Fungal Periprosthetic Knee Joint Infection in a Patient with Metamizole-Induced Agranulocytosis.
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ABSTRACT:
SUBMITTER: Oenning S
PROVIDER: S-EPMC7475080 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lyme arthritis, caused by the spirochete Borrelia burgdorferi sensu stricto, is a common tick-borne illness in New England and the upper Midwest. Most often, the disease affects the knee and has typically been reported as a cause of native joint infection. There has been only 1 case of Lyme periprosthetic joint infection (associated with a total knee arthroplasty) reported in the literature, and to our knowledge, no other reported cases of Lyme periprosthetic joint infections exist. In this article, we report on 2 patients diagnosed with prosthetic joint infections who were subsequently found to have Lyme prosthetic joint infections, with B burgdorferi as the infectious organism. We discuss the medical and surgical management of these patients.
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Project description:A 58-year-old female treated at an outside facility with knee arthrodesis due to persistent periprosthetic joint infection fulfilled all prerequisites for a conversion back to arthroplasty, as part of a 2-stage revision. Owing to the detection of Candida parapsilosis, the treatment concept was converted to a three-stage procedure. A scheduled spacer exchange with additional amphotericin B-loaded polymethylmethacrylate was conducted as an intermediate revision before reimplantation. Conversion in the setting of fungal periprosthetic joint infection presents a challenge, and successful treatment hinges on the use of proper antifungal and antimicrobial protocols, advanced surgical techniques, and a multidisciplinary team approach. At the 3-year follow-up, successful infection eradication as measured by the Delphi-based consensus definition was achieved with a range of motion of 0°-100°.
| S-EPMC7772458 | biostudies-literature
Project description:Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations (p < 1 × 10-7) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41-6.68, p = 1.01 × 10-7) and rs4427239 (OR = 5.47, 95%CI: 2.81-10.65, p = 5.75 × 10-7), of which the latter is located in the SVEP1 gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.
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Project description:While antibiotic-eluting polymethylmethacrylate space maintainers have shown efficacy in the treatment of bacterial periprosthetic joint infection and osteomyelitis, antifungal-eluting space maintainers are associated with greater limitations for treatment of fungal musculoskeletal infections including limited elution concentration and duration. In this study, we have designed a porous econazole-eluting space maintainer capable of greater inhibition of fungal growth than traditional solid space maintainers. The eluted econazole demonstrated bioactivity in a concentration-dependent manner against the most common species responsible for fungal periprosthetic joint infection as well as staphylococci. Lastly, these porous space maintainers retain compressive mechanical properties appropriate to maintain space before definitive repair of the joint or bony defect.
| S-EPMC6009980 | biostudies-literature
Project description:Background and Objective: Agranulocytosis is a rare and potentially life-threatening complication of metamizole (dipyrone) intake that is characterized by a loss of circulating neutrophil granulocytes. While the mechanism underlying this adverse drug reaction is not well understood, involvement of the immune system has been suggested. In addition, associations between genetic variants in the Human Leukocyte Antigen (HLA) region and agranulocytosis induced by other drugs have been reported. The aim of the present study was to assess whether genetic variants in classical HLA genes are associated with the susceptibility to metamizole-induced agranulocytosis (MIA) in a European population by targeted resequencing of eight HLA genes. Design: A case-control cohort of Swiss patients with a history of neutropenia or agranulocytosis associated with metamizole exposure (n = 53), metamizole-tolerant (n = 39) and unexposed controls (n = 161) was recruited for this study. A high-throughput resequencing (HTS) and high-resolution typing method was used to sequence and analyze eight HLA loci in a discovery subset of this cohort (n = 31 cases, n = 38 controls). Identified candidate alleles were investigated in the full Swiss cohort as well as in two independent cohorts from Germany and Spain using HLA imputation from genome-wide SNP array data. In addition, variant calling based on HTS data was performed in the discovery subset for the class I genes HLA-A, -B, and -C using the HLA-specific mapper hla-mapper. Results: Eight candidate alleles (p < 0.05) were identified in the discovery subset, of which HLA-C∗04:01 was associated with MIA in the full Swiss cohort (p < 0.01) restricted to agranulocytosis (ANC < 0.5 × 109/L) cases. However, no candidate allele showed a consistent association in the Swiss, German and Spanish cohorts. Analysis of individual sequence variants in class I genes produced consistent results with HLA typing but did not reveal additional small nucleotide variants associated with MIA. Conclusion: Our results do not support an HLA-restricted T cell-mediated immune mechanism for MIA. However, we established an efficient high-resolution (three-field) eight-locus HTS HLA resequencing method to interrogate the HLA region and demonstrated the feasibility of its application to pharmacogenetic studies.
