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1.
Sci Rep ; 12(1): 18387, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319854

RESUMO

Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria.


Assuntos
Antibacterianos , Bactérias Anaeróbias , Materiais Revestidos Biocompatíveis , Implantes Experimentais , Osteomielite , Prata , Animais , Camundongos , Antibacterianos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Íons/farmacologia , Osteomielite/microbiologia , Osteomielite/prevenção & controle , Prata/farmacologia , Titânio/química , Porphyromonas gingivalis/efeitos dos fármacos , Implantes Experimentais/efeitos adversos , Implantes Experimentais/microbiologia , Fêmur , Proteína C-Reativa
2.
Infect Immun ; 90(11): e0041722, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36226943

RESUMO

Staphylococcus aureus is the major causative agent of bacterial osteomyelitis, an invasive infection of bone. Inflammation generated by the immune response to S. aureus contributes to bone damage by altering bone homeostasis. Increases in the differentiation of monocyte lineage cells into bone-resorbing osteoclasts (osteoclastogenesis) promote bone loss in the setting of osteomyelitis. In this study, we sought to define the role of Toll-like receptor (TLR) signaling in the pathogenesis of S. aureus osteomyelitis. We hypothesized that S. aureus-sensing TLRs 2 and 9, both of which are known to alter osteoclastogenesis in vitro, promote pathological changes to bone, including increased osteoclast abundance, bone loss, and altered callus formation during osteomyelitis. Stimulation of osteoclast precursors with S. aureus supernatant increased osteoclastogenesis in a TLR2-dependent, but not a TLR9-dependent, manner. However, in vivo studies using a posttraumatic murine model of osteomyelitis revealed that TLR2-null mice experienced similar bone damage and increased osteoclastogenesis compared to wild type (WT) mice. Therefore, we tested the hypothesis that compensation between TLR2 and TLR9 contributes to osteomyelitis pathogenesis. We found that mice deficient in both TLR2 and TLR9 (Tlr2/9-/-) have decreased trabecular bone loss in response to infection compared to WT mice. However, osteoclastogenesis is comparable between WT and Tlr2/9-/- mice, suggesting that alternative mechanisms enhance osteoclastogenesis in vivo during osteomyelitis. Indeed, we discovered that osteoclast precursors intracellularly infected with S. aureus undergo significantly increased osteoclast formation, even in the absence of TLR2 and TLR9. These results suggest that TLR2 and TLR9 have context-dependent roles in the alteration of bone homeostasis during osteomyelitis.


Assuntos
Osteomielite , Infecções Estafilocócicas , Camundongos , Animais , Staphylococcus aureus , Receptor 2 Toll-Like/genética , Receptor Toll-Like 9 , Infecções Estafilocócicas/microbiologia , Osteomielite/microbiologia , Receptores Toll-Like , Camundongos Knockout , Camundongos Endogâmicos C57BL
3.
BMC Microbiol ; 22(1): 212, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36050654

RESUMO

BACKGROUND: Bone loss and deformation due to damage caused by injury or recurrent invasive infections presents a major clinical obstacle. While bone substitute biomaterials promote osseous tissue regeneration, their application in sites complicated by microbial infections such as osteomyelitis, is limited. Bioactive glass biomaterials (Bioglass) have been shown to have efficient mechanisms of repairing the integrity of bone, while inhibiting growth of a range of bacterial strains. There are several commercially available bioactive glass compounds, each with a unique chemical composition. One compound in particular, S53P4, has demonstrated antimicrobial effects in previous studies but the antimicrobial activity of the parent compound 45S5 has not been investigated. RESULTS: To assess whether antimicrobial activity is common among bioglass compounds, 45S5-the parent compound, was evaluated in comparison to S53P4 for antibacterial and antibiofilm effects against multiple strains of aerobic and anaerobic bacteria associated with various types of osteomyelitis. Experiments of antimicrobial effects in liquid cultures demonstrated that both compounds were antimicrobial against various microbial genera including S. gordonii, V. parvula, P. aeruginosa and MRSA; particles of the smallest size (32-125 µm) invariably showed the most robust antimicrobial capabilities. When employed against biofilms ecological biofilms grown on hydroxyapatite, 45S5 particles produced a stronger reduction in biofilm mass compared to S53P4 particles when considering small particle ranges. CONCLUSION: We found that 45S5 seems to be as effective as S53P4 and possibly even more capable of limiting bacterial infections. The efficacy of bioactive glass was not limited to inhibition of planktonic growth, as it also extended to bacterial biofilms. The increased antibacterial activity of 45S5 compared to S53P4 is true for a variety of size ranges.


Assuntos
Antibacterianos , Osteomielite , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Biofilmes , Humanos , Osteomielite/microbiologia , Pseudomonas aeruginosa
4.
JBJS Case Connect ; 12(2)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099497

RESUMO

CASE: A 56-year-old immunosuppressed man presented with pain and swelling in the medial and anterior right foot with accompanied numbness in the second and third toes 1 month after a puncture wound by a Sylvester palm tree thorn. An intraoperative culture/biopsy returned positive for septic arthritis of the naviculocuneiform joint and fungal osteomyelitis of the navicular, medial, and intermediate cuneiforms due to Phaeoacremonium venezuelense. CONCLUSION: Fungal osteomyelitis is extremely rare. Only 5 cases by Phaeoacremonium venezuelense have been reported previously in the literature. To the best of our knowledge, this is the first case of osteomyelitis by this strain.


Assuntos
Artrite Infecciosa , Ascomicetos , Osteomielite , Ossos do Tarso , Artrite Infecciosa/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia
5.
Microbiol Spectr ; 10(5): e0054422, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36069576

RESUMO

Treatment of osteomyelitis is still challenging, as conventional antibiotic therapy is limited by the emergence of resistant strains and the formation of biofilms. Sonoantimicrobial chemotherapy (SACT) is a novel therapy of low-frequency and low-intensity ultrasound (LFLIU) combined with a sonosensitizer. Therefore, in our study, a sonosensitizer named emodin (EM) was proposed to be combined with LFLIU to relieve acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) through antibacterial and antibiofilm effects. The efficiencies of different intensities of ultrasound, including single (S-LFLIU, 15 min) and multiple ultrasound (M-LFLIU, 3 times for 5 min at 4-h intervals), against bacteria and biofilms were compared, contributing to developing the best treatment regimen. Our results demonstrated that EM plus S-LFLIU or M-LFLIU (EM+S-LFLIU or EM+M-LFLIU) had significant combined bactericidal and antibiofilm effects, with EM+M-LFLIU in particular exhibiting superior antibiofilm performance. Furthermore, it was suggested that EM+M-LFLIU could produce a large amount of reactive oxygen species (ROS), destroy the integrity of the bacterial membrane and cell wall, and downregulate the expression of genes involved in oxidative stress, membrane wall synthesis, and bacterial virulence, as well as that of other related genes (agrB, pbp3, sgtB, gmk, zwf, and msrA). In vivo studies, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and bacterial quantification of bone tissue indicated that EM+M-LFLIU could also relieve osteomyelitis due to MRSA infection. Our work proffers an original approach to bacterial osteomyelitis treatment that weakens drug-resistant bacteria and suppresses and degrades biofilm formation through SACT, which may provide new prospects for clinical treatment. IMPORTANCE Antibiotic therapy is the first choice for clinical treatment of osteomyelitis, but the formation of bacterial biofilms and the emergence of many drug-resistant strains also create an urgent need to find an alternative treatment to effectively eliminate the infection. Recently, LFLIU has come to be considered a safe and promising method of debridement and antibacterial therapy. In this study, we found that ultrasound and EM have a significant combined antibacterial effect in vivo and in vitro, which may play an antibacterial role by stimulating the production of ROS, destroying the bacterial cell wall, and inhibiting the expression of related genes. Our study expands the body of knowledge on the antibacterial effect of drugs-specifically emodin (EM)-through combined physiotherapy. If successfully integrated into clinical practice, these methods may reduce the burden of high concentrations of drugs needed to treat bacterial biofilms and avoid the growing resistance of bacteria to antibiotics.


