Inflammatory turmoil within: an exploration of autoinflammatory disease genetic underpinnings, clinical presentations, and therapeutic approaches.

Systemic autoinflammatory diseases (SAIDs) arise from dysregulated innate immune system activity, which leads to systemic inflammation. These disorders, encompassing a diverse array of genetic defects classified as inborn errors of immunity, are significant diagnostic challenges due to their genetic heterogeneity and varied clinical presentations. Although recent advances in genetic sequencing have facilitated pathogenic gene discovery, approximately 40% of SAIDs patients lack molecular diagnoses. SAIDs have distinct clinical phenotypes, and targeted therapeutic approaches are needed. This review aims to underscore the complexity and clinical significance of SAIDs, focusing on prototypical disorders grouped according to their pathophysiology as follows: (i) inflammasomopathies, characterized by excessive activation of inflammasomes, which induces notable IL-1ß release; (ii) relopathies, which are monogenic disorders characterized by dysregulation within the NF-κB signaling pathway; (iii) IL-18/IL-36 signaling pathway defect-induced SAIDs, autoinflammatory conditions defined by a dysregulated balance of IL-18/IL-36 cytokine signaling, leading to uncontrolled inflammation and tissue damage, mainly in the skin; (iv) type I interferonopathies, a diverse group of disorders characterized by uncontrolled production of type I interferons (IFNs), notably interferon α, ß, and ε; (v) anti-inflammatory signaling pathway impairment-induced SAIDs, a spectrum of conditions characterized by IL-10 and TGFß anti-inflammatory pathway disruption; and (vi) miscellaneous and polygenic SAIDs. The latter group includes VEXAS syndrome, chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis, Schnitzler syndrome, and Still's disease, among others, illustrating the heterogeneity of SAIDs and the difficulty in creating a comprehensive classification. Therapeutic strategies involving targeted agents, such as JAK inhibitors, IL-1 blockers, and TNF inhibitors, are tailored to the specific disease phenotypes.

Tricalcium phosphate-loaded injectable hydrogel as a promising osteogenic and bactericidal teicoplanin-delivery system for osteomyelitis treatment: An in vitro and in vivo investigation.

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (ß-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and ß-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements.

Analysis of epidemiological and clinical aspects in cases of fungal osteomyelitis caused by non-Candida species.

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.

Osteomyelitis by Microsporum canis and Staphylococcus spp. in cat (Felis catus) - case report.

BACKGROUND: Staphylococcus spp and Microsporum canis are zoonotic microorganisms which can cause infections and systemic diseases. The bone infection is usually caused by invasion of pathogen through the hematologic route. Mixed osteomyelitis caused by bacteria and fungi is rare, and to date, there have been no reports of mixed osteomyelitis with Staphylococcus spp. and Microsporum canis. CASE PRESENTATION: This essay reports an atypical presentation of mixed osteomyelitis (Staphylococcus spp. and Microsporum canis) in a domestic cat. A 15-month-old female Persian cat was presented to a veterinary service; the main complaint was the appearance of a nodule in the mandibular ventral rostral region. A radiographic exam performed on the animal showed proliferative and osteolytic bone lesions. The patient was submitted to a biopsy for histopathological evaluation, along with bacterial and fungal cultures. Results showed mixed osteomyelitis by Staphylococcus spp. and Microsporum canis. Microbial Sensitivity Test was performed to choose a more suitable treatment. Two surgical procedures were executed to resect and curette the lesion, and treatments with anti-inflammatory, antibiotic, and antifungal drugs were established, showing a positive clinical evolution. After 8 months of treatment, the patient's owner moved to a different city, and the animal was seen by other veterinarians, who followed along with the same treatment. However, due to complications and a diminishing quality of life over 4 years of diagnosis, the patient was euthanized. CONCLUSION: Given the above, mixed osteomyelitis is difficult to treat and can cause losses of life quality resulting death, especially in infections where M. canis is the agent causing the disease. Bacterial osteomyelitis is more frequently reported. But the lack of investigation of microorganisms other than bacteria, such as fungal cases, may imply in underdiagnosed cases. Treatment of osteomyelitis can be difficult considering the difficulties in isolating the pathological agent, resistance to the drug used, prolonged treatment time, and cost.

Bone and joint infection complicated with sepsis in neonates and infants under three months of age.

OBJECTIVE: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. METHODS: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. RESULTS: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. CONCLUSION: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

Osteomielitis crónica no bacteriana: a propósito del caso de una adolescente / Chronic non-bacterial osteomyelitis: clinical case study of an adolescent / Osteomielite crônica não bacteriana: relato de caso de um adolescente

Introducción: la osteomielitis crónica no bacteriana (CNO) es una enfermedad autoinflamatoria ósea y se manifiesta con un amplio espectro clínico, presentándose con afectación monofocal o multifocal. Dado que no es siempre multifocal o recurrente, o ambas, fue propuesto que CNO se utilice como un término que comprenda a todas las presentaciones y la osteomielitis multifocal crónica recurrente (CRMO) se utilice para formas recurrentes y multifocales. Objetivo: presentar un caso clínico inédito, de baja prevalencia a nivel mundial, en una adolescente portadora de una enfermedad autoinflamatoria ósea que planteó desafíos diagnósticos y terapéuticos. Descripción: adolescente, mujer, 11 años, previamente sana que se presentó con dorso-lumbalgia invalidante de un mes de evolución, sin otra sintomatología asociada. Tras varias consultas en emergencia, ingresa a planta de internación pediátrica del Hospital Central de las Fuerzas Armadas (HCFFAA) en octubre de 2021. Resonancia nuclear magnética (RNM) de columna evidencia foco de edema óseo en cuerpo de T11, hemograma normal; VES 48 mm/h, ANA, anti-DNA, FR y HLA B27 negativos. Resultados: luego de descartar procesos infecciosos, oncohematológicos y una vez obtenido el resultado de una biopsia por punción ósea que evidenciaba elementos inflamatorios, se llegó al diagnóstico de CNO en el mes de febrero de 2022, tiempo récord comparando este caso con la literatura internacional. El diagnóstico de esta entidad clínica promedio a nivel mundial es de 12 meses.

Introduction: chronic Non-Bacterial Osteomyelitis (CNO) is an autoinflammatory bone disease that presents a broad clinical spectrum with monofocal or multifocal involvement. Since it is not always multifocal and/or recurrent, it was proposed that CNO be used as a term that encompasses all presentations and Chronic Recurrent Multifocal Osteomyelitis (CRMO) for recurrent and multifocal forms. Objective: to present an unprecedented low prevalence clinical case of an adolescent carrier of an autoinflammatory bone disease that posed diagnostic and therapeutic challenges. Description: a previously healthy female adolescent, 11 years old presented disabling lower back pain for a month without other associated symptoms. After several emergency consultations, she was admitted to the pediatric hospitalization at the Armed Forces Hospital (HCFFAA) in October 2021. A spine MRI showed a T11 body bone edema focus, normal blood count; ESR 48 mm/h, ANA, Anti DNA, RF and negative HLA B27. Results: after ruling out infectious and oncohematological processes, and once the result of a bone puncture biopsy was obtained, which showed inflammatory elements, an ONC diagnosis was made in February 2022, a record time comparing this case with the international literature. The average diagnosis of this clinical condition worldwide is 12 months.

Introdução: a Osteomielite Crônica Não Bacteriana (CNO) é uma doença óssea autoinflamatória, manifestando-se com amplo espectro clínico, apresentando-se com acometimento monofocal ou multifocal. Como nem sempre é multifocal e/ou recorrente, foi proposto que CNO seja usado como um termo que engloba todas as apresentações e Osteomielite Multifocal Recorrente Crônica (OMC) e que seja usado para formas recorrentes e multifocais. Objetivo: apresentar um caso clínico inédito, de baixa prevalência mundial, no caso de uma adolescente portadora de uma doença óssea autoinflamatória que representou desafios diagnósticos e terapêuticos. Descrição: adolescente do sexo feminino, 11 anos, previamente saudável, apresentava há um mês dorso-lombalgia incapacitante sem outros sintomas associados. Após várias consultas de urgência, foi internada na enfermaria pediátrica do Hospital Central das Forças Armadas (HCFFAA) em outubro de 2021. RM da coluna mostra foco de edema ósseo no corpo de T11, hemograma normal; ESR 48 mm/h, ANA, Anti DNA, RF e HLA B27 negativos. Resultados: após a exclusão de processos infecciosos e onco-hematológicos e obtido o resultado de uma biópsia por punção óssea, que evidenciou elementos inflamatórios, o diagnóstico de CNO foi feito em fevereiro de 2022, tempo recorde comparando este caso com a literatura internacional. A média de diagnóstico dessa entidade clínica no mundo é de 12 meses.

