Antibiotic cement-coated rigid locked nails in infected femoral and tibial nonunion. Reoperation rates of commercial versus custom-made nails.

INTRODUCTION: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails. METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates. RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036). CONCLUSION: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement. LEVEL OF EVIDENCE: III comparative, observational, non-randomized.

Osteomielite: perfil epidemiológico e desfechos verificados em pacientes internados em um hospital público de Curitiba / Osteomyelitis: epidemiologic profile and outcomes of inpatients of a public hospital in Curitiba

Introdução: Osteomielite é inflamação aguda ou crônica de ossos trabeculares ou corticais, periósteo, medula óssea e tecidos moles próximos. É classificada pela localização dentro do osso, extensão da dispersão e fonte de infecção. Objetivo: Avaliar os aspectos epidemiológicos dos pacientes internados com osteomielite e analisar relação entre o tempo de internamento e fatores correlatos.Métodos: Estudados dados de 33 pacientes de uma seleção inicial de 42 prontuários. Resultados: O grupo de 0 a 20 anos com 8 (24,4%) pacientes ficou 18 ± 24 dias, 13 (39,4%) adultos jovens (21 a 40 anos): 12,3 ± 12,4 d; 6 (18,1%) adultos (41 a 60 anos) e 6 (18,1%) >60 anos receberam cuidados hospitalares por 31,8 ± 36 e 19,6 ± 15,8 dias respectivamente. O periodo maior de permanência foi de 91 dias. O etilismo (6%), o tabagismo (6%) e o diabetes (6%) foram as comorbidades mais encontradas. A mortalidade foi de 15%, sendo que 60% eram usuários de álcool. O perfil epidemiológico também mostrou o predomínio do sexo masculino na faixa de 21 a 40 anos e o principal agente infeccioso encontrado foi S. aureus. Conclusão: A alta taxa de mortalidade em indivíduos maiores de 50 anos, com maior permanência hospitalar e presença de comorbidades como o etilismo e diabetes mellitus alerta para a necessidade de planejamento estratégico visando intervenções que diminuam prejuízos tanto para o paciente quanto para o sistema de saúde.

Introduction: Osteomyelitis is an acute or chronic inflammation of trabecular or cortical bones, periosteum, bone marrow, and nearby soft tissue. It is classified by location within the bone, extent and source of infection. Objective: Assess the epidemiological aspects of hospitalized patients with osteomyelitis and analyze the relationship between length of stay and correlated factors. Methods: Data were collected from 33 patients from an initial selection of 42. Results: The groups were arranged as follows: 8 (24.4%) individuals from 0-20 yo and with a hospital stay of 18 ± 24 d; 13 (39.4%) young adults (21-40 yo) and 12.3 ± 12.4 d; 6 (18.1%) adults (41-60 yo) and 31.8 ± 36 d; and 6 (18.1%) over 60 yo who were under hospital care for 19.6 ± 15.8 d. The longest period of hospital stay was 91 days. Alcoholism (6%), smoking habits (6%) and diabetes (6%) were the most common comorbidities. Mortality rate was 15%, among which 60% were alcohol users. The epidemiologic profile also showed that the majority of the hospitalized were males between the ages 21-40 yo and the most common infective agent was S. aureus. Conclusion: the high mortality rate in individuals over 50, with comorbidities and longer hospital stays highlights the need for strategic planning yielding interventions that diminish harm to the patients and the health system.

[Infected nonunion: diagnostic and therapeutic work-up]. / Infizierte Pseudarthrose: diagnostischer und therapeutischer Ablauf.

