Bacterial infections and antimicrobial resistance are posing substantial difficulties to the worldwide healthcare system. The constraints of conventional diagnostic and therapeutic approaches in dealing with continuously changing infections highlight the necessity for innovative solutions. Aptamers, which are synthetic oligonucleotide ligands with a high degree of specificity and affinity, have demonstrated significant promise in the field of bacterial infection management. This review examines the use of aptamers in the diagnosis and therapy of bacterial infections. The scope of this study includes the utilization of aptasensors and imaging technologies, with a particular focus on their ability to detect conditions at an early stage. Aptamers have shown exceptional effectiveness in suppressing bacterial proliferation and halting the development of biofilms in therapeutic settings. In addition, they possess the capacity to regulate immune responses and serve as carriers in nanomaterial-based techniques, including radiation and photodynamic therapy. We also explore potential solutions to the challenges faced by aptamers, such as nuclease degradation and in vivo instability, to broaden the range of applications for aptamers to combat bacterial infections.
20 October 2021 in Journal of Bone and Joint Infection
Introduction: Two-stage revision surgery is the most frequently performed procedure in patients with a chronic periprosthetic joint infection (PJI). The infection eradication rates in the current literature differ between 54 % and 100 %, which could be attributed to different treatment strategies. The aim of this study was to retrospectively evaluate the infection eradication rate in patients with chronic PJI treated with two-stage revision surgery of the hip or knee in primary and re-revision cases. Methods: All patients treated with a two-stage revision for chronic PJI between 2005 and 2011 were analysed. Patient and infection characteristics were retrieved. Primary outcome was successful infection eradication at last follow-up. Successful eradication is specified as no need for subsequent revision surgery or suppressive antibiotic treatment. Results: Forty-seven patients were treated with a two-stage revision. Infection eradication was achieved in 36 out of 47 cases. Thirty-eight patients had positive cultures: 35 monomicrobial infections and 3 polymicrobial infections. Nine cases of culture-negative infections were identified. Accompanying eradication rates were 26 out of 35 cases, 2 out of 3 cases, and 8 out of 9 cases respectively. Mean follow-up was 128 (27–186) months. For hip and knee revisions the eradication rates were 22 out of 31 cases and 14 out of 16 cases respectively. After primary arthroplasty the infection was eradicated in 29 out of 38 cases and after re-revision in 7 out of 9 cases. Conclusion: In this study, the infection eradication rate for two-stage revision surgery after PJI of the hip and knee in primary and re-revision cases was 77 %. No statistically significant patient, infection and micro-organism characteristics were found which influence the infection eradication rates at long-term follow-up of 128 (27–186) months.
Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A”-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm.
Background: Addressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to Staphylococcus aureus (S. aureus) further complicates the scenario.Objective: To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections.Methods: Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 (225Ac) and lutetium-177 (177Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays.Results: Both [225Ac]4497-IgG1 and [177Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus in planktonic cultures and biofilms over a 96-h exposure period, compared to non-specific antibody control groups. Specifically, doses of 7.4 kBq and 7.4 MBq of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [225Ac]4497-IgG1 and 14.8 Mbq [177Lu]4497-IgG1 led to reductions of two and four logs, respectively.Conclusion: Our findings underscore the effectiveness of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm.
Targeted radionuclide therapy (TRT) has been burgeoning worldwide, with several radiopharmaceuticals for the treatment of metastatic cancers being approved for clinical use
Background and purpose: The Chiari osteotomy was a regular treatment for developmental hip dysplasia before it became mostly reserved as a salvage therapy. However, the long-term survival of the Chiari osteotomy has not been systematically investigated. We investigated the survival time of the Chiari osteotomy until conversion to total hip arthroplasty (THA) in patients with primary hip dysplasia, and factors which correlated with survival, complications, and the improvement measured in radiographic parameters. Patients and methods: Studies were included when describing patients (> 16 years) with primary hip dysplasia treated with a Chiari osteotomy procedure with 8 years’ follow-up. Data on patient characteristics, indications, complications, radiographic parameters, and survival time (endpoint: conversion to THA) were extracted. Results: 8 studies were included. The average postoperative center–edge angle, acetabular head index, and Sharp angle were generally restored within the target range. 3 studies reported Kaplan-Meier survival rates varying from 96% at 10 years to 72% at 20 years’ follow-up. Negative survival factors were high age at intervention and pre-existing advanced preoperative osteoarthritis. Moreover, reported complications ranged between 0% and 28.3 %. Interpretation: The Chiari osteotomy has high reported survival rates and is capable of restoring radiographic hip parameters to healthy values. When carefully selected by young age, and a low osteoarthritis score, patients benefit from the Chiari osteotomy with satisfactory survival rates. The position of the Chiari osteotomy in relation to the periacetabular osteotomies should be further (re-)explored.