Absceso de Brodie en la clavícula: una forma poco frecuente de presentación / Brodie abscess in the clavicle: an uncommon presentation

La osteomielitis (OM) se define como la inflamación ósea de origen infeccioso. La forma aguda es frecuente en la edad pediátrica. El absceso de Brodie es un tipo de osteomielitis subaguda, históricamente con baja incidencia, pero que actualmente se presenta un aumento de la misma. De poca repercusión clínica, con pruebas de laboratorio inespecíficas y estudios radiológicos de difícil interpretación, es crucial la sospecha diagnóstica. Se asemeja a procesos neoplásicos, benignos o malignos. Recae en la experiencia del profesional realizar el diagnóstico adecuado. El tratamiento consiste en antibioticoterapia, tanto parenteral como por vía oral, y eventualmente drenaje quirúrgico. Presentamos una paciente sana que consultó por una tumoración en topografía de clavícula izquierda de 3 meses de evolución. Se realizó diagnóstico de absceso de Brodie, inició tratamiento y se obtuvo una buena respuesta. Resulta imprescindible tener un alto índice de sospecha de esta entidad para no someter al paciente a estudios, pruebas invasivas o tratamientos erróneos, y evitar secuelas a futuro.

Osteomyelitis is defined as an inflammation of the bone caused by infection. Acute osteomyelitis is common in pediatrics. A Brodie abscess is a type of subacute osteomyelitis, with a historically low incidence; however, its incidence is currently increasing. Given its little clinical impact, with non-specific laboratory tests and radiological studies of difficult interpretation, diagnostic suspicion is crucial. It resembles neoplasms, either benign or malignant. An adequate diagnosis falls on the health care provider's experience. Treatment consists of antibiotics, both parenteral and oral, with potential surgical drainage. Here we describe the case of a healthy female patient with a tumor found in the topography of the left clavicle 3 months before. She was diagnosed with Brodie abscess; treatment was started with a good response. A high index of suspicion of Brodie abscess is critical to avoid invasive tests and studies or inadequate treatments, and to prevent future sequelae.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Osteomielitis primaria de esternón / Primary sternal osteomyelitis

La osteomielitis primaria de esternón es muy infrecuente en niños, con menos de 100 casos publicados hasta la actualidad. Su presentación clínica es a menudo inespecífica, lo que causa un retraso en el diagnóstico. Se presentan dos nuevos casos de osteomielitis primaria de esternón. Ambos referían un cuadro de fiebre, malestar general, dolor torácico y rechazo del decúbito, con eritema preesternal en uno de los casos. La velocidad de sedimentación globular y la proteína C-reactiva estaban elevadas en ambos casos. El diagnóstico se confirmó mediante estudios de imagen y en un caso se aisló Staphylococcus aureus sensible a meticilina en el hemocultivo. Ambos se recuperaron sin complicaciones con tratamiento antibiótico. Debe tenerse en cuenta la osteomielitis primaria de esternón en el diagnóstico diferencial del dolor torácico, especialmente si se acompaña de fiebre, signos inflamatorios locales, intolerancia al decúbito o elevación de reactantes de fase aguda.

Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a diagnostic delay. Here we describe 2 new cases of primary sternal osteomyelitis. Both referred fever, malaise, chest pain, and refusal to lie down, with pre-sternal erythema in one of the cases. The erythrocyte sedimentation rate and C-reactive protein values were high in both cases. The diagnosis was confirmed by imaging studies; methicillin-sensitive Staphylococcus aureus was isolated in the blood culture of one of them. Both recovered without complications with antibiotic treatment. Primary sternal osteomyelitis should be considered in the differential diagnosis of chest pain, especially if accompanied by fever, local inflammatory signs, intolerance to lying down, or increased acute phase reactants.