BACKGROUND: Septic nonunion is one of the major complications in fracture healing. The challenge is to identify the infection as the cause of nonunion first and then to achieve healing of the infection and the bone. OBJECTIVE: Because of the more heterogeneous appearance of an infected nonunion, the prevalence of germ detection in surgical nonunion revision is often underestimated. MATERIAL AND METHODS: In a retrospective study between 2010 and 2017, 86 patients with radiologically confirmed femoral shaft nonunion without clinical evidence and unremarkable medical history of a florid infection as the cause of nonunion, who had undergone primary single-stage surgical nonunion revision were analyzed. At least four intraoperatively obtained samples were evaluated for microbiological diagnosis. A distinction was made between tissue samples with subsequent 48­h short-term incubation and tissue samples with 14-day long-term cultivation. The finding "germ detection" was made if at least two of the samples demonstrated bacterial growth. RESULTS: In 18 of 86 patients with a nonunion preoperatively judged to be aseptic, positive bacterial evidence was obtained after short-term incubation. After long-term cultivation, positive bacterial detection was possible in 38 of 86 patients with a femoral shaft nonunion initially classified as aseptic. Regarding potential risk factors, the two groups demonstrated no relevant differences. In 29 patients, 1 pathogen was isolated from the obtained samples, whereas in the remaining 9 patients, a mixed culture with an average of 2.9 ± 0.5 different bacteria was detected. Identification revealed mainly low-virulence bacteria, most commonly Staphylococcus epidermidis. CONCLUSION: If the preoperative diagnostics including clinical, laboratory and radiological examination as well as a careful anamnesis reveal indications of a possible infectious event, the surgical nonunion revision should be performed in two stages with specimen collection before definitive nonunion revision. For microbiological diagnosis, several representative tissue samples should independently be obtained from the nonunion site and incubated for 14 days. Only in the absence of evidence of septic nonunion is a single-stage procedure suggested.

Chronic recurrent multifocal osteomyelitis in pediatrics in a tertiary center / Osteomielitis crónica multifocal recurrente en pediatría en un hospital terciario

ABSTRACT Introduction: Chronic recurrent multifocal osteomyelitis (CRMO), also called chronic non-bacterial osteomyelitis, is an autoinflammatory disease characterized by bone involvement, recurrent flare-ups, and the lack of microbiological isolation. It is a diagnosis of exclusion, and the fundamental basis of treatment is non-steroidal anti-inflammatory drugs. The objective of the study is to describe our experience as a result of three girls diagnosed with CRMO, highlighting the clinical presentation, the findings in the complementary tests, the treatment, and the evolution of the disease. Patients and methods: Retrospective chart review of children with CRMO in the last 5 years, being followed-up in a pediatric rheumatology clinic in a tertiary center. Results: The cases are presented of 3 patients diagnosed with CRMO, all of them young girls, with a mean age of 11 years, who consulted due to pain and functional impotence. It was in single location in two cases, and the other with several sources of pain, at cervical and lumbar level, associated with weakness of the upper and lower limbs. Two of the cases received antibiotic treatment. One girl responded to treatment with anti-inflammatory drugs and another required combining corticosteroids. The remaining case, in addition to anti-inflammatory drugs and corticosteroids, required intravenous pamidronate. Conclusions: With this study, and despite the small sample size, the aim was to highlight the importance of this, in many cases unknown and underdiagnosed, pathology, and to stress the importance of establishing a diagnostic and therapeutic protocol for the correct approach to this disease.

RESUMEN Introducción: La osteomielitis crónica multifocal recurrente (OCMR), también conocida como osteomielitis crónica no bacteriana, es una enfermedad autoinflamatoria caracterizada por afectación ósea, de curso en brotes y en ausencia de aislamiento microbiológico. El diagnóstico es de exclusión y el pilar fundamental del tratamiento son los antiinflamatorios no esteroideos (AINES). El objetivo del estudio es describir nuestra experiencia de tres niñas diagnosticadas de OCMR, destacando la presentación clínica, los hallazgos en las pruebas complementarias, el tratamiento y la evolución de la enfermedad. Pacientes y métodos: Revisión retrospectiva de historias clínicas de niños diagnosticados de OCMR en los últimos cinco años, en seguimiento en consulta de reumatología pediátrica de un hospital terciario. Resultados: Presentamos tres pacientes diagnosticadas de OCMR, todas ellas mujeres adolescentes, con media de edad de 11 años. Consultaron por dolor e impotencia funcional, dos en una única localización y la otra por varios focos de dolor, a nivel cervical y lumbar, asociando debilidad de miembros superiores e inferiores. Con respecto al tratamiento, dos recibieron tratamiento antibiótico. Una niña respondió a antiinflamatorios; otra precisó asociar corticoides, y la restante, además de antiinflamatorios y corticoides, necesitó pamidronato intravenoso. Conclusiones: Con este estudio y a pesar del pequeño tamaño muestral, se pretende resaltar la importancia de esta patología, en muchos casos desconocida e infradiagnosticada, e insistir en la importancia de establecer un protocolo diagnóstico y terapéutico para su correcto abordaje.