| S-EPMC7473498 | biostudies-literature
Project description:Periprosthetic joint infection (PJI) can be protracted, incapacitating, needing multiple interventions and could even lead to mortality. Early post-operative PJI has been ascribed to peri-operative introduction of highly virulent bacteria, while delayed post-operative to low-virulence bacteria. Non-tuberculous mycobacteria (NTM) do not figure in the usual list of etiological agents. We report a case of difficult diagnosis of bilateral PJI caused by Mycobacterium abscessus, following bilateral total knee arthroplasty in an elderly male, but treated successfully despite prolonged infection. M. abscessus complex comprises a group of rapidly growing, multidrug-resistant NTM, capable of forming biofilms on prostheses, responsible for wide spectrum of hospital acquired infections. M. abscessus as a cause of PJI is not reported widely. There are a few cases described in literature worldwide. There are no policy guidelines available for treating such cases. High clinical suspicion, with a concerted effort to grow and identify the causal pathogen is important. Standard anti-tubercular therapy is not recommended for treatment due to inherent resistance. Complete excision of infected tissues and removal of prosthesis along with prolonged combination antimicrobial regimen is the treatment of choice.
| S-EPMC6505037 | biostudies-literature
Project description:Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4), and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.
2024-02-19 | GSE255786 | GEO
Project description:The volume of joint replacement surgery has risen steadily in recent years, because the population is aging and increasingly wishes to reserve a high functional status onward into old age. Infection is among the more common complications of joint replacement surgery, arising in 0.2% to 2% of patients, or as many as 9% in special situations such as the implantation of megaprostheses. The associated morbidity and mortality are high. It is thus very important to minimize risk factors for infection and to optimize the relevant diagnostic and therapeutic strategies.This review is based on pertinent publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations.The crucial diagnostic step is joint biopsy for the identification of the pathogenic organism, which succeeds with over 90% sensitivity and specificity. If the prosthesis is firmly anchored in bone, the pathogen is of a type that responds well to treatment, and symptomatic infection has been present only for a short time, then rapidly initiated treatment can save the prosthesis in 35-90% of cases. The pillars of treatment are thorough surgical care (radical débridement) and targeted antibiotic therapy. On the other hand, if the prosthesis is loose or the pathogen is of a poorly treatable type, the infection can generally only be cured by a change of the prosthesis. This can be performed in either one or two procedures, always in conjunction with systemic antibiotic therapy tailored to the specific sensitivity and resistance pattern of the pathogen.The risk of infection of an artificial joint is low, but the overall prevalence of such infections is significant, as the number of implanted joints is steadily rising. Artificial joint infections should be treated by a standardized algorithm oriented toward the recommendations of current guidelines. Many of these recommendations, however, are based only on expert opinion, as informative studies providing high-grade evidence are lacking. Thus, for any particular clinical situation, there may now be multiple therapeutic approaches with apparently comparable efficacy. Randomized trials are urgently needed.
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Project description:Patients with malignancy are often profoundly immunocompromised due to chemotherapy, placing them at potential increased risk for periprosthetic joint infection (PJI). However, there is little information regarding PJI management in these patients. We describe 4 patients with a history of primary total knee arthroplasty followed by diagnosis of multiple myeloma or Waldenström macroglobulinemia who received chemotherapy within 4 months prior to PJI. The Musculoskeletal Infection Society major and minor criteria and either debridement, antibiotics, and implant retention or a 2-stage approach appear to be effective for acute or chronic PJI, respectively. We recommend an anticoagulant be administered concomitantly with antineoplastics that significantly increase deep vein thrombosis risk, and we recommend long-term oral suppressive antibiotics postoperatively, especially if chemotherapy will be resumed. Additional studies are needed to investigate risks and benefits of PJI prophylaxis during chemotherapy and long-term suppressive antibiotics after PJI treatment.
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Project description:We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.
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