First report of oral cryptococcal osteomyelitis in a cat.

Cryptococcosis is a worldwide-distributed fungal disease affecting humans and animals and is considered the most common systemic mycosis in cats. Classically, the clinical presentation of cryptococcal infection in cats consists of solitary or multiple nodules located on the planum nasale or the bridge of the nose. Bone involvement as cryptococcal osteomyelitis is a rare clinical entity of cryptococcosis. Herein, this case report describes a domestic shorthair cat with osteomyelitis of the mandibular bone resulting from Cryptococcus spp. infection. During the physical examination, a subcutaneous mass measuring approximately 6 cm in diameter was identified at the mandibular region. Cytological evaluation revealed numerous encapsulated yeasts resembling Cryptococcus spp. Histopathological examination revealed multifocal to coalescent subcutaneous granulomatous inflammation with a large number of spherical yeasts surrounded by a clear capsule. These yeasts were positive for periodic acid-Schiff (PAS) staining. The cat was successfully treated with a combination of itraconazole therapy and surgical management. To the author's knowledge, this is the first clinical report of oral cryptococcal osteomyelitis in a cat.

Molecular identification and antimicrobial resistance pattern of Nocardia isolated from 14 diseased dogs and cats.

Nocardia are ubiquitous, saprophytic and opportunistic bacteria. They cause a set of pyogenic clinical infections in animals and humans, particularly immunocompromised patients, mostly affecting the skin and respiratory tract, with refractoriness to conventional therapy. The most descriptions of nocardial infections in companion animals involve case reports, and there are scarce case series studies focused on canine and feline nocardiosis in which diagnosis has been based on molecular techniques. We investigated epidemiological aspects, clinical findings, in vitro susceptibility profile, and molecular identification of Nocardia using PCR-based method targeted 16S rRNA gene in twelve dogs and two cats. Among dogs were observed cutaneous lesions (8/12 = 67%), pneumonia (3/12 = 25%), and encephalitis (2/12 = 17%), whereas cats developed cutaneous lesions and osteomyelitis. Nocardia and canine morbillivirus coinfection was described in six dogs (6/12 = 50%). A high mortality rate (6/8 = 75%) was seen among dogs. Three dogs (3/4 = 75%) and one cat (1/2 = 50%) with systemic signs (pneumonia, encephalitis, osteomyelitis), and 83% (5/6) of dogs with a history of concomitant morbillivirus infection died. N. nova (5/12 = 42%), N. cyriacigeorgica (3/12 = 25%), N. farcinica (2/12 = 17%), N. veterana (1/12 = 8%), and N. asteroides (1/12 = 8%) species were identified in dogs, whereas N. africana and N. veterana in cats. Among the isolates from dogs, cefuroxime (12/12 = 100%), amikacin (10/12 = 83%), gentamycin (10/12 = 83%), and imipenem (10/12 = 83%) were the most effective antimicrobials, whereas cefuroxime, cephalexin, amoxicillin/clavulanic acid, imipenem, and gentamycin were efficient against isolates from cats. Multidrug resistance was observed in 36% (5/14) of isolates. We describe a variety of Nocardia species infecting dogs and cats, multidrug-resistant ones, and a high mortality rate, highlighting a poor prognosis of nocardiosis in companion animals, particularly among animals systemically compromised or coinfected by canine morbillivirus. Our study contributes to species identification, in vitro antimicrobial susceptibility profile, clinical-epidemiological aspects, and outcome of natural Nocardia-acquired infections in dogs and cats.

Brodie abscess in the clavicle: an uncommon presentation. / Absceso de Brodie en la clavícula: una forma poco frecuente de presentación.

Osteomyelitis is defined as an inflammation of the bone caused by infection. Acute osteomyelitis is common in pediatrics. A Brodie abscess is a type of subacute osteomyelitis, with a historically low incidence; however, its incidence is currently increasing. Given its little clinical impact, with non-specific laboratory tests and radiological studies of difficult interpretation, diagnostic suspicion is crucial. It resembles neoplasms, either benign or malignant. An adequate diagnosis falls on the health care provider's experience. Treatment consists of antibiotics, both parenteral and oral, with potential surgical drainage. Here we describe the case of a healthy female patient with a tumor found in the topography of the left clavicle 3 months before. She was diagnosed with Brodie abscess; treatment was started with a good response. A high index of suspicion of Brodie abscess is critical to avoid invasive tests and studies or inadequate treatments, and to prevent future sequelae.