Brucellosis and sacroiliitis: A differential diagnosis to keep in mind / Sacroiliitis por brucelosis: Un diagnóstico diferencial para tener presente

ABSTRACT Brucellosis is a zoonosis that causes a multi-organ granulomatous infection. It has diverse and non-specific clinic features that can make diagnosis difficult. Medical personnel often do not recognize it early. Delayed treatment is associated with high morbidity and even mortality. Its timely diagnosis requires a high index of suspicion. The case is presented of a 35-year-old male zootechnologist, previously healthy, with a progressive picture of two months of evolution of irradiated low back pain to the left hip, nocturnal diaphoresis, and unintentional weight loss. Elevation of acute phase reactants was documented and magnetic resonance imaging found signs of iliopsoas tendonitis and inflammatory changes in the left sacroiliac joint. The IgG and IgM antibodies using an immunoassay forbrucella were positive. After establishing antibiotic treatment, a marked clinical improvement, with resolution of the inflammatory process was evident.

RESUMEN La brucelosis es una zoonosis que genera una infección granulomatosa multiorgánica. Tiene una clínica diversa e inespecífica que puede hacer difícil el diagnóstico. Con frecuencia, el personal médico no la reconoce de forma temprana. El retraso en el tratamiento se asocia con una gran morbilidad e incluso mortalidad. Su diagnóstico oportuno requiere un alto índice de sospecha. Se presenta el caso de un hombre de 35 arios, zootecnista, previamente sano, con un cuadro progresivo de dos meses de evolución de dolor lumbar irradiado a cadera izquierda, diaforesis nocturna y pérdida no intencional de peso. Se documentó elevación de reactantes de fase aguda y en la resonancia magnética se encontraron signos de tendinitis del psoas y cambios inflamatorios en la articulación sacroilíaca izquierda. Los anticuerpos IgG e IgM por inmunoensayo para Brucella fueron positivos, y luego de instaurar tratamiento antibiótico se evidenció marcada mejoría clínica con resolución del proceso inflamatorio.

Metodología de la gammagrafía con leucocitos marcados en el diagnóstico de infección osteoarticular protésica/no protésica: ¿análisis visual o semicuantitativo? ¿Protocolo de uno o 2 días? / Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

