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Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G. [ABSTRACT FROM AUTHOR]

Infections by bacteria are a serious complication following orthopedic implant surgery, that can usually only be cured by removing the implant, since the biofilm mode of growth of infecting bacteria on an implant surface protects the organisms from the host immune system and antibiotic therapy. Over the past few decades, attempts have been made to prevent and cure orthopedic implant infections by incorporating antibiotics in polymethylmethacrylate bone cements, in primary and revision surgery. However, the clinical efficacy of antibiotic-releasing bone cements is not accepted by all and the long-term exposure to low doses from antibiotic-releasing bone cements in patients is strongly related to the emerging threat of antibiotic resistance in medicine today. In this article, we start by reviewing the mechanisms governing the formation of an infectious biofilm on orthopedic implant materials, the release mechanisms and properties of clinically-used, antibiotic-loaded bone cements. The clinical efficacy of antibiotic-loaded bone cements is evaluated analyzing separatedly the prophylactic and therapeutic uses of these products. [ABSTRACT FROM AUTHOR]

Abstract Background Around about 1970, a gentamicin-loaded poly (methylmethacrylate) (PMMA) bone cement brand (Refobacin Palacos R) was introduced to control infection in joint arthroplasties. In 2005, this brand was replaced by two gentamicin-loaded follow-up brands, Refobacin Bone Cement R and Palacos R + G. In addition, another gentamicin-loaded cement brand, SmartSet GHV, was introduced in Europe in 2003. In the present study, we investigated differences in gentamicin release and the antibacterial efficacy of the eluent between these four cement brands. Methods 200 μm-wide gaps were made in samples of each cement and filled with buffer in order to measure the gentamicin release. Release kinetics were related to bone cement powder particle characteristics and wettabilities of the cement surfaces. Gaps were also inoculated with bacteria isolated from infected prostheses for 24 h and their survival determined. Gentamicin release and bacterial survival were statistically analysed using the Student's t-test. Results All three Palacos variants showed equal burst releases but each of the successor Palacos cements showed significantly higher sustained releases. SmartSet GHV showed a significantly higher burst release, while its sustained release was comparable with original Palacos. A gentamicin-sensitive bacterium did not survive in the high gentamicin concentrations in the interfacial gaps, while a gentamicin-resistant strain did, regardless of the type of cement used. Survival was independent of the level of burst release by the bone cement. Conclusions Although marketed as the original gentamicin-loaded Palacos cement, orthopaedic surgeons should be aware that the successor cements do not appear to have the same release characteristics as the original one. Overall, high gentamicin concentrations were reached inside our prosthesis-related interfacial gap model. These concentrations may be expected to effectively decontaminate the prosthesis-related interfacial gap directly after implantation, provided that these bacteria are sensitive for gentamicin.

It is well established that extreme prematurity can be associated with cerebellar lesions potentially affecting the neurologic prognosis. One of the commonly observed lesions in these cases is pontocerebellar hypoplasia resulting from prematurity, which can pose challenges in distinguishing it from genetically caused pontocerebellar hypoplasia. This confusion leads to unacceptable and prolonged diagnostic ambiguity for families as well as difficulties in genetic counseling. Therefore, it is crucial to identify the clinical and neuroradiologic features allowing to differentiate between acquired and genetic forms of pontocerebellar hypoplasia in order to guide clinical practices and improve patient care. In this regard, we report in the present manuscript the clinical, developmental, and radiologic characteristics of 19 very premature children (gestational age <28 weeks, now aged 3-14 years) with cerebellar lesions and discuss the causal mechanisms. Our findings support the notion that a combination of specific clinical and radiologic criteria is essential in distinguishing between acquired and genetic forms of pontocerebellar hypoplasia., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: The popularity of playing games among adolescents has increased during the last decades, possibly affecting the prevalence of problematic gaming behavior. The current study aimed to compare country-level prevalence rates of adolescents' problematic gaming behavior in five countries and identify cross-cultural similarities and differences in the relationship between problematic gaming and well-being (life satisfaction, psychological complaints, and peer support)., Methods: Cross-national data from the Health Behavior in School-aged Children (HBSC) study were used. The sample comprised 14,398 gamers (61% boys) aged 11 to 16 (average age between 13.31 and 13.85) from Azerbaijan, England, Serbia, Slovenia, and the Netherlands., Results: The findings showed that the prevalence of problematic gaming differs between countries. The highest prevalence of problematic gaming was seen in Azerbaijan (16.1%) and the lowest in the Netherlands (4.3%). In contrast, Azerbaijan reported the lowest gaming intensity, whereas the Netherlands and England showed the highest gaming intensity. Additional analyses revealed that problematic gaming was associated with lower life satisfaction, more psychological complaints, and lower peer support in all countries, although the strength of these associations varied between countries., Discussion and Conclusions: The current study's results are consistent with the assumption that problematic gaming negatively affects adolescents' social and mental well-being. These findings are further discussed in light of the normalization theory which suggests that cultural gaming norms (i.e., the percentage of gamers per country) would influence the strength of the relationship between problematic gaming and adolescents' well-being. The present findings highlight the need for adequate prevention strategies aiming at problematic gaming among youngsters.

Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) was introduced to decrease wear debris and osteolysis. During cross-linking, free radicals are formed, making highly cross-linked polyethylene vulnerable to oxidative degradation. In order to reduce this process, anti-oxidant vitamin E can be incorporated in polyethylene. This review provides an overview of the effects of vitamin E incorporation on major complications in total joint arthroplasty: material failure due to oxidative degradation, wear debris and subsequent periprosthetic osteolysis, and prosthetic joint infections. Secondly, this review summarizes the first clinical results of total hip and knee arthroplasties with vitamin E incorporated highly cross-linked polyethylene. Based on in vitro studies, incorporation of vitamin E in polyethylene provides good oxidative protection and preserves low wear rates. Incorporation of vitamin E may have the beneficial effect of reduced inflammatory response to its wear particles. Some microorganisms showed reduced adherence to vitamin E-incorporated UHMWPE; however, clinical relevance is doubtful. Short-term clinical studies of total hip and knee arthroplasties with vitamin E-incorporated highly cross-linked UHMWPE reported good clinical results and wear rates similar to highly cross-linked UHMWPE without vitamin E.

Background.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success., Methods.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy., Results.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using β-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with β-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34)., Conclusions.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of β-lactams are confirmed and maybe also a potential benefit from adding rifampin., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Standard antibiotic therapy in osteomyelitis patients is of limited value when methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), or small-colony variants (SCV) are present. Far better results are obtained by local drug delivery of antibiotic combinations including rifampicin, using a suitable carrier. We therefore investigated release kinetics of antibiotics from biodegradable poly(trimethylene carbonate) (PTMC) and in vitro biofilm inhibition of MRSA, MRSE, and S. aureus SCV strains in the course of 24, 72, and 168 h treatment by PTMC, either unloaded, gentamicin-loaded, loaded with rifampicin and fosfomycin, or rifampicin and vancomycin. PTMC appeared to be a suitable carrier for rifampicin alone or in combination with other antibiotics. Biofilm colony forming units and metabolic activity measurement (MTT assay) demonstrated significant (p < 0.05) inhibition for all strains when PTMC loaded with rifampicin and vancomycin was employed, especially after 168 h treatment. Confocal laser scanning microscopy images showed similar qualitative results. PTMC loaded with only gentamicin did not show any inhibition. This exemplifies that PTMC loaded with rifampicin and vancomycin holds promise for the treatment of recalcitrant osteomyelitis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1828-1837, 2016., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

We summarize different studies describing mechanisms through which bacteria in a biofilm mode of growth resist mechanical and chemical challenges. Acknowledging previous microscopic work describing voids and channels in biofilms that govern a biofilms response to such challenges, we advocate a more quantitative approach that builds on the relation between structure and composition of materials with their viscoelastic properties. Biofilms possess features of both viscoelastic solids and liquids, like skin or blood, and stress relaxation of biofilms has been found to be a corollary of their structure and composition, including the EPS matrix and bacterial interactions. Review of the literature on viscoelastic properties of biofilms in ancient and modern environments as well as of infectious biofilms reveals that the viscoelastic properties of a biofilm relate with antimicrobial penetration in a biofilm. In addition, also the removal of biofilm from surfaces appears governed by the viscoelasticity of a biofilm. Herewith, it is established that the viscoelasticity of biofilms, as a corollary of structure and composition, performs a role in their protection against mechanical and chemical challenges. Pathways are discussed to make biofilms more susceptible to antimicrobials by intervening with their viscoelasticity, as a quantifiable expression of their structure and composition., (© The Author 2015. Published by Oxford University Press on behalf of Federation of European Microbiological Society.)

A degradable, poly (lactic-co-glycolic acid) (PLGA), gentamicin-loaded prophylactic coating for hydroxyapatite (HA)-coated cementless hip prostheses is developed with similar antibacterial efficacy as offered by gentamicin-loaded cements for fixing traditional, cemented prostheses in bone. We describe the development pathway, from in vitro investigation of antibiotic release and antibacterial properties of this PLGA-gentamicin-HA-coating in different in vitro models to an evaluation of its efficacy in preventing implant-related infection in rabbits. Bone in-growth in the absence and presence of the coating was investigated in a canine model. The PLGA-gentamicin-HA-coating showed high-burst release, with antibacterial efficacy in agar-assays completely disappearing after 4 days, minimising risk of inducing antibiotic resistance. Gentamicin-sensitive and gentamicin-resistant staphylococci were killed by the antibiotic-loaded coating, in a simulated prosthesis-related interfacial gap. PLGA-gentamicin-HA-coatings prevented growth of bioluminescent staphylococci around a miniature-stem mounted in bacterially contaminated agar, as observed using bio-optical imaging. PLGA-gentamicin-HA-coated pins inserted in bacterially contaminated medullary canals in rabbits caused a statistically significant reduction in infection rates compared to HA-coated pins without gentamicin. Bone ingrowth to PLGA-gentamicin-HA-coated pins, in condylar defects of Beagle dogs was not impaired by the presence of the degradable, gentamicin-loaded coating. In conclusion, the PLGA-gentamicin-HA-coating constitutes an effective strategy for infection prophylaxis in cementless prostheses.

We report on three patients presenting moderate intellectual disability, delayed language acquisition, and mild facial dysmorphia. Array-CGH studies revealed overlapping interstitial 12p13.1 microdeletions encompassing all or part of GRIN2B. GRIN2B encodes the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor. This receptor is a heteromeric glutamate-activated ion channel, present throughout the central nervous system. It plays a critical role in corticogenesis, neuronal migration, and synaptogenesis during brain development. GRIN2B alterations, including mutation and gene disruption by apparently balanced chromosomal rearrangements, have been described in patients with intellectual disability and autism spectrum disorder. We report here on the first cases of GRIN2B deletion, enlarging the spectrum of GRIN2B abnormalities. Our findings confirm the involvement of this gene in neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

Introduction: Chronic osteomyelitis, or bone infection, is a major worldwide cause of morbidity and mortality, as it is exceptionally hard to treat due to patient and pathogen-associated factors. Successful treatment requires surgical debridement together with long-term, high antibiotic concentrations that are best achieved by local delivery devices, either made of degradable or non-degradable materials., Areas Covered: Non-degradable delivery devices are frequently constituted by polymethylmethacrylate-based carriers. Drawbacks are the need to remove the carrier (as the carrier itself may provide a substratum for bacterial colonization), inefficient release kinetics and incompatibility with certain antibiotics. These drawbacks have led to the quest for degradable alternatives, but also devices made of biodegradable calcium sulphate, collagen sponges, calcium phosphate or polylactic acids have their specific disadvantages., Expert Opinion: Antibiotic treatment of osteomyelitis with the current degradable and non-degradable delivery devices is effective in the majority of cases. Degradable carriers have an advantage over non-degradable carriers that they do not require surgical removal. Synthetic poly(trimethylene carbonate) may be preferred in the future over currently approved lactic/glycolic acids, because it does not yield acidic degradation products. Moreover, degradable poly(trimethylene carbonate) yields a zero-order release kinetics that may not stimulate development of antibiotic-resistant bacterial strains due to the absence of long-term, low-concentration tail-release.

Cementless prostheses are increasingly popular in total hip arthroplasties. Therewith, common prophylactic measures to reduce the risk of postoperative infection like the use of antibiotic-loaded bone cements, will no longer be available. Alternative prophylactic measures may include the use of antibiotic-releasing coatings. Previously, we developed a gentamicin-releasing coating for cementless titanium hip prostheses and derived an appropriate dosing of this coating by adjusting the amount of gentamicin in the coating to match the antibacterial efficacy of clinically employed gentamicin-loaded bone cement. In this manuscript, we investigated two important issues regarding the prophylactic use of this 1 mg cm(-2) bioactive gentamicin-releasing coating in cementless total hip arthroplasty: (1) its ability to prevent bacterial growth in a geometrically relevant set-up and (2) its antibacterial spectrum. A geometrically relevant set-up was developed in which miniature titanium stems were surrounded by agar, contaminated with bioluminescent Staphylococcus aureus. Novel, bio-optical imaging was performed allowing noninvasive, longitudinal monitoring of staphylococcal growth around miniature stems with and without the gentamicin-releasing coating. Furthermore, the antibacterial efficacy of the gentamicin-releasing coating was determined against a wide variety of clinical isolates, including bioluminescent Staphylococcus aureus strains, using traditional zone of inhibition measurements. The gentamicin-releasing coating demonstrated a wide-spectrum of antibacterial efficacy and successfully prevented growth of bioluminescent staphylococci around a miniature stem mounted in bacterially contaminated agar for at least 60 h. This implies that the gentamicin-releasing coating has potential to contribute to the improvement of infection prophylaxis in cementless total hip arthroplasty., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: The aim of this study was to evaluate the outcome of patients with oesophageal atresia type III (EA), focusing on the presence of late sequelae and quality of life., Methods: This was a retrospective case ascertainment followed by clinical assessment of patients. The study parameters included the patients' demographic characteristics, associated abnormalities, presence of gastro-oesophageal reflux disease (GERD) and digestive or respiratory symptoms, results of a clinical examination to evaluate nutritional status, spirometry results and quality of life assessed using the PedsQL 4.0 questionnaire., Results: Of 81 patients with EA type III treated in our institution over a 10-year period, 57 (mean age 13.3 (SE 2.8) years) participated in the study. 39% of the patients underwent fundoplication and 46% presented with anastomotic stenosis requiring dilation. 75% of patients had normal nutritional status (16% were obese, 9% were undernourished). Only 19% of participants had no digestive symptoms; 61% had dysphagia and 35% had symptoms of GERD at the last follow-up. The main respiratory symptoms were chronic cough (19%) and dyspnoea on exertion (37%). Only 37% of patients had no respiratory symptoms. Spirometry showed that 50% of patients had proximal obstruction and/or pulmonary distension, and 11% had restriction syndrome. Their quality of life was good but was lower than in healthy controls (80 vs 84, p<0.05) and lower in patients born prematurely, with symptoms of GERD and with a barky cough., Conclusion: The high frequency of late sequelae in EA type III justifies regular and multidisciplinary follow-up through to adulthood.

Wear of metal-on-metal (cobalt-chromium, Co-Cr particles) and metal-on-polyethylene (ultra-high-molecular-weight polyethylene, UHMWPE particles) bearing surfaces in hip prostheses is a major problem in orthopedics. This study aimed to compare the influence of Co-Cr and UHMWPE particles on the persistence of infection. Bioluminescent Staphylococcus aureus Xen36 were injected in air pouches prepared in subcutaneous tissue of immuno-competent BALB/c mice (control), as a model for the joint space, in the absence or presence of Co-Cr or UHMWPE particles. Bioluminescence was monitored longitudinally up to 21 days, corrected for absorption and reflection by the particles and expressed relative to the bioluminescence found in the presence of staphylococci only. After termination, air pouch fluid and air pouch membrane were cultured and histologically analyzed. Bioluminescence was initially lower in mice exposed to UHMWPE particles with staphylococci than in mice injected with staphylococci only, possibly because UHMWPE particles initially stimulated a higher macrophage presence in murine air pouch membranes. For mice exposed to Co-Cr particles with staphylococci, bioluminescence was observed to be higher in two out of six animals compared to the presence of staphylococci alone. In the majority of mice, infection risk in the absence or presence of Co-Cr and UHMWPE particles appeared similar, assuming that the longevity of an elevated bioluminescence is indicative of a higher infection risk. However, the presence of Co-Cr particles yielded a higher bioluminescence in two out of six mice, possibly because the macrophage degradative function was hampered by the presence of Co-Cr particles., (Copyright © 2011 Orthopaedic Research Society.)

The prevalence and characterization of migraine triggers have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined trigger factors in a clinic-based population. In 102 children and adolescents fulfilling the Second Edition of The International Headache Classification criteria for paediatric migraine, at least one migraine trigger was reported by the patient and/or was the parents' interpretation in 100% of patients. The mean number of migraine triggers reported per subject was 7. Mean time elapsed between exposure to a trigger factor and attack onset was comprised between 0 and 3 h in 88 patients (86%). The most common individual trigger was stress (75.5% of patients), followed by lack of sleep (69.6%), warm climate (68.6%) and video games (64.7%). Stress was also the most frequently reported migraine trigger always associated with attacks (24.5%). In conclusion, trigger factors were frequently reported by children and adolescents with migraine and stress was the most frequent.

Cementless prostheses are increasingly popular but require alternative prophylactic measures than the use of antibiotic-loaded bone cements. Here, we determine the 24-h growth inhibition of gentamicin-releasing coatings from grit-blasted and porous-coated titanium alloys, and compare their antibacterial efficacies and gentamicin release-profiles to those of a commercially available gentamicin-loaded bone cement. Antibacterial efficacy increased with increasing doses of gentamicin in the coating and loading with 1.0 and 0.1 mg gentamicin/cm(2) on both grit-blasted and porous-coated samples yielded comparable efficacy to gentamicin-loaded bone cement. The coating had a higher burst release than bone cement, and also inhibited growth of gentamicin-resistant strains. Antibacterial efficacy of the gentamicin coatings disappeared after 4 days, while gentamicin-loaded bone cement exhibited efficacy over at least 7 days. Shut-down after 4 days of gentamicin-release from coatings is advantageous over the low-dosage tail-release from bone cements, as it minimizing risk of inducing antibiotic-resistant strains. Both gentamicin-loaded cement discs and gentamicin-coated titanium coupons were able to kill gentamicin-sensitive and -resistant bacteria in a simulated prothesis-related interfacial gap. In conclusion, the gentamicin coating provided similar antibacterial properties to those seen by gentamicin-loaded bone cement, implying protection of a prosthesis from being colonized by peri-operatively introduced bacteria in cementless total joint arthroplasty., (Copyright © 2011 Orthopaedic Research Society.)

Purpose: In the last decades, hip prostheses with a metal-on-metal (MOM) bearing have been implanted by orthopedic surgeons worldwide. However, concerns are now raised towards the metal particles and degradation products released by MOM-bearings into surrounding tissue, although effects of Co-Cr wear on infection are also unknown. Therefore, we here determine the viable volumes of staphylococcal biofilms formed on polystyrene in the absence and presence of Co-Cr particles and Co-Cr ions., Methods: Three clinically derived and two commercially available staphylococcal strains were grown in the presence of 2 mg/mL Co-Cr particles or 1000/500 µg/L Co-Cr ions derived from Co-Cr salts or from particle supernatant, under static and dynamic growth conditions. A dynamic model simulates the conditions that apply for biofilm formation in the human body, as synovial fluid in mobile patients with hip prostheses is in constant motion with accompanying shear rates. Images of 24 h old biofilms were made with confocal laser scanning microscopy and analyzed with the mathematical computer program COMSTAT, yielding the biovolume of a biofilm. X-ray photoelectron spectroscopy was performed on the particles to study their elemental surface composition., Results: Most isolates showed a tendency of reduced biofilm growth in the presence of Co-Cr particles compared to growth during exposure to metal ions, but this was only significant in one strain under the dynamic growth condition (Staphylococcus aureus 7388). Characterization of the outer surface of the particles revealed a Co-Cr oxide layer enriched by Mo relative to the bulk concentration., Conclusions: MOM bearings produce metal particles which were found to possess antibacterial characteristics under dynamic growth conditions. Further research is needed towards the clinical relevance of this finding.

Background and Purpose: Joint replacement with metal-on-metal (MOM) bearings have gained popularity in the last decades in young and active patients. However, the possible effects of MOM wear debris and its corrosion products are still the subject of debate. Alongside the potential disadvantages such as toxicity, the influences of metal particles and metal ions on infection risk are unclear., Methods: We reviewed the available literature on the influence of degradation products of MOM bearings in total hip arthroplasties on infection risk., Results: Wear products were found to influence the risk of infection by hampering the immune system, by inhibiting or accelerating bacterial growth, and by a possible antibiotic resistance and heavy metal co-selection mechanism., Interpretation: Whether or not the combined effects of MOM wear products make MOM bearings less or more prone to infection requires investigation in the near future.

Background and Purpose: Many investigations on biodegradable materials acting as an antibiotic carrier for local drug delivery are based on poly(lactide). However, the use of poly(lactide) implants in bone has been disputed because of poor bone regeneration at the site of implantation. Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polymer that does not produce acidic degradation products. We explored the suitability of PTMC as an antibiotic releasing polymer for the local treatment of osteomyelitis., Methods: This study addressed 2 separate attributes of PTMC: (1) the release kinetics of gentamicin-loaded PTMC and (2) its behavior in inhibiting biofilm formation. Both of these characteristics were compared with those of commercially available gentamicin-loaded poly(methylmethacrylate) (PMMA) beads, which are commonly used in the local treatment of osteomyelitis., Results: In a lipase solution that mimics the in vivo situation, PTMC discs with gentamicin incorporated were degraded by surface erosion and released 60% of the gentamicin within 14 days. This is similar to the gentamicin release from clinically used PMMA beads. Moreover, biofilm formation by Staphylococcus aureus was inhibited by approximately 80% over at least 14 days in the presence of gentamicin-loaded PTMC discs. This is similar to the effect of gentamicin-loaded PMMA beads. In the absence of the lipase, surface erosion of PTMC discs did not occur and gentamicin release and biofilm inhibition were limited., Interpretation: Since gentamicin-loaded PTMC discs show antibiotic release characteristics and biofilm inhibition characteristics similar to those of gentamicin-loaded PMMA beads, PTMC appears to be a promising biodegradable carrier in the local treatment of osteomyelitis.

Background and Purpose: Commercial gentamicin-loaded bone cement beads (Septopal) constitute an effective delivery system for local antibiotic therapy. These beads are not available in all parts of the world, and are too expensive for frequent use in others. Thus, orthopedic surgeons worldwide make antibiotic-loaded beads themselves. However, these beads are usually not as effective as the commercial beads because of inadequate release kinetics. Our purpose was to develop a simple, cheap, and effective formulation to prepare gentamicin-loaded beads with release properties and antibacterial efficacy similar to the commercially ones., Methods: Acrylic beads were prepared with variable monomer content: 100% (500 microL/g polymer), 75%, and 50% to increase gentamicin release through creation of a less dense polymer matrix. Using the optimal monomer content, different gel-forming polymeric fillers were added to enhance the permeation of fluids into the beads. Polyvinylpyrrolidone (PVP) 17 was selected as a suitable filler; its concentration was varied and the antibiotic release and antibacterial efficacy of these beads were compared with the corresponding properties of the commercial ones., Results: Gentamicin release rate and the extent of release from beads prepared with 50% monomer increased when the PVP17 content was increased. Beads with 15 w/w% PVP17 released 87% of their antibiotic content. This is substantially more than the gentamicin release from Septopal beads (59%). Acrylic beads with 15 w/w% PVP17 reduced bacterial growth by up to 93%, which is similar to the antibacterial properties of the commercial ones., Interpretation: A simple, cheap, and effective formulation and preparation process has been described for hand-made gentamicin-releasing acrylic beads, with better release kinetics and with antibacterial efficacy similar to that of the commercial ones.