Assuntos
Emodina , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Emodina/farmacologia , Emodina/uso terapêutico , Espécies Reativas de Oxigênio/farmacologia , Espécies Reativas de Oxigênio/uso terapêutico , Testes de Sensibilidade Microbiana , Microtomografia por Raio-X , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Osteomielite/diagnóstico por imagem , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
6.
J Biomed Mater Res A ; 110(11): 1786-1800, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36082973

RESUMO

A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)-based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3-E1 pre-osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin-Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug-loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX-based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18-loaded HG at 300 µM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 µM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose-dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub-millimolar doses of VH combined with LL18 at 300 µM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy-to-handle, shape-fitting HG formulation with the potential to treat MRSA-infected bone with low VH doses associated with LL18.


Assuntos
Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Vancomicina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Portadores de Fármacos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/metabolismo , Osteomielite/microbiologia , Ratos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-36166203

RESUMO

Sternoclavicular joint infections and osteomyelitis of the clavicle are extremely rare infections, especially in the pediatric population. Early signs of these infections are nonspecific and can be mistaken for common upper respiratory infections such as COVID-19 and influenza. Rapid diagnosis and treatment are critical for preventing potentially fatal complications such as mediastinitis. We present three cases of sternoclavicular joint infections in the past year during the COVID-19 pandemic. All three patients had delayed diagnoses likely secondary to COVID-19 workup. Each patient underwent surgical irrigation and débridement. Two of three patients required multiple surgeries and prolonged antibiotic courses. Placement of antibiotic-impregnated calcium sulfate beads into the surgical site cleared the infection in all cases where they were used. All three patients made a full recovery; however, the severity of their situations should not be overlooked. Children presenting to the hospital with chest pain, fever, and shortness of breath should not simply be discharged based on a negative COVID-19 test or other viral assays. A higher index of suspicion for bacterial infections such as clavicular osteomyelitis is important. Close attention must be placed on the physical examination to locate potential areas of concentrated pain, erythema, or swelling to prompt advanced imaging if necessary.


Assuntos
COVID-19 , Osteomielite , Articulação Esternoclavicular , Antibacterianos/uso terapêutico , Teste para COVID-19 , Sulfato de Cálcio , Criança , Clavícula/diagnóstico por imagem , Clavícula/microbiologia , Clavícula/cirurgia , Diagnóstico Tardio , Humanos , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Pandemias , Articulação Esternoclavicular/diagnóstico por imagem , Articulação Esternoclavicular/microbiologia , Articulação Esternoclavicular/cirurgia
8.
Am J Emerg Med ; 61: 1-6, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35994972

RESUMO

INTRODUCTION: Transient synovitis (TS) is a common and benign cause of hip pain in children, but must be distinguished from more serious entities such as septic arthritis, osteomyelitis, and pyomyositis. Our objectives were to determine the risk of missed bacterial musculoskeletal infection and rates of diagnostic testing in children diagnosed with TS. METHODS: We performed a cohort study using the Pediatric Heath Information System of children 1-10 years diagnosed with TS in the ED. We determined rates of missed bacterial musculoskeletal infection (defined as a new diagnosis of septic arthritis, osteomyelitis, or pyomyositis within 14 days of initial ED visit). We described the initial diagnostic evaluation and ED management of children diagnosed with TS and variability between sites. RESULTS: We analyzed 6419 encounters from 37 hospitals. 62 (1.0%, 95%CI: 0.7-1.2%) children were diagnosed with a missed bacterial musculoskeletal infection. Children with missed infection were younger than those without (median age 2.6 vs. 4.6 years, p < 0.01). Serum laboratory testing was performed in 76% of encounters with minimal variation across sites. There was significant variation in the rates of hip ultrasound by site (2 to 92%), which has increased in use over time (from 42% in 2016 to 62% in 2021). CONCLUSION: In this large observational study, missed bacterial musculoskeletal infection in children diagnosed with TS was rare but more common in younger children. The optimal combination of bloodwork and radiographic testing, especially ultrasound, to distinguish TS from more serious disease remains unclear.


Assuntos
Artrite Infecciosa , Infecções Bacterianas , Doenças Musculoesqueléticas , Osteomielite , Piomiosite , Sinovite , Humanos , Criança , Pré-Escolar , Piomiosite/diagnóstico , Estudos de Coortes , Articulação do Quadril/diagnóstico por imagem , Estudos Retrospectivos , Diagnóstico Diferencial , Sinovite/diagnóstico por imagem , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Osteomielite/diagnóstico , Osteomielite/microbiologia , Infecções Bacterianas/diagnóstico , Erros de Diagnóstico
9.
Front Cell Infect Microbiol ; 12: 910970, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811672

RESUMO

S. aureus infection of bone is difficult to eradicate due to its ability to colonize the osteocyte-lacuno-canalicular network (OLCN), rendering it resistant to standard-of-care (SOC) antibiotics. To overcome this, we proposed two bone-targeted bisphosphonate-conjugated antibiotics (BCA): bisphosphonate-conjugated sitafloxacin (BCS) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS). Initial studies demonstrated that the BCA kills S. aureus in vitro. Here we demonstrate the in vivo efficacy of BCS and HBCS versus bisphosphonate, sitafloxacin, and vancomycin in mice with implant-associated osteomyelitis. Longitudinal bioluminescent imaging (BLI) confirmed the hypothesized "target and release"-type kinetics of BCS and HBCS. Micro-CT of the infected tibiae demonstrated that HBCS significantly inhibited peri-implant osteolysis versus placebo and free sitafloxacin (p < 0.05), which was not seen with the corresponding non-antibiotic-conjugated bisphosphonate control. TRAP-stained histology confirmed that HBCS significantly reduced peri-implant osteoclast numbers versus placebo and free sitafloxacin controls (p < 0.05). To confirm S. aureus killing, we compared the morphology of S. aureus autolysis within in vitro biofilm and infected tibiae via transmission electron microscopy (TEM). Live bacteria in vitro and in vivo presented as dense cocci ~1 µm in diameter. In vitro evidence of autolysis presented remnant cell walls of dead bacteria or "ghosts" and degenerating (non-dense) bacteria. These features of autolyzed bacteria were also present among the colonizing S. aureus within OLCN of infected tibiae from placebo-, vancomycin-, and sitafloxacin-treated mice, similar to placebo. However, most of the bacteria within OLCN of infected tibiae from BCA-treated mice were less dense and contained small vacuoles and holes >100 nm. Histomorphometry of the bacteria within the OLCN demonstrated that BCA significantly increased their diameter versus placebo and free antibiotic controls (p < 0.05). As these abnormal features are consistent with antibiotic-induced vacuolization, bacterial swelling, and necrotic phenotype, we interpret these findings to be the initial evidence of BCA-induced killing of S. aureus within the OLCN of infected bone. Collectively, these results support the bone targeting strategy of BCA to overcome the biodistribution limits of SOC antibiotics and warrant future studies to confirm the novel TEM phenotypes of bacteria within OLCN of S. aureus-infected bone of animals treated with BCS and HBCS.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Fluoroquinolonas , Camundongos , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Distribuição Tecidual , Vancomicina/farmacologia
10.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 40(6): 296-301, Jun-Jul, 2022. tab
Artigo em Espanhol | IBECS | ID: ibc-206891

RESUMO

Objetivo: Describir la experiencia clínica con dalbavancina en el tratamiento de la infección de pie diabético en una unidad multidisciplinar de un hospital de segundo nivel. Métodos: Estudio descriptivo retrospectivo de pacientes con infección de pie diabético tratados con dalbavancina en la Unidad de Pie Diabético del Hospital Universitario Fundación Alcorcón de septiembre de 2016 a diciembre de 2019. Se recogieron parámetros demográficos y comorbilidades, características de la infección y del tratamiento con dalbavancina. Se estimó la tasa de curación a los 90 días tras finalizar el tratamiento. Resultados: Un total de 23 pacientes con infección de pie diabético (osteomielitis) fueron tratados con dalbavancina; 19 eran hombres con una edad media de 65 años. Los microorganismos más frecuentemente aislados fueron Staphylococcus aureus (11) y Corynebacterium striatum (7). En 22 casos se usó dalbavancina como terapia de segunda elección, en 11 debido a toxicidad de otros antibióticos. La mediana de duración del tratamiento fue de 5 (4-7) semanas; la dosis más frecuente de dalbavancina (8 pacientes) fue de 1.000mg seguido de 500mg semanales durante 5 semanas. Tres pacientes presentaron efectos secundarios leves (náuseas y molestias gastrointestinales). A los 90 días de finalizar el tratamiento, el 87% (20) de los pacientes se curaron (IC95%: 65,2-94,52%). Conclusión: Los pacientes con osteomielitis por microorganismos grampositivos que recibieron como parte del tratamiento multidisciplinar antibioterapia con dalbavancina tuvieron una elevada tasa de curación, con una adecuada tolerancia y escasos efectos secundarios. Dalbavancina ofrece una alternativa segura en el tratamiento de la infección profunda de pie diabético.(AU)


Objective: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. Methods: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate was estimated at 90 days after finishing the treatment. Results: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000mg followed by 500mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). Conclusion: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.(AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Pé Diabético/microbiologia , Anti-Infecciosos , Staphylococcus aureus , Corynebacterium , Diabetes Mellitus/tratamento farmacológico , Osteomielite/complicações , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Microbiologia , Doenças Transmissíveis , Epidemiologia Descritiva
11.
J Antimicrob Chemother ; 77(9): 2532-2535, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35696322

RESUMO

BACKGROUND: Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. OBJECTIVES: To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. METHODS: We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan-Meier curve. RESULTS: Sixty-six patients were included. Median age was 75 (IQR 69-81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12-40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1-15); P = 0.03]. CONCLUSIONS: NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome.


Assuntos
Diabetes Mellitus , Osteomielite , Otite Externa , Infecções por Pseudomonas , Idoso , Humanos , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Otite Externa/tratamento farmacológico , Otite Externa/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Recidiva , Estudos Retrospectivos , Fatores de Risco
12.
Eur Rev Med Pharmacol Sci ; 26(11): 4069-4073, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35731077

RESUMO

OBJECTIVE: Osteomyelitis is a relatively understudied disease with no standardized and evidence-based approach to treatment. We aimed to evaluate a cohort of patients with osteomyelitis, comparing the outcomes between intravenous (IV) and oral treatment. PATIENTS AND METHODS: We performed an observational retrospective study on osteomyelitis cases in adult patients seen for care between 2017 and 2019. We collected information on patient characteristics, microbiological etiology, infection treatment, and outcome. In addition, we divided osteomyelitis cases by antibiotic regimens [oral (OTG) vs. intravenous±oral (ITG)] and therapy durations to evaluate outcomes differences. RESULTS: A total of 235 episodes of osteomyelitis were evaluated, with a higher prevalence in male gender. Staphylococci, especially S. aureus, were the most common strains. Out of the 235 evaluated episodes, we selected 142 cases. Of these, 75 were treated with OTG and 67 with ITG. Gram-positive bacteria were the most frequent aetiological agents, with 81 isolates (61.8%). Full recovery was observed in 79 (55.6%) cases; of these, 36 (53.7%) were in the ITG and 43 (57.3%) in the OTG (p = 0.666). At the logistic regression, a polymicrobial infection [OR 4.16 (95%CI 1.28-13.4), p = 0.017] and a less than six weeks treatment duration [OR 4.24 (95%CI 1.38-5.43) p = 0.004] were significantly associated with a higher risk of treatment failure. CONCLUSIONS: Our study suggests that oral treatment efficacy is comparable to ITG therapy for osteomyelitis, confirming the most recent evidence suggesting that oral therapy is non-inferior to intravenous therapy to treat osteomyelitis.