Objetivo: Como hay poca literatura sobre el tema, nos propusimos comparar la utilidad diagnóstica del análisis semicuantitativo versus el análisis visual en la escintigrafía de glóbulos blancos etiquetados (WBCS) para la infección osteoarticular. Se evaluaron protocolos de uno y dos días, en particular en los dispositivos ortopédicos.Material y métodos: Estudio prospectivo de 79 pacientes consecutivos con sospecha de infección osteoarticular. En todos los pacientes, la SCBM se realizó a los 30 min, 4 h, 8 h y 24 h. Las imágenes se analizaron agrupándolas en dos protocolos: protocolo de un día (los expertos evaluaron imágenes planas de 30 min, 4 h y 8 h) y protocolo de dos días (los expertos evaluaron imágenes planas de 30 min, 4 h y 24 h). Las imágenes planas se interpretaron cualitativa y semicuantitativamente y también se compararon agrupando a los pacientes con y sin dispositivos ortopédicos. Para determinar qué valor de corte de la variación porcentual podía predecir la infección osteoarticular, se calcularon múltiples valores de corte en ambos protocolos a partir del índice de Youden. Tres lectores ciegos analizaron las imágenes.Resultados: Comparando el diagnóstico final, el análisis visual del protocolo de un día proporcionó mejores resultados con una sensibilidad del 95,5%, una especificidad del 93% y una precisión diagnóstica del 93,7% (p < 0,01) que el protocolo de dos días con valores del 86,4%, 94,7% y 92,4%, respectivamente (p < 0,01). Para el análisis semicuantitativo, el protocolo de un día también obtuvo mejores resultados con una sensibilidad del 72,7%, una especificidad del 78,9% y una precisión del 77,2% (p < 0,01) que el protocolo de dos días (sin resultados significativos; p = 0,14), especialmente en el grupo de pacientes con aparatos ortopédicos (sensibilidad del 100%, especificidad del 79,5% y precisión del 82,7%; p < 0,01)

Objective: As scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices.Material and methods: Prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images.Results: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (P<.01) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (P<.01). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (P<.01) than two-day-protocol (no significant results; P=.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; P<.01).Conclusions: Most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful

Paediatric osteoarticular infections caused by staphylococcus aureus producing panton-valentine leucocidin in morocco: Risk factors and clinical features.

OBJECTIVE: We aimed to estimate the prevalence of Staphylococcus aureus producing Panton-Valentine leucocidin (PVL) isolated from children diagnosed with osteoarticular infections (OAIs), and to examine risk factors and clinical features. METHODS: This prospective study was conducted from January 2017 to December 2018. All hospitalised children diagnosed with S. aureus OAI are included. Blood cultures, articular fluids, synovial tissues and/or bone fragments were collected for bacteriological culture. Antimicrobial susceptibility tests were determined by disk diffusion method. Genes encoding methicillin resistance (mecA) and PVL virulence factors (luk-S-PV and luk-F-PV) were detected by multiplex polymerase chain reaction. The demographic, clinical, laboratory, radiographic and clinical features were reviewed prospectively from medical records. RESULTS: A total of 37 children with S. aureus OAIs were included, 46% of them have PVL-positive infection and 70.6% were male. The mean age was 8.12 years (±4.57), and almost were from rural settings (76.5%). Children with Staphylococcus aureus producing Panton-Valentine leucocidin (SA-PVL) were significantly associated with type of infection (P = 0.005), location of infection (P = 0.037) and abnormal X-ray (P = 0.029). All strains SA-PVL+ are sensitive to methicillin, but one strain SA-PVL negative was methicillin-resistant S. aureus, confirmed by gene mecA positive. CONCLUSION: The prevalence of S. aureus infections producing PVL toxin was high in OAIs amongst Moroccan children, mainly due to methicillin-susceptible S. aureus. Type and location of infections and abnormal X-ray were significantly associated with SA-PVL. Routine diagnostic testing of PVL-SA, continuous epidemiological surveillance and multidisciplinary management of OAI is essential to prevent serious complications.

Lysosomal alkalization to potentiate eradication of intra-osteoblastic Staphylococcus aureus in the bone and joint infection setting.

