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Novel Local Antifungal Treatment for Fungal Periprosthetic Joint Infection With Continuous Local Antibiotic Perfusion: A Surgical Technique.

ABSTRACT: Fungal periprosthetic joint infections are one of the most intractable orthopedic disorders. Continuous local antibiotic perfusion allows direct administration of the antifungal agent micafungin into the local infection area at biofilm-disruptive concentrations, while controlling the dead space in addition to conventional treatment. Although the appropriate use of continuous local antibiotic perfusion requires familiarity with the characteristics of local antibiotic perfusion, it is a versatile treatment modality that can improve the clinical outcomes of fungal periprosthetic joint infection in combination with conventional treatment methods.

SUBMITTER: Choe H

PROVIDER: S-EPMC10665700 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Novel Local Antifungal Treatment for Fungal Periprosthetic Joint Infection With Continuous Local Antibiotic Perfusion: A Surgical Technique.

Choe Hyonmin H Maruo Akihiro A Hieda Yuta Y Abe Koki K Kobayashi Naomi N Ike Hiroyuki H Kumagai Ken K Takeyama Masanobu M Kawabata Yusuke Y Inaba Yutaka Y

Arthroplasty today 20231107

Fungal periprosthetic joint infections are one of the most intractable orthopedic disorders. Continuous local antibiotic perfusion allows direct administration of the antifungal agent micafungin into the local infection area at biofilm-disruptive concentrations, while controlling the dead space in addition to conventional treatment. Although the appropriate use of continuous local antibiotic perfusion requires familiarity with the characteristics of local antibiotic perfusion, it is a versatile ...[more]

PMID: 38023642

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Project description:BackgroundAntimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for chronic PJI after total knee arthroplasty performed at our hospital.Subjects and methodsSix patients (male; one case, female; five cases, mean age 79.5 years (70-94)) underwent CLAP for chronic PJI after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17-219), with a mean follow-up of 24.3 months (12-36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment, and CLAP with gentamicin were performed using NPWT. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events.ResultTwo of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients could preserve their components. The organisms responsible for the flare-ups were MSSA in three cases: ESBL-producing E. coli, mixed MSSA and streptococcal infection, Klebsiella pneumonia in one case each, and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5-16); iSAP, mean: 19.3 days (15-28); GM dose, mean: 162.5 mg/day (80-240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection. DAIR with CLAP for chronic post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.

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.

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.

Dataset Information

Novel Local Antifungal Treatment for Fungal Periprosthetic Joint Infection With Continuous Local Antibiotic Perfusion: A Surgical Technique.

Publications

Novel Local Antifungal Treatment for Fungal Periprosthetic Joint Infection With Continuous Local Antibiotic Perfusion: A Surgical Technique.

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