronic clavicle osteomyelitis confirmed by percutaneous biopsy and lesion biopsy. INTERVENTIONS: This patient accepted a long-term conservative treatment, which did not gain satisfactory outcomes. Thus, a subtotal removal and two-stage reconstruction of the right clavicle with a 3D-printed polyether-ether-ketone prosthesis stabilized by screw fixation system was performed. OUTCOMES: At 2-year follow-up, complete pain relief and satisfactory functional recovery of her right shoulder were observed. LESSONS: Personalized 3D printed prosthesis is an effective and feasible method for reconstruction of complex bone defects.

Skull base osteomyelitis: Comprehensive analysis and a new clinicoradiological classification system.

OBJECTIVE: Skull baseosteomyelitis (SBO) is a rare phenomenon that typically occurs in diabetic or immunocompromised patients, causing significant morbidity and mortality. This study aimed to analyze a single institution's treatment results in SBO patients and propose anew integrated clinicoradiological classification system. METHODS: The medical records of 32 SBO patients that were treated at a tertiary care center between 2006 and 2017 were retrospectively reviewed. A scoring system based on anatomical involvement according to MRI was created. Subsequently, the scoring system was integrated with cranial nerve dysfunction status and a clinical grading system (CGS) was proposed. RESULTS: Among the 32 patients, 78.1% were diabetic and 63% had cranial nerve dysfunction at presentation. Bone erosion based on CT was greater in the patients without regression (P = 0.046). The regression rate decreased from clinical grade (CG)1 to CG3 (P = 0.029). Duration of hospitalization increased as CG increased (P = 0.047). Surgery had no effect on regression status at the time of discharge (P = 0.41). The 1-year, 2-year, and 5-year overall survival rates were 82.2%, 70.8%, and 45.8%, respectively. CG was significantly correlated with overall survival but not with disease-specific survival (log-rank; P = 0.017, P = 0.362, respectively). CONCLUSION: SBO continues to pose a challenge to clinicians, and causes significant morbidity and mortality. The proposed new classification system can be an option for grouping SBO patients according to clinical and radiological findings, helping clinicians estimate prognosis.

Rare case of osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a postmenopausal woman.

Vertebral osteomyelitis is an infection of the vertebrae that can lead to spinal degeneration, most commonly caused by Staphylococcus aureus Here, we report an unusual case of pyogenic osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a 61-year-old postmenopausal woman. The patient presented with a 2-week history of worsening lower back pain and fever and a recent episode of cystitis following re-engagement of sexual activity. Imaging revealed a deterioration of vertebrae discs and spinal canal stenosis at the L3-L4 levels with a formation of abscess in the right psoas muscle. Needle aspiration of the abscess identified G. vaginalis and S. parasanguinis and the patient was successfully treated with a 6-week course of ceftriaxone and metronidazole. This case describes an unusual coinfection of two pathogens that normally reside in the urogenital tract and oral cavity, respectively, and highlights the risk posed when these organisms breach the body's normal barriers.

Foot and Ankle Surgery for Chronic Nonhealing Wounds.

Chronic wounds often are the result of bone deformities, compounded by musculotendinous and ligamentous imbalance. Sensory neuropathy places patients at greater risk for acute wounds to develop into chronic wounds. Etiologies of these deforming forces include Charcot neuroarthropathy, trauma, and congenital and acquired neuromuscular disorders. Management of these deformities ranges from simple relief of pressure with soft inserts to bracing for mechanical instability. Correction of more complex deformities requires resection of bone, osteotomies, fusions, and external fixation. Tendon and ligament imbalance must be addressed at all levels of deformity. Postoperatively, patients must be re-evaluated for continuation of orthoses and bracing.

Extensive maxillary osteomyelitis following tooth extraction in a patient with osteopetrosis.

Osteopetrosis (OP), also known as marble bone disease is an extremely rare inherited skeletal disorder, characterised by abnormal functioning of the osteoclasts that results in incremental bone deposition with lack of normal bone remodelling. This leads to the formation of hard and brittle bone can readily fracture. The compromised quality of marrow tissue with poor vascularity reduces bone healing and increases the risk of infections. The risk of jawbone osteomyelitis in patients with OP is high and invariably involves mandible. Involvement of maxilla is rare and has been sparingly reported in the literature. This paper highlights a case of extensive necrosis of maxilla and mid-face skeleton following tooth extraction in a patient with OP. Review of the English literature identifying 23 previously published reports of maxillary osteomyelitis in patients with OP is also presented. Demographic details, history of tooth extraction, extent of involvement, clinical presentation, imaging finding, treatment provided and the outcome have been discussed.

