A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study.
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ABSTRACT:
SUBMITTER: Gimeno M
PROVIDER: S-EPMC4644989 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Surgeries' sterile conditions and perioperative antibiotic therapies decrease implant associated infections rates significantly. However, up to 10% of orthopedic devices still fail due to infections. An implant infection generates a high socio-economic burden. An early diagnosis of an infection would significantly improve patients' outcomes. There are numerous clinical tests to diagnose infections. The "Gold Standard" is a microbiological culture, which requires an invasive sampling and lasts up to several weeks. None of the existing tests in clinics alone is sufficient for a conclusive diagnosis of an infection. Meanwhile, there are functional imaging modalities, which hold the promise of a non-invasive, quick, and specific infection diagnostic. This review focuses on orthopedic implant-associated infections, their pathogenicity, diagnosis and functional imaging.
| S-EPMC4665528 | biostudies-literature
Project description:The anaerobic Gram-positive coccus Finegoldia magna is a rare cause of infections of bone and joints. The aim of this study was to describe the microbiological and clinical characteristics of orthopedic implant-associated infections caused by F. magna We retrospectively analyzed samples consisting of anaerobic Gram-positive cocci and samples already identified as F. magna from patients with orthopedic infections. The isolates found were determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern was determined by Etest. Whole-genome sequencing (WGS) was performed. Clinical data were extracted from each patient's journal. In nine patients, orthopedic joint implant-associated infections were identified as being caused by F. magna The isolates were susceptible to most of the antibiotics tested, with the exception of rifampin and moxifloxacin in a few cases. Five of the nine infections were monomicrobial. The most common antibiotic used to treat the infection was penicillin V, but five of the nine patients received a combination of antibiotics. Eight patients underwent surgical treatment, with extraction of the implant performed in seven cases and reimplantation in only two cases. The WGS showed a relatively small core genome, with 126,647 single nucleotide polymorphisms identified within the core genome. A phylogenomic analysis revealed that the isolates clustered into two distinct clades. Orthopedic implant-associated infections caused by F. magna are rare, but the bacteria are generally susceptible to antibiotics. Despite this, surgical treatment combined with long-term antibiotics is often necessary. The WGS analysis revealed a high heterogeneity and suggested the existence of at least two different Finegoldia species.
| S-EPMC5654912 | biostudies-literature
Project description:Antibiotic-loaded bone graft substitutes are attractive clinical options and have been used for years either for prophylaxis or therapy for periprosthetic and fracture-related infections. Calcium sulfate and hydroxyapatite can be combined in an injectable and moldable bone graft substitute that provides dead space management with local release of high concentrations of antibiotics in a one-stage approach. With the aim to test preventive strategies against bone infections, a commercial hydroxyapatite/calcium sulfate bone graft substitute containing either gentamicin or vancomycin was tested against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, harboring different resistance determinants. The prevention of bacterial colonization and biofilm development by selected microorganisms was investigated along with the capability of the eluted antibiotics to select for antibiotic resistance. The addition of antibiotics drastically affected the ability of the selected strains to adhere to the tested compound. Furthermore, both the antibiotics eluted by the bone graft substitutes were able to negatively impair the biofilm maturation of all the staphylococcal strains. As expected, P. aeruginosa was significantly affected only by the gentamicin containing bone graft substitutes. Finally, the prolonged exposure to antibiotic-containing sulfate/hydroxyapatite discs did not lead to any stable or transient adaptations in either of the tested bacterial strains. No signs of the development of antibiotic resistance were found, which confirms the safety of this strategy for the prevention of infection in orthopedic surgery.
| S-EPMC7729858 | biostudies-literature
Project description:OBJECTIVES:This pilot study aimed to compare the commercial Unyvero ITI multiplex PCR application (U-ITI, Curetis GmbH) with conventional culturing concerning (a) detection of pathogens, (b) time to detection of pathogens and (c) time to and quality of antibiotic treatment recommendation in diagnostics of orthopedic implant-associated infections (OIAI). RESULTS:72 tissue biopsies from 15 consecutive patients with deep OIAI infections were analyzed with conventional culturing including phenotypic antibiotic susceptibility testing and the U-ITI. U-ITI showed lower sensitivity than conventional culturing concerning detection of pathogens (73% vs 93%). 4/15 patients would have been given false negative results by U-ITI, all of which were culture-positive for Staphylococcus species. Median time to detection of pathogens was 47 h and antibiotic resistance 89 h by conventional methods compared to 13.5 h with the U-ITI. The U-ITI did not detect antibiotic resistance, whereas conventional culturing showed resistance to antibiotics covered by the U-ITI panel in 2 patients. Time to detection of pathogens was improved, but the detection limit for staphylococci was unsatisfactory. Although the time to antibiotic treatment recommendation was significantly reduced, the U-ITI would have resulted in incorrect antibiotic recommendation in 2 patients. Our data do not support use of this assay in diagnostics.
| S-EPMC6836655 | biostudies-literature
Project description:Prevention of orthopedic implant-related infections is a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current therapies, based on antibiotic administration, have proven to be insufficient, and infection prevalence may rise due to the dissemination of antibiotic resistance. Antimicrobial peptides (AMPs) have attracted attention as promising substitutes of conventional antibiotics, owing to their broad-spectrum of activity, high efficacy at very low concentrations, and, importantly, low propensity for inducing resistance. The aim of this review is to offer an updated perspective of the development of AMPs-based preventive strategies for orthopedic and dental implant-related infections. In this regard, two major research strategies are herein addressed, namely (i) AMP-releasing systems from titanium-modified surfaces and from bone cements or beads; and (ii) AMP immobilization strategies used to graft AMPs onto titanium or other model surfaces with potential translation as coatings. In overview, releasing strategies have evolved to guarantee higher loadings, prolonged and targeted delivery periods upon infection. In addition, avant-garde self-assembling strategies or polymer brushes allowed higher immobilized peptide surface densities, overcoming bioavailability issues. Future research efforts should focus on the regulatory demands for pre-clinical and clinical validation towards clinical translation.
| S-EPMC8625235 | biostudies-literature
Project description:Staphylococcus spp. remain the leading biofilm-forming agents causing orthopedic implant-associated infections (OIAI). This is a descriptive study of phenotypic and genomic features identified in clinical isolates of S. aureus and coagulase-negative Staphylococcus (CoNS) recovered from OIAIs patients that progressed to treatment failure. Ten isolates were identified by matrix-time-of-flight laser-assisted desorption mass spectrometry (MALDI-TOF-MS) and tested for antibiotic susceptibility and biofilm formation. Genotypic characteristics, including, MLST (Multi Locus Sequence Typing), SCCmec typing, virulence and resistance genes were assessed by whole-genome sequencing (WGS). All S. aureus harbored mecA, blaZ, and multiple resistance genes for aminoglycosides and quinolones. All MRSA were strong biofilm producers harboring the complete icaADBC and icaR operon. Seven CoNS isolates comprising five species (S. epidermidis, S. haemolyticus, S. sciuri, S. capitis and S. lugdunensis) were analyzed, with mecA gene detected in five isolates. S. haemolitycus (isolate 95), and S. lugdunensis were unable to form biofilm and did not harbor the complete icaADBCR operon. High variability of adhesion genes was detected, with atl, ebp, icaADBC operon, and IS256 being the most common. In conclusion, MRSA and CoNS isolates carrying genes for biofilm production, and resistance to β-lactam and aminoglycosides are associated with treatment failure in OIAIs.
| S-EPMC9230661 | biostudies-literature
Project description:Staphylococcus aureus is a major human pathogen causing serious implant–associated infections. Combination treatment with rifampin (10 to 15 mg/kg per day), which has dose-dependent activity, is recommended to treat S. aureus orthopedic implant–associated infections. Rifampin, however, has limited bone penetration. Here, dynamic 11C-rifampin positron emission tomography (PET) performed in prospectively enrolled patients with confirmed S. aureus bone infection (n = 3) or without orthopedic infection (n = 12) demonstrated bone/plasma area under the concentration-time curve ratio of 0.14 (interquartile range, 0.09 to 0.19), exposures lower than previously thought. PET-based pharmacokinetic modeling predicted rifampin concentration-time profiles in bone and facilitated studies in a mouse model of S. aureus orthopedic implant infection. Administration of high-dose rifampin (human equipotent to 35 mg/kg per day) substantially increased bone concentrations (2 mg/liter versus <0.2 mg/liter with standard dosing) in mice and achieved higher bacterial killing and biofilm disruption. Treatment for 4 weeks with high-dose rifampin and vancomycin was noninferior to the recommended 6-week treatment of standard-dose rifampin with vancomycin in mice (risk difference, −6.7% favoring high-dose rifampin regimen). High-dose rifampin treatment ameliorated antimicrobial resistance (0% versus 38%; P = 0.04) and mitigated adverse bone remodeling (P < 0.01). Last, whole-genome sequencing demonstrated that administration of high-dose rifampin in mice reduced selection of bacterial mutations conferring rifampin resistance (rpoB) and mutations in genes potentially linked to persistence. These data suggest that administration of high-dose rifampin is necessary to achieve optimal bone concentrations, which could shorten and improve treatments for S. aureus orthopedic implant infections.
| S-EPMC8693472 | biostudies-literature
Project description:BackgroundPerioperative antibiotic prophylaxis in non-infected orthopedic surgery is evident, in contrast to prophylaxis during surgery for infection. Epidemiological data are lacking for this particular situation.Methods and findingsIt is a single-center cohort on iterative surgical site infections (SSIs) in infected orthopedic patients. We included 2480 first episodes of orthopedic infections (median age 56 years and 833 immune-suppressed): implant-related infections (n = 648), osteoarticular infections (1153), and 1327 soft tissue infections. The median number of debridement was 1 (range, 1-15 interventions). Overall, 1617 infections (65%) were debrided once compared to 862 cases that were operated multiple times (35%). Upon iterative intraoperative tissue sampling, we detected pathogens in 507 cases (507/862; 59%), of which 241 (242/507; 48%) corresponded to the initial species at the first debridement. We witnessed 265 new SSIs (11% of the cohort) that were resistant to current antibiotic therapy in 174 cases (7% of the cohort). In multivariate analysis, iterative surgical debridements that were performed under current antibiotic administration were associated with new SSIs (odds ratio 1.6, 95%CI 1.2-2.2); mostly occurring after the 2nd debridement. However, we failed to define an ideal hypothetic prophylaxis during antibiotic therapy to prevent further SSIs.ConclusionsSelection of new pathogens resistant to ongoing antibiotic therapy occurs frequently during iterative debridement in orthopedic infections, especially after the 2nd debridement. The new pathogens are however unpredictable. The prevention, if feasible, probably relies on surgical performance and wise indications for re-debridement instead of new maximal prophylactic antibiotic coverage in addition to current therapeutic regimens.
| S-EPMC6919616 | biostudies-literature
Project description:ObjectivesTotal joint arthroplasty is one of the most frequent and effective surgeries today. However, despite improved surgical techniques, a significant number of implant-associated infections still occur. Suitable in vitro models are needed to test potential approaches to prevent infection. In the present study, we aimed to establish an in vitro co-culture setup of human primary osteoblasts and S. epidermidis to model the onset of implant-associated infections, and to analyze antimicrobial implant surfaces and coatings.Materials and methodsFor initial surface adhesion, human primary osteoblasts (hOB) were grown for 24 hours on test sample discs made of polystyrene, titanium alloy Ti6Al4V, bone cement PALACOS R®, and PALACOS R® loaded with antibiotics. Co-cultures were performed as a single-species infection on the osteoblasts with S. epidermidis (multiplicity of infection of 0.04), and were incubated for 2 and 7 days under aerobic conditions. Planktonic S. epidermidis was quantified by centrifugation and determination of colony-forming units (CFU). The quantification of biofilm-bound S. epidermidis on the test samples was performed by sonication and CFU counting. Quantification of adherent and vital primary osteoblasts on the test samples was performed by trypan-blue staining and counting. Scanning electron microscopy was used for evaluation of topography and composition of the species on the sample surfaces.ResultsAfter 2 days, we observed approximately 104 CFU/ml biofilm-bound S. epidermidis (103 CFU/ml initial population) on the antibiotics-loaded bone cement samples in the presence of hOB, while no bacteria were detected without hOB. No biofilm-bound bacteria were detectable after 7 days in either case. Similar levels of planktonic bacteria were observed on day 2 with and without hOB. After 7 days, about 105 CFU/ml planktonic bacteria were present, but only in the absence of hOB. Further, no bacteria were observed within the biofilm, while the number of hOB was decreased to 10% of its initial value compared to 150% in the mono-culture of hOB.ConclusionWe developed a co-culture setup that serves as a more comprehensive in vitro model for the onset of implant-associated infections and provides a test method for antimicrobial implant materials and coatings. We demonstrate that observations can be made that are unavailable from mono-culture experiments.
| S-EPMC4794246 | biostudies-literature
Project description:New antibiotics should ideally exhibit activity against drug-resistant bacteria, delay the development of bacterial resistance to them and be suitable for local delivery at desired sites of infection. Here, we report the rational design, via molecular-docking simulations, of a library of 17 candidate antibiotics against bone infection by wild-type and mutated bacterial targets. We screened this library for activity against multidrug-resistant clinical isolates and identified an antibiotic that exhibits potent activity against resistant strains and the formation of biofilms, decreases the chances of bacterial resistance and is compatible with local delivery via a bone-cement matrix. The antibiotic-loaded bone cement exhibited greater efficacy than currently used antibiotic-loaded bone cements against staphylococcal bone infections in rats. Potent and locally delivered antibiotic-eluting polymers may help address antimicrobial resistance.
| S-EPMC10101771 | biostudies-literature