Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model.

BACKGROUND: Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. QUESTIONS/PURPOSES: (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? METHODS: Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. RESULTS: The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0-10 CFU/mL) when compared with CONT (median = 5.7 × 10(4), range = 4.0 × 10(3)-8.0 × 10(5) CFU/mL; difference of medians = -5.6 × 10(4); p < 0.001) and VANCO (median = 4.9 × 10(3), range = 9.0 × 10(2)-2.1 × 10(4) CFU/mL; difference of medians = -4.9 × 10(3); p < 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0-0 CFU/mL) when compared with CONT (median = 1.3 × 10(2), range = 0-9.4 × 10(2) CFU/mL; difference of medians = -1.3 × 10(2); p < 0.001) but was not different from VANCO (median = 0, range = 0-1.3 × 10(2) CFU/mL; difference of medians = 0; p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0-8.0 × 10(1) CFU/mL) and bone CFU (median = 0, range = 0-2.0 × 10(1) CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0-10 CFU/mL; difference of medians = 0; p = 0.334) and bone CFU (median = 0, range = 0-0 CFU/mL; difference of medians = 0; p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. CONCLUSIONS: Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. CLINICAL RELEVANCE: CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made.

A novel mouse model of Staphylococcus aureus chronic osteomyelitis that closely mimics the human infection: an integrated view of disease pathogenesis.

Osteomyelitis is a serious bone infection typically caused by Staphylococcus aureus. The pathogenesis of osteomyelitis remains poorly understood, mainly for lack of experimental models that closely mimic human disease. We describe a novel murine model of metastatic chronic osteomyelitis initiated after intravenous inoculation of S. aureus microorganisms. The bacteria entered bones through the bloodstream and, after an acute phase with progressive growth (first 2 weeks after infection), they remained at constant numbers for up to 56 days (chronic phase). Clinical signs of illness and systemic inflammation were apparent only during the acute phase. Bone destruction and remodeling processes were readily detectable by magnetic resonance and X-ray imaging 3 weeks after infection, and high levels of bone deformation were observed during the chronic phase. Histological examination of infected bones demonstrated suppurative inflammation with foci of intense bacterial multiplication and necrosis during acute infection and osteoclastic resorption accompanied by new woven bone formation during chronic infection. Transmission electron microscopy revealed S. aureus microorganisms forming microcolonies within the nonmineralized collagen matrix or located intracellularly within neutrophils. In summary, our mouse model of staphylococcal hematogenous osteomyelitis precisely reproduces most features of the human disease. Although the extent of lesions in the chronic phase was subject to variation, this model is ideal for testing and monitoring novel treatment modalities via noninvasive imaging.

Acute osteomyelitis of the humerus mimicking malignancy: Streptococcus pneumoniae as exceptional pathogen in an immunocompetent adult.

BACKGROUND: Chronic osteomyelitis due to direct bone trauma or vascular insufficiency is a frequent problem in orthopaedic surgery. In contrast, acute haematogenous osteomyelitis represents a rare entity that almost exclusively affects prepubescent children or immunodeficient adults. CASE PRESENTATION: In this article, we report the case of acute pneumococcal osteomyelitis of the humerus in an immunocompetent and otherwise healthy 44-year-old male patient presenting with minor inflammation signs and misleading clinical features. CONCLUSIONS: The diagnosis had to be confirmed by open biopsy which allowed the initiation of a targeted therapy. A case of pneumococcal osteomyelitis of a long bone, lacking predisposing factors or trauma, is unique in adults and has not been reported previously.

The effect of sterilization on the mechanical properties of intact rabbit humeri in three-point bending, four-point bending and torsion.

Load bearing bone allografts are used to replace the mechanical function of bone that has been removed or to augment bone that has been damaged in trauma. In order to minimize the risk of infection and immune response, the bone is delipidated and terminally sterilized prior to implantation. The optimal method for bone graft sterilization has been the topic of considerable research. Recently, supercritical carbon dioxide (SCCO(2)) treatments have been shown to terminally sterilize bone against a range of bacteria and viruses. This study aimed to evaluate the effect of SCCO(2) treatment compared with two doses of gamma irradiation, on the mechanical properties of whole bone. Paired rabbit humeri were dissected and randomly assigned into either SCCO(2) control, SCCO(2) additive or gamma irradiation at 10 or 25 kGy treatment groups. The bones were mechanically tested in three-point and four-point bending and torsion, with the lefts acting as controls for the treated rights. Maximum load, energy to failure and stiffness were evaluated. This study found that SCCO(2) treatment with or without additive did not alter maximum load, energy to failure or stiffness significantly under any loading modality. Gamma irradiation had a deleterious dose dependant effect, with statistically significant decreases in all mechanical tests at 25 kGy; while at 10 kGy there were reductions in all loading profiles, though only reaching statistical significance in torsion. This study highlights the expediency of SCCO(2) treatment for bone allograft processing as terminal sterilization can be achieved while maintaining the intrinsic mechanical properties of the graft.

