Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant.

We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen. Quantitative bone cultures were performed throughout the 14-day period. The mean ± SD quantity of staphylococci in the bone after a 1-week infection period was 4.5 ± 1.0 log10 CFU/g bone, with this bacterial load remaining stable after 3 weeks of infection (4.9 ± 1.4 log10 CFU/g bone). Vancomycin monotherapy was the most slowly bactericidal treatment, whereas ceftaroline monotherapy was the most rapidly bactericidal treatment. The addition of rifampin significantly increased the bacterial reduction for vancomycin, linezolid, and daptomycin. All tibias were sterilized after 2 weeks of treatment except for animals receiving vancomycin or daptomycin alone (66.6% and 50% of sterilization, respectively). These results show that ceftaroline and linezolid alone remain good options in the treatment of MRSE osteitis without implant. The combination with rifampin increases the antibiotic effect of vancomycin and daptomycin lines.

A new sequential animal model for infection-related non-unions with segmental bone defect.

BACKGROUND: The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects. METHODS: After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 103 CFU Staphylococcus aureus (infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis. RESULTS: We developed and presented a new two-stage non-union animal model through a targeted S. aureus infection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and non-infected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculated S. aureus strain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the µ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001). CONCLUSIONS: We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.

New perspectives on traumatic bone infections.

In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.

Interferon-γ and interleukin-12 production in relation to gene polymorphisms in bacillus Calmette-Guérin osteitis.

BACKGROUND: Interferon-γ (IFN-γ) and interleukin-12 (IL-12) play a crucial role in the defense against mycobacteria, and in the response to bacillus Calmette-Guérin (BCG) vaccination. We have previously reported clinical and outcome data of 222 BCG osteitis cases diagnosed in 1960-1988 in Finland. The immunological and genetic reports have been based on 132 blood samples obtained in 2007-2008. METHODS: We compared IFNγ rs2430561 and rs35314021, IL12A rs568408 and rs2243115, and IL12B rs3212227 single-nucleotide polymorphisms (SNP) between 132 BCG osteitis patients and 99 population-based controls. In addition, stimulated production of IFN-γ and IL-12 in cell culture was evaluated in relation to the presence of IFNγ and IL12 wild versus variant genotypes, respectively. RESULTS: The distributions of IFNγ rs2430561, IFNγ rs35314021, IL12A rs568408, IL12A rs2243115 and IL12B rs3212227 SNP did not differ between BCG osteitis patients and Finnish population-based controls. For IFNγ rs2430561, IFNγ rs35314021 and IL12A rs2243115, the negative result was confirmed by comparing the minor allele frequencies (MAF) in BCG osteitis cases with those in the publicly available genome aggregation database, including data for 3,472 Finnish persons. Instead, for IL12A rs568408 and IL12B rs3212227, the comparison of MAF in BCG osteitis cases with those in population-based and in aggregation-based controls gave conflicting results. The presence of the wild versus variant genotype had no significant association with IL-12 or IFN-γ production in BCG-stimulated cell cultures. CONCLUSION: IFNγ gene polymorphisms did not show any association with BCG osteitis after newborn vaccination.

Melioidosis mimicking tuberculous vertebral osteitis: Case report and review of literature.

Whitmore's disease or melioidosis is an infectious disease caused by Burkholderia pseudomallei. The reported cases are but the tip of the iceberg. This pathogenic saprophyte is commonly found in wet soil and water. An accidental or occupational exposure (in field workers, farmers, gardeners or villagers) to B. pseudomallei contaminated soil or pooled water is the primary source of infection. Neurosurgeons need to consider this as a possible rare cause of back pain and possible neurological deterioration. A diabetic type 2 rice farmer with severe lumbago and fever, misdiagnosed as vertebral tuberculous osteitis based on his radiological findings, was confirmed to harbour Burkholderia Pseudomallei, which was diagnosed using laboratory cultures. He made a remarkable recovery with antibiotic therapy. The empiric anti-tuberculous (ATT) drugs were stopped. The rare differential diagnosis of melioidosis should be thought of in diabetic patients with a psoas abscess and vertebral osteitis, especially in rice farmers from endemic regions that includes India.

Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study.

Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1-24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.