Residual foreign body in the foot causing chronic osteomyelitis mimicking a pseudotumor: A case report.

Osteomyelitis from a retained foreign body should be included in the differential diagnosis of any osteolytic lesion of the foot. We report here a case of a 59-year-old man who presented with swelling over the dorsolateral aspect of the right foot. Plain x-ray showed an osteolytic lesion that mimicked a pseudotumor. Magnetic resonance imaging (MRI) showed multilocular fluid collection over the right cuboid with a hypointense lesion over the plantar fascia. The patient underwent surgery and a rubber fragment (1 cm × 0.8 cm) was removed from his foot that had been present for two years following a stabbing injury. The patient fully recovered without complication or disability.

Mid-term walking ability after Charcot foot reconstruction using the Ilizarov ring fixator.

BACKGROUND: Failed conservative treatment and complications are indications for foot reconstruction in Charcot arthropathy. External fixation using the Ilizarov principles offers a one-stage procedure for deformity correction and resection of osteomyelitic bone. The aim of this study was to determine whether external fixation with an Ilizarov ring fixator leads reliably to walking ability. MATERIALS AND METHODS: 29 patients treated with an Ilizarov ring fixator for Charcot arthropathy were retrospectively analyzed. Radiologic fusion at final follow up was assessed separately on conventional X-rays by two authors. The association between walking ability and the presence of osteomyelitis at the time of reconstruction, and the presence of fusion at final follow up was investigated using Fisher's exact test. RESULTS: Mean follow up was 35 months (range 5.3-107) months; mean time of external fixation was 113 days. Ten patients (34.5%) reached fusion, but 19 did not (65.5%). Two patients needed below knee amputation. 26 of the remaining 27 patients maintained walking ability, 23 of those without assistive devices. Walking ability was independent from the presence of osteomyelitis at the time of reconstruction and from the presence of fusion. CONCLUSION: Foot reconstruction with an Ilizarov ring fixator led to limb salvage in 93%. The vast majority (96.3%) of patients with successful limb salvage was ambulatory, independent from radiologic fusion, and presence of osteomyelitis at the time of reconstruction. These findings encourage limb salvage and deformity correction in this difficult-to-treat disease, even with underlying osteomyelitis.

Role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics.

OBJECTIVE: To analyse the predictive role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics. METHODS: An observational study of patients with diabetic foot ulcers (DFU) and clinically suspected osteomyelitis. The patients underwent surgical or antibiotic treatment for bone infection in a specialised diabetic foot unit. Blood samples were taken from each patient to analyse biomarkers. The main outcome was the number of weeks until healing occurred. RESULTS: A total of 116 patients took part in the study. The number of weeks until healing was similar for both groups (surgical n=96 and antiobiotic n=20, treatments). No association was observed among biomarkers as predictors of time-to-healing. CONCLUSION: There is not enough evidence to define the prognostic role of inflammatory markers in the healing time of DFUs complicated with diabetic foot osteomyelitis, regardless of the treatment administered.

Does an antibiotic nail made in a lubricated tube release antibiotic?

INTRODUCTION: The treatment of long-bone osteomyelitis has long been a difficult problem. Recently, antibiotic-impregnated intramedullary rods for the treatment of infected long-bone fractures have been gaining popularity but they are quite difficult to fabricate. Recently, a new technique that utilizes mineral oil to coat the inside of a chest tube mold prior to introduction of cement has been proven to ease fabrication. We hypothesized that the use of mineral oil would alter the elution characteristics of tobramycin from the intramedullary device. METHODS: Two groups of antibiotic nails were fabricated under sterile conditions. The control group utilized a chest tube mold. The study group utilized a chest tube that was coated with mineral oil prior to cement injection. Each intramedullary nail was placed in pooled human serum and incubated under physiologic conditions. The level of tobramycin in each sample was measured at timepoints 0, 1, 6, and 24 h. RESULTS: There was no significant difference when comparing control with the experimental group at any timepoint. Antibiotic nails eluted tobramycin at a rapid rate in the first 6 h of exposure to serum, regardless of their preparation with oil or without oil. The rate of elution fell precipitously between 6 and 24 h. CONCLUSION: We believe that although this study, as with any study, cannot perfectly recreate in vivo conditions, we have clearly shown that mineral oil has no significant effect on elution of tobramycin from antibiotic nails.

