Treatment Of Implant-associated Infections Research Articles

Factors affecting the course and prognosis of implant-associated infection caused by Klebsiella spp.

Background. The outcome of complex treatment of implant-associated infection (IAI) depends on various factors, but one of the most important is the etiology of the inflammatory process. Treatment of orthopedic infection caused by gram-negative microorganisms in general and representatives of the Enterobacteria family in particular causes many difficulties, one of which is the rapid growth of antibiotic resistance. Aim of the stydy - to evaluate the factors affecting the course and prognosis of IAI caused by Klebsiella spp. Methods. A retrospective case history of 85 patients who were treated in the clinical departments of the center from January 1, 2017 to December 31, 2021 for the treatment of IAI caused by Klebsiella spp was performed. According to the results of the telephone survey, the patients were divided into 2 main groups depending on the outcome of the 2-year follow-up period determined according to the Delphi criteria. The groups were comparable in terms of gender, age and anthropometric data. Further, in the IBM SPSS STATISTICS program (version 26), a statistical analysis of the impact on the outcome of various parameters was carried out: anamnesis data, laboratory studies, type of surgical intervention, the course of the postoperative period, antibiotic therapy at the inpatient and outpatient stages. Results. During the studied period, it was found that the prognosis was significantly worsened by the number of sanitizing surgical interventions in the anamnesis (p=0.022), the need for sanitizing intervention in the early postoperative period (p0.001) and the presence of Klebsiella spp. growth in postoperative crops (p=0.002), hypoalbuminemia on 7-14 days after the operation (p=0.008). At the same time, the appointment of trimethoprim-sulfamethoxazole for the outpatient period significantly improved the outcome (p=0.038).

Recent Advances in Antibacterial Coatings to Combat Orthopedic Implant-Associated Infections.

Implant-associated infections (IAIs) represent a major health burden due to the complex structural features of biofilms and their inherent tolerance to antimicrobial agents and the immune system. Thus, the viable options to eradicate biofilms embedded on medical implants are surgical operations and long-term and repeated antibiotic courses. Recent years have witnessed a growing interest in the development of robust and reliable strategies for prevention and treatment of IAIs. In particular, it seems promising to develop materials with anti-biofouling and antibacterial properties for combating IAIs on implants. In this contribution, we exclusively focus on recent advances in the development of modified and functionalized implant surfaces for inhibiting bacterial attachment and eventually biofilm formation on orthopedic implants. Further, we highlight recent progress in the development of antibacterial coatings (including self-assembled nanocoatings) for preventing biofilm formation on orthopedic implants. Among the recently introduced approaches for development of efficient and durable antibacterial coatings, we focus on the use of safe and biocompatible materials with excellent antibacterial activities for local delivery of combinatorial antimicrobial agents for preventing and treating IAIs and overcoming antimicrobial resistance.

In vitro co-culture models for the assessment of orthopedic antibacterial biomaterials.

The antibacterial biofunctionality of bone implants is essential for the prevention and treatment of implant-associated infections (IAI). In vitro co-culture models are utilized to assess this and study bacteria-host cell interactions at the implant interface, aiding our understanding of biomaterial and the immune response against IAI without impeding the peri-implant bone tissue regeneration. This paper reviews existing co-culture models together with their characteristics, results, and clinical relevance. A total of 36 studies were found involving in vitro co-culture models between bacteria and osteogenic or immune cells at the interface with orthopedic antibacterial biomaterials. Most studies (∼67%) involved co-culture models of osteogenic cells and bacteria (osteo-bac), while 33% were co-culture models of immune cells and bacterial cells (im-bac). All models involve direct co-culture of two different cell types. The cell seeding sequence (simultaneous, bacteria-first, and cell-first) was used to mimic clinically relevant conditions and showed the greatest effect on the outcome for both types of co-culture models. The im-bac models are considered more relevant for early peri-implant infections, whereas the osteo-bac models suit late infections. The limitations of the current models and future directions to develop more relevant co-culture models to address specific research questions are also discussed.

Electron Orbital Hybridization‐Enhanced Copper‐Nanocatalysis for Anti‐Infection

AbstractRecurrent bacterial infections, impenetrable microbial biofilms, and irremediable antibiotic resistance are the most perilous threats in orthopedic implant‐associated infections (IAIs). Recently, chemodynamic therapy (CDT) has been considered a promising therapy, while the clinical practices for existing CDT agents are limited by the low therapeutic efficiency in physiological circumstances. Herein, it is demonstrated that silica‐copper nanosheets (Si@Cu NSs) exhibit a combined therapeutic photothermal‐chemodynamic strategy for IAIs treatment with superior capacity and biocompatibility. This unique design endows the nanostructure with enhanced copper‐based Fenton‐like properties via p‐d orbital hybridization by incorporating copper nanoclusters (Cu NCs) on silicene nanosheets (Si NSs) matrix, integrating inherent photothermal performance of Si NSs with specific catalytic anti‐infection of Cu NCs against planktonic bacteria and biofilms both in vitro and in vivo. This study not only reveals the promising bio‐application prospects of 2D nanocatalytic biomaterials but also demonstrates the feasibility of constructing novel CDT agents by orbital hybridization for the catalytic treatment of IAIs.

Comparative Genomic Analysis of Cutibacterium spp. Isolates in Implant-Associated Infections.

Bacteria of the genus Cutibacterium are Gram-positive commensals and opportunistic pathogens that represent a major challenge in the diagnosis and treatment of implant-associated infections (IAIs). This study provides insight into the distribution of different sequence types (STs) of C. acnes, and the presence of virulence factors (VFs) in 64 Cutibacterium spp. isolates from suspected or confirmed IAIs obtained during routine microbiological diagnostics. Fifty-three C. acnes, six C. avidum, four C. granulosum, and one C. namnetense isolate, collected from different anatomical sites, were included in our study. Using whole-genome sequencing and a single-locus sequencing typing scheme, we successfully characterized all C. acnes strains and revealed the substantial diversity of STs, with the discovery of six previously unidentified STs. Phylotype IA1, previously associated with both healthy skin microbiome and infections, was the most prevalent, with ST A1 being the most common. Some minor differences in STs' distribution were observed in correlation with anatomical location and association with infection. A genomic analysis of 40 investigated VFs among 64 selected strains showed no significant differences between different STs, anatomical sites, or infection-related and infection undetermined/unlikely groups of strains. Most differences in VF distribution were found between strains of different Cutibacterium spp., subspecies, and phylotypes, with CAMP factors, biofilm-related VFs, lipases, and heat shock proteins identified in all analyzed Cutibacterium spp.

In Vivo Prevention of Implant-Associated Infections Caused by Antibiotic-Resistant Bacteria through Biofunctionalization of Additively Manufactured Porous Titanium.

Additively manufactured (AM) porous titanium implants may have an increased risk of implant-associated infection (IAI) due to their huge internal surfaces. However, the same surface, when biofunctionalized, can be used to prevent IAI. Here, we used a rat implant infection model to evaluate the biocompatibility and infection prevention performance of AM porous titanium against bioluminescent methicillin-resistant Staphylococcus aureus (MRSA). The specimens were biofunctionalized with Ag nanoparticles (NPs) using plasma electrolytic oxidation (PEO). Infection was initiated using either intramedullary injection in vivo or with in vitro inoculation of the implant prior to implantation. Nontreated (NT) implants were compared with PEO-treated implants with Ag NPs (PT-Ag), without Ag NPs (PT) and infection without an implant. After 7 days, the bacterial load and bone morphological changes were evaluated. When infection was initiated through in vivo injection, the presence of the implant did not enhance the infection, indicating that this technique may not assess the prevention but rather the treatment of IAIs. Following in vitro inoculation, the bacterial load on the implant and in the peri-implant bony tissue was reduced by over 90% for the PT-Ag implants compared to the PT and NT implants. All infected groups had enhanced osteomyelitis scores compared to the noninfected controls.

Hyaluronic acid-based hydrogel coatings on Ti6Al4V implantable biomaterial with multifunctional antibacterial activity

Today, the treatment of implant-associated infections with conventional mono-functional antibacterial coatings has not been effective enough for a prosperous long-term implantation. Therefore, biomedical industry is making considerable efforts on the development of novel antibacterial coatings with a combination of more than one antibacterial strategies that interact synergistically to reinforce each other. Therefore, in this work hyaluronic acid-based (HA) hydrogel coatings were created on the surface Ti6Al4V biomaterial with 1,4-butanediol diglycidyl ether (Ti-HABDDE) and divinyl sulfone (Ti-HADVS) crosslinking agents. Hydrogel coatings displayed an extraordinary in vivo biocompatibility, a remarkable ability to promote cell proliferation, differentiation and mineralization, and capability to sustainedly release drugs. Finally, HA-based hydrogel coatings demonstrated an outstanding multifunctional antibacterial activity: bacteria-repelling (51–55 % of S. aureus and 27–40 % of E. coli), bacteria-killing (82–119 % of S. aureus and 83–87 % of E. coli) and bactericide release killing (drug-loaded hydrogel coatings, R > 2).

Microbiological spectrum of causative agents of implant-associated infection in the treatment of complications of transpedicular fixation of the spine using the negative pressure method

Objective. To analyze the leading pathogens of implant-associated infection (IAI) after spinal surgery and identification of trends in the change in the pattern of microorganisms at the stages of treatment using the negative pressure method (NPWT systems).Material and Methods. The results of microbiological cultures of 25 patients with IAI of the spine were studied. The frequency of occurrence of Gram-positive and Gram-negative pathogens was estimated. The leading pathogens in the species spectrum were identified. Changes in the structure of identified microorganisms were studied at various time intervals of treatment.Results. A total of 136 microbiological studies were performed in 25 patients at the stages of treatment with the negative pressure method, with the identification of microorganisms in 127 (93.3 %) cases. The frequency of gram-negative microflora was 50.0 %, gram-positive – 42.6 %, Candida sp. – 0.7%, in 15.4 % microbial associations with the dominance of gram-negative microflora were identified at all periods of treatment. Not only the diversity of the isolated flora was noted (E. faecalis – 16.5 %, P. aeruginosa – 14.2 %, K. pneumoniae – 11.0 %, S. aureus and A. baumannii – 9.4 % each and S. epidermidis – 8.6 %), but also changes in the spectrum of flora at the stages of treatment: on the 1st and 2nd weeks from the first debridement intervention and the installation of the NPWT system, E. faecalis was most often detected, on the 3rd and 4th weeks – P. aeruginosa and A. baumannii, during the 2nd month – E. faecalis and P. aeruginosa, later – gram-negative bacteria against the background of an increase in the incidence of K. pneumoniae. The frequency of verification of other species of microorganisms had no statistically significant differences. Microbial associations were found from the 2nd month of treatment. The change in pathogens was noted in 72 % of cases during the treatment of IAI of the spine. On average, this treatment required 7–8 NPWT dressing changes per patient. This method of treatment made it possible to achieve both negative results of microbiological examination and stable relief of the infectious process.Conclusion. IAI, which complicates surgical interventions on the spine, is characterized by a change in pathogens during treatment, which requires not only multiple debridement with the replacement of the NPWT dressing, but also adequate long-term rational (etiologically justified) antibacterial therapy, based on the control of data on both the spectrum and on microbial resistance.

Dual-functional antimicrobial coating based on the combination of zwitterionic and quaternary ammonium cation from rosin acid

Treatment of implant-associated infection is becoming more challenging, especially when bacterial biofilms form on the surface of implants. To address the challenge of biofilm infection, developing dual-functional antimicrobial coatings (antimicrobial and antifouling) to combat bacterial biofilm infection are superior to those based on a single modality due to avoiding the adverse effects arising from the latter. In this work, we reported an effective dual-functional coating based on the use of synthetic terpolymers, which combined dopamine, zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and maleopimaric acid quaternary ammonium cation (MPA-N + ). The modified surfaces were characterized by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), X-ray spectroscopy (XPS) and water contact angle measurements . The bactericidal efficacies of dual-functional coating were demonstrated by 1.00, 1.09 and 0.94 log reduction of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli , Pseudomonas aeruginosa , respectively, and effectively inhibited pathogenic biofilm formation . Moreover, the dual-function coating reduced protein and platelet absorption, while showing minimal cytotoxicity to the mammalian cells. Notably, an in vivo implantation model showed that the dual-functional coating eradicated the pathogenic biofilm from the implants, preventing host tissue damage and inflammation. Taken together, this dual-functional coating displayed great therapeutic potential in treating the formidable clinic problems caused by pathogenic biofilm and the accompanying inflammation. • Dual-functional antimicrobial coating based on quaternary ammonium salt from rosin acid was prepared. • The antimicrobial coating exhibits excellent antimicrobial and antibiofilm activity. • The antimicrobial coating was non-hemolysis and non-cytotoxicity. • The antimicrobial coating with multi-performances has promising potential for biomedical devices.

Recent Advances in Research on Antibacterial Metals and Alloys as Implant Materials.

Implants are widely used in orthopedic surgery and are gaining attention of late. However, their use is restricted by implant-associated infections (IAI), which represent one of the most serious and dangerous complications of implant surgeries. Various strategies have been developed to prevent and treat IAI, among which the closest to clinical translation is designing metal materials with antibacterial functions by alloying methods based on existing materials, including titanium, cobalt, tantalum, and biodegradable metals. This review first discusses the complex interaction between bacteria, host cells, and materials in IAI and the mechanisms underlying the antibacterial effects of biomedical metals and alloys. Then, their applications for the prevention and treatment of IAI are highlighted. Finally, new insights into their clinical translation are provided. This review also provides suggestions for further development of antibacterial metals and alloys.

Copper ferrite heterojunction coatings empower polyetheretherketone implant with multi-modal bactericidal functions and boosted osteogenicity through synergistic photo/Fenton-therapy

Drug-free antibacterial therapy, such as photodynamic therapy and chemodynamic therapy, has become a mainstream in the treatment of implant-associated infection (IAI) due to its considerable potential on effective eradication of pathogenic bacteria via yielding overwhelming reactive oxygen species (ROS). However, superfluous ROS after therapeutical process may elicit a detrimental effect on subsequent tissue regeneration. To address this tough issue, we innovatively devise a photo-activated copper ferrite (CuFe2O4) heterojunction coating on bioinert polyetheretherketone (PEEK) implant through hydrothermal treatment and π-π-π stacking. The heterojunction coatings not only generate localized hyperthermia and ROS upon 808 nm NIR illumination, but also trigger Fenton(-like) reaction and glutathione (GSH) depletion in bacterial infectious microenvironment (IME), all leading to robust and cyclic antibacterial property through synergistic photothermal/photodynamic/chemodynamic therapy. Besides, the decorated implants are demonstrated to show superior cytocompatibility and osteogenic-promoting capability. The mice subcutaneous implantation further confirms the excellent in vivo photo-disinfection. The advantage of the heterojunction coatings lies on its enhancement in tissue generation and osteogenesis after antibacterial dynamic therapy because the liberation of micronutrient element (Cu, Fe) is significantly augmented exposed to NIR light, showing photo-enhanced osteogenicity. As envisaged, this work provides a new strategy to empower PEEK implants with an integrative feature of bacteriostasis and osteogenicity to combat intractable IAI through synergistic photo/Fenton-therapy.

Antibacterial Titanium Implants Biofunctionalized by Plasma Electrolytic Oxidation with Silver, Zinc, and Copper: A Systematic Review.

Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.

Сравнительная оценка поведения гелей на основе поливинилпирролидона в условиях in vitro и in vivo

A series of experiments aimed at studying antimicrobial properties of gel experimental samples has been carried out, and their prolonged action in vivo and in vitro has been compared. The gel under study is a processed composition based on polyvinylpyrrolidone (PVP) and antimicrobial drugs; it is intended for the prevention and treatment of implant-associated infection in traumatology and orthopedics. Two methods were used to process the composition: ionizing radiation and heating. PVP treated in this way is a matrix for drug delivery to the structures of the articular cavity, which allows using antimicrobial medicines, in particular gentamicin and fosfomycin, for targeted influence on infectious agents. All gel samples, regardless of the method for their preparation, exhibited antimicrobial activity against Staphylococcus aureus, the main causative agent of postoperative infectious processes. The antimicrobial properties of the gel were long-lasting; they were observed for 14 days. No pathological changes were found in the tissues adjacent to the gel. Key words: implant-associated infection, surgery, traumatology, biofilm, polymer hydrogel, gentamicin, fosfomycin

Conformal Coating of Orthopedic Plates with X-ray Scintillators and pH Indicators for X-ray Excited Luminescence Chemical Imaging through Tissue.

We describe a pH-indicating material that can be directly implanted or coated on orthopedic implant surfaces to provide high-spatial-resolution pH mapping through tissue by X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting local pH changes during treatment of implant-associated infections. The material has two layers: an X-ray scintillator layer with Gd2O2S:Eu in epoxy, which emits 620 and 700 nm light when irradiated with X-rays, and a pH indicator dye layer, which absorbs some of the 620 nm light in a pH-dependent fashion. To acquire each pixel in the image, a focused X-ray beam irradiates a small region of scintillators and the ratio of 620 to 700 nm light is acquired through the tissue. Scanning the X-ray beam across the implant surface generates high-spatial-resolution chemical measurements. Two associated challenges are (1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations specifically for metal orthopedic implants and (2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor onto the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein, we describe a chemically sensitive and biocompatible XELCI sensor material that can conformally coat the implant surface. A two-part commercial-grade epoxy resin was mixed with Gd2O2S:Eu and adhered to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase the surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This combination of epoxy-PEG layers was found to adhere well to the metal implant unlike other previously tested polymer surfaces, which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm-thick tissue. The pH sensor-coated orthopedic plate was imaged with XELCI, through tissue, with different pH levels to acquire a calibration curve. The plates were also imaged through tissue, with a low pH region on one section due to growth of a Staphylococcus aureus biofilm. A pH sensor-coated stainless-steel rod with two distinct pH regions was inserted in a rabbit tibia specimen, and the pH was imaged through both bone and soft tissue. These studies demonstrate the use of pH sensor-coated orthopedic plates and rods for mapping the local pH through tissue during biofilm formation by XELCI.

Synergistic antibacterial activity of physical-chemical multi-mechanism by TiO2 nanorod arrays for safe biofilm eradication on implant

Treatment of implant-associated infection is becoming more challenging, especially when bacterial biofilms form on the surface of the implants. Developing multi-mechanism antibacterial methods to combat bacterial biofilm infections by the synergistic effects are superior to those based on single modality due to avoiding the adverse effects arising from the latter. In this work, TiO2 nanorod arrays in combination with irradiation with 808 near-infrared (NIR) light are proven to eradicate single specie biofilms by combining photothermal therapy, photodynamic therapy, and physical killing of bacteria. The TiO2 nanorod arrays possess efficient photothermal conversion ability and produce a small amount of reactive oxygen species (ROS). Physiologically, the combined actions of hyperthermia, ROS, and puncturing by nanorods give rise to excellent antibacterial properties on titanium requiring irradiation for only 15 min as demonstrated by our experiments conducted in vitro and in vivo. More importantly, bone biofilm infection is successfully treated efficiently by the synergistic antibacterial effects and at the same time, the TiO2 nanorod arrays improve the new bone formation around implants. In this protocol, besides the biocompatible TiO2 nanorod arrays, an extra photosensitizer is not needed and no other ions would be released. Our findings reveal a rapid bacteria-killing method based on the multiple synergetic antibacterial modalities with high biosafety that can be implemented in vivo and obviate the need for a second operation. The concept and antibacterial system described here have large clinical potential in orthopedic and dental applications.

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

BackgroundIn orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology.ResultsClinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control.ConclusionDespite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.

Burst Release of Antibiotics Combined with Long-Term Release of Silver Targeting Implant-Associated Infections: Design, Characterization and in vitro Evaluation of Novel Implant Hybrid Surface.

Implant-associated infections represent a serious risk in human medicine and can lead to complications, revisions and in worst cases, amputations. To target these risks, the objective was to design a hybrid implant surface that allows a local burst release of antibiotics combined with long-term antimicrobial activity based on silver. The efficacy should be generated with simultaneous in vitro cytocompatibility. The investigations were performed on titanium K-wires and plates and gentamicin was selected as an illustrative antibiotic. A gentamicin depot (max 553 µg/cm2) was created on the surface using laser structuring. The antibiotic was released within 15 min in phosphate buffered saline (PBS) or agar medium. Metallic silver particles (4 µg/cm2) in a titanium dioxide layer were deposited using plasma vapor deposition (PVD). About 16% of the silver was released within 28 days in the agar medium. The local efficacy of the incorporated silver was demonstrated in a direct contact assay with a reduction of more than 99.99% (Escherichia coli). The local efficacy of the hybrid surface was confirmed in a zone of inhibition (ZOI) assay using Staphylococcus cohnii. The biocompatibility of the hybrid surface was proven using fibroblasts and osteoblasts as cell systems. The hybrid surface design seems to be promising as treatment of implant-associated infections, considering the achieved amount and release behavior of the active ingredients (gentamicin, silver). The generated in vitro results (efficacy, biocompatibility) proofed the concept. Further in vivo studies will be necessary translate the hybrid surface towards clinical applied research.

Treatment Outcomes of Periprosthetic Joint Infection in HIV-positive Patients

Relevance. There is a limited number of publications reporting outcomes of primary large joint arthroplasty in patients with human immunodeficiency virus (HIV). The authors were unable to find papers on revision arthroplasty in patients with periprosthetic infection. Purpose of the study — to evaluate short term outcomes after revision arthroplasty in HIV-positive patients with periprosthetic infection of the hip and knee joint. Materials and methods. 13 HIV-positive patients with periprosthetic infection of the hip (10 cases) and knee (3 cases) joint underwent treatment in the period from 2015 to 2019. Patients were examined by clinical, laboratory and roentgenological methods. Harris Hip Score and Knee Society Score were used for evaluation prior to and after the surgery. Results. Mean follow up period was 21,4±2,6 months. Successful two-stage treatment was performed in two (15,4%) out of 13 patients with periprosthetic infection. In 5 cases (38,5%) control over infection was achieved by resection arthroplasty, and in one case (7,7%) – by arthrodesis. Five patients (38,5%) refused from interchange of spacer to prosthesis. Mean Harris Hip score demonstrated insignificant increase postoperatively — from 45,3±2,2 to 52,2±4,15 (р = 0,2). Conclusion. Despite following the international protocols for treatment of implant-associated infection the infection recurrence rate in HIV-positive patients in the asymptomatic phase remains very high. Efficiency of twostage treatment using antibacterial spacers in the present group of patients amounted only to 15,4%.

Clinical Characteristics and Outcomes of Staphylococcus aureus Implant-associated Infections in Children.

Staphylococcus aureus is a significant cause of implant-associated infections (IAIs). Data detailing the optimal treatment of IAIs are lacking in children. We describe the clinical features and outcomes of pediatric patients with S. aureus IAIs seen at Texas Children's Hospital. Patients and their isolates were identified from a S. aureus surveillance database from 2008 to 2016 in Houston, TX. Demographic and clinical data were collected retrospectively. Fisher's exact was used for statistical analysis. Forty-five patients with 47 IAIs were identified. Most patients had an infected orthopedic implant: 22 (47%) spinal rods and 19 (40%) with other orthopedic hardware. Thirty (64%) IAIs developed within 90 days of implant placement. Six patients had polymicrobial infections and 3 patients were bacteremic. Of the 47 IAI isolates, 34 (72%) were methicillin-susceptible S. aureus (MSSA) and 13 (28%) were methicillin-resistant S. aureus. All children underwent surgical irrigation, debridement and antibiotic therapy. Of the 47 IAI episodes, 22 of the implants were removed at time of initial presentation, 7 implants had delayed removal, and 18 implants remained in place. Successful treatment was achieved in all patients with immediate implant removal (22/22) and in 83% of patients with implant retention (15/18), including 10 patients with early postoperative infections (<3 months) and 5 patients with late postoperative infections (>3 months). Four patients had recurrence of infection. The majority of S. aureus IAIs were methicillin-susceptible S. aureus. All children with immediate implant removal and most children with retained implants were treated successfully with surgery and antibiotic therapy.

Surgeons' Dilemma: Treatment of Implant-Associated Infection in the Cosmetic Breast Augmentation Patient.

Augmentation mammaplasty is the most common plastic surgical procedure performed in the USA. The management of severe implant-associated infection is a challenge, and the traditional two-stage treatment is associated with significant limitations. The aim of this literature review is to provide a comprehensive analysis of all studies dealing with the management of severe infection or implant exposure following cosmetic breast augmentation. The PubMed and Cochrane databases were searched through February 2018 for studies on the management of severe infection and threatened or actual implant exposure following primary augmentation mammaplasty. Search terms used were "breast implant," "breast prosthesis," "breast augmentation," "breast augmentation complications," "infected implant," "implant salvage" and "implant exposure." Five articles met inclusion criteria. There was inconsistency in the reporting of several key factors, such as the antibiotic regimens employed, culture sensitivities, time from diagnosis to treatment, implant characteristics, as well as the precise treatment of the capsule and pocket. A total of 58 implants were treated, of which 37 (63.8%) were exposed in the setting of infection and 21 (36.2%) were infected without exposure. One-stage implant salvage was employed in 31 implants and was successful in all. The capsular contracture rate with this approach was 6.5%. Antibiotic-alone, non-operative treatment was employed in the salvage of 22 implants, with success and capsular contracture rates of 77.3 and 13.6%, respectively. In the setting of severe periprosthetic infection in the absence of implant exposure, antibiotic-alone treatment was successful in the salvage of 13 out of 14 implants (92.9%). The inconsistency and paucity of the data in the literature preclude definitive conclusions with regard to the optimal management of the threatened implant following augmentation mammaplasty. Given the excellent salvage rates in this setting, a more prominent role and liberal utilization of implant salvage are proposed. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .