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Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.
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Cobre , Osteomielitis , Osteomielitis/tratamiento farmacológico , Animales , Cobre/química , Cobre/farmacología , Concentración de Iones de Hidrógeno , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratones , Peróxido de Hidrógeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Humanos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.
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Antibacterianos , Gentamicinas , Osteomielitis , Infecciones Estafilocócicas , Staphylococcus aureus , Andamios del Tejido , Animales , Andamios del Tejido/química , Antibacterianos/farmacología , Antibacterianos/química , Infecciones Estafilocócicas/tratamiento farmacológico , Osteomielitis/tratamiento farmacológico , Conejos , Staphylococcus aureus/efectos de los fármacos , Gentamicinas/farmacología , Gentamicinas/administración & dosificación , Gentamicinas/química , Gentamicinas/uso terapéutico , Ratones , Vancomicina/farmacología , Vancomicina/química , Vancomicina/administración & dosificación , Durapatita/química , Cinética , Cicatrización de Heridas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Colágeno/química , FemeninoRESUMEN
Skull base osteomyelitis is a rare and serious condition that primarily affects immunocompromised individuals and can be life threatening if not treated promptly. It can have various origins, with the most common being an extension of necrotizing external otitis. It is difficult to diagnose due to a wide array of clinical presentations. Imaging plays an important role in the diagnosis, identification of the possible source of infection, the extent of the disease, the pattern of spread and identification of associated complications. Early diagnosis is crucial to promptly initiate appropriate treatment. We report here a rare case of a 68-year-old patient presenting with skull base osteomyelitis resulting from bilateral otitis media, which is a rare condition.
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OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.
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Skull base osteomyelitis (SBO) is a severe and uncommon infection that typically affects the skull base and may arise from undiagnosed otogenic or sinonasal infection. This case describes a rare presentation of SBO, accompanied by thrombosis of the bilateral internal carotid artery with neurological deficits in a resource-limited environment, illustrating diagnostic and management dilemmas. A male patient aged 40 years with poorly controlled type 2 diabetes presented with sudden onset loss of consciousness and worsening right-sided weakness. MRI studies revealed SBO with cerebral involvement with thrombosis in major cerebral arteries and multiple brain infarcts. After receiving broad-spectrum antibiotics and supportive care shortly after admission, the patient developed septic shock and died two days after admission. The fast course of the disease in this case shows how severe SBO and its complications may be, calling for early diagnosis and intensive management of SBO, especially in diabetic patients. The fact that Staphylococcus epidermidis was established as a causative agent of disease in the absence of artificial heart valves or joints, it is becoming clear that there is a need to increase awareness of such rare pathogens, and probably new strategies for handling such infections should be developed. Additional research is required to elucidate the precise role of the pathogen and refine treatment approaches, especially for low-resource healthcare systems.
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Introduction: Open clavicle fractures are rare, and there are no current reported cases in the literature of a missed open clavicle with resultant fracture-related infection and osteomyelitis. Case Report: We present a 65-year-old female with no reported medical history, who presented to our institution with left clavicular pain and wound drainage 8 days after she was struck by a motor vehicle in her home country of Guyana. She was found to have a missed open clavicle fracture with an associated severe infection. She was subsequently treated with irrigation, debridement, and distal clavicle excision. Conclusion: We present this unique case with a potential procedure which could prove beneficial in cases of infection, trauma, or oncologic lesions in which the distal clavicle is deemed unsalvageable.
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Background: Surgical treatment of spinal infections, refractory to medical treatments, is increasing in incidence. Here, we present a unique case of discitis secondary to an iatrogenic cause, spinal steroid injection, that resulted in acute neurology, ventral phlegmon, and osteomyelitis requiring multiple surgical interventions for treatment. Case Description: With the adoption of minimally invasive spinal surgery, the patient underwent full endoscopic debridement and decompression at our hospital. The endoscopic technique offers a unique avenue to the anatomically difficult ventral phlegmon for surgical excision, cultures, and pathogen identification. The endoscopic debridement was paired with percutaneous pedicle screw fixation to stabilize the spine from the worsening bone destruction. Outcome: The patient recovered well postoperatively, with the resolution of her neurological symptoms and improved mobility. Conclusions: Full endoscopic spinal debridement and decompression is a powerful tool to manage severe spinal discitis and preliminary studies encourage its adoption in surgical practices.