The peculiarities and treatment outcomes of the spinal form of chronic non-bacterial osteomyelitis in children: a retrospective cohort study.

Chronic non-bacterial osteomyelitis (CNO) is a group of immune-mediated diseases which appears in bone inflammation, destruction and some orthopaedic consequences, especially in the cases of spinal involvement. This study is to compare characteristics and treatment outcomes of CNO patients with spinal involvement. The retrospective cohort study included data from 91 pediatric patients with CNO. The diagnosis is based on Jannson's criteria with morphological confirmation (nonspecific chronic inflammation). Spine involvement detected by X-ray, computed tomography, magnetic resonance imaging, and bone scan in 29 (31.9%) patients. No differences in the family history, concomitant immune-mediated diseases between spinal (SpCNO) and peripheral (pCNO) forms of CNO have been revealed. Only 5 (10.2%) SpCNO patients (10.2%) had monofocal monovertebral involvement. The main risk factors of spinal involvement were female sex: RR = 2.0 (1.1; 3.9), sensitivity (Se) = 0.66, specificity (Sp) = 0.6; multifocal involvement: RR = 2.1 (0.9; 5.0), Se = 0.83, Sp = 0.37; no foot bones involvement: RR = 3.1 (1.3; 7.5), Se = 0.83, Sp = 0.5; sternum involvement RR = 2.3 (1.3; 4.1), Se = 0.24, Sp = 0.94. In the linear regression analysis only female sex (p = 0.005), multifocal involvement (p = 0.000001) and absence of foot bones involvement (p = 0.000001) were independent risk factors of spinal involvement (p = 0.000001). The response rate on bisphosphonates and tumor necrosis factor-a inhibitors was 90.9% and 66.7%, consequently. Only 4/29 (13.8%) SpCNO patients underwent surgery due to severe spinal instability or deformities. The spinal involvement is frequent in CNO and could be crucial for choosing a treatment strategy. Bisphosphonates and TNFa-inhibitors could be effective treatment options for severe SpCNO.

Non-union in lateral locked plating for distal femoral fractures: A systematic review.

INTRODUCTION: This study aims to identify patient and intra-operative factors that contribute to non-union in locked lateral plating for distal femoral fractures. METHODS: Systematic searches of English-language articles in Ovid Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were undertaken in February 2018 according to the PRISMA guidelines. The search terms were (fracture or fracture*) AND (distal femur or distal femoral) AND (malunion or non-union). Eligible studies published at any time reported non-union rates and compared patient and intraoperative factors in patients who underwent locked lateral plating for traumatic distal femoral fractures. The quality of included papers was assessed using The Journal of Bone and Joint Surgery levels of evidence (Wright et al., 2003), and further appraised using the Downs and Black score (Downs and Black, 1998). RESULTS: Eight studies investigating 1380 distal femoral fractures were found to satisfy the inclusion and exclusion criteria. These studies analysed a variety of patient and intra-operative factors that may contribute to non-union. These include high BMI, open fracture, comminution, fracture infection, stainless steel plate material, shorter working length, open reduction and internal fixation when compared with minimally invasive plate osteosynthesis, high construct rigidity scores and purely locking screw constructs. CONCLUSION: This review has identified multiple factors which potentially contribute to non-union including stainless steel plate material, high construct rigidity scores and purely locking screw constructs. These findings may reflect that overly rigid plating constructs can contribute to non-union. However, they should be taken in the context of heterogeneity amongst included studies, with further research necessary to support these findings.

Adipose-Derived Stromal Cells Are Capable of Restoring Bone Regeneration After Post-Traumatic Osteomyelitis and Modulate B-Cell Response.

Bone infections are a frequent cause for large bony defects with a reduced healing capacity. In previous findings, we could already show diminished healing capacity after bone infections, despite the absence of the causing agent, Staphylococcus aureus. Moreover, these bony defects showed reduced osteoblastogenesis and increased osteoclastogenesis, meaning elevated bone resorption ongoing with an elevated B-cell activity. To overcome the negative effects of this postinfectious inflammatory state, we tried to use the regenerative capacity of mesenchymal stem cells derived from adipose tissue (adipose-derived stem cells [ASCs]) to improve bone regeneration and moreover were curious about immunomodulation of applicated stem cells in this setting. Therefore, we used our established murine animal model and applicated ASCs locally after sufficient debridement of infected bones. Bone regeneration and resorption as well as immunological markers were investigated via histology, immunohistochemistry, Western blot, and fluorescence-activated cell scanning (FACS) analysis and µ-computed tomography (CT) analysis. Interestingly, ASCs were able to restore bone healing via elevation of osteoblastogenesis and downregulation of osteoclasts. Surprisingly, stem cells showed an impact on the innate immune system, downregulating B-cell population. In summary, these data provide a fascinating new and innovative approach, supporting bone healing after bacterial infections and moreover gain insights into the complex ceremony of stem cell interaction in terms of bone infection and regeneration. Stem Cells Translational Medicine 2019;8:1084-1091.

Staged arthrodesis using the Masquelet technique for osteomyelitis of the finger with articular destruction: a report of two cases.

Osteitis of the fingers is a serious infection that needs early diagnosis and appropriate surgical debridement and antibiotic treatment of the infected bone. If the effects of treatments are insufficient, long-term antibiotic treatment and repeated operations could be required. In worst cases, some patients may have to undergo amputation. Recently, the usefulness of the Masquelet technique in extensive traumatic bone defects has been reported. We herein describe two cases of immunocompromised patients with purulent osteitis involving joint destruction of the finger treated by two-stage arthrodesis using the Masquelet technique. They obtained good infection control and better function of the finger than before the operation. Moreover, there was no recurrence of the infection. The Masquelet technique could be an alternative technique for osteitis with high risk of amputation.

Increased perioperative C-reactive protein and decreased postoperative albumin is associated with acute posttraumatic osteomyelitis in patients with high-energy tibial fractures.

BACKGROUND: Early diagnosis of acute posttraumatic osteomyelitis (POM) is of vital importance for avoiding devastating complications. Diagnosing POM is difficult due to the lack of a highly specific and sensitive test, such as in myocardial infarct, stroke and intracranial bleeding. Serum inflammatory markers, C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC) can support clinical findings but they are not able to differentiate between inflammatory response to infection and the host response to non-infection insult with high specificity and sensitivity. AIM: The objectives of the study were to investigate whether the biochemical and immunoinflammatory patient profile could facilitate postoperative monitoring, guide the antibiotic treatment and timing of revision surgery. PATIENTS AND METHODS: This prospective nonrandomised cohort study included 86 patients after high-energy injury to the shin requiring primary surgical treatment (open or closed reduction and internal fixation of tibial fracture). Values of the biochemical and immunoinflammatory profile were measured on admission (ADD), first postoperative day (POD1) and fourth-postoperative day (POD4). RESULTS: We discovered on our sample that the development of POM is associated with increased CRP on ADD, POD1 and decreased albumins on POD4. Further studies are needed to prove that these differences can be useful in diagnosing the risk of infection. The assessment of other important risk factors such as: the extent of soft tissue damage, multiple fractures, transfusion rate, need for conversion primary external fixation to intramedullary (IM) nailing or locking plate fixation can empower our clinical judgment of POM. CONCLUSIONS: We can improve prediction of posttraumatic osteomyelitis by using the perioperative inflammatory biomarker CRP in combination with postoperative albumins levels and other associated independent risk factors.

Surgical Treatment With Thoracic Pedicle Screw Fixation of Vertebral Osteomyelitis With Long-Term Follow-up.

BACKGROUND: While recent data has demonstrated the utility of lumbar pedicle screws for the treatment of vertebral osteomyelitis, the data are limited for thoracic pedicle screws. OBJECTIVE: To investigate the effectiveness of thoracic pedicle screws for the surgical treatment of vertebral osteomyelitis. METHODS: A retrospective review of all operations performed by 2 spinal neurosurgeons from 1999 to 2012 yielded 30 cases of vertebral osteomyelitis that were treated with thoracic pedicle screws. Sixteen (53%) of which underwent combined anterior and posterior fusion and 14 patients (47%) underwent standalone posterior fusion. Postoperative records were analyzed for pertinent clinical, laboratory, and radiographic data. RESULTS: Of the 30 patients, 21 were males (70%), 8 were females (27%), and 1 was transsexual (3%). The mean age was 47 yr (range 18-69). The most common organism cultured was Staphylococcus aureus in 12 cases (50%). The mean patient stay in the hospital was 12.4 d after surgery (range 5-38 d). The mean antibiotic duration after discharge was 8 wk (range 1-24 wk). Of the 25 patients with long-term follow-up (mean, 49 mo), 92% had improved back pain (6/25 marked improvement, 17/25 complete resolution), 83% had improved muscle weakness (8/18 marked improvement, 7/18 complete resolution), and 100% had improved urinary incontinence (3/8 marked improvement, 5/8 complete resolution). Two patients (7%) required additional surgical revision due to instrumentation failure or wound infection. CONCLUSION: This study demonstrates the efficacy of utilizing thoracic pedicle screws as a primary intervention to treat vertebral osteomyelitis.

Biomimetic multilayer coatings deliver gentamicin and reduce implant-related osteomyelitis in rats.

Implant-related infections like periprosthetic joint infections (PJI) are still a challenging issue in orthopedic surgery. In this study, we present a prophylactic anti-infective approach based on a local delivery of the antibiotic gentamicin. The local delivery is achieved via a nanoscale polyelectrolyte multilayer (PEM) coating that leaves the bulk material properties of the implant unaffected while tuning the surface properties. The main components of the coating, i.e. polypeptides and sulfated glycosaminoglycans (sGAG) render this coating both biomimetic (matrix mimetic) and biodegradable. We show how adaptions in the conditions of the multilayer assembly process and the antibiotic loading process affect the amount of delivered gentamicin. The highest concentration of gentamicin could be loaded into films composed of polypeptide poly-glutamic acid when the pH of the loading solution was acidic. The concentration of gentamicin on the surface could be tailored with the number of deposited PEM layers. The resulting coatings reveal a bacteriotoxic effect on Staphylococcus cells but show no signs of cytotoxic effects on MC3T3-E1 osteoblasts. Moreover, when multilayer-coated titanium rods were implanted into contaminated medullae of rat tibiae, a reduction in the development of implant-related osteomyelitis was observed. This reduction was more pronounced for the multifunctional, matrix-mimetic heparin-based coatings that only deliver lower amounts of gentamicin.

A retrospective clinico-pathologic analysis of cemento-osseous dysplasia in a South African patient population.

BACKGROUND: Cemento-osseous dysplasia (COD) is a fibro-osseous jaw bone lesion. The affected bone in COD progressively becomes sclerotic, poorly vascularized and susceptible to secondary osteomyelitis. OBJECTIVE: To provide a clinico-pathologic appraisal of COD in a South African patient population. METHODS: Archived records of 133 patients diagnosed with COD were reviewed for patient demographics, COD location, COD type, osteomyelitis or simple bone cyst secondary to COD. RESULTS: The mean age was 53.4 ± 13.5 years with a 94.7% female predilection. COD mainly affected the mandible (57.1%), followed by involvement of both jaws (38.3%) and maxilla (4.5%). Florid COD was the most prevalent (69.9%), followed by focal COD (18%) and periapical COD (12%). Florid COD showed a clear trend of increasing with age, peaking in the sixth decade and decreasing thereafter. Osteomyelitis and simple bone cyst presented as complications of COD in 74.4% and 5.3% of cases respectively, while 21.8% of all cases of jaw osteomyelitis during the study period were secondary to COD. CONCLUSION: A higher frequency of jaw osteomyelitis secondary to COD was found compared to previous studies. No significant association was shown between any of the COD types and secondary osteomyelitis.

Modified Masquelet's technique with nail and allograft: A case report.

The large bone defect treatment is a challenge issue in modern orthopaedic trauma surgery. One of the most used technique is the Masquelet's technique. In this case report we used a modified Masquelet technique to fill a six centimeters bone gap in the proximal femur. A 18-year-old boy with a septic pseudoarthrosis was treated with a two stages procedure: in the first step we used a hollow antibiotic spacer and an intramedullary nail. In the second step, we used both omologous (6 cm of bone allograft) and autologous bone graft with a new intramedullary nail. Immediate partial weight bearing was allowed and after 3 months the patient started walking with complete weight bearing. A year later the fracture had healed uneventfully. The modification of the Masquelet Technique that we have made allows the patient to immediately weight bearing safely, speeding up the functional recovery. Further studies are needed to standardize this type of combined technique.