La osteomielitis (OM) se define como la inflamación ósea de origen infeccioso. La forma aguda es frecuente en la edad pediátrica. El absceso de Brodie es un tipo de osteomielitis subaguda, históricamente con baja incidencia, pero que actualmente se presenta un aumento de la misma. De poca repercusión clínica, con pruebas de laboratorio inespecíficas y estudios radiológicos de difícil interpretación, es crucial la sospecha diagnóstica. Se asemeja a procesos neoplásicos, benignos o malignos. Recae en la experiencia del profesional realizar el diagnóstico adecuado. El tratamiento consiste en antibioticoterapia, tanto parenteral como por vía oral, y eventualmente drenaje quirúrgico. Presentamos una paciente sana que consultó por una tumoración en topografía de clavícula izquierda de 3 meses de evolución. Se realizó diagnóstico de absceso de Brodie, inició tratamiento y se obtuvo una buena respuesta. Resulta imprescindible tener un alto índice de sospecha de esta entidad para no someter al paciente a estudios, pruebas invasivas o tratamientos erróneos, y evitar secuelas a futuro.

Primary sternal osteomyelitis. / Osteomielitis primaria de esternón.

Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a diagnostic delay. Here we describe 2 new cases of primary sternal osteomyelitis. Both referred fever, malaise, chest pain, and refusal to lie down, with pre-sternal erythema in one of the cases. The erythrocyte sedimentation rate and C-reactive protein values were high in both cases. The diagnosis was confirmed by imaging studies; methicillin-sensitive Staphylococcus aureus was isolated in the blood culture of one of them. Both recovered without complications with antibiotic treatment. Primary sternal osteomyelitis should be considered in the differential diagnosis of chest pain, especially if accompanied by fever, local inflammatory signs, intolerance to lying down, or increased acute phase reactants.

La osteomielitis primaria de esternón es muy infrecuente en niños, con menos de 100 casos publicados hasta la actualidad. Su presentación clínica es a menudo inespecífica, lo que causa un retraso en el diagnóstico. Se presentan dos nuevos casos de osteomielitis primaria de esternón. Ambos referían un cuadro de fiebre, malestar general, dolor torácico y rechazo del decúbito, con eritema preesternal en uno de los casos. La velocidad de sedimentación globular y la proteína C-reactiva estaban elevadas en ambos casos. El diagnóstico se confirmó mediante estudios de imagen y en un caso se aisló Staphylococcus aureus sensible a meticilina en el hemocultivo. Ambos se recuperaron sin complicaciones con tratamiento antibiótico. Debe tenerse en cuenta la osteomielitis primaria de esternón en el diagnóstico diferencial del dolor torácico, especialmente si se acompaña de fiebre, signos inflamatorios locales, intolerancia al decúbito o elevación de reactantes de fase aguda.

Neutralization of Staphylococcus aureus Protein A Prevents Exacerbated Osteoclast Activity and Bone Loss during Osteomyelitis.

Osteomyelitis caused by Staphylococcus aureus is an important and current health care problem worldwide. Treatment of this infection frequently fails not only due to the increasing incidence of antimicrobial-resistant isolates but also because of the ability of S. aureus to evade the immune system, adapt to the bone microenvironment, and persist within this tissue for decades. We have previously demonstrated the role of staphylococcal protein A (SpA) in the induction of exacerbated osteoclastogenesis and increased bone matrix degradation during osteomyelitis. The aim of this study was to evaluate the potential of using anti-SpA antibodies as an adjunctive therapy to control inflammation and bone damage. By using an experimental in vivo model of osteomyelitis, we demonstrated that the administration of an anti-SpA antibody by the intraperitoneal route prevented excessive inflammatory responses in the bone upon challenge with S. aureus. Ex vivo assays indicated that blocking SpA reduced the priming of osteoclast precursors and their response to RANKL. Moreover, the neutralization of SpA was able to prevent the differentiation and activation of osteoclasts in vivo, leading to reduced expression levels of cathepsin K, reduced expression of markers associated with abnormal bone formation, and decreased trabecular bone loss during osteomyelitis. Taken together, these results demonstrate the feasibility of using anti-SpA antibodies as an antivirulence adjunctive therapy that may prevent the development of pathological conditions that not only damage the bone but also favor bacterial escape from antimicrobials and the immune system.

Infección osteoarticular multifocal en un recién nacido / Multifocal osteoarticular infection in a neonate / Infecção osteoarticular multi-focal num recém-nascido

Tanto la osteomielitis como la osteoartritis séptica en el período neonatal son patologías infrecuentes. La afectación ósea de la columna cervical es aún más rara, siendo excepcional en neonatos. Son patologías graves, con elevada morbimortalidad, donde el diagnóstico y tratamiento precoz agresivo son de suma importancia para el pronóstico vital y funcional. Presentamos el caso de un neonato que presentó una sepsis a S. Aureus multirresistente, asociada a una osteomielitis de la primera vértebra cervical y a una osteoartritis séptica de la cadera izquierda. Fue tratado precozmente de forma quirúrgica y con antibioticoterapia, presentando una buena evolución.

Both osteomyelitis and septic osteoarthritis in the neonatal period are infrequent pathologies. Bone involvement of the cervical spine is even rarer, being exceptional in neonates. These are serious pathologies, with high morbimortality, where early diagnosis and aggressive treatment are of utmost importance for the vital and functional prognosis. We present the case of a neonate who presented with sepsis due to multidrug-resistant S. Aureus, associated with osteomyelitis of the first cervical vertebra and septic osteoarthritis of the left hip. He was treated early surgically and with antibiotic therapy, presenting a good evolution

Tanto a osteomielite como a osteoartrose séptica no período neonatal são patologias raras. O envolvimento ósseo da coluna cervical é ainda mais raro, sendo excepcional nos recém-nascidos. Estas são patologias graves, com elevada morbimortalidade, onde o diagnóstico precoce e o tratamento agressivo são da maior importância para o prognóstico vital e funcional. Apresentamos o caso de um recém-nascido que apresentou sepse devido a S. Aureus multirresistente, associado a osteomielite da primeira vértebra cervical e osteoartrose séptica da anca esquerda. Foi tratado precocemente cirurgicamente e com terapia antibiótica, com uma boa evolução.

Use of bedaquiline in spinal osteomyelitis and soft tissue abscess caused by multidrug-resistant Mycobacterium tuberculosis: A case report.

INTRODUCTION: Spinal Tuberculosis (STB) represents between 1% and 2% of total tuberculosis cases. STB management remains challenging; the first-line approach consists of medical treatment, while surgery is reserved for patients with complications. No data regarding STB treatment with bedaquiline-containing regimens are available in the literature. CASE DESCRIPTION: Herein, we report the case of a 21-year-old man from Côte d'Ivoire with a multidrug resistance STB with subcutaneous abscess. After approval of the hospital off-label drug committee, we started bedaquiline 400 mg daily for two weeks, followed by 200 mg three times per week, for 22 weeks, associated with linezolid 600 mg daily, rifabutin 450 mg daily, and amikacin 750 mg daily (interrupted after eight weeks). During treatment, we performed a weekly EKG. No QT prolongation was shown, but inverted T waves appeared, requiring several cardiological consultations and cardiac MRI, but no cardiac dysfunction was found. After 24 weeks, bedaquiline was replaced with moxifloxacin 400 mg daily. The patient continued treatment for another year. We performed another computer tomography at the end of treatment, confirming the cure. DISCUSSION: A salvage regimen containing bedaquiline proved effective in treating multidrug-resistance tuberculosis spinal infection without causing severe adverse effects. However, further studies are needed to evaluate better bedaquiline bone penetration and the correct duration of treatment with bedaquiline in MDR spinal tuberculosis.

Microbiology and Treatment Outcomes of Community-Acquired Hematogenous Osteoarticular Infections in Infants ≤12 Months of Age.

We investigated the microbiology, management, and orthopedic outcomes of osteoarticular infections in infants age ≤1 year at our institution. Among 87 patients, Staphylococcus aureus was the most common pathogen (44.8%), followed by group B Streptococcus. Twenty-nine patients (33%), with a median age of 9.2 months, were transitioned to oral antibiotic therapy after ≤14 days of parenteral therapy; orthopedic outcomes were similar to those with prolonged parenteral therapy.

Comparative study of reliability of inflammatory markers over 18-FDG-PET CT scan in monitoring skull base osteomyelitis.

INTRODUCTION: The end point of treatment in skull base osteomyelitis is a matter of debate. A treatment based on symptoms alone is fraught with recurrence. There is a need to restrict imaging though more informative. The inflammatory markers like C-reactive protein and erythrocyte sedimentation rate used commonly need a detailed evaluation to optimize its utility. OBJECTIVES: To compare the diagnostic accuracy of inflammatory markers with a hybrid PET scan in monitoring skull base osteomyelitis. The secondary objective was to obtain a cut-off value of these markers to decide upon antibiotic termination. METHODS: A prospective cohort study was conducted in a tertiary care center with fifty-one patients with skull base osteomyelitis meeting eligibility criteria. Patients diagnosed with skull base osteomyelitis were serially monitored with weekly markers and PET scan after the initiation of treatment. A hybrid scan was taken at 6-8 weeks of treatment and repeated if required. The follow-up period varied from 6 weeks to 15 months. The outcome measures studied were the values of markers and the metabolic activity of PET scan when the patient became asymptomatic and when disease-free. RESULTS: C-reactive protein and erythrocyte sedimentation rate had a statistically significant correlation to disease activity in PET tomography scan as a prognostic marker. Both showed good clinical correlation. A cut off value of ≤ 3.6mg/L for C-reactive protein and ≤ 35mm/hour for erythrocyte sedimentation rate were taken as normalized values. CONCLUSION: A consistent normalized value of C-reactive protein and erythrocyte sedimentation rate for 8-12 weeks in an asymptomatic patient may be an indicator of disease control, though not cure. So, relying solely on markers alone for antibiotic termination may cause relapse. It may be used cautiously in a peripheral setting without access to more specific hybrid scans. In a tertiary care, follow-up scans may be done based on the titres, thereby limiting the radiation exposure.

Osteomielitis multifocal por Serratia marcescens en un niño con enfermedad granulomatosa crónica / Serratia marcescens multifocal osteomyelitis in a child with chronic granulomatous disease

Resumen La enfermedad granulomatosa crónica (EGC) es una inmunode-ficiencia primaria poco frecuente. Se caracteriza por una alteración en la función de los fagocitos, causando infecciones recurrentes bacterianas y fúngicas. Presentamos el caso clínico de un niño con una osteomielitis multifocal por Serratia marcescens , microorganismo infrecuente como causa de infecciones óseas en niños, aunque asociado a la EGC. El estudio de infecciones con presentación clínica y agentes inhabituales deben hacer sospechar una EGC. Su diagnóstico precoz en la vida, así como el tratamiento antimicrobiano oportuno y el uso posterior de una profilaxis antimicrobiana adecuada logrará evitar recurrencias infecciosas y secuelas.

Abstract Chronic granulomatous disease (CGD) is a rare primary immuno-deficiency. It is characterized by an alteration in the function of phagocytes causing recurrent bacterial and fungal infections. This is a case report of a child with multifocal osteomyelitis by Serratia marcescens, an infrequent as a cause of bone infections, although associated with CGD. The study of infections with clinical presentation and unusual agents should lead to suspicion of CGD. The diagnosis early in life, as well as timely antimicrobial treatment and the subsequent antimicrobial prophylaxis will avoid infectious recurrences and sequelae.

[Myroides odoratimimus, a rare cause of soft tissue infection and osteomyelitis. Case report]. / Myroides odoratimimus, una causa infrecuente de infección de tejidos blandos y osteomielitis.

Infections due to Gram-negative bacteria of the genus Myroides are very rare and generally affect the skin and soft tissues of patients with some degree of immunocompromise. We present a case of a 23-year-old patient with a history of myelomeningocele surgically resolved at 3 years of age and bot foot, who presented with a deep infection of the right lower extremity by Myroides odoratimimus. The species identification was carried out with MALDI-TOF and the treatment was initially carried out with meropenem and finally then ciprofloxacin, in addition to right supramaleolar amputation.