Brief communication: evidence of Bartonella quintana infections in skeletons of a historical mass grave in Kassel, Germany.

In 2008, a mass grave was found on the grounds of the University of Kassel, Germany. Historians hypothesized that the individuals died in a typhoid fever epidemic in winter 1813/14. To test this hypothesis, the bones were investigated on the presence of specific DNA of pathogens linked to the historical diagnosis oftyphoid fever. It was possible to prove the specific DNA of Bartonella quintana in three individuals, suggesting that their cause of death is linked to an epidemic background.

A case of acute and severe thrombocytopenia due to readministration of rifampicin.

A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10(3) to 3 × 10(3)/µl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.

Salmonella enteritidis infection of the musculoskeletal system - case report.

This article presents diagnostic and therapeutic problems in 2 patients with blood-borne infection of the coxofemoral joint and the humeral diaphysis caused by Salmonella enteritidis (S. enteritidis). These patients accounted for 4.6% of cases of blood-borne infections treated between 2002 and 2009 and 1.1% of all musculoskeletal infections treated at the Department of Orthopaedics and Traumatology of N. Copernicus Regional Specialized Hospital in Lódz. The inflammations developed nearly a year after an episode of Salmonella gastroenteritis. The aetiology and time of onset of manifestations raised some doubts as to the accuracy of diagnosis and required not only conventional microbiological methods but also serological tests to confirm the presence of specific antibodies to S. enteritidis antigens. The finding of osteolytic foci in imaging studies of bones necessitates extensive work-up that should also account for atypical causes of musculoskeletal inflammation.

Cryptococcal Osteomyelitis of the Entire Humerus: A Case Report.

CASE: We describe a case of cryptococcal osteomyelitis in a 70-year-old man who presented with left elbow and shoulder pain. Subsequent imaging indicated osteomyelitis of the entire humerus, and he underwent debridement of the elbow and shoulder. Pathological findings revealed Cryptococcus neoformans infection. Surgical management was followed by a prolonged course of antibiotics. CONCLUSION: Although C. neoformans is rare as the etiology of infection of the entire humerus, orthopaedic surgeons should consider cryptococcosis as a potential cause of infection.

Osteomyelitis--a case report.

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) infection has classically been associated with institutional health care settings such as hospitals and nursing homes. OBJECTIVE: This article presents a case of community acquired MRSA infection resulting in severe osteomyelitis of the humerus, followed by a brief discussion and literature review. DISCUSSION: Over the past few years, more community acquired cases of MRSA have occurred. Methicillin resistant S. aureus usually infects skin and soft tissue. Occasionally, a life threatening infection occurs involving the blood, lungs, heart and bone.

Abscess-forming lymphadenopathy and osteomyelitis in children with Bartonella henselae infection.

Bartonella henselae is the agent of cat-scratch disease (CSD), a chronic lymphadenopathy among children and adolescents. A systemic infection is very rare and most of these cases are found in patients with immunodeficiency. Here, cases involving four children of 6-12 years of age are reported. Three of the children had an abscess-forming lymphadenopathy and surrounding myositis in the clavicular region of the upper arm. The diagnosis was made serologically and, in one case, using eubacterial universal PCR. One child was treated with erythromycin for 10 days, the second received cefotaxime and flucloxacillin for 14 days and the third child was not treated with antibiotics. The fourth child had a different course: a significantly elevated signal intensity affecting the complete humerus was found in magnetic resonance imaging, consistent with osteomyelitis. A lymph node abscess was also found in the axilla. Diagnosis was established by indirect fluorescence assay and lymph node biopsy. Antibiotic therapy using clarithromycin, clindamycin and rifampicin was gradually successful. Immunodeficiency was excluded. All described lesions healed without residues. In immunocompetent patients, infection affects skin and draining lymph nodes; however, prolonged fever of unknown origin as in the fourth patient indicated a systemic complication of CSD.

Successful bony integration of a porous tantalum implant despite longlasting and ongoing infection: Histologic workup of an explanted shoulder prosthesis.

Infection associated with an implant is a complication feared in surgery, as it leads to loosening and dysfunction. This report documents an unexpected good bony integration of a porous tantalum shoulder prosthesis despite infection. A shoulder prosthesis with a porous tantalum glenoidal base plate was retrieved after 3 years of ongoing infection with Staphylococcus spp. Methyl-methacrylate embedded sections of the retrieved glenoidal component were analyzed by optical and scanning electron beam microscopy (SEM). Bone ongrowth and ingrowth were quantified. Bone had formed at the implant surface and within the open cell structure of the porous tantalum. The bone implant contact index was 32%. The bone ingrowth or relative bone area within the open structure was 8.2%, respectively 11.9% in the outer 50% of the thickness. Due to the section thickness, bone ongrowth could best be documented in SEM. Despite long-lasting and ongoing infection, the glenoidal base plate of the prosthesis showed good bony integration upon removal. The bone ingrowth into the porous tantalum was comparable to the values previously reported for the undersurface of retrieved proximal humerus resurfacing implants. Good integration of the implant however did not solve the problem of infection, and related morbidity. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2924-2931, 2018.

Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

UNLABELLED: Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. STATEMENT OF SIGNIFICANCE: Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel thermo-responsive hyaluronan based hydrogel with control over gelation temperature is reported. The efficacy of this gentamicin loaded hyaluronan derivative is demonstrated in an in vivo fracture model in the presence of fracture fixation hardware. The bacterial burden is cleared in all of the inoculated rabbits in the presence of the ALB. Thus, the proposed injectable thermo-responsive hyaluronan presents an effective ALB for the prevention of infection.

Diffuse chronic sclerosing osteomyelitis and the synovitis, acne, pustolosis, hyperostosis, osteitis (SAPHO) syndrome in two sisters.

Two sisters with diffuse chronic sclerosing osteomyelitis of the mandible and the humerus and the synovitis, acne, pustolosis, hyperostosis and osteitis syndrome (SAPHO syndrome) are presented. The diagnoses of diffuse chronic sclerosing osteomyelitis at the age of 12 years and 27 years, respectively, were based on typical medical history, clinical symptoms and radiographic, histologic and scintigraphic findings. Because skin lesions and scintigraphic enhancement of the sternoclavicular joints with hyperostosis were present, a SAPHO syndrome was diagnosed in both sisters. Microbiological cultures of biopsy specimens revealed coagulase-negative Staphylococcus aureus at the humerus and Haemophilus parainfluenzae, Streptococcus, Actinomyces and Veilonella species at the mandible. Repeated operative procedures, including decortications, resection and reconstruction, and multiple histologic and microbiologic studies were performed over a period of up to 20 years. Since HLA typing yielded identical gene loci, we suggest that hereditary and autoimmune factors may play a role in the pathogenesis of these cases.

[Recurrent osteitis and Coxiella burnetii: the relation to chronic recurrent multifocal osteomyelitis]. / Ostéites récidivantes et Coxiella burnetti: relation avec l'ostéomyélite chronique récurrente multifocale.

UNLABELLED: Chronic recurrent multifocal osteomyelitis (CRMO) is a disorder of suspected--but unproved-infectious etiology. OBSERVATION: A girl presented with a typical CRMO involving successively the left fibula, radius, humerus and the right carpus. A Coxiella burnetii infection was indicated during the first attack. Two recurrences occurred in spite of suitable antibiotic treatment and with negative infectious investigation. Two months after stopping antibiotic treatment, a new recurrence associated with antibodies increase and positive bone culture occurred. CONCLUSION: Coxiella burnetii can initiate a CRMO. The mechanism involved is probably a delayed hypersensitivity. CRMO would therefore be the first type of reactive osteitis.

Multifocal bacterial osteomyelitis after varicella infection: a rare but dreaded complication of chickenpox.

Chickenpox is an infectious disease common in children, which in most cases is benign toward the self-limited resolution. There are, however, serious systemic and musculoskeletal complications, especially in patients with immunosuppression. We report a case of multifocal skeletal muscle involvement, as a complication of chickenpox by Streptococcus pyogenes.

Tuberculosis of the elbow joint in children: a review of ten patients who were managed nonoperatively.

BACKGROUND: There is scarce information regarding osteoarticular tuberculosis of the elbow in children, even in countries where tuberculosis is endemic. We report our experience with ten patients who were managed nonoperatively. METHODS: We retrospectively assessed ten children with elbow tuberculosis with regard to their presentation, diagnosis, management, response to standard antitubercular drugs, and outcome at the completion of antitubercular therapy. All patients were managed nonoperatively with splinting for as long as six weeks, followed by mobilization along with multidrug antitubercular medication for twelve months. RESULTS: Swelling of the elbow that did not respond to initial treatment was the most common cause for referral to our clinic. The proximal ulnar metaphysis was most commonly involved. The average duration of follow-up was twenty-six months. The average time for healing of draining sinuses was twelve weeks (range, four to fourteen weeks). Lytic lesions, including coke-like sequestrum, healed radiographically at an average of 7.4 months (range, six to nine months). Range of motion improved with treatment, but some motion restriction always persisted, depending on the extent of joint destruction. CONCLUSIONS: In the Indian subcontinent, the presentation of elbow tuberculosis is usually exudative with abscess formation, and the disease is fairly advanced at the time of diagnosis. An "ice cream scoop" appearance of the proximal part of the ulna in children should raise suspicion for tuberculosis. Elbow tuberculosis in children can be treated adequately with use of nonoperative means, regardless of the extent of osseous destruction, with a good outcome.