Abstract: We set out to evaluate the clinical efficacy of individual antibiotic agents for bone and joint infections in adults. Published and unpublished controlled trials reported between 1966 and 2000 were reviewed to determine if they involved random or quasi-random allocation to systemically administered antimicrobials or local antibiotic therapy for osteomyelitis and septic arthritis. Quiescence of infection after 1 year of follow-up was defined as the primary outcome measure. 22 trials containing 927 patients were eligible for final analysis. Varying proportions of the entire study population could be evaluated with respect to primary and secondary endpoints. Methodological quality was poor among most studies, and interpretability of results was further limited by small sample sizes, missing descriptions of patient populations and disease characteristics, and the frequent application of concomitant antibiotics. A trend towards improved, long-lasting infection control was observed in favour of a rifampicin-ciprofloxacin combination versus ciprofloxacin monotherapy for the treatment of staphylococcal infections related to orthopaedic devices (absolute risk difference [ARD] 28-9%; 95% CI -0.7 to 54.4%). Obviously unbalanced comparative studies showed some benefit of ticarcillin for bone infections caused by Pseudomonas species. No significant differences in therapeutic efficacy were found among trials comparing oral fluoroquinolones with intravenous beta-lactam drugs for both end-of-treatment (OR 0.8; 0.5 to 1.4) and long-term results (OR 1.3; 0.8 to 2.1). A variety of drugs was used as controls, thereby leading to inconsistent findings of drug-related side effects. Only one randomised trial was suitable to investigate the impact of polymethylmethacrylate gentamicin bead chains compared with parenteral antibiotics for skeletal infections, although this study was biased by patients receiving both combined local and systemic antibiotic therapy. Whereas intention-to-treat evaluation suggested a therapeutic advantage of systemic over local therapy, this trend diminished in the per-protocol analysis (1-year follow-up ARD -2.3;-17.5 to 10.8%). There exists little high-quality evidence on antibiotic therapy for osteomyelitis and septic arthritis. The observed heterogeneity among patient populations and medical and surgical treatment concepts preclude reliable inferences from the available data.

Abstract: We studied prospectively a consecutive series of 50 patients with chronic osteomyelitis. Patients were allocated to the following treatment groups: 1) wide resection, with a clearance margin of 5 mm or more; 2) marginal resection, with a clearance margin of less than 5 mm; and 3) intralesional biopsy, with debulking of the infected area. All patients had a course of antibiotics, intravenously for six weeks followed by orally for a further six weeks. No patients in group 1 had recurrence. In patients treated by marginal resection (group 2), 8 of 29 (28%) had recurrence. All patients who had debulking had a recurrence within one year of surgery. We performed a survival analysis to determine the time of the recurrence of infection. In group 2 there was a higher rate of recurrence in type-B hosts (p < 0.05); no type-A hosts had recurrence. This information is of use in planning surgery for chronic osteomyelitis.

Abstract: We have reviewed the incidence of bacteriologically or radiologically confirmed acute haematogenous osteomyelitis in children under 13 years of age resident in the area of the Greater Glasgow Health Board between 1990 and 1997. In this period there was a fall of 44% in the incidence of both acute and subacute osteomyelitis, mainly involving the acute form (p = 0.005). This mirrors the decline of just over 50% previously reported in the same population between 1970 and 1990. Using multiple regression analysis a decline in incidence of 0.185 cases per 100 000 population per year was calculated for the 28-year period (p < 0.001). Staphylococcus was the most commonly isolated pathogen (70%). Only 20% of patients required surgery and there was a low rate of complications (10%). In general, patients with a subacute presentation followed a benign course and there were no complications or long-term sequelae in this group. Haematogenous osteomyelitis in children in this area is becoming a rare disease with an annual incidence of 2.9 new cases per 100 000 population per year.

Abstract: We reviewed medical records and laboratory and diagnostic evaluations for 8 pediatric patients with spinal epidural abscesses who were treated during the last 15 years at our institution. Staphylococcus aureus was isolated from 5 of 8 epidural abscesses, including 2 abscesses with methicillin-resistant S. aureus. Unusual isolates were group B Streptococcus in a patient with chronic vesicouretral reflux associated with the posterior urethral valves and Aspergillus flavus in a patient with acute myelogenous leukemia. An analysis incorporating our results and a review of the English-language literature about abscesses in children and adults revealed differences related to age. Abscesses in children were more posterior in epidural location, had greater spinal column extension, and were associated with more favorable clinical outcomes than were abscesses in adults. Magnetic resonance imaging is the diagnostic procedure of choice; however, radionuclide bone scans should be considered for associated distant osteomyelitis in children. Prompt diagnosis and combined medical and surgical treatment remain the cornerstones for the prevention of adverse outcomes.

Abstract: Objectives: To evaluate the feasibility, efficacy, and cost of outpatient parenteral antimicrobial therapy (OPAT) in the treatment of osteomyelitis. Subjects: 39 patients with an osteomyelitis requiring parenterally administered antibiotics for more than 4 weeks, and able to receive antibiotics at home. Methods: All patients had a totally implanted catheter. Antibiotics were administered by continuous infusion using a portable elastomeric infusion system, which was changed every day by the patient or by the home-care nurse. Laboratory monitoring and surveillance were performed weekly. Clinical efficacy, adverse effects and quality of life were recorded. Results: The most commonly used antibiotics were vancomycin (51%) and β-lactam (44%) antibiotics. Thirty patients were available for follow-up for a minimum of 12 months after completion of therapy. Twenty-eight (93%) were considered cured of their infection with a mean of 24 ± 4 months after completion of antibiotic therapy. Adverse effects among the study patients were rare. The 39 patients in our OPAT programme resulted in a potential saving of US $1 873 885 relative to conventional therapy. Conclusion: OPAT is practicable and effective and may be the best alternative treatment for patients suffering from osteomyelitis requiring intravenous therapy.

Abstract: Seventeen diabetic patients with moderate to mild foot lesions associated with 20 osteomyelitic bones diagnosed by both bone scan and bone biopsy received rifampicin plus ofloxacin for a median duration of 6 months. Cure was defined as disappearance of all signs and symptoms of infection at the end of the treatment and absence of relapse during follow up. At the end of the treatment period, cure was achieved in 15 patients (88.2%) and was maintained in 13 patients (76.5%) at the end of an average post-treatment follow-up of 22 months. No serious drug-related adverse events were recorded.

Abstract: Background Streptococcus milleri, a commensal organism, has the potential to cause significant morbidity. There is a paucity of published data regarding this organism in the head and neck. Objectives To identify and assess the presentation, treatment, and outcomes of pediatric patients affected by this pathogen. Study Design Review of the Department of Pathology database at Children's Hospital of Wisconsin, Milwaukee, between 1997 and 1999 identified 26 patients with cultures positive forS millerigroup (SMG) bacteria. Retrospective chart analysis examined the demographic data, site of origin of infection, additional organisms cultured, symptoms, treatments, and complications. Results Sixteen patients had SMG infections involving the head and neck region. Sites of origin included the paranasal sinuses, dental, facial soft tissues, deep neck spaces, peritonsillar region, and a tracheostomy site. The paranasal sinuses were the most common site in 37% (6/16).Streptococcus milleriwas the only isolate in 69% (11) of the infections. Significant local extension occurred in 56% (9/16) of the patients and included the orbit, skull base, cranium, and deep neck spaces. All patients had surgical drainage and 15 also received intravenous antibiotic treatment. One complication of osteomyelitis of the frontal bone occurred with resolution after surgical debridement and intravenous antibiotic treatment. Conclusions Streptococcus millerican be an aggressive pathogen in the head and neck with a propensity for abscess formation and local extension of the infection in a pediatric population. Surgical drainage with antibiotics is generally successful in management of the condition. However, emerging penicillin resistance and the ability for local extension require suspicion of incomplete treatment if clinical symptoms persist.