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The chronic and incapacitating condition of infected non-union of the long bones continues to be a challenging issue for surgeons in terms of efficient and economical treatment. A number of variables, such as open fractures, soft tissue or bone loss, infection following internal fixation, persistent osteomyelitis with pathologic fractures, and surgical debridement of infected bone, can result in infected non-unions. An infected non-union is typically treated in two stages. To transform an infected non-union into an aseptic non-union, the initial step involves debridement, either with or without the insertion of antibiotic cement beads and systemic antibiotics. In order to ensure stability, external or internal fixation - with or without bone grafting - is carried out in the second stage. There is a wealth of literature supporting the use of antibiotic-impregnated cement-coated intramedullary (IM) nailing for infected non-union of tibia and femur fractures. In contrast to cement beads, the cement nail offers stability throughout the fracture site, and osseous stability is crucial for the treatment of an infected non-union. When using antibiotics for this purpose, they should possess unique qualities, including low allergenicity, heat stability, and a broad spectrum of activity. The most commonly utilised medication has been gentamicin, which is followed by vancomycin. Furthermore, it has been discovered that solid nails are more resistant to local infection than cannulated IM nails. In this case study, the patient was treated with a solid IM nail that had a specially designed slot on its exterior surface for the application of cement impregnated with antibiotics. In conclusion, an easy, affordable, and successful treatment for infected non-union of the tibia is antibiotic cement-impregnated nailing. It has strong patient compliance and removes the problems associated with external fixators, which makes it superior to them. A few benefits of this approach are early weight-bearing, stabilisation of the fracture, local antibiotic treatment, and the potential for accelerated rehabilitation. Additionally, lowering the requirement for continuous antibiotic medication may lessen the chance that antibiotic resistance may arise.
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A 63-year-old man presented with a 1-month history of worsening mouth pain, particularly under the tongue bilaterally, with left more than right. A physical examination revealed multiple dental caries and bilateral mandibular tori, with the left mandibular torus being exquisitely tender to palpation. Lab tests showed increased inflammatory markers in the absence of leukocytosis. A maxillofacial computed tomography scan revealed findings concerning for chronic osteomyelitis with osteolysis of the left mandibular torus. The patient was started on intravenous antibiotics and transferred to another institution for further management through their oral and maxillofacial surgery service. The surgical pathology after torectomy confirmed the diagnosis of acute osteomyelitis with osteonecrosis. Although rare, this case underscores the importance of familiarity with osteomyelitis in tori of the oral cavity, also highlighting the imaging and clinical correlation. Further research is necessary to understand the risk factors and optimal management strategies for similar cases.
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BACKGROUND: Septic arthritis of shoulder is a rare clinical entity as the metaphysis is extracapsular and there is no communication between epiphyseal and metaphyseal vessels. Septic arthritis of the shoulder joint is a diagnostic and surgical emergency because joint destruction develops rapidly and can cause significant morbidity and mortality. Unusual complications of septic arthritis of the shoulder joint may include extra-articular abscess extension to the upper arm through the biceps groove and osteomyelitis of the greater tuberosity. CASE PRESENTATION: Septic arthritis of the shoulder, if left untreated, can lead to complications such as extra-articular abscess extension and osteomyelitis. Three patients with septic arthritis of the shoulder joint with no clear history of trauma were reported in this study. The initial presentation was pseudoparalysis with upper arm swelling. MRI diagnosed septic arthritis of shoulder joint together with an upper arm abscess. Arthroscopic debridement with through irrigation and open drainage of the extra-articular abscess extension to the upper arm improved both the shoulder pain and abscess completely. However, if shoulder pain or abnormalities in laboratory findings continue after initial treatment, uncontrolled septic arthritis or secondary osteomyelitis are possibilities that should be concerned. MRI is a useful tool for detecting those atypical complications. CONCLUSIONS: Rarely, septic arthritis of the shoulder joint can extend to the upper arm through the biceps tendon groove and cause an abscess. Also, acute osteomyelitis of the tuberosity should be considered in patients with long-standing refractory septic arthritis of the shoulder joint who have continued pain and uncontrolled laboratory findings after initial treatment.
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Currently, despite advancements in diagnostic and therapeutic modalities, osteomyelitis and prosthetic joint infection (PJI) continue to pose significant challenges for orthopaedic surgeons. These challenges are primarily attributed to the high degree of heterogeneity exhibited by these disorders, which are influenced by a combination of environmental and host factors. Recent research efforts have delved into the pathogenesis of osteomyelitis and PJI by investigating single nucleotide polymorphisms (SNPs). This review comprehensively summarizes the current evidence regarding the associations between SNPs and the predisposition to osteomyelitis and PJI across diverse populations. The findings suggest potential linkages between SNPs in genes such as IL-1, IL-6, IFN-γ, TNF-α, VDR, tPA, CTSG, COX-2, MMP1, SLC11A1, Bax, NOS2, and NLRP3 with the development of osteomyelitis. Furthermore, SNPs in genes like IL-1, IL-6, TNF-α, MBL, OPG, RANK, and GCSFR are implicated in susceptibility to PJI. However, it is noted that most of these studies are single-center reports, lacking in-depth mechanistic research. To gain a more profound understanding of the roles played by various SNPs in the development of osteomyelitis and PJI, future multi-center studies and fundamental investigations are deemed necessary.
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Predisposición Genética a la Enfermedad , Osteomielitis , Polimorfismo de Nucleótido Simple , Infecciones Relacionadas con Prótesis , Humanos , Osteomielitis/genética , Infecciones Relacionadas con Prótesis/genética , AnimalesRESUMEN
BACKGROUND: Chronic osteomyelitis poses a formidable challenge for orthopedic practitioners in clinical practice. Chimeric perforator flap is a commonly used repair method for chronic osteomyelitis. The purpose of this study was to compare the clinical efficacy of chimeric anterolateral thigh flap (C-ALTP) and chimeric thoracodorsal artery perforator flap (C-TDAP) for the treatment of chronic osteomyelitis. METHODS: A retrospective analysis was performed on patients with chronic osteomyelitis of the lower extremity who underwent two kinds of treatment with chimeric perforator flaps from January 2014 to March 2022. The preoperative basic data and the operative and postoperative basic information of the two groups were collected and statistically analyzed. RESULTS: Sixty-six patients were included in this study, and both groups achieved satisfactory aesthetic and functional results. Intraoperative results showed that the intraoperative blood loss and flap acquisition time in the C-TDAP group were less than those in the C-ALTP group. The incidence of postoperative complications in the donor and recipient sites in the C-TDAP group was significantly lower than that in the C-ALTP group, which led to a high reoperation rate in the C-ALTP group. Long-term follow-up showed that the wound healing time and weight-bearing walking time in the C-TDAP group were less than those in the C-ALTP group. CONCLUSIONS: Chimeric perforator flaps can effectively be used to treat osteomyelitis with composite tissue defects, eliminate inflammation of the affected limbs, and promote wound healing. However, C-TDAP flaps have more reliable healing effects on wounds and donor sites, and have fewer complications. LEVEL OF EVIDENCE: III, Case-control study.
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The aim of this study was to compare the in vitro activity of delafloxacin with other fluoroquinolones against bacterial pathogens recovered from inpatients with osteomyelitis, Acute Bacterial Skin and Skin-Structure Infections (ABSSSI). In total, 100 bacterial isolates (58â¯% Gram-negative and 42â¯% Gram-positive) recovered from inpatients between January and April 2021, were reidentified at species level by MALDI-TOF MS. Antimicrobial susceptibility testing was conducted using the broth microdilution method and the detection of biofilm formation was assessed through the microtiter plate assay. The screening for mecA was carried out by PCR, while mutations in the Quinolone Resistance Determining Regions (QRDR), specifically gyrA and parC, were analyzed using PCR followed by Sanger sequencing. Results showed that delafloxacin exhibited greater in vitro potency (at least 64-times) than the other tested fluoroquinolones (levofloxacin and ciprofloxacin) when evaluating Staphylococcus aureus (MIC50 ≤0.008â¯mg/L) and coagulase-negative Staphylococcus (MIC50 0.06â¯mg/L). Furthermore, delafloxacin (MIC50 0.25â¯mg/L) was at least 4 times more potent than other tested fluoroquinolones (MIC50 1â¯mg/L) against P. aeruginosa. No difference in delafloxacin activity (MIC50 0.03â¯mg/L) was observed against Enterobacter cloacae when compared with ciprofloxacin (MIC50 0.03â¯mg/L). Despite presenting low activity against K. pneumoniae isolates (22.2â¯%), delafloxacin exhibited twice the activity compared to both levofloxacin and ciprofloxacin. Delafloxacin also exhibited a strong activity (71.4â¯%â85.7â¯%.) against biofilm producing bacterial pathogens tested in this study. Interestingly, 82.14â¯% of the staphylococci tested in this study harbored mecA gene. In addition, the gyrA and parC genes in fluoroquinolone-resistant Gram-negative isolates displayed different mutations (substitutions and deletions). Herein, we showed that delafloxacin was the most active fluoroquinolone against staphylococci (including MRSA) and P. aeruginosa when compared to other fluoroquinolones such as ciprofloxacin and levofloxacin.