Bone and joint infections by Mucorales, Scedosporium, Fusarium and even rarer fungi.

Mucorales, Scedosporium and Fusarium species are rarely considered as cause for bone and joint infections. However, these moulds are emerging as important fungal pathogens in immunocompromised and immunocompetent patients. Typical pre-disposing host conditions are immunosuppression and diabetes. Most common causative pathogens are Mucorales followed by Scedosporium and Fusarium. Acremonium and Phialemonium species are rare but some case reports exist. MRI is the gold standard imaging technique. Tissue specimens obtained as aspirates, imaging guided biopsy or open surgery need mycological and histopathological work-up for genus and species identification. Multimodal treatment strategies combine surgical debridement, drainage of joints or abscesses, removal of infected prosthetic joints and systemic antifungals. The treatment of mucormycosis is polyene based and may be combined with either posaconazole or - in rare cases - caspofungin. As Scedosporium species are intrinsically resistant to polyenes and azoles show absence of in vitro activity, voriconazole plus synergistic treatment regimens become the therapeutic standard. In fusariosis, fungal susceptibility is virtually impossible to predict, so that combination treatment of voriconazole and lipid-based amphotericin B should be the first-line strategy while susceptibility results are pending. In the absence of randomized controlled trials, infections due to the above moulds should be registered, e.g. in the registries of the European Confederation of Medical Mycology (ECMM).

First isolation of Clostridium indolis in a patient with chronic osteitis: a case report and literature review of human infections related to Clostridium saccharolyticum group species.

Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.

[Syphilitic osteitis in an HIV-negative patient]. / Ostéite syphilitique chez un patient séronégatif pour le VIH.

BACKGROUND: Secondary syphilis with skeletal involvement is rare; herein we report a case concerning an HIV-negative patient. PATIENTS AND METHODS: During the course of secondary syphilis, a 28-year-old male homosexual, HIV-negative and with no medical history, presented intense and localized headaches persisting despite three weeks of antibiotic therapy. Bone scintigraphy revealed three bone lesions evocative of syphilitic osteitis, for which prolonged antibiotic therapy was instituted. DISCUSSION: Few cases of syphilitic osteitis have been described in the recent literature and these are linked to haematogenous diffusion of Treponema pallidum. Skeletal disease is suggested when febrile bone pain is present. Bone scintigraphy remains the best diagnostic tool and treatment comprises prolonged penicillin G or ceftriaxone.

A new animal model for delayed osseous union secondary to osteitis.

BACKGROUND: The treatment of infection-related delayed bone unions is still very challenging for the orthopedic surgeon. The prevalence of such infection-related types of osteitis is high in complex fractures, particularly in open fractures with extensive soft-tissue damage. The aim of this study was to develop a new animal model for delayed union due to osteitis. METHODS: After randomization to infected or non-infected groups 20 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia. After intramedullary inoculation with staphylococcus aureus (10(3) CFU) fracture stabilization was done by intramedullary titanium K-wires. After 5 weeks all rats were euthanized and underwent biomechanical testing to evaluate bone consolidation or delayed union, respectively. Micro-CT scans were additionally used to quantitatively evaluate the callus formation by the score of Lane and Sandhu. Blood samples were taken to analyze infectious disease markers (day 1, 14 and 35). RESULTS: Biomechanical testing showed a significant higher maximum torque in the non-infected group 5 weeks postoperatively compared with the infected group (p < 0.001). According to the Lane and Sandhu score a significantly higher callus formation was found in the non-infected group (p < 0.001). Similarly, the leucocyte count in the infected group was significantly higher than in the non-infected group (p < 0.05). CONCLUSIONS: Here we have established a new animal model for delayed osseous union secondary to osteitis. The animal model appears to be appropriate for future experimental studies to test new therapeutic strategies in these difficult to treat bone healing complications.

[Osteoarticular pneumococcal infections observed in a tertiary hospital over a period of 11 years]. / Infección osteoarticular neumocócica en un hospital terciario durante un período de 11 años.

INTRODUCTION: Osteoarticular pneumococcal infection is an infrequent complication of pneumococcal bacteremia, due to the advances in antibiotic therapy and in the pattern of immunization. METHODS: A retrospective study was conducted on patients diagnosed with osteoarticular pneumococcal infection between January 2003 and December 2013 in the University Hospital Marqués de Valdecilla in Santander. RESULTS: Five out of 321 patients diagnosed with pneumococcal bacteremia had osteoarticular infection. All of them had at least one chronic underlying disease and had been immunized according to the standard vaccination schedule. Hip and vertebra were the most common joints involved. Outcome was favorable in all cases. CONCLUSIONS: The clinical findings of pneumococcal osteoarticular infection should be borne in mind. Its optimal prevention in high-risk patients should include the 13V conjugate vaccine.

[Mycetoma of the foot: a case report]. / Mycétome actino-mycosique du pied, à propos d'un cas.

Mycetoma is a chronic inflammatory cutaneous and subcutaneous pathology caused by either a fongic (eumycetoma) or bacterial (actinomycetoma) infection, which lead to a granulomatous tumefaction with multiple sinuses. When localized in the foot this infection is named "Madura foot". This infection is endemic to tropical and subtropical regions and rarely occurs in western countries. A historical case in Europe of a foot mycetoma evolving since 20 years without any treatment is presented. A histopathologic diagnosis of actinomycetoma has been done in 1987. The patient presented a severe Staphylococcus aureus chronic osteitis leading to a trans-tibial amputation. This case allows to present this infection which, even if rarely presented in France, can be meet especially among a migrant's population.

[Profile of non-traumatic osteoarticular diseases in elderly black Africans: about 157 cases seen in Abidjan]. / Profil des affections ostéoarticulaires des sujets ages noirs africains : A propos de 157 cas vus à Abidjan.

BACKGROUND: The aging of the world population is a phenomenon that is growing progressively. Specific knowledge of osteoarticular disorders in the elderly in black Africa seems limited. AIM: Describe the epidemiological, clinical and etiological characteristics of non-traumatic osteoarticular disorders in elderly black Africans. METHODS: Retrospective and descriptive study concerning black africans patients aged 60 years and over hospitalized in the department of Rheumatology of hospital center of Cocody (Abidjan) in a period of 7 years from January 2000 to December 2007. Were included, 157 records of black africans patients, suffering from a osteoarticular disorder non traumatic with an accurate diagnosis. A structured questionnaire was used to gather epidemiological, clinical and etiological characteristics. RESULTS: The prevalence of elders was 5% of all patients seen in the period of study. The average age was 67 years with the predominance of women (59,7%) and sex-ratio was 0,68. Housewives were predominant (40,6%). The reason for hospitalization was a pain from spine (85,8%) dominated by common low back pain (84,4%). Fever (51,9%) and impaired general health (53.4%) were dominant extraarticular signs. The main etiologies were degenerative (50.5%) with a predominance of common low back pain (38.2%), followed by bacterial osteitis and/or bacterial arthritis (20.5%) and malignancies (hematologic malignancies and metastasis of cancer) in 15.9% of cases. Degenerative pathology was significantly observed in females (p=0.004). CONCLUSION: Non-traumatic osteoarticular diseases in elderly black africans are little frequent in Abidjan and are dominated by degenerative diseases of spine.

First human case of Fastidiosipila sanguinis infection.

Fastidiosipila sanguinis is a Gram-positive anaerobic coccus. We report the first case of osteitis implicating this species. The strain was accurately identified by 16S rRNA sequence analysis, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification having failed. The reservoir remained unclear; an endogenous origin is suspected.

Bone and joint infections due to anaerobic bacteria: an analysis of 61 cases and review of the literature.

The diagnosis of anaerobic bone and joint infections (BJI) were underestimated before the advent of molecular identification and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We report 61 cases of anaerobic infections based on our 4-year experience with the management of BJI. A total of 75% of cases were post-surgical infections, associated with osteosynthesis devices (65%). Early infections occurred in 27% of cases, delayed infections in 17.5% of cases, and late infections in 55% of cases. We recorded 36 species of 93 anaerobic strains using MALDI-TOF MS (91) and molecular methods (2). We identified 20 strains of Propionibacterium acnes, 13 of Finegoldia magna, six of Peptoniphilus asaccharolyticus, and six of P. harei. Polymicrobial infections occurred in 50 cases. Surgical treatment was performed in 93.5% of cases. The antibiotic treatments included amoxicillin (30%), amoxicillin-clavulanic acid (16%), metronidazole (30%), and clindamycin (26%). Hyperbaric oxygen therapy was used in 17 cases (28%). The relapse rate (27%) was associated with lower limbs localization (p = 0.001). P. acnes BJI was associated with shoulder (p = 0.019), vertebra (p = 0.021), and head flap localization (p = 0.011), and none of these cases relapsed (p = 0.007). F. magna BJI was associated with ankle localization (p = 0.014). Anaerobic BJI is typically considered as a post-surgical polymicrobial infection, and the management of this infection combines surgical and medical treatments. MALDI-TOF MS and molecular identification have improved diagnosis. Thus, physicians should be aware of the polymicrobial nature of anaerobic BJI to establish immediate broad-spectrum antibiotic treatment during the post-surgical period until accurate microbiological results have been obtained.

Control of an outbreak due to orthopedic infections caused by Enterobacteriaceae producing IMP-4 or IMP-8 carbapenemases.

OBJECTIVE: To investigate control of an outbreak due to orthopedic infections caused by Enterobacteriaceae producing IMP carbapenemases. METHODS: The sporadic orthopedic infections with Enterobacteriaceae producing carbapenemase (CPE) were retrospectively analyzed in a Chinese tertiary care hospital from November 2010 to September 2012. RESULTS: The CPE were isolated from four distinct orthopedic patients, three patients infected with Enterobacter cloacae while the other with Klebsiella oxytoca. All strains were resistant to almost all the conventional antimicrobial. The strains produced IMP-4 type detected in the two early patients, while other strains could produce IMP-8 type. All of the four patients had ever undergoing invasive surgical procedure, and three of them were given fluoroquinolones for anti-infection treatment while the other patients was treated with meropenem. Ultimately, all patients were cured and discharged, without outbreak of nosocomial infection caused by CPE. CONCLUSION: Our study shows that strict infection control plays an important role in limiting dissemination of Enterobacteriaceae producing IMP carbapenemase. In addition, reasonable supporting treatment and disinfection protection seems to be more effective for the infection of strains.

Efficacy of lysostaphin-coated titanium plates on implant-associated MRSA osteitis in minipigs.

PURPOSE: The growing incidence of implant-associated infections (IAIs) caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance to antibiotics requires new therapeutic strategies. Lysostaphin has been shown to eliminate this biofilm. Own studies confirm the effectiveness in a murine model. The current study characterizes the effects of lysostaphin-coated plates in an IAI minipig model. METHODS: The femur of 30 minipigs was stabilized with a five-hole plate, a bone defect was created, and in 20 cases methicillin-resistant Staphylococcus aureus was applied. Ten animals served as control group. After 14 days, local debridement, lavage, and plate exchange (seven-hole plate) were performed. Ten of the infected minipigs received an uncoated plate and 10 a lysostaphin-coated plate. On day 84, the minipigs were again lavaged, followed by euthanasia. Bacterial load was quantified by colony-forming units (CFU). Immunological response was determined by neutrophils, as well as interleukins. Fracture healing was assessed radiologically. RESULTS: CFU showed significant difference between infected minipigs with an uncoated plate and minipigs with a lysostaphin-coated plate (p = 0.0411). The infection-related excessive callus formation and calcification was significantly greater in the infected animals with an uncoated plate than in animals with a lysostaphin-coated plate (p = 0.0164/p = 0.0033). The analysis of polymorphonuclear neutrophils and interleukins did not reveal any pioneering findings. CONCLUSION: This study confirms the minipig model for examining IAI. Furthermore, coating of plates using lysostaphin could be a promising tool in the therapeutic strategies of IAI. Future studies should focus on coating technology of implants and on translation into a clinical model.

Polyostotic osteitis in secondary syphilis in an HIV-infected patient.

We herein describe a case of secondary syphilis in a patient with HIV infection that presented with an unusually diffuse polyostotic osteitis with skull involvement. Syphilis has to be added to the differential diagnosis of extensive inflammatory bone pain in patients at risk, especially if pain worsens at night.