OBJECTIVES: Beyond intracellular penetration, acidic lysosomal pH might affect the intracellular activity of some antimicrobials. This study evaluated the ability of lysosomotropic alkalizing agents to potentiate the antimicrobial eradication of an intra-osteoblastic Staphylococcus aureus reservoir in the setting of bone and joint infection (BJI). METHODS: MICs of 16 anti-staphylococcal molecules active against methicillin-sensitive S. aureus (MSSA) were evaluated at pH 5 and pH 7. Additionally, the lysosomal alkalizing potential (spectrofluorometry) and cytotoxicity (MTT assay) of hydroxychloroquine, amantadine and ammonium chloride were assessed. The results led to further investigation of clindamycin, cotrimoxazole, daptomycin and levofloxacin-alone or in combination with hydroxychloroquine-in an in vitro model of osteoblast infection. The impact of hydroxychloroquine on autophagy was finally investigated using Western blot detection of two autophagic flux indicators, the LC3 membrane protein and the SQSTM1 cargo protein. RESULTS: Daptomycin, cotrimoxazole, clindamycin and levofloxacin alone significantly decreased the intracellular staphylococcal reservoir (5.12 log10 CFU/100 000 cells) by 0.14 (95%CI 0.01-0.34), 0.25 (95%CI 0.12-0.43), 0.16 (95%CI 0.004-0.39) and 1.18 (95%CI 1.04-1.38) log10 CFU/100 000 cells, respectively (p < 10-3). Adding hydroxychloroquine (20 mg/L) increased intralysosomal pH from 4.8 to 7, and concomitantly the inoculum of each antimicrobial was reduced by 0.50 (95%CI 0.30-0.84), 0.73 (95%CI 0.59-0.96), 0.59 (95%CI 0.46-0.78) and 1.8 (95%CI 1.66-2.1) log10 CFU/100 000 cells, respectively (p < 10-4). Cellular levels of LC3II and SQSTM1 showed that hydroxychloroquine has direct activity on the autophagic flux, fostering the eradication of intracellular S. aureus by antimicrobials. CONCLUSION: At high concentrations, hydroxychloroquine used as an adjuvant to antimicrobials improves eradication of an S. aureus intra-osteoblastic reservoir in our in vitro cell infection model. These findings advocate further in vivo evaluation of alkalization efficacy and tolerance in S. aureus BJI.

An injectable gellan gum-based hydrogel that inhibits Staphylococcus aureus for infected bone defect repair.

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against Staphylococcus aureus growth and biofilm formation in vitro. We successfully established an infected calvarial defect rat model. Bacterial colony numbers were significantly lower in tissues surrounding the bone in rats of the GG/nHA/CHX group after debride surgery and hydrogel implantation in the defect regions than in rats of the blank group. Rats in the GG/nHA/CHX group exhibited significantly increased new bone formation compared to those in the blank group at 4 and 8 weeks. These findings indicate that gellan gum-based hydrogel with nHA/CHX can accelerate the repair of infected bone defects.

Past and Future of Phage Therapy and Phage-Derived Proteins in Patients with Bone and Joint Infection.

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being "GMP-like") targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally "phage therapy 2.0" has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial-academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

Anaerobio osteomyelitis. A rare condition in children / Osteomielitis por anaerobios. Una entidad poco frecuente en pediatría

ABSTRACT Osteoarticular infections due to anaerobes are very rare in children, with the Fusobacterium genus being the most frequently isolated. The course is usually subacute and, although there are predisposing factors described, most patients do not present with them. Generally, joint fluid cultures are sterile since these microorganisms are very sensitive to contact with oxygen, so they require specific culture media. All of the above causes the diagnosis to be delayed, increasing the risk of long-term sequelae. However, the prognosis improves when treatment is started early. The case is presented of a 10-year-old patient who was admitted for 30 days due septic arthritis of the right hip caused by Fusobacterium nucleatum During the admission, he required three surgical interventions, and completed 6 weeks of effective antibiotic therapy, with a good outcome and remaining asymptomatic at the current time.

RESUMEN Las infecciones osteoarticulares por anaerobios son muy raras en los niños, siendo el género Fusobacterium el que se aisla con más frecuencia. El curso suele ser subagudo y, aunque hay factores predisponentes descritos, la mayoría de los pacientes no los presenta. Generalmente, los cultivos de liquido articular son estériles ya que estos microorganismos son muy sensibles al contacto con el oxigeno, por lo que precisan medios de cultivo específicos. Todo lo anterior hace que el diagnóstico se retrase y que el riesgo de secuelas a largo plazo aumente. Sin embargo, el pronóstico mejora cuando el tratamiento se inicia de modo precoz. Por todo ello, presentamos el caso de un paciente de 10 anos con una artritis séptica de cadera derecha por Fusobacterium nucleatum que permaneció ingresado 30 dias. Durante el ingreso precisó 3 intervenciones quirúrgicas y cumplió 6 semanas de antibioterapia efectiva, con buena evolución; permanece asintomático en el momento actual.

Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.

Antibiotic cement plate composite structure internal fixation after debridement of bone infection.

An internal fixation composite structure of antibiotic cement plates was created. The aim of this study was to analyse the infection control effect of this structure when applied to treat a bone infection. We retrospectively analysed patients with bone infection admitted to our hospital between January 2013 and June 2019. After debridement, an antibiotic cement plate composite structure was used to fill and stabilize the defects. The treatment effect was evaluated at six months after surgery, and the infection control rate, factors associated with the recurrence of infection, and complications were analysed. If the patients had bone defects, the defect was repaired after infection control, and the infection control rate of all of the patients was re-evaluated at 12 months after surgery. A total of 548 patients were treated with this technique, including 418 men and 130 women. The infection sites included 309 tibias, 207 femurs, 16 radii and ulnae, 13 humeri, and 3 clavicles. After at least 6 months of follow-up, 92 patients (16.79%) had an infection recurrence and needed further treatment. The recurrence rate of the tibia was higher than that of the femur (P = 0.025). Eighty-nine out of 92 patients who relapsed underwent a second debridement with the same method, and the infection control rate after the second debridement was 94.71%. Complications included 8 cases of epidermal necrosis around the incision, 6 cases of internal fixation failure, and 30 cases of lower limb swelling. By the follow-up time of 12 months, another 6 patients had experienced recurrence of infection, and 4 cases were controlled after debridement. Finally, among all 548 cases, 7 patients remained persistently infected, and 6 underwent amputation. The infection control rate was 97.6% at the 1-year follow-up. The clinical efficacy of this new antibiotic cement plate composite structure for internal fixation after debridement of bone infection is stable and reliable.

First report of Kingella kingae diagnosed in pediatric bone and joint infections in Morocco.

BACKGROUND: The progress of diagnostic strategies and molecular methods improved the detection of Kingella kingae in bone and joint infections, and now, Kingella kingae is being increasingly recognized as the most frequent cause of bone and joint infection BJI in early childhood. The main objective of this prospective study is to report the frequency of Kingella Kingae in negative culture bone and joint pediatric infections, and to describe the clinical and biologic features of these children. METHODS: From December 2016 to June 2019, we selected all hospitalized patients with suspected BJI. When culture was negative on the fifth day, children under 10 years were subsequently included in the study, and PCR assay was performed systematically for researching K. kingae specific gene cpn60. Microbial culture and identification were made using standard bacteriological methods. The demographics, clinical, laboratory, radiographic and clinical features were reviewed from medical records. RESULTS: We enrolled 65 children with culture negative BJI, 46 of them having under 10 years old have been screened for the cpn60 gene. Thus, the gene encoding Kingella kingae was positive for 27 BJI cases (58.7%). The mean age of children was 3.02 years, 55.6% were aged 6 months-4 years and 29.6% of them were aged 5-10 years. The male to female ratio was 1.7 and 16 cases (59.26%) occurred during the fall-winter period. The most frequent BJI type was septic arthritis (77.8%) and the most affected sites were knee (51.9%) and hip (37.0%). We recorded a mild clinical picture with normal to mildly raised inflammatory markers. All patients had good clinical and functional outcomes, with no serious orthopedic sequelae.. CONCLUSION: K kingae is an important pathogen of culture-negative BJI in Moroccan children. PCR testing should be performed in culture-negative cases of children not only in the typical age range of 6 months to 4 years. When implemented in the routine clinical microbiology laboratory, a specific K. kingae PCR assay can provide a better diagnostic performance of BJI.

Antibacterial, conductive, and osteocompatible polyorganophosphazene microscaffolds for the repair of infectious calvarial defect.

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.

Prolonged cefazolin course for treatment of methicillin susceptible staphylococcus species infections and the impact on the emergence of multidrug-resistant bacteria during cloxacillin shortage.

OBJECTIVES: To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. METHODS: Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. RESULTS: Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. CONCLUSION: Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.

Adherence to oral antibiotic therapy in patients with bone and joint infection: A pilot study.

OBJECTIVES: The management of bone and joint infections (BJI) is complex and requires prolonged antimicrobial therapy. Few data exist on adherence to anti-infectious treatment other than HIV, and none on BJI, even though compliance is considered as a major determinant of clinical outcome. This work aimed at evaluating adherence to oral antimicrobial treatment in patients with BJI. PATIENTS AND METHODS: This is a prospective observational blinded pilot study evaluating adherence by a 6-item questionnaire at 6 weeks (W6) and 3 months (M3) post-surgery. The primary endpoint was the proportion of patients with high, moderate and poor adherence at W6. Secondary endpoints included change in adherence between W6 and M3, and the exploration of potential variables influencing adherence. RESULTS: Analysis was performed on 65 questionnaires obtained from 43 patients including 35 with device-associated BJI. At W6, 11 out of 34 patients were highly adherent to oral antibiotic therapy, 22 moderately adherent and 1 poorly adherent. There was no significant change in adherence to antibiotic therapy between W6 and M3. The only variable significantly associated with the level of adherence at W6 and M3 was the number of daily doses of antibiotic (P=0.04 and 0.02 at W6 and M3, respectively). CONCLUSIONS: This study provided a snapshot of patients' adherence in BJI. Adherence to antibiotic therapy appeared to be stable up to 3 months and a higher number of daily doses of antibiotic was associated with poorer adherence. These observations need to be confirmed in future large-scale studies using electronic pill monitoring systems.

Clinical, biological and bacteriological characteristics of osteoarticular infections in infants less than 12 months of age.

Aim: This retrospective study's objective was to evaluate osteoarticular infection in infants less than 12 months of age, with a particular focus on biological features and bacteriological etiology. Material & methods: We retrospectively reviewed the medical records of every infant younger than 12 months old admitted in our institution for a suspected osteoarticular infection between January 1980 and December 2016. Results: Sixty-nine patients records were reviewed, including eight neonates, 16 infants from 1 to 5 months old, and 45 from 6 to 12 months old. Conclusion: Neonates and infants aged from 6 to 12 months old were more exposed to infections. Staphylococcus aureus remained the main pathogen in children <6 months, whereas Kingella kingae has become the most frequently isolated microorganism in infants aged from 6 to 12 months old.

Anti-biofilm activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) isolated from human bone infection.

The presence of methicillin-resistant Staphylococcus aureus (MRSA) in bone infections difficults its treatment and is a sign of concern. The aim of this study was to evaluate in vitro activity of dalbavancin on pre-established adhered cells and 24 h old biofilms of MRSA strains isolated from a human bone infection. Thirty-three MRSA were isolated from osteomyelitis episodes. The antimicrobial susceptibility of these strains was assessed by the Kirby-Bauer disc diffusion method and the presence of resistance genes was screened by PCR. MRSA planktonic minimum inhibitory concentration and minimum bactericidal concentration were assessed. Minimum biofilm eradication concentration (MBEC) was performed by the microtiter biofilm formation assay. All 33 MRSA strains were classified as multidrug-resistant strains and susceptible to dalbavancin. Dalbavancin inhibited the growth of 54.6% and 52% of strains at the concentrations of 0.05 µg/mL and 1 µg/mL, respectively. The MBEC values up to 0.4 µg/mL demonstrated that dalbavancin was active against most strains in pre-established adhered cells and 24 h old biofilms. The current results show that dalbavancin is active against adhered cells and biofilms in vitro, suggesting that this antimicrobial agent may be an option for the treatment of bone infections caused by MRSA.