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Whipple disease (WD) is a rare chronic multisystem infectious disorder caused by the bacterium Tropheryma whipplei (T. whipplei) and is more prevalent than previously thought. Its diagnosis is often delayed by months to years owing to its rarity, non-specific manifestations and insidious course. WD classically presents with polyarthropathy followed months to years later by the development of gastrointestinal symptoms, which often lead to the diagnosis. Pyrexia of unknown origin (PUO) without gastrointestinal involvement is an extremely rare presentation. We describe a case of WD presenting as genuine PUO following immunosuppression with the tumour necrosis factor-alpha monoclonal antibody adalimumab for seronegative polyarthropathy.

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OBJECTIVES: Bone and joint infections (BJI) pose formidable challenges in orthopaedics due to antibiotic resistance and the complexities of biofilm, complicating treatment. This comprehensive exploration addresses the intricate challenges posed by BJI and highlights the significant role of phage therapy as a non-antibiotic strategy. METHODS: BJI, which encompass prosthetic joint infections, osteomyelitis, and purulent arthritis, are exacerbated by biofilm formation on bone and implant surfaces, hindering treatment efficacy. Gram-negative bacterial infections, characterized by elevated antibiotic resistance, further contribute to the clinical challenge. Amidst this therapeutic challenge, phage therapy emerges as a potential strategy, showing unique characteristics such as strict host specificity and biofilm disruption capabilities. RESULTS: The review unveils the dynamics of phages, including their origins, lifecycle outcomes, and genomic characteristics. Animal studies, in vitro investigations, and clinical research provide compelling evidence of the efficacy of phages in treating Staphylococcus aureus infections, particularly in osteomyelitis cases. Phage lysins exhibit biofilm-disrupting capabilities, offering a meaningful method for addressing BJI. Recent statistical analyses reveal high clinical relief rates and a favourable safety profile for phage therapy. CONCLUSIONS: Despite its promise, phage therapy encounters limitations, including a narrow host range and potential immunogenicity. The comprehensive analysis navigates these challenges and charts the future of phage therapy, emphasizing standardization, pharmacokinetics, and global collaboration. Anticipated strides in phage engineering and combination therapy hold promise for combating antibiotic-resistant BJI.

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Streptococcal toxic shock syndrome (STSS) is an uncommon disorder characterised by hypotension and multiorgan failure in the setting of streptococcal infection. Recurrent STSS is rare and has been due to recurrence of the same streptococcal species. Here, we present a case of a patient who developed recurrent STSS from a Streptococcus dysgalactiae right native joint septic arthritis and subsequently from a Streptococcus agalactiae left native joint septic arthritis.

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BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality rates. Optimal antibiotic dosage plays a crucial role in reducing MRSA burden; thus, the use of therapeutic drug monitoring (TDM) in the clinical practice, especially of new drugs such as ceftobiprole, ceftaroline, dalbavancin and oritavancin, should be implemented. OBJECTIVES: We aim to examine and summarize the available evidence about TDM of anti-MRSA molecules, with a focus on pneumonia, endocarditis and vascular infections, and bone and joint infections. SOURCES: We applied "therapeutic drug monitoring" and "Staphylococcus aureus" as search terms in PubMed, considering a time frame of 24 years (2001-2024). Articles in English language, non-duplicated, evaluating antibiotic therapeutic target and role of TDM were included in the study. CONTENT: In this review, available data for therapeutic target and TDM were critically analyzed and summarized and suggestions about the use of old and new anti-MRSA antibiotics were provided, focusing on optimal dosages, tissue penetration according to infection types and toxicity. Limitations to the widespread use of TDM in the clinical practice were discussed. IMPLICATIONS: The use of TDM may play an important role for the optimal management of patients with MRSA infections and may impact on patient outcomes by increasing efficacy and reducing the risk of adverse events. TDM may be implemented in clinical practice, however several limitations such as the wide variability in the methodology and the need for skilled personnel need to be considered.

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Septic arthritis (SA) is a serious infection of the joint which can lead to irreversible destruction of the joint.We report a case of right hip SA with septic pulmonary embolism following a complicated dental extraction in a woman in her early 40s with sickle cell trait (SCT).The patient presented with severe right thigh pain and left jaw pain.Initial workup revealed raised C reactive protein and positive blood cultures. Right hip joint SA was confirmed following intraoperative joint aspiration. The patient had right hip debridement with long-term intravenous antibiotics.The incidence of SA in adults with sickle cell disease is low: 0.3% in a study in France and Brazil and 10.3% incidence of haematogenous osteoarticular infection in children with SCT in West Africa.

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Many clinical conditions can cause fever of unknown origin (FUO) in children, but the etiological diagnosis remains challenging despite the variety of inspection methods available at present. This study aims to investigate the effectiveness of droplet digital polymerase chain reaction (ddPCR) in identifying pathogens in children with FUO as a novel application. A 7-month-old boy failed to obtain etiology evidence for his disease through various tests. After collecting peripheral blood for ddPCR analysis, Staphylococcus aureus and Escherichia coli were detected, and Sanger sequencing confirmed the pathogens. During the disease, the child developed septic arthritis and osteomyelitis in the femur. Despite the patient's fever being removed, his limb activity improving, and inflammatory biomarkers decreasing, avascular necrosis of the femoral head remained after targeted antibiotic treatment and surgery. If the patient had undergone ddPCR analysis at an early stage, it may be possible to avoid sequelae. ddPCR helps identify pathogens in the diagnosis of children with FUO and could be a promising complementary tool.

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A man in his 20s with a medical history of syphilis, chlamydia and HIV presented to the emergency department (ED) with 2 months of right hip pain and was found to have advanced avascular necrosis (AVN) of the right femoral head with secondary haemorrhage. The patient lacked the common risk factors of AVN in patients with HIV (PWH): ≥10 years of HIV diagnosis, extended duration on highly active antiretroviral therapy, trauma, corticosteroid use, alcohol abuse, systemic lupus erythematosus, obesity, smoking and dyslipidaemia. Given the extensive destructive changes in the hip joint and muscles, a right hip resection arthroplasty was performed, and the patient recovered well postoperatively. This case presents a learning opportunity for understanding bone pathologies in PWH and offers clinical guidance for the management of HIV-infected patients with a focus on optimising bone health.

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After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC2-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r2 > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.

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Cat-scratch disease is a zoonosis caused by Bartonella henselae, characterised by regional lymphadenopathy. Rarer presentations, such as osteomyelitis, can occur.We present an adolescent girl with severe right lumbar pain and fever, without animal contacts or recent travels. On examination, pain on flexion of torso, movement limitation and marked lordosis were noted, but there were no inflammatory signs, palpable masses or lymph nodes. Serological investigations revealed elevated inflammatory markers. Imaging revealed a paravertebral abscess with bone erosion. Several microbiological agents were ruled out. After a second CT-guided biopsy, PCR for Bartonella spp was positive. At this point, the family recalled having a young cat some time before. Cat-scratch disease was diagnosed, and complete recovery achieved after treatment with doxycycline and rifampicin.Cat-scratch disease is a challenging diagnosis in the absence of typical features. However, B. henselae must be investigated if common pathogens are ruled out and response to therapy is poor.

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Staphylococcus caprae (S. caprae) is a gram positive, coagulase-negative Staphylococci (CoNS) that occurs as a commensal pathogen on the human skin. It recently has been recognized in causing nosocomial infections involving the bloodstream, urinary tract, heart, bone, and joints, particularly in immunosuppressed patients or individuals with prosthetic devices. Previously, S. caprae was underreported as it was difficult to identify in the clinical microbiology laboratory; however, due to advances in molecular identification methods and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), more clinical cases are being identified in human isolates and appropriately treated. S. caprae osteoarticular infections are usually associated with polymicrobial infections and presence of orthopedic prostheses in immunocompromised adults. This pathogen has an even rarer presentation of bone and joint infections (BJIs) in immunocompetent individuals without orthopedic devices. Our case is of a 65-year-old immunocompetent male with diet-controlled diabetes mellitus type 2 and end-stage renal disease (ESRD) on hemodialysis who presented with worsening mid-thoracic pain after a ground-level fall and was diagnosed with biopsy-proven S. caprae thoracic discitis/osteomyelitis, associated with recurrent catheter-related bloodstream infection (CRBSI). It illustrates the importance of recognizing S. caprae as an emerging human pathogen, even in immunocompetent individuals without orthopedic hardware, requiring prompt targeted treatment of native BJIs to prevent unfavorable outcomes.

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INTRODUCTION: There are currently limited data regarding the clinical and economic significance of skin and soft tissue infections (SSTI) and bone and joint infections in Australian people who inject drugs (PWID). METHODS: Retrospective cohort study in adult PWID admitted to Monash Health, a large heath care network with six hospitals in Victoria, Australia. Inpatients were identified using administrative datasets and International Classification of Disease (ICD-10) coding for specific infection-related conditions. Cost analysis was based on mean ward, intensive care and hospital-in-the-home (HITH) lengths of stay. Spinal infections and endocarditis were excluded as part of previous studies. RESULTS: A total of 185 PWID (61 female, 124 male, median age 37) meeting the study criteria were admitted to Monash Health between January 2010 and January 2021. Admitting diagnoses included 78 skin abscesses, 80 cellulitis, 17 septic arthritis, 4 osteomyelitis, 3 thrombophlebitis and 1 each of necrotising fasciitis, vasculitis and myositis. Pain (87.5%) and swelling (75.1%) were the most common presenting complaints. Opioids (67.4%) and methamphetamine (37.5%) were the most common primary drugs injected. Almost half (46.5%) of patients had concurrent active hepatitis C (HCV) infection on admission. Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) were uncommon. The most significant causative organism was methicillin-susceptible Staphylococcus aureus (24.9%). In 40.0% (74/185) no organism was identified. Patients required a median acute hospital stay of 5 days (2-51 days). There were 15 patients admitted to the intensive care unit (ICU) with median duration 2 days. PICC line insertion for antibiotics was required in 16.8% of patients, while 51.4% required surgical intervention. Median duration of both oral and IV antibiotic therapy was 11 days. Almost half (48.6%) of patients were enrolled in an opioid maintenance program on discharge. Average estimated expenditure was AUD $16, 528 per admission. CONCLUSION: Skin and soft tissue and joint infections are a major cause of morbidity for PWID. Admission to hospital provides opportunistic involvement of addiction specialty services.

