Positron Emission Tomography-Computed Tomography and Magnetic Resonance Imaging Assessments in a Mouse Model of Implant-Related Bone and Joint Staphylococcus aureus Infection.

Osteomyelitis is an infection of the bone, associated with an inflammatory process. Imaging plays an important role in establishing the diagnosis and the most appropriate patient management. However, data are lacking regarding the use of preclinical molecular imaging techniques to assess osteomyelitis progression in experimental models. This study aimed to compare structural and molecular imaging to assess disease progression in a mouse model of implant-related bone and joint infections caused by Staphylococcus aureus. In SWISS mice, the right femur was implanted with a resorbable filament impregnated with S. aureus (infected group, n = 10) or sterile culture medium (uninfected group, n = 6). Eight animals (5 infected, 3 uninfected) were analyzed with magnetic resonance imaging (MRI) at 1, 2, and 3 weeks postintervention, and 8 mice were analyzed with [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT) at 48 h and at 1, 2, and 3 weeks postintervention. In infected animals, CT showed bone lesion progression, mainly in the distal epiphysis, although some uninfected animals presented evident bone sequestra at 3 weeks. MRI showed a lesion in the articular area that persisted for 3 weeks in infected animals. This lesion was smaller and less evident in the uninfected group. At 48 h postintervention, FDG-PET showed higher joint uptake in the infected group than in the uninfected group (P = 0.025). Over time, the difference between groups increased. These results indicate that FDG-PET imaging was much more sensitive than MRI and CT for differentiating between infection and inflammation at early stages. FDG-PET clearly distinguished between infection and postsurgical bone healing (in uninfected animals) from 48 h to 3 weeks after implantation. IMPORTANCE Our results encourage future investigations on the utility of the model for testing different therapeutic procedures for osteomyelitis.

Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus.

Osteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis. STATEMENT OF SIGNIFICANCE: In this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect.

Arabic gum plus colistin coated moxifloxacin-loaded nanoparticles for the treatment of bone infection caused by Escherichia coli.

Osteomyelitis is an inflammatory process of bone and bone marrow that may even lead to patient death. Even though this disease is mainly caused by Gram-positive organisms, the proportion of bone infections caused by Gram-negative bacteria, such as Escherichia coli, has significantly increased in recent years. In this work, mesoporous silica nanoparticles have been employed as platform to engineer a nanomedicine able to eradicate E. coli- related bone infections. For that purpose, the nanoparticles have been loaded with moxifloxacin and further functionalized with Arabic gum and colistin (AG+CO-coated MX-loaded MSNs). The nanosystem demonstrated high affinity toward E. coli biofilm matrix, thanks to AG coating, and marked antibacterial effect because of the bactericidal effect of moxifloxacin and the disaggregating effect of colistin. AG+CO-coated MX-loaded MSNs were able to eradicate the infection developed on a trabecular bone in vitro and showed pronounced antibacterial efficacy in vivo against an osteomyelitis provoked by E. coli. Furthermore, AG+CO-coated MX-loaded MSNs were shown to be essentially non-cytotoxic with only slight effect on cell proliferation and mild hepatotoxicity, which might be attributed to the nature of both antibiotics. In view of these results, these nanoparticles may be considered as a promising treatment for bone infections caused by enterobacteria, such as E. coli, and introduce a general strategy against bone infections based on the implementation of antibiotics with different but complementary activity into a single nanocarrier. STATEMENT OF SIGNIFICANCE: In this work, we propose a methodology to address E.coli bone infections by using moxifloxacin-loaded mesoporous silica nanoparticles coated with Arabic gum containing colistin (AG+CO-coated MX-loaded MSNs). The in vitro evaluation of this nanosystem demonstrated high affinity toward E. coli biofilm matrix thanks to the Arabic gum coating, a disaggregating and antibacterial effect of colistin, and a remarkable antibiofilm action because of the bactericidal ability of moxifloxacin and colistin. This anti-E. coli capacity of AG+CO-coated MX-loaded MSNs was brought out in an in vivo rabbit model of osteomyelitis where the nanosystem was able to eradicate more than 90% of the bacterial load within the infected bone.

Usefulness of sonication procedure in mesh infection diagnosis associated with hernia repair.

BACKGROUND: The use of prosthetic meshes is a common practice in hernia repair surgery. However, infection can appear as an important complication where antibiotic selection must be directed by the etiology of the infection. In recent years, sonication has appeared as an important tool for the diagnosis of many biomaterial-associated infections. Here, we evaluated our experience with this methodology for the diagnosis of mesh infection. METHODS: We retrospectively reviewed the microbiological records between 2015 and 2019 looking for sonicated meshes in the microbiology laboratory. All samples were processed according to the sonication protocol described by Esteban J et al. (J Clin Microbiol. 2008 Feb; 46 (2): 488-92). RESULTS: 26 samples were processed during the study period. 21 of them gave a positive result for culture (11 polymicrobial and 10 monomicrobial ones). Staphylococcus aureus and Candida albicans were the commonest monomicrobial isolates (4 cases each). There were five cases of mixed gut microbiota. The median (interquartile range) UFC count was > 100,000 (50,000- > 100,000) CFU/mL. CONCLUSION: Sonication is a useful technique for the diagnosis of mesh infection.

Functionalization of sol-gel coatings with organophosphorus compounds for prosthetic devices.

Sol-gel coatings are proposed as surface treatments for titanium-based materials to promote the osseointegration of prosthetic devices with the host. As precursors of sol-gel synthesis, two silanes were selected: 3-methacryloxypropyltrimethoxy silane and 2 tetramethyl orthosilane. Sol-gel synthesis was functionalized with the addition of two different organophosphorus compounds, namely, tris(trimethylsilyl) phosphite and tris(trimethylsilyl) phosphate. Depending on the organophosphorus compound, phosphorus was incorporated into the sol-gel network by different mechanisms: organophosphate was incorporated following a hydrolysis/polycondensation reaction with the precursors of synthesis (two organopolysiloxanes), whereas organophosphite was introduced into the network through transformation of trivalent phosphorus to pentavalent phosphorus following a Michaelis-Arbuzov reaction and subsequent reaction of hydrolysis/polycondensation. When compared to the control coating, which has good adhesion coating-substrate, only the addition of the organophosphite ensured good adhesion without altering synthesis. The resulting coating modified with organophosphite was subjected to cellular study and the concentration of this compound was varied to reach the highest enhancement of proliferation. It was demonstrated that by increasing the amount of organophosphite cell proliferation increased. Inspection of the surfaces of the coatings revealed that by increasing the quantity of organophosphite, adhesion to the substrate was compromised. Thus, an intermediate quantity of organophosphite was considered the most suitable for application on metallic prosthetic devices.