Assuntos
Infecções Bacterianas , Osteomielite , Administração Oral , Adulto , Antibacterianos , Infecções Bacterianas/tratamento farmacológico , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Estudos Retrospectivos , Staphylococcus aureus
13.
BMJ Case Rep ; 15(5)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35618338

RESUMO

An immunocompetent man in his 40s presented with 3 months of mid-thoracic back pain which progressed to include progressive paraesthesias and lower extremity weakness. Investigations revealed thoracic spine osteomyelitis with signs of cord compression. He underwent neurosurgical intervention, including laminectomy, spinal cord decompression and partial resection of an epidural mass. Initial intraoperative biopsy and surgical pathology results were concerning for an acid-fast bacillus as the causative pathogen, and the patient was given empiric therapy for presumed Mycobacterium tuberculosis However, microbiology speciation revealed the presence of the non-tuberculous mycobacterium (NTM) Mycobacterium kansasii, which resulted in an alteration of his antimicrobial therapy. This case highlights the importance of considering NTM as a possible aetiology of spinal osteomyelitis, even among immunocompetent individuals or in low-prevalence regions.


Assuntos
Mycobacterium kansasii , Osteomielite , Compressão da Medula Espinal , Antibacterianos/uso terapêutico , Humanos , Masculino , Micobactérias não Tuberculosas , Osteomielite/microbiologia , Compressão da Medula Espinal/etiologia
14.
BMJ Case Rep ; 15(5)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35641085

RESUMO

Zygomatic osteomyelitis is a rare occurrence due to rich collateral blood supply of bone. A man in his 30s presented with complaints of pain over bilateral cheek and pus discharge below the eye on lateral aspect. He was a known case of COVID-19 associated mucormycosis postendoscopic debridement of sinuses 3 months back. Radiology revealed bilateral destruction of zygoma with discharging sinus. Microbiological analysis confirmed aseptate hyphae in pus, and a diagnosis of bilateral fungal zygomatic osteomyelitis made. Under general anaesthesia, sequestrectomy done using bilateral lateral rhinotomy with extended Dieffenbach's approach (batwing incision). Postsurgery 3000 mg of liposomal amphotericin was administered. There was no enophthalmos or restricted eye movements postoperatively. Follow-up MRI suggested minimal inflammatory enhancement in maxillary sinus. Patient was discharged on oral antifungals.


Assuntos
COVID-19 , Mucormicose , Osteomielite , Ferida Cirúrgica , Humanos , Masculino , Mucormicose/diagnóstico , Mucormicose/cirurgia , Osteomielite/diagnóstico por imagem , Osteomielite/microbiologia , Osteomielite/cirurgia , Supuração , Zigoma/cirurgia
15.
Diagnosis (Berl) ; 9(3): 359-363, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35619048

RESUMO

OBJECTIVES: Identifying the causative bacterial pathogen for children with acute hematogenous musculoskeletal infections (MSKIs) allows for improved care. The purpose of our study was to determine if clinical markers could predict which patients will have a causative pathogen found on source culture alone, thus being highest yield to undergo operative diagnostic procedures. METHODS: A single-center, retrospective cohort study was performed. Medical records for patients between 6 months and 18 years of age admitted between July 2014 and September 2018 with a discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis were reviewed. Patients were stratified based on results of blood and source cultures. Predictors of interest were screened on a univariable basis with significant predictors retained in a multivariate analysis. RESULTS: There were 170 patients included. No predictors were significantly associated with increased odds of having a causative pathogen found on source culture alone. Degree of C-reactive protein elevation and history of fever were associated with decreased odds of being source culture positive, OR (95% CI); 0.92 (0.87, 0.98) and 0.39 (0.19, 0.81), respectively. CONCLUSIONS: Predictive modeling failed to identify children with MSKIs whose causative pathogen was found by source culture alone. It is difficult to predict which MSKI patients will be highest yield for operative diagnostic procedures.


Assuntos
Artrite Infecciosa , Infecções , Osteomielite , Piomiosite , Artrite Infecciosa/complicações , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Criança , Humanos , Osteomielite/complicações , Osteomielite/diagnóstico , Osteomielite/microbiologia , Piomiosite/complicações , Piomiosite/diagnóstico , Piomiosite/microbiologia , Estudos Retrospectivos
16.
J Trop Pediatr ; 68(3)2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35595253

RESUMO

BACKGROUND: The epidemiological characteristics of the common pathogens underlying acute haematogenous osteoarticular infection (AHOI) and their resistance to drugs have temporal and regional differences. AIMS: To determine the antimicrobial treatment most effective for culture-negative AHOI patients and those without bacterial cultures. METHODS: Retrospective analysis of clinical data of children with AHOI who were culture positive from January 2007 to December 2021. And the distribution of the main pathogens and the drug resistance Staphylococcus aureus were analysed in different time periods, age groups and infection types. RESULTS: A total of 188 cases met the inclusion criteria, including 97 cases of acute haematogenous osteomyelitis (AHO), 75 cases of septic arthritis (SA) and 16 cases of AHO concomitant with SA. The commonest causative pathogen in local children was S. aureus of Gram-positive cocci, followed by Streptococcus, and occasionally Gram-negative bacilli. The distribution of S. aureus had no significant correlation with age or infection type. Staphylococcus aureus accounted for 81.82%, 90.91% and 96.15% of all pathogens, and methicillin-resistant S. aureus (MRSA) accounted for 24.22%, 53.33% and 76.00% of S. aureus in 2007-11, 2012-16 and 2017-21, respectively. The frequency of MRSA infection showed an increasing trend over time. CONCLUSION: Staphylococcus aureus is still the main pathogen of AHOI in local children. The proportion of MRSA in S. aureus has also increased over time to 76% in the last 5 years, and the increased proportion of MRSA can affect the choice of initial empirical medication.


Assuntos
Artrite Infecciosa , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Doença Aguda , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/epidemiologia , Criança , Farmacorresistência Bacteriana , Humanos , Osteomielite/tratamento farmacológico , Osteomielite/epidemiologia , Osteomielite/microbiologia , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus
17.
Front Cell Infect Microbiol ; 12: 854242, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531332

RESUMO

Staphylococcus aureus is an opportunistic pathogen that causes a range of devastating diseases including chronic osteomyelitis, which partially relies on the internalization and persistence of S. aureus in osteoblasts. The identification of the mechanisms of the osteoblast response to intracellular S. aureus is thus crucial to improve the knowledge of this infectious pathology. Since the signal from specifically infected bacteria-bearing cells is diluted and the results are confounded by bystander effects of uninfected cells, we developed a novel model of long-term infection. Using a flow cytometric approach we isolated only S. aureus-bearing cells from mixed populations that allows to identify signals specific to intracellular infection. Here we present an in-depth analysis of the effect of long-term S. aureus infection on the transcriptional program of human osteoblast-like cells. After RNA-seq and KEGG and Reactome pathway enrichment analysis, the remodeled transcriptomic profile of infected cells revealed exacerbated immune and inflammatory responses, as well as metabolic dysregulations that likely influence the intracellular life of bacteria. Numerous genes encoding epigenetic regulators were downregulated. The later included genes coding for components of chromatin-repressive complexes (e.g., NuRD, BAHD1 and PRC1) and epifactors involved in DNA methylation. Sets of genes encoding proteins of cell adhesion or neurotransmission were also deregulated. Our results suggest that intracellular S. aureus infection has a long-term impact on the genome and epigenome of host cells, which may exert patho-physiological dysfunctions additionally to the defense response during the infection process. Overall, these results not only improve our conceptual understanding of biological processes involved in the long-term S. aureus infections of osteoblast-like cells, but also provide an atlas of deregulated host genes and biological pathways and identify novel markers and potential candidates for prophylactic and therapeutic approaches.


Assuntos
Osteomielite , Infecções Estafilocócicas , Epigênese Genética , Humanos , Osteomielite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Transcriptoma
18.
BMC Infect Dis ; 22(1): 367, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410176

RESUMO

BACKGROUND: Cutibacterium modestum was named in 2020. C. modestum was previously called Propionibacterium humerusii. Several implant-associated infections caused by Cutibacterium species have been previously reported, but native vertebral osteomyelitis due to these bacteria has rarely been reported. CASE PRESENTATION: A 72-year-old man, who had previously received several nerve block injections for low back pain, was referred to our hospital for deterioration in back pain in the last 1 month. MRI findings were suggestive of L5-S1 vertebral osteomyelitis. Blood cultures and bone biopsy culture revealed the presence of Gram-positive bacilli. The isolate was identified as C. modestum by 16SrRNA gene sequencing. A diagnosis of vertebral osteomyelitis caused by C. modestum was made. Minocycline followed by oral amoxicillin was administered for 3 months. His symptom improved and did not recur after treatment completion. CONCLUSION: A case of vertebral osteomyelitis caused by C. modestum was encountered. Although C. modestum is very similar to C. acnes, it could be accurately identified by 16SrRNA gene sequencing. This case represents the first documented C. modestum infection in humans.


Assuntos
Osteomielite , Idoso , Dor nas Costas , Osso e Ossos , Humanos , Imageamento por Ressonância Magnética , Masculino , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-35490091

RESUMO

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate is estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000 mg followed by 500 mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.


Assuntos
Doenças Transmissíveis , Diabetes Mellitus , Pé Diabético , Osteomielite , Idoso , Antibacterianos , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/induzido quimicamente , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Feminino , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Estudos Retrospectivos , Teicoplanina/análogos & derivados
20.
Jt Dis Relat Surg ; 33(1): 193-202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35361095

RESUMO

OBJECTIVES: In this experimental study, we aimed to investigate the specific value of receptor activator of nuclear factor kappa-Β ligand (RANKL) plasma level in osteomyelitis to show the bone destruction and to determine its correlation with classical markers of infection in mice model of osteomyelitis. MATERIALS AND METHODS: Sixty Balb/c female mice (30 to 40 g weight, 3.5 to 4 month-old) were divided into two groups: Controls (n=15) and study group (n=45). All mice underwent tibial decortication and received an injection of sclerosing agent into the intramedullary cavity. The next process was proceeded in two steps to observe the detectability of osteomyelitis-induced bone destruction (step 1) and treatment response (step 2) using the variables examined in our study. In step 1, the study group received 1 mL solution containing Staphylococcus aureus (S. aureus) bacteria (2X108 per mL) into the intramedullary cavity. Five mice from each group were sacrificed every seven days for three weeks and tibia and blood samples were obtained. In step 2, the remaining 30 infected mice were further divided into two groups to investigate the possible value of RANKL plasma level as a marker of treatment response. Fifteen of these mice received teicoplanin 20 mg/kg for four weeks, while the rest did not receive antibiotics. Eight mice from each group were sacrificed at the end of the second week and the remaining 14 mice were sacrificed at the end of four weeks. Complete blood count, procalcitonin level, C-reactive protein (CRP), and RANKL concentrations were measured from blood samples of each sacrificed mouse. RESULTS: Median RANKL concentration of the control subjects was significantly higher than recipients of intervention at the first and third weeks in step 1 where bone destruction of osteomyelitis was examined. No significant changes occurred in groups receiving and not receiving antimicrobial treatment in terms of RANKL, CRP, and procalcitonin levels throughout four weeks in step 2. The RANKL concentration was significantly correlated with colony growth in subjects allocated to the S. aureus inoculation group (r=-0.547, p=0.035). CONCLUSION: The RANKL levels in mice with S. aureus osteomyelitis are not correlated with colony growth or other markers of inflammation and not useful for monitoring the response to antimicrobial treatment during osteomyelitis.


Assuntos
Osteomielite , Staphylococcus aureus , Animais , Modelos Animais de Doenças , Feminino , Humanos , Ligantes , Camundongos , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Ligante RANK/metabolismo , Staphylococcus aureus/metabolismo
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