Contemporary Prosthetic Joint Infection Management: Is There a Role for Suppressive Antibiotic Therapy?
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ABSTRACT:
SUBMITTER: Sandiford NA
PROVIDER: S-EPMC8347675 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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Contemporary Prosthetic Joint Infection Management: Is There a Role for Suppressive Antibiotic Therapy?
Sandiford Nemandra A NA Kendoff Daniel O DO
Arthroplasty today 20210731
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Project description:Periprosthetic joint infection (PJI) is one of the major complications following arthroplasty implantation. Management of PJIs is a challenge for surgeons and various classification systems have been introduced, which consider variables such as onset of symptoms, pathogenesis and clinical manifestation. In an attempt to overcome the shortcomings which may limit their usefulness in borderline cases, a new classification system focusing on the topography of the infectious process has been proposed. This theory relies on the identification of the exact location of the bacterial colonization thus allowing to decide between a conservative or a more radical intervention irrespectively of the timing. The use of nuclear medicine device like radiolabelled white blood cells (WBC) scan could lead the path in identifying pathogenetic processes and their exact location thus guiding orthopaedic surgeons to the most appropriate diagnosis and treatment options. Currently management relies on debridement, antibiotics and implant retention (DAIR), which is traditionally performed at early stages, 1- or 2-stage revision arthroplasty which is commonly limited to chronic cases. Reports have demonstrated similar rates of infection recurrence following one and two-stage revisions, and the use of one-stage revision surgery is gaining popularity. More recently, satisfying results following partial implant retention during revision total arthroplasty for septic failures have been reported. In addition, in severe cases, definitive articulating antibiotic spacer, excision arthroplasty, arthrodesis or amputation can be performed.
| S-EPMC10929296 | biostudies-literature
Project description:Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study was to describe our approach and its first results in a case series. We analyzed data from patients who received suppressive antibiotic therapy by subcutaneous (SC) route with beta-lactams as salvage therapy for prosthetic joint infection (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and four men with a mean age of 77 years) were included from January 2017 to May 2020. The drugs administered by SC route were ceftazidime (n = 4), ertapenem (n = 4), and ceftriaxone (n = 2). In each patient, PK/PD-guided dosage individualization was performed based on TDM and minimum inhibitory concentration (MIC) measurements. The dose interval could be prolonged from twice daily to thrice weekly in some patients, while preserving the achievement of PK/PD targets. The infection was totally controlled by the strategy in nine out the 10 patients during a median follow-up of 1,035 days (~3 years). No patient acquired carbapenem-resistant Gram-negative bacteria during the follow-up. One patient presented treatment failure with acquired drug resistance under therapy, which could be explained by late MIC determination and insufficient exposure, retrospectively. To conclude, our innovative approach, based on model-based TDM, MIC determination, and individualized PK/PD goals, facilitates, and optimizes suppressive outpatient beta-lactam therapy administered by SC route for PJI. These encouraging results advocate for larger clinical evaluation.
| S-EPMC8044368 | biostudies-literature
Project description:ImportanceIndefinite suppressive antibiotic therapy (SAT) is sometimes prescribed after initial antibiotic treatment for prosthetic joint infection (PJI). Limited evidence on outcomes after SAT exists, and using SAT for patients at low risk who may not need it could be associated with antibiotic resistance and adverse events.ObjectivesTo characterize clinical decision-making about SAT after PJI and identify stewardship intervention opportunities to stop or reduce SAT for patients who may not benefit.Design, setting, and participantsIn this qualitative study, interviews were conducted with 41 clinicians involved in decision-making about SAT after PJI at 8 US Veterans Affairs hospitals between November 1, 2019, and July 31, 2021. Analysis was conducted from June 9, 2020, to August 31, 2022.Main outcomes and measuresSystematic thematic analysis of transcripts of semistructured interviews was conducted to assess the decision-making process for SAT after PJI, including identifying decision-makers, risks and benefits of SAT, and significant time points that occur before or after the SAT prescribing decision.ResultsA total of 41 clinicians were interviewed. Interviewees reported a complex, usually patient-specific, sometimes collaborative decision-making process. Decisions were emotionally charged because of serious possible repercussions for patients and limited evidence about benefits and risks associated with SAT. Surgeons and infectious diseases physicians were the primary SAT prescribers. Their initial risk-benefit calculation for SAT usually included whether revision surgery could be performed and what type, the organism, patient factors, and clinical signs of infection, as well as their perception of the existing evidence base for SAT after PJI. Interviewees identified significant time points that occured before or after the SAT prescribing decision, including PJI treatment decisions and follow-up appointments. Other potential decision-makers over time included patients, primary care physicians, and pharmacists. Interviewees identified opportunities to discuss SAT-associated benefits and risks with patients as well as other clinicians. Interviewees wanted more evidence about patient outcomes to inform prescribing decisions and emphasized the importance of clinician autonomy and buy-in for practice change.Conclusions and relevanceThis qualitative study found that surgeons and infectious diseases physicians often made initial decisions about SAT and identified other potential decision-makers (patients, primary care physicians, pharmacists) and significant time points that occur before or after the SAT prescribing decision, including PJI treatment decisions and follow-up appointments. Stewardship interventions should take into account decision points for patients with PJI across time and the range of decision-makers, including patients, across time.
| S-EPMC11923720 | biostudies-literature
Project description:Identification of Corynebacterium species may be challenging. Corynebacterium species are occasional causes of prosthetic joint infection (PJI), but few data are available on the subject. Based on the literature, C. amycolatum, C. aurimucosum, C. jeikeium, and C. striatum are the most common Corynebacterium species that cause PJI. We designed a rapid PCR assay to detect the most common human Corynebacterium species, with a specific focus on PJI. A polyphosphate kinase gene identified using whole-genome sequence was targeted. The assay differentiates the antibiotic-resistant species C. jeikeium and C. urealyticum from other species in a single assay. The assay was applied to a collection of human Corynebacterium isolates from multiple clinical sources, and clinically relevant species were detected. The assay was then tested on Corynebacterium isolates specifically associated with PJI; all were detected. We also describe the first case of C. simulans PJI.
| S-EPMC3347109 | biostudies-other
Project description:Biofilms are bacterial communities characterized by antibiotic tolerance. Staphylococcus aureus is a leading cause of biofilm infections on medical devices, including prosthetic joints, which represent a significant health care burden. The major leukocyte infiltrate associated with S. aureus prosthetic joint infection (PJI) is granulocytic myeloid-derived suppressor cells (G-MDSCs), which produce IL-10 to promote biofilm persistence by inhibiting monocyte and macrophage proinflammatory activity. To determine how S. aureus biofilm responds to G-MDSCs and macrophages, biofilms were cocultured with either leukocyte population followed by RNA sequencing. Several genes involved in fermentative pathways were significantly upregulated in S. aureus biofilm following G-MDSC coculture, including formate acetyltransferase (pflB), which catalyzes the conversion of pyruvate and coenzyme-A into formate and acetyl-CoA. A S. aureus pflB mutant (ΔpflB) did not exhibit growth defects in vitro. However, ΔpflB formed taller and more diffuse biofilm compared to the wild-type strain as revealed by confocal microscopy. In a mouse model of PJI, the bacterial burden was significantly reduced with ΔpflB during later stages of infection, which coincided with decreased G-MDSC influx and increased neutrophil recruitment, and ΔpflB was more susceptible to macrophage killing. Although formate was significantly reduced in the soft tissue surrounding the joint of ΔpflB-infected mice levels were increased in the femur, suggesting that host-derived formate may also influence bacterial survival. This was supported by the finding that a ΔpflBΔfdh strain defective in formate production and catabolism displayed a similar phenotype to ΔpflB. These results revealed that S. aureus formate metabolism is important for promoting biofilm persistence.
| S-EPMC9670962 | biostudies-literature
Project description:The treatment paradigm for osteoarticular infections (OAIs) has changed drastically over the past 80 years, from the advent of penicillin to the use of broad-spectrum antibiotics. Before these drugs, surgery was the only available treatment for OAIs; today, antibiotic therapy is considered the primary response to them. As a result, surgical treatment of OAIs is thus far more rarely indicated, sometimes even considered outdated and obsolete. However, long experience has taught us that many OAI contexts can still benefit from surgical management, constituting an essential complement to medical treatment. The present article seeks to contextualize this discussion by providing a chronological review of the surgical treatments used in cases of OAI and describing the quality of evidence supporting their rehabilitation in well-established situations.
| S-EPMC9806351 | biostudies-literature
Project description:Prosthetic joint infection caused by Mycobacterium tuberculosis (TBPJI) is uncommon but can be encountered in immunocompromised patients or those from tuberculosis-endemic regions. A lack of clinical suspicion and experience with TBPJI often leads to a delay in diagnosis. We report 2 cases of TBPJI in a Hungarian-Canadian and Iranian-Canadian immigrant, respectively. Both were treated with concurrent surgical and medical therapy. We also performed a literature review on TBPJI case reports, outlining their diagnosis and management.
| S-EPMC8496762 | biostudies-literature
Project description:The empirical use of vancomycin in combination with a broad-spectrum beta-lactam is currently recommended after the initial surgery of prosthetic joint infection (PJI). However, the tolerability of such high-dose intravenous regimens is poorly known. Adult patients receiving an empirical antimicrobial therapy (EAT) for a PJI were enrolled in a prospective cohort study (2011 to 2016). EAT-related adverse events (AE) were described according to the common terminology criteria for AE (CTCAE), and their determinants were assessed by logistic regression and Kaplan-Meier curve analysis. The EAT of the 333 included patients (median age, 69.8 years; interquartile range [IQR], 59.3 to 79.1 years) mostly relies on vancomycin (n = 229, 68.8%), piperacillin-tazobactam (n = 131, 39.3%), and/or third-generation cephalosporins (n = 50, 15%). Forty-two patients (12.6%) experienced an EAT-related AE. Ten (20.4%) AE were severe (CTCAE grade ≥ 3). The use of vancomycin (odds ratio [OR], 6.9; 95% confidence interval [95%CI], 2.1 to 22.9), piperacillin-tazobactam (OR, 3.7; 95%CI, 1.8 to 7.2), or the combination of both (OR, 4.1; 95%CI, 2.1 to 8.2) were the only AE predictors. Acute kidney injury (AKI) was the most common AE (n = 25; 51.0% of AE) and was also associated with the use of the vancomycin and piperacillin-tazobactam combination (OR, 6.7; 95%CI, 2.6 to 17.3). A vancomycin plasma overexposure was noted in nine (37.5%) of the vancomycin-related AKIs only. Other vancomycin-based therapies were significantly less at risk for AE and AKI. The EAT of PJI is associated with an important rate of AE, linked with the use of the vancomycin and the piperacillin-tazobactam combination. These results corroborate recent findings suggesting a synergic toxicity of these drugs in comparison to vancomycin-cefepime, which remains to be evaluated in PJI. (This study has been registered at ClinicalTrials.gov under identifier NCT03010293.).
| S-EPMC6153819 | biostudies-literature
Project description:We performed a meta-analysis to evaluate use of PCR assays for diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.77 to 0.92) and 0.91 (CI, 0.81 to 0.96), respectively. Subgroup analyses showed that use of tissue samples may improve sensitivity, and quantitative PCR and sonication of prostheses fluid may improve specificity. The results showed that PCR is reliable and accurate for detection of PJI.
| S-EPMC3719604 | biostudies-literature
Project description:Helcococcus kunzii was isolated by sonication and conventional cultures obtained from a case of infection following total knee prosthesis in an immunocompetent patient. The patient recovered uneventfully. This is the first known case of an H. kunzii prosthetic joint infection.
| S-EPMC3264187 | biostudies-literature