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BACKGROUND: Calcaneal osteomyelitis (CO) poses a formidable challenge in treatment due to the distinct anatomical structure and functional properties of the calcaneus. The present study endeavors to furnish a thorough and comprehensive understanding of the clinical manifestations, therapeutic strategies, and therapeutic outcomes pertaining to pediatric calcaneal osteomyelitis (PCO) by conducting a meticulous synthesis and analysis of cases reported in the literature. METHODS: A systematic search of the PubMed, Embase, and Cochrane Library databases was conducted to identify English-language studies analyzing PCO between 2000 and 2021. The quality of the included studies was assessed using the National Institutes of Health (NIH) assessment scale. Effective data were extracted and analyzed. RESULTS: A total of 42 studies, encompassing 128 patients, fulfilled the established inclusion criteria. The gender distribution revealed a male-to-female ratio of 2:1 (81 boys and 40 girls). The median age at the time of diagnosis was 8 years, while the median duration of symptoms was 0.6 month. Trauma emerged as the primary etiology (41 cases, 54%), and limited activity was the most prevalent symptom (68 cases). The positive rate for pathogen culture was 75.4% (49/65), with Staphylococcus aureus being the most commonly isolated pathogen (28 cases, 57.1%). Surgical intervention was performed in 51% (64/126) of the patients, with debridement serving as the primary surgical strategy. The rate of infection recurrence was 6.8% (8/118), and the risk of below-knee amputation was 0.8% (1/124). CONCLUSIONS: PCO occurred more frequently in male patients, with trauma being the primary underlying cause and Staphylococcus aureus being the most prevalent bacterial pathogen isolated. Over half of the patients underwent surgical intervention. Nonetheless, it is imperative that treatment strategies undergo further refinement, as approximately 7% of patients experienced infection recurrence.
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Calcáneo , Osteomielitis , Humanos , Osteomielitis/microbiología , Calcáneo/cirugía , Calcáneo/microbiología , Calcáneo/patología , Niño , Masculino , Femenino , Preescolar , Adolescente , Antibacterianos/uso terapéutico , Staphylococcus aureus/aislamiento & purificación , LactanteRESUMEN
The switch to alternate cell types by Staphylococcus aureus creates sub-populations even within an active population, that are highly resilient, tolerant to antibiotics and lack clinical symptoms of infection. These cells present a challenge for clinical treatment where even after initial intervention has seemingly cleared the infection, these alternate cell types persist within tissue to revert and cause disease. Small colony variants (SCV) are a cell type which facilitate persistent infection but clinically isolated SCVs are often unstable in laboratory conditions. We have isolated a pair of S. aureus isolates from an individual patient with osteomyelitis presenting with heterogenous phenotypes; a stable SCV (sSCV) and a SCV that reverts upon laboratory culturing to the usual, active and non-SCV cell type. Thus we are able use this pair to investigate and compare the genetic mechanisms that underlie the clinical variatons of SCV phenotype. The switch to the sSCV phenotype was associated with frameshift mutations in the enolase eno and the histidine kinase arlS. The phenoptye of the sSCV was an impeded growth dependent on amino acid catabolism and modulated biofilm. These mutations present potentially a new molecular mechanism which confer persistence within osteomyelitis.
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Sickle cell disease includes various inherited hemoglobinopathies due to the production of abnormal hemoglobin molecules. This can lead to significant clinical complications and sequelae. Hemoglobin SC (HbSC) is a notable variant of SCD, requiring early diagnosis and management to prevent severe outcomes. This case report highlights the critical need for SCD screening, particularly among immigrant populations where current U.S. guidelines do not mandate arrival screening. We present the case of a West African male, age 45, with chronic osteomyelitis, who developed a life-threatening pulmonary embolism (PE) due to peripherally inserted central catheter (PICC line) thrombosis, triggering a hemolytic crisis and thereby revealing HbSC disease. The authors of this report advocate for routine SCD screening in high-risk populations through targeted screening programs. Through multidisciplinary management and public health initiatives, we can address the gap in screening and ensure early detection and treatment of SCD in vulnerable populations.
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Wohlfahrtiimonas chitiniclastica (W. chitiniclastica) is an emerging gram-negative bacillus rarely found in patients presenting with fly myiasis or parasitic larvae infection. Here, we present the case of a 58-year-old male who presented with W. chitiniclastica bacteremia from lower extremity wounds complicated by fly larvae infestation. Blood cultures were analyzed with matrix-assisted laser desorption ionization-time of flight mass spectrometry, which identified W. chitiniclastica. The patient was treated with empiric antibiotic therapy with piperacillin-tazobactam and de-escalated to ceftriaxone. We discuss the potential impact of environmental interactions with zoonotic vectors and the concern for the increasing incidence of this new emerging zoonotic infection. This appears to be the first reported case of W. chitiniclastica bacteremia in the southern United States and demonstrates a growing list of climates and locations in which this organism can be present. Further evaluation of potential vectors for W. chitiniclastica continues to be a priority for how cases are distributed and can present in patients.
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To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = <0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p < 0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes.