Implant-related Osteomyelitis Research Articles

Adipose-derived stem cells and antibiotics: A novel synergistic approach for treating implant-related osteomyelitis.

Implant-related osteomyelitis poses a significant challenge in orthopedic practice, particularly due to the increasing prevalence of antibiotic-resistant infections and biofilm-associated complications. This article focused on exploring the potential of combination therapy with adipose-derived stem cells (ADSCs) and antibiotics to overcome these challenges, thereby enhancing treatment efficacy. A systematic synthesis of the results of recent in vivo studies, predominantly those using rat models, was performed. Studies that evaluated the effectiveness of ADSCs combined with antibiotics against common pathogens in implant-related osteomyelitis, particularly Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, were selected. A significant reduction in symptoms such as swelling, abscess formation, and bacterial burden in the ADSCs + antibiotic-treated group was observed in all studies. In addition, microcomputed tomography revealed reduced osteolysis, indicating enhanced bone preservation. Furthermore, histological examination revealed improved tissue structure and altered immune response, signifying the dual role of ADSCs in enhancing antibiotic action and modulating the immune system. This review highlights the promising role of the concurrent use of ADSCs and antibiotics in the treatment of implant-related osteomyelitis. This novel therapeutic strategy has the potential to revolutionize the management of complex orthopedic infections, especially those resistant to conventional treatments. However, further research is required to translate the results of animal studies into clinical applications and to develop optimized treatment protocols for human use.

Magnesium implants with alternating magnetic field-enhanced hydrogen release and proton depletion for anti-infection treatment and tissue repair

Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H2 gas and ions (OH− and Mg2+) for the treatment of osteomyelitis. H2 released by Mg rods under AMFs effectively scavenged cytotoxic ROS, exhibiting anti-inflammatory effects and consequently disrupting the environment of bacterial infections. In addition, the OH− hindered the energy metabolism of bacteria by effectively neutralizing protons within the microenvironment. Moreover, H2 impaired the permeability of bacterial membranes and expedited the damage induced by OH−. This synergistic AMF-induced H2 and proton depletion treatment approach not only killed both gram-negative and gram-positive bacteria but also effectively treated bacterial infections (abscesses and osteomyelitis). Moreover, Mg2+ released from the Mg rods enhanced and accelerated the process of bone osteogenesis. Overall, our work cleverly exploited the eddy-thermal effect and chemical activity of Mg implants under AMFs, aiming to eliminate the inflammatory environment and combat bacterial infections by the simultaneous release of H2, OH−, and Mg2+, thereby facilitating tissue regeneration. This therapeutic strategy achieved multiple benefits in one, thus presenting a promising avenue for clinical application.

Occurrence and significance of elevated D-dimer levels in different types of osteomyelitis: a clinical study.

Plasma D-dimer levels >0.5 mg/L are encountered in various conditions besides venous thromboembolism (VTE). Recent studies use them as a prognostic indicator for systemic and inflammatory diseases. The clinical significance of abnormal levels is unclear in osteomyelitis patients with baseline elevation. Our study reviews the occurrence and significance of >0.5 mg/L D-dimer levels in different types of osteomyelitis. This study involved 125 individuals, out of which 94 were male and 31 were female. The patients were divided into two groups based on the results of bacterial culture testing. Group A comprised those who tested positive for bacterial culture, while group B included those who tested negative. Out of 68 samples tested, 56% were found to have Staphylococcus aureus. All 125 patients underwent blood testing, which included measuring the D-dimer levels, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and MHR monocyte to high-density lipoprotein cholesterol (HDL-C) ratio in different types of osteomyelitis. The statistical analysis of these tests was carried out. Although there were no significant differences in white blood cell (WBC) count, Neutrophil count, Lymphocyte count, or erythrocyte sedimentation rate (ESR) as well as the NLR, PLR, LMR, MHR, HDL-C ratio. The C-reactive protein (CRP) levels were significantly higher in group A (26.13±50.30) than in group B (10.76±18.70) (p<0.05). D-dimer levels were elevated in 40.8% of patients with bacterial culture-positive osteomyelitis, negative culture osteomyelitis, implants with fractures, and no trauma osteomyelitis. No correlation was found between the increase in D-dimer levels and the presence of bacterial culture or implant-related osteomyelitis in patients. No significant correlation was found between D-dimers and osteomyelitis, including positive bacterial cultures, implant-related osteomyelitis, or osteomyelitis without trauma. However, 40% of the patients had higher D-dimer levels.

The clinical significance of inflammatory biomarkers, IL6 cytokine, and systemic immune inflammatory index in rabbit model of acute and chronic Methicillin-resistant Staphylococcus epidermidis-induced osteomyelitis.

Infections are a major complication of open fractures and fracture fixation. In this study, an innovative bioactive medical device was used to experimentally treat MRSE-induced osteomyelitis in rabbit tibia. This paper investigates the clinical significance of inflammatory biomarkers (NLR, PLR, MLR and PMR), SII and IL-6 and assesses their role in the development of osteomyelitis. The main objective is to identify the utility of hematological reports derived from neutrophils, leukocytes, monocytes and platelets in the evolution of implant-related osteomyelitis and the estimation of treatment efficiency. In particular, this study compares the response of these inflammatory markers to different treatments in the presence or absence of bioactive materials and/or topical antibiotics over time. The analysis of the threads showed that NLR, PLR and SII had high values in the acute phase of the disease, so that after chronicization, they decrease. The animals treated with vancomycin nano-functionalized peptide-enriched silk fibroin-coated implants showed lower levels of inflammatory biomarkers compared to the other groups (empty implants and peptide-enriched silk fibroin-coated implants). NLR, PLR and SII, complemented by IL-6 can be used as fairly accurate biomarkers for the diagnosis of osteomyelitis.

Pyro-piezoelectric effect of BaTiO3 bio-nanocarrier for osteomyelitis therapy

Implant-related osteomyelitis harms patients’ health and lives. Non-invasive treatments triggered by external physical stimuli have been brought into focus in antibiosis. Herein, a therapeutic strategy through coupling piezoelectricity and pyroelectricity of BaTiO3 nanotubes (BNT) by synchronous treatments of ultrasound (US) and near-infrared light (NIR) is applied to kill bacteria in an osteomyelitis model. NIR or US treatment reduces spontaneous polarization of BNT, inducing pyroelectric/piezoelectric field and energy band tilting. Compared with single treatment, their synergistic effect further enhances charge transfer and electron-hole pair separation, improving the pyro-piezoelectric catalysis and thus the yield of reactive oxygen species (ROS); meanwhile, the tilting of energy bands induces an irreversible conductive circuit from bacteria to BNT, resulting in membrane electron loss and the disrupted bacterial metabolic balance. As a result, 99.8% of bacteria are killed under the pyro-piezoelectric therapy of BNT. Additionally, BNT with nanotubular structure acts as nanocarriers to load and release bone morphogenetic protein-2 (BMP-2), improving bone regeneration obviously after antibacterial therapy. This study provides a promising pyro-piezoelectric therapy by BMP-2 loaded BaTiO3 nanotubes for antibiosis and bone regeneration in treating osteomyelitis. It also brings new insight for developing pyro-piezoelectric sensors to deal with tissue infection.

Extended Release Combination Antibiotic Therapy from a Bone Void Filling Putty for Treatment of Osteomyelitis.

In spite of advances in Total Joint Replacements (TJR), infection remains a major concern and a primary causative factor for revision surgery. Current clinical standards treat these osteomyelitis infections with antibiotic-laden poly(methyl methacrylate) (PMMA)-based cement, which has several disadvantages, including inadequate local drug release kinetics, antibiotic leaching for a prolonged period and additional surgical interventions to remove it, etc. Moreover, not all antibiotics (e.g., rifampicin, a potent antibiofilm antibiotic) are compatible with PMMA. For this reason, treatment of TJR-associated infections and related complications remains a significant concern. The objective of this study was to develop a polymer-controlled dual antibiotic-releasing bone void filler (ABVF) with an underlying osseointegrating substrate to treat TJR implant-associated biofilm infections. An ABVF putty was designed to provide sustained vancomycin and rifampicin antibiotic release for 6 weeks while concurrently providing an osseointegrating support for regrowth of lost bone. The reported ABVF showed efficient antibacterial and antibiofilm activity both in vitro and in a rat infection model where the ABVF both showed complete bacterial elimination and supported bone growth. Furthermore, in an in vivo k-wire-based biofilm infection model, the ABVF putty was also able to eliminate the biofilm infection while supporting osseointegration. The retrieved k-wire implants were also free from biofilm and bacterial burden. The ABVF putty delivering combination antibiotics demonstrated that it can be a viable treatment option for implant-related osteomyelitis and may lead to retention of the hardware while enabling single-stage surgery.

Biomimetic multilayer coatings deliver gentamicin and reduce implant-related osteomyelitis in rats.

Implant-related infections like periprosthetic joint infections (PJI) are still a challenging issue in orthopedic surgery. In this study, we present a prophylactic anti-infective approach based on a local delivery of the antibiotic gentamicin. The local delivery is achieved via a nanoscale polyelectrolyte multilayer (PEM) coating that leaves the bulk material properties of the implant unaffected while tuning the surface properties. The main components of the coating, i.e. polypeptides and sulfated glycosaminoglycans (sGAG) render this coating both biomimetic (matrix mimetic) and biodegradable. We show how adaptions in the conditions of the multilayer assembly process and the antibiotic loading process affect the amount of delivered gentamicin. The highest concentration of gentamicin could be loaded into films composed of polypeptide poly-glutamic acid when the pH of the loading solution was acidic. The concentration of gentamicin on the surface could be tailored with the number of deposited PEM layers. The resulting coatings reveal a bacteriotoxic effect on Staphylococcus cells but show no signs of cytotoxic effects on MC3T3-E1 osteoblasts. Moreover, when multilayer-coated titanium rods were implanted into contaminated medullae of rat tibiae, a reduction in the development of implant-related osteomyelitis was observed. This reduction was more pronounced for the multifunctional, matrix-mimetic heparin-based coatings that only deliver lower amounts of gentamicin.

Gentamicin coating of nanotubular anodized titanium implant reduces implant-related osteomyelitis and enhances bone biocompatibility in rabbits.

Titanium and titanium alloy are widely used as orthopedic implants for their favorable mechanical properties and satisfactory biocompatibility. The aim of the present study was to investigate the antibacterial effect and bone cell biocompatibility of a novel implant made with nanotubular anodized titanium coated with gentamicin (NTATi-G) through in vivo study in rabbits. The animals were divided into four groups, each receiving different kinds of implants, that is, NTATi-G, titanium coated with gentamicin (Ti-G), nanotubular anodized titanium uncoated with gentamicin (NTATi) and titanium uncoated with gentamicin (Ti). The results showed that NTATi-G implant prevented implant-related osteomyelitis and enhanced bone biocompatibility in vivo. Moreover, the body temperature of rabbits in NTATi-G and Ti-G groups was lower than those in Ti groups, while the weight of rabbits in NTATi-G and Ti-G groups was heavier than those in NTATi and Ti groups, respectively. White blood cell counts in NTATi-G group were lower than NTATi and Ti groups. Features of myelitis were observed by X-ray films in the NTATi and Ti groups, but not in the NTATi-G and Ti-G groups. The radiographic scores, which assessed pathology and histopathology in bone tissues, were significantly lower in the NTATi-G and Ti-G groups than those in the NTATi and Ti groups, respectively (P<0.05). Meanwhile, explants and bone tissue culture demonstrated significantly less bacterial growth in the NTATi-G and Ti-G groups than in the NTATi and Ti groups, respectively (P<0.01). The bone volume in NTATi-G group was greater than Ti-G group, and little bone formation was seen in NTATi and Ti groups.

Active and Passive Immunization Against Staphylococcus aureus Periprosthetic Osteomyelitis in Rats.

Staphylococcus aureus infection associated with orthopedic implants cannot always be controlled. We used a knee prosthesis model with implant-related osteomyelitis in rats to explore induction of an effective immune response with active and passive immunization. Fifty-two Sprague-Dawley rats were divided into active (N=28) and passive immunization groups (N=24). A bacterial inoculum of 103 S. aureus MN8 was injected into the tibia and the femur marrow before insertion of a non-constrained knee prosthesis in each rat. The active-immunization group received a synthetic oligosaccharide of polysaccharide poly-N-acetylglucosamine (PNAG), 9G1cNH2 and the passive-immunization group received immunization with immunoglobulin from rabbits infected with S. aureus. Active immunization against PNAG significantly reduced the consequences of osteomyelitis infection from PNAG-producing intercellular adhesion (ica+) but not ica- S. aureus. Passive immunization resulted in better clinical assessments in animals challenged with either ica+ or ica- S. aureus, suggesting a lack of specificity in this antiserum.

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings invivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S.aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C=0.111±0.023; D=0.056±0.006) compared to the positive control group (B: 0.244±0.015; p<0.05) was observed. The radiographic osteomyelitis scores confirmed these histological findings.

A new model of implant-related osteomyelitis in the metaphysis of rat tibiae.

BackgroundAnimal models serve as an important tool to understand peri-implant infection. Most of the models use high bacterial loads (>104 colony forming units, CFU) to provide high infection rates. Therefore these animals evolve rather similarly, making comparison between groups and statistical analysis possible. On the other hand, to mimic clinical constellation of surgery-related infections the use of low amounts of bacteria would be more advantageous.MethodsWe developed a metaphyseal rat model of peri-implant bone infection with low amount of bacterial loads (102 and 103 CFU of Staphylococcus aureus) and investigated osseointegration of the implants coated with hydroxyapatite (HA) and low-dosed HA-silver (HA-Ag). Non-infected implants served as controls. After 6 weeks rats were sacrificed and implants evaluated for osseointegration and infection.ResultsInfection of implanted devices was reliably induced, independently whether 102 or 103 CFU of S. aureus were inoculated and HA or HA-Ag coated implants were used. No systemic infection was present in any of the animals at the time of sacrifice, and no animal developed acute infection requiring premature sacrifice. All CFU counts of the implant and the bone at sacrifice were significantly higher than the inoculated load (p < .05). All sterilely inserted implants showed excellent osseointegration and no infection.ConclusionsOur present study of a rat tibia model reliably induced osteomyelitis in the metaphysis with low-doses of bacteria. The addition of low-dosed Ag to the implant coating was not able to reduce the infection rates. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with low amounts of bacteria to better mimic clinical constellations. No other promoters of infection besides insertion of the screw implant were used in this model.

A rabbit humerus model of plating and nailing osteosynthesis with and without Staphylococcus aureus osteomyelitis.

The local mechanical environment at a fracture is known to influence biological factors such as callus formation, immune cell recruitment and susceptibility to infection. Infection models incorporating a fracture are therefore required to evaluate prevention and treatment of infection after osteosynthesis. The aim of this study was to create humane, standardised and repeatable preclinical models of implant-related bone infection after osteosynthesis in the rabbit humerus. Custom-designed interlocked intramedullary nails and commercially available locking plates were subjected to biomechanical evaluation in cadaveric rabbit humeri; a 10-week in vivo healing study; a dose response study with Staphylococcus aureus over 4 weeks; and finally, a long-term infection of 10 weeks in the plate model.Outcome measures included biomechanical testing, radiography, histology, haematology and quantitative bacteriology. Both implants offered similar biomechanical stability in cadaveric bones, and when applied in the in vivo study, resulted in complete radiographic and histological healing and osteotomy closure within 10-weeks. As expected in the infection study, higher bacterial doses led to an increasing infection rate. In both infected groups, there was a complete lack of osteotomy closure at 4 weeks. C-reactive protein (CRP), lymphocyte: granulocyte ratio and weight loss were increased in infected animals receiving IM nails in comparison with non-inoculated equivalents, although this was less evident in the plate group. In the 10-week infection group, healing does not occur in the plated rabbits. We have successfully developed a rabbit model that is suitable for further studies, particularly those looking into preventative strategies for post-traumatic implant-related osteomyelitis.

A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus

Implant-associated bone infections caused by antibiotic-resistant pathogens pose significant clinical challenges to treating physicians. Prophylactic strategies that act against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are urgently required. In the present study, we investigated the efficacy of a biodegradable Polymer-Lipid Encapsulation MatriX (PLEX) loaded with the antibiotic doxycycline as a local prophylactic strategy against implant-associated osteomyelitis. Activity was tested against both a doxycycline-susceptible (doxyS) methicillin-susceptible S. aureus (MSSA) as well as a doxycycline-resistant (doxyR) methicillin-resistant S. aureus (MRSA).In vitro elution studies revealed that 25% of the doxycycline was released from the PLEX-coated implants within the first day, followed by a 3% release per day up to day 28. The released doxycycline was highly effective against doxyS MSSA for at least 14days in vitro. A bolus injection of doxycycline mimicking a one day release from the PLEX-coating reduced, but did not eliminate, mouse subcutaneous implant-associated infection (doxyS MSSA). In a rabbit intramedullary nail-related infection model, all rabbits receiving a PLEX-doxycycline-coated nail were culture negative in the doxyS MSSA-group and the surrounding bone displayed a normal physiological appearance in both histological sections and radiographs. In the doxyR MRSA inoculated rabbits, a statistically significant reduction in the number of culture-positive samples was observed for the PLEX-doxycycline-coated group when compared to the animals that had received an uncoated nail, although the reduction in bacterial burden did not reach statistical significance.In conclusion, the PLEX-doxycycline coating on titanium alloy implants provided complete protection against implant-associated MSSA osteomyelitis, and resulted in a significant reduction in the number of culture positive samples when challenged with a doxycycline-resistant MRSA.

Propionibacterium acnes and Staphylococcus lugdunensis Cause Pyogenic Osteomyelitis in an Intramedullary Nail Model in Rabbits

Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an "aseptically failed" prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as "aseptic" failure.

A novel knee prosthesis model of implant-related osteo- myelitis in rats

Background and purpose There have been numerous reports of animal models of osteomyelitis. Very few of these have been prosthesis models that imitate human conditions. We have developed a new rat model of implant-related osteomyelitis that mimics human osteomyelitis, to investigate the pathology of infection after orthop edic implant surgery.Methods 2 wild-type strains of Staphylococcus aureus, MN8 and UAMS-1, and their corresponding mutants that are unable to produce poly-N-acetyl glucosamine (PNAG) (ica::tet) were injected into the medullary canals of the femur and tibia at 3 different doses: 102, 103, and > 104 CFU/rat. We measured clinical signs, inflammatory markers, radiographic signs, histopathology, and bacteriology in the infected animals.Results An inoculum of at least 104 cfu of either wild-type bacterial strain resulted in histological, bacteriological, and radiographic signs of osteomyelitis with loosening of the prosthesis. An inoculum of 103 CFU gave signs of osteomyelitis but the prosthesis remained in situ. Bacterial inocula of 102 cfu gave no signs of osteolysis.Interpretation We have established a new knee prosthesis model that is suitable for reliable induction of experimental implant-associated osteomyelitis with the prosthesis in situ, using a small inoculum of S. aureus. At a dose of 103 CFU/rat, bacteria unable to produce PNAG (ica::tet) had only minor defects in their virulence.

Experimental model of biofilm implant‐related osteomyelitis to test combination biomaterials using biofilms as initial inocula

Currently, the majority of animal models that are used to study biofilm-related infections use planktonic bacterial cells as initial inocula to produce positive signals of infection in biomaterials studies. However, the use of planktonic cells has potentially led to inconsistent results in infection outcomes. In this study, well-established biofilms of methicillin-resistant Staphylococcus aureus were grown and used as initial inocula in an animal model of a Type IIIB open fracture. The goal of the work was to establish, for the first time, a repeatable model of biofilm implant-related osteomyelitis, wherein biofilms were used as initial inocula to test combination biomaterials. Results showed that 100% of animals that were treated with biofilms developed osteomyelitis, whereas 0% of animals not treated with biofilm developed infection. The development of this experimental model may lead to an important shift in biofilm and biomaterials research by showing that when biofilms are used as initial inocula, they may provide additional insights into how biofilm-related infections in the clinic develop and how they can be treated with combination biomaterials to eradicate and/or prevent biofilm formation.

Emerging Pathogenetic Mechanisms of the Implant-Related Osteomyelitis by Staphylococcus Aureus

Implant-related osteomyelitis is a severe and deep infection of bone that arises and develops all around an implant. Staphylococcus aureus is the first cause of osteomyelitis, whether implant-related or not. Bone is an optimal substratum for S. aureus, since this bacterium expresses various adhesins by which can adhere to bone proteins and to the biomaterial surfaces coated with the proteins of the host extracellular matrix. S. aureus is able not only to colonize bone tissues, but also to invade and disrupt them by entering bone cells and inducing cell death and osteolysis. Here we illustrate the pathogenetic mechanisms that can explain how the osteomyelitis sets in and develops around an implant.

New Trends in Diagnosis and Control Strategies for Implant Infections

In implant infections, a quick and reliable identification of the etiological agent is crucial to realizing efficacious therapies. Among molecular methods, automated ribotyping has proven to be an accurate and rapid technique. More recently, MALDI-TOF/MS and PCR-electrospray ionization (ESI)/MS have been applied successfully to microbiological diagnosis. In implant infections, biofilm is still the major problem for bacterial persistence and recalcitrance to antibiotic therapy. Among biofilm-disrupting agents, enzymes promise the greatest therapeutic possibilities. DNase I degrades biofilm extracellular DNA and has been shown to sensitize biofilm to various biocides and anionic detergents, while dispersin B acts on biofilm exopolysaccharide and, combined with antiseptic, gives a broad-spectrum antibiofilm and antimicrobial activity. The novel antimicrobial approach based on photodynamic treatment (PDT) applies, in combination with antibiotics, to the implant or medical devices reachable by optical fibers. Better progress could be gained by the development of infection-resistant biomaterials able to both inhibit bacterial adhesion and promote tissue integration. New knowledge regarding the fibronectin-mediated internalization of Staphylococcus aureus by osteoblasts, and on its role in the pathogenesis of implant-related osteomyelitis, paves the way for the development of vaccines against staphylococcal adhesins, to prevent both adhesion on biomaterials and bacterial invasion of bone cells.

Gentamycin delivered from a PDLLA coating of metallic implants: In vivo and in vitro characterisation for local prophylaxis of implant-related osteomyelitis

Locally applied antibiotics support prophylaxis of highly feared implant associated infections. Implant coatings with poly( d, l-lactide) (PDLLA)/gentamicin seem to be a promising approach. Aims of this study were to analyse the release kinetics of gentamicin in vivo, in vitro, to analyse the antibacterial efficacy, the resistance development and its impact on osteoblasts. For the in vitro release experiments titanium implants were coated with PDLLA/gentamicin and the antibiotic release in aqueous solution was analysed at 20 time points (from 10 s to 110 days). For the in vivo experiments PDLLA/gentamicin-coated kirschner wires were implanted in the tibiae of 18 rats. Gentamicin concentration in the bone was analysed at several time points ( n = 3 each, 1 h to 7 days). Bactericidal efficacy, bacterial adhesion on the implants and resistance development were tested. AP activity, cell count and CICP expression of osteoblasts were analysed. Gentamicin was released rapidly with an initial burst in aqueous solution and followed by a slow release. Similarly, in vivo gentamicin concentration reached a high peak initially followed by a decrease to a low level. No development of resistance was observed in the investigated setting, the antibacterial efficacy was not affected by the coating process and significantly fewer bacteria were attached to the implant. Osteoblasts were not negatively affected by the gentamicin released from the coating. PDLLA/gentamicin coating resulted in a desired antibiotic peak concentration within the bone. Bacterial adhesion was successfully prevented. No bacterial resistances were developed. This coating seems to be a suitable supplement for prophylaxis of implant-associated infections.

Comparing the efficacy of three bioceramic matrices for the release of vancomycin hydrochloride

A number of calcium phosphate materials have been investigated as drug release matrices for the prophylactic treatment of implant-related osteomyelitis. However, some studies have shown the influence of processing on the efficacy of the delivered drug. The objective of this study was to evaluate the influence of pH during processing on the efficacy of vancomycin hydrochloride (VH) against Staphylococcus aureus. VH was loaded into a brushite cement (CaHPO(4).2H(2)O; pH 2.4); a hydroxyapatite cement (Ca(10)(PO(4))(6)OH(2); pH 9.4); and an apatite xerogel (pH 7.4). The pH of the material during processing had a significant influence on the mechanism of release from the cement. VH released from the apatite cement (pH 9.4) was not released in accordance with the Higuchi model. In addition to affecting release, the basic pH was shown to diminish the antibacterial potency of the released VH. Despite exceeding the minimum inhibitory concentration, the eluent from the apatite cement was ineffective against a culture of S. aureus. The findings of this study reinforce the importance of evaluating not only the release of the drug from the material matrix but also the antibacterial potency of the released drug.