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Objective: There is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI. Methods: In this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis. Results: Only SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively. Conclusion: This represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.

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A female infant presented to an Irish hospital with a 4-day history of fever, irritability and reduced oral intake. Initial inflammatory markers were significantly elevated, an erythematous tympanic membrane was noted on examination and an initial diagnosis of acute otitis media was made. By the third hospital day, the infant was noted to be irritable when being lifted up; pseudoparalysis of the right upper limb was observed. A radiograph of the right shoulder was normal; MRI identified acute scapular osteomyelitis with subperiosteal abscess formation. The child underwent 3 washout procedures and received 6 weeks of antibiotic therapy, with full clinical recovery at 3 months. This case highlights the importance of remaining flexible in the context of an evolving presentation and recognising hallmarks of musculoskeletal infection, fever, localised pain and pseudoparalysis. Additionally, we review the literature to highlight clues in diagnosis, treatment and outcome for paediatric acute scapular osteomyelitis.

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Mycobacterium avium complex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients. In this case, we describe the presentation of an otherwise healthy man in his 50s presenting with months of malaise and severe hip pain, with aspiration initially yielding no bacteria and presumed fastidious infection. He was treated with irrigation and debridement, surgical stabilisation of the femoral neck and conventional broad-spectrum antibiotics with final cultures diagnostic of MAC osteomyelitis. This case serves to demonstrate the importance of clinical suspicion and appropriate workup of this unusual case of MAC hip osteomyelitis in an otherwise immunocompetent patient.

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Primary tropical pyomyositis, commonly caused by Staphylococcus aureus, is characterised by suppuration in skeletal muscles, which manifests as single or multiple abscesses. Another rare causative organism is Mycobacterium tuberculosis in endemic areas. Here, we report a case of primary tuberculous pyomyositis presenting as septic arthritis of the right knee and multiple site pyomyositis of the right thigh and chest wall. A tuberculous aetiology was overlooked at first, which resulted in a diagnostic delay. The patient was initially diagnosed, using ultrasonography, MRI and an absence of systemic symptoms of tuberculosis, with bacterial pyomyositis and treated with broad-spectrum antibiotics. However, further investigations performed on knee joint aspirate yielded negative cultures and a positive cartridge-based nucleic acid amplification test, which, along with a non-resolution of his symptoms, suggested a primary tuberculous pyomyositis. He was successfully managed with incision and drainage of the lesions and completion of anti-tubercular therapy.

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PURPOSE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.

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We describe a case of a previously healthy unvaccinated man in his 70s who developed penicillin-susceptible bacteraemic invasive pneumococcal disease due to non-vaccine serotype 23B with the unusual manifestations of multifocal myositis, intramuscular abscesses, polyarticular septic arthritis and synovitis. Blood cultures drawn prior to antibiotic therapy and culture of iliopsoas collection were helpful in making the diagnosis. At follow-up, he had persistent hip pain attributed to avascular necrosis of the head of femur, a possible late complication of his pyomyositis.

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There is a strong rationale for using phages in patients with bone and joint infections (BJIs). Indeed, specific phages can infect and replicate in bacterial pathogens and have also demonstrated their activity in vitro against biofilm produced by different bacteria. However, there is a high variability of the different clinical forms of BJI, and their management is complex and frequently includes surgery followed by the administration of antibiotics. Regardless of the availability of active phages, optimal ways of phage administration in patients with BJIs are unknown. Otherwise, all BJIs are not relevant for phage therapy. Except for diabetic foot infection, a BJI with bone exposure is potentially not a relevant indication for phage therapy. On the counterpart, prosthetic joint infections in patients for whom a multidisciplinary expert team judges a conservative approach as the best option to keep the patient's function seem to be a relevant indication with the hypothesis that phage therapy could increase the rate of infection control. The ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA) was created in 2022. One century after the first use of phages as a therapy, the phage therapy 2.0 era, with the possibility to evaluate personalized phage therapy in modern medicine and orthopedic surgery, is just open.

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Acute septic arthritis is a rare, potentially severe infection that requires immediate treatment to avoid long-term morbidity. Most common aetiological agents are commonly used for empirical treatment, but the choice of antibiotics may be influenced by other factors, such as the patient's age and the epidemiological context.We report an infant with elbow arthritis, whose treatment was changed after Streptococcus pneumoniae serotype 9N was isolated in the blood and synovial fluid. The child underwent arthrocentesis and received intravenous ampicillin followed by oral amoxicillin, with a favourable response and no sequelae at 1-year follow-up.We report an uncommon manifestation of invasive pneumococcal disease in a young immunised healthy infant caused by a non-vaccine serotype. The presence of S. pneumoniae should be considered in joint infections, especially in infants and those with a history of respiratory symptoms.

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