Abstract: Background: Fungal infections of the spine are noncaseating, acid-fast-negative infections that occur primarily as opportunistic infections in immunocompromised patients. We analyzed eleven patients with spinal osteomyelitis caused by a fungus, and we developed suggestions for treatment. Methods: All patients with a fungal infection of the spine treated by the authors over a sixteen-year period at three teaching institutions were evaluated. There was a total of eleven patients. Medical records and roentgenograms were available for every patient. Long-term follow-up of the nine surviving patients was performed by direct examination by the authors or by the patient's primary physician. Results: For ten of the eleven patients, the average delay in the diagnosis was ninety-nine days. Nine patients were immunocompromised secondary to diabetes mellitus, corticosteroid use, chemotherapy for a tumor, or malnutrition. The sources of the spinal infections included direct implantation from trauma (one patient), hematogenous spread (four patients), and local extension (two patients). The infection followed elective spine surgery in three patients, and the cause was unknown in one. Paralysis secondary to the spine infection developed in eight patients. Ten patients were treated with surgical debridement. All eleven patients were treated with systemic anti-fungal medications for a minimum of six weeks. One patient died of generalized sepsis at thirty-three days, and another patient died of gastrointestinal hemorrhage at five months. After an average of 6.3 years of follow-up, the infection had resolved in all nine surviving patients. Conclusions: Treatment of fungal spondylitis is often delayed because of difficulty with the diagnosis. Delay in the diagnosis led to poorer results in terms of neurologic recovery in our study. Performing fungal cultures whenever a spinal infection is suspected might hasten the diagnosis. Patients should be given a guarded prognosis and informed of the many possible complications of the disease.

Abstract: in an adult who hadundergone multiple revisions of a hipprosthesis. Treatment was with ampho-tericin B-loaded bone cement. We be-lieve this is the first report of such treat-ment for fungal osteomyelitis.Case report A 59-year-old man (height 180 cm,weight 82 kg) was admitted to the Vancouver Hospital & Health SciencesCentre with a suspected infection after asecond revision total hip arthroplasty.His medical history included an undiag-nosed inflammatory arthropathy forwhich he had undergone a right-sidedtotal hip replacement in 7 years earlier.This had been revised twice because ofaseptic loosening, first 6 years after theoriginal replacement and subsequently 2months before the current admission.The erythrocyte sedimentation rate, C-reactive protein levels and intraoperativesynovial tissue cultures obtained at thetime of these revisions revealed no infec-tion. His course after the second revisionoperation was uncomplicated until 10days before this admission when he hadnight sweats, fever, redness and swellingover the right hip. He did not report anydrug allergies and only reported takingdiclofenac 50 mg orally twice daily, forhis inflammatory arthropathy. On admission, his vital signs includeda blood pressure of 165/90 mm Hg,heart rate of 110 beats/min, and a bodytemperature of 38.1°C. Findings onphysical examination were unremarkableexcept for an area of erythema over themedial portion of the wound on theright hip; the area from the right hipdown to the knee was also edematousand tender. Ultrasonography revealed asmall fluid collection from which 30 mLof turbid serosanguineous fluid was aspirated. This contained 19.7 × 10

Abstract: Osteomyelitis secondary to diabetic foot infections can lead to proximal amputation if not diagnosed in a timely and accurate manner. The authors have found no studies to date that correlate a specific erythrocyte sedimentation rate with osteomyelitis. A retrospective chart review of 29 diabetic patients admitted to the hospital with diagnoses of osteomyelitis or cellulitis of the foot during a 1-year period was performed. Of the various lab values and demographic factors compared, erythrocyte sedimentation rate was the only measure that differed significantly between the two groups. A receiver operating characteristic curve was used to obtain the optimal cutoff value of 70 mm/h, a level above which osteomyelitis was present with the highest sensitivity (89.5%) and highest specificity (100%), along with a positive predictive value of 100% and a negative predictive value of 83%. This study shows that in combination with clinical suspicion in diabetic foot infections, the erythrocyte sedimentation rate is highly predictive of osteomyelitis, and that the value of 70 mm/h is the optimal cutoff to predict accurately the presence or absence of bone infection.

Abstract: Between 1990 and 1998 we saw 21 children with primary subacute haematogenous osteomyelitis. Pain, swelling and a limp had been present for two to 12 weeks with little functional impairment. Laboratory tests were non-contributory. The lesions were classified radiologically into metaphyseal, diaphyseal, epiphyseal and vertebral. There were 24 sites involved, with most (20) being in the tibia; 17 lesions were in the diaphysis, five in the metaphysis and two in the epiphysis. The diagnosis was confirmed histologically in all cases. Staphylococcus aureus was cultured in six patients. Healing occurred in all patients after treatment with antibiotics for six weeks and radiological improvement was seen after three to six months. Subacute osteomyelitis develops as a result of increased host resistance and decreased bacterial virulence. The radiological features can mimic various benign or malignant bone tumours and non-pyogenic infections. Histological confirmation is necessary to avoid a delay in diagnosis.

Abstract: Diffuse sclerosing osteomyelitis of the mandible is characterized by bouts of intense pain, sometimes associated with trismus and paresthesia, and leads to progressive deformity. It is of unknown etiopathology, but it is suggested to be one manifestation of the synovitis, acne, pustulosis, hyperostosis, osteomyelitis syndrome, the other features of which may have been overlooked. Treatment results are disappointing, and decortication may be necessary to achieve an acceptable outcome. We report a case restricted to the mandible that responded favorably to treatment with pamidronate. Further trials of pamidronate in patients with diffuse sclerosing osteomyelitis of the mandible, even in those with the aforementioned syndrome, are needed to assess its effectiveness.

Abstract: Juvenile and adolescent "Chronic Recurrent Multifocal Osteomyelitis" (CRMO) is described on the basis of literature and analysis of 43 own cases (23 cases in children or adolescents) This systemic, non-purulent inflammatory disease occurs mainly metaphyseal in long bones, in pelvic bones or as spondylitis and is not as rare as it seemed Basis of the disease is a primarily chronic, sterile, in phase of onset often monotopic (eg clavicle) and later frequently polytopic osteomyelitis, possibly triggered by an immuno-pathological process (eg Proprionibacterium acnes), and showing histologically plasmacellular invasion and a sclerosing process in different stages Association with pustulous dermatosis (psoriasis, acne, palmo-plantar pustulosis) is found in about 25 % of children and adolescents and in more than 50 % of the adult patients 5 differents types of distribution of osteomyelitic lesions can be found by using Te99m-bone scan primarily, of which the "pelvic type" is the most common Because of the close neighbourhood of meta-/epiphyseal osteomyelitic focuses, "sympathetic arthritis" with synovitis is seen frequently A therapeutic approach with azithromycine and calcitonine is presented

Abstract: We describe three patients with multifocal osteomyelitis caused by Mycobacterium avium and a family history of one or more first degree family members diagnosed with various clinical presentations of infections with nontuberculous mycobacteria. There was a significant delay in the diagnosis and they had a protracted course of their illness, which responded only slowly to prolonged multi-drug treatment. In one patient, additional treatment with interferon-γ (IFN-γ) was necessary. Macrophages of these patients had decreased in vitro responsiveness to IFN-γ. Genomic sequencing revealed that these patients and their affected family members were heterozygous for a previously described dominant negative mutation in the gene encoding the IFN-γ binding receptor-1 chain. The clinical presentations of the infections with nontuberculous mycobacteria in these families, with spread limited to skin, bone and lymph nodes, is discussed in the light of the immune mechanisms that are responsible for the clearance of otherwise poorly pathogenic environmental mycobacteria.

Abstract: Aim To review the results of the management of chronic post-traumatic osteomyelitis and infected non-union with bone defects of femur using the Ilizarov technique with a modified apparatus assembly Patients and methods Thirty patients treated by the Ilizarov method because of chronic fistulous osteomyelitis and infected pseudoarthroses of the femur were included in the prospective study between 1989 and 1999 Their mean age was 394+/-144 years (range, 25-80 years) The follow-up period lasted for 24 to 126 months Results The infection was eradicated in 29 patients before the fixator removal Excellent bone healing was found in 12, and excellent functional result in 5 out of 30 patients There was a total of 87 complications in 30 patients Conclusion Ilizarov technique is a method of choice in saving the limb with chronic osteomyelitis and infected pseudoarthrosis Because of the additional injuries, bone healing in affected limb may be superior to the functional result

Abstract: Diabetic foot problems remain all too common and are likely to increase in prevalence over the next few decades. It has been estimated that an individual with diabetes now has a 25% risk of developing a foot ulcer at some time during their lifespan. A number of controversies are discussed in this chapter starting with the key question of the best screening methods for the “at risk foot” for ulceration. The key message is that simple clinical techniques of examination of the feet and lower limbs are probably the most accurate way to assess for further risk of foot lesions. A foot ulcer will normally heal if the circulation is intact, infection is treated and pressure is taken off the lesion. Physicians find it hard to believe that patients with large plantar foot lesions would actually walk on this lesion, but they forget that sensory loss in the diabetic foot permits walking without discomfort. Thus offloading is frequently neglected and if applied properly, will lead to satisfactory healing in most plantar neuropathic ulcers. In the area of infection, the key question is whether an ulcer is infected or colonized and this is discussed in some detail as is the differential diagnosis between osteomyelitis and Charcot neuroarthropathy. The use and abuse of expensive topical treatments is then discussed and finally the role of footwear in the prevention of recurrent ulcers is described.

Abstract: Because osteomyelitis requires lengthy parenteral antibiotic treatment in patients who are often otherwise healthy, it lends itself well to outpatient parenteral antibiotic therapy (OPAT). Four delivery models for OPAT are (1) self-administration at home, (2) administration by a visiting nurse in the home, (3) infusion center and (4) nursing home. Patient selection is critical to the success of any OPAT program. Clinical and microbiologic data were compiled for more than 500 osteomyelitis patients reported in a registry of OPAT cases in the United States. The most commonly isolated pathogen was Staphylococcus aureus. The antibiotics used most frequently were vancomycin and ceftriaxone. Of 255 patients assessed for bacteriologic outcome, 2 patients developed infection with a new organism and 2 failed to eliminate the causative organism by the end of OPAT therapy. Of 266 patients who were assessed for clinical outcome, 259 improved and 7 failed. Data collected by the OPAT Outcomes Registry confirms that osteomyelitis can be safely and effectively treated with intravenous antibiotics outside the hospital.

Abstract: The clinical efficacy of long-term roxithromycin treatment was examined objectively in nine patients with chronic diffuse sclerosing osteomyelitis of the mandible. Roxithromycin was administered orally at a dose of 300 mg/day for between 68 days and 66 months. In seven of the nine cases (77.8%), the symptoms disappeared 1‐12 months after the start of therapy. Radiography showed that osteolytic changes (evident from ‘moth-eaten’ appearance of bone) had improved but that osteosclerosis had persisted or become more predominant by the end of therapy. Therefore, the optimum duration of treatment should be decided according to the amelioration of symptoms along with the disappearance of osteolytic findings in radiographs. Diarrhoea and stomach discomfort occurred in one case, and liver dysfunction in another, but these adverse reactions were relatively mild. The mechanism of action of roxithromycin in this study is not yet fully understood, but our results indicate that long-term roxithromycin treatment may be useful for diffuse sclerosing osteomyelitis of the mandible and should be attempted before surgical treatment is considered.

Abstract: This brief review discusses one possible approach to evaluating the sickle cell patient with bone pain. The major differential diagnoses include osteomyelitis and bone infarction. Based on previous studies, we provide an approach to assessing and treating patients with the possible diagnosis of osteomyelitis. An algorithm has been provided, which emphasizes the importance of the initial history and physical examination. Specific radiographic studies are recommended to aid in making the initial assessment and to determine whether the patient has an infarct or osteomyelitis. Differentiating osteomyelitis from infarction in sickle cell patients remains a challenge for the pediatrician. This algorithm can be used as a guide for physicians who evaluate such patients in the acute care setting.

Abstract: Tuberculous osteomyelitis is an uncommon infection that usually involves the vertebrae. An otherwise healthy young man with a chronic discharging sinus on his right foot caused by tuberculous osteomyelitis is described. The risk factors, clinical features, radiological findings, and investigations of tuberculous osteomyelitis are briefly reviewed. Tuberculous osteomyelitis usually runs an insidious course; emergency physicians should be aware of the possibility of tuberculous osteomyelitis especially when patients present with chronic unexplained musculoskeletal symptoms.

Abstract: A new mouse model of locally induced osteomyelitis was used to study the importance for pathogenicity of the specific binding ability of Staphylococcus aureus to collagen and fibronectin. This method appears to be convenient, reproducible, and suitable for large-scale experiments. In contrast to previous studies in experimental arthritis and endocarditis models, no difference in infection rates was found between the strains deficient in binding to collagen compared with the corresponding adherence-proficient strains. However, fibronectin binding ability in this model, in contrast to the endocarditis model, is thought to enhance the microorganisms' capacity to establish an infection. Infections caused by the fibronectin-binding strain also are thought to be clinically more aggressive than those caused by the nonbinding strain. Specific adherence mechanisms are thought to be operative in the pathogenesis of biomaterial associated osteomyelitis, and an improved understanding of such mechanisms may have an important prophylactic and therapeutic impact.

Abstract: Early and accurate diagnosis of osteomyelitis remains a clinical problem. Acute osteomyelitis often occurs in infants and most often is located in the long bones. Radiologic images show changes only in advanced stages of disease. Scintigraphic imaging with 99mTc-methylene diphosphonate (MDP), or bone scanning, is much more sensitive in detecting acute osteomyelitis but lacks specificity. We evaluated the performance of 99mTc-interleukin-8 (IL-8) in an experimental model of acute osteomyelitis. Methods: Acute pyogenic osteomyelitis was induced in 10 rabbits by inserting sodium morrhuate and Staphylococcus aureus into the medullary cavity of the right femur. The cavity was closed with liquid cement. A sham operation was performed on the left femur. Routine radiographs were obtained just before scintigraphy. Ten days after surgery, the rabbits were divided into 2 groups of 5 animals, received an injection of either 18.5 MBq 111In-granulocytes or 18.5 MBq 67Ga-citrate, and were imaged both 24 h after injection and 48 h after injection. On day 12, the rabbits received either 18.5 MBq 99mTc-MDP or 18.5 MBq 99mTc-IL-8, and serial images were acquired at 0, 1, 2, 4, 8, 12, and 24 h after injection. Uptake in the infected femur was determined by drawing regions of interest. Ratios of infected femur (target) to sham-operated femur (background) (T/Bs) were calculated. After the final images were obtained, the rabbits were killed and the right femur was dissected and analyzed for microbiologic and histopathologic evidence of osteomyelitis. Results: Acute osteomyelitis developed in 8 of 10 rabbits. All imaging agents correctly detected the acute osteomyelitis in these animals. The extent of infection was optimally visualized with 67Ga-citrate and delayed bone scanning, whereas diaphyseal photopenia was noted with both 99mTc-IL-8 and 111In-granulocytes. In 1 rabbit with osteomyelitis, imaging results were falsely negative with 111In-granulocytes and falsely positive with 99mTc-MDP. Quantitative analysis of the images revealed that the uptake in the infected region was highest with 67Ga-citrate (4.9 ± 0.8 percentage injected dose [%ID]) and 99mTc-MDP (4.7 ± 0.7 %ID), whereas the uptake in the infected area was significantly lower with 99mTc-IL-8 (2.2 ± 0.2 %ID) and 111In-granulocytes (0.8 ± 0.2 %ID) (P