Biodegradable delivery systems that do not produce acidic compounds during degradation are preferred for local antibiotic delivery in bone infections in order to avoid adverse bone reactions. Poly(trimethylene carbonate) (PTMC) has good biocompatibility, and is such a polymer. The objective of this in vitro study was to explore the suitability of PTMC as an antibiotic releasing polymer for the local treatment of bone infections. Degradation behaviour and corresponding release profiles of gentamicin and vancomycin from slowly degrading PTMC168 and faster degrading PTMC339 discs were compared in the absence and presence of a lipase solution. Gentamicin release in the absence of lipase was diffusion-controlled, while vancomycin release was limited. Surface erosion of PTMC only occurred in the presence of lipase. Both antibiotics were released in high concentrations from PTMC in the presence of lipase through a combination of surface erosion and diffusion. This illustrates the major advantage of surface-eroding biodegradable polymers, allowing release of larger antibiotic molecules like vancomycin.

The acidic gastric environment of mammals can be chronically colonized by pathogenic Helicobacter species, which use the nickel-dependent urea-degrading enzyme urease to confer acid resistance. Nickel availability in the mammal host is low, being mostly restricted to vegetarian dietary sources, and thus Helicobacter species colonizing carnivores may be subjected to episodes of nickel deficiency and associated acid sensitivity. The aim of this study was to investigate how these Helicobacter species have adapted to the nickel-restricted diet of their carnivorous host. Three carnivore-colonizing Helicobacter species express a second functional urea-degrading urease enzyme (UreA2B2), which functions as adaptation to nickel deficiency. UreA2B2 was not detected in seven other Helicobacter species, and is in Helicobacter mustelae only expressed in nickel-restricted conditions, and its expression was higher in iron-rich conditions. In contrast to the standard urease UreAB, UreA2B2 does not require activation by urease or hydrogenase accessory proteins, which mediate nickel incorporation into these enzymes. Activity of either UreAB or UreA2B2 urease allowed survival of a severe acid shock in the presence of urea, demonstrating a functional role for UreA2B2 in acid resistance. Pathogens often express colonization factors which are adapted to their host. The UreA2B2 urease could represent an example of pathogen adaptation to the specifics of the diet of their carnivorous host, rather than to the host itself.

Biomaterial-related infection of joint replacements is the second most common cause of implant failure, with serious consequences. Chronically infected replacements cannot be treated without removal of the implant, as the biofilm mode of growth protects the bacteria against antibiotics. This review discusses biofilm formation on joint replacements and the important clinical phenomenon of small-colony variants (SCVs). These slow-growing phenotypic variants often remain undetected or are misdiagnosed using hospital microbiological analyses due to their unusual morphological appearance and biochemical reactions. In addition, SCVs make the infection difficult to eradicate. They often lead to recurrence since they respond poorly to standard antibiotic treatment and can sometimes survive intracellularly.

Intraoperative bacterial contamination increases risk for postoperative wound-healing problems and periprosthetic infection, but to what extent remains unclear. We asked whether bacterial contamination of the instruments and bone during primary prosthesis insertion was associated with prolonged wound discharge and subsequent periprosthetic infection. During 100 total hip arthroplasties, four intraoperative cultures were taken from the instruments and two portions of removed bone. Postoperatively, the duration of wound discharge was monitored, with Day 5 as the cut-off point. All patients were followed for 2 years to determine whether periprosthetic infection occurred. Bacterial contamination occurred in 36 operative procedures (36%). We found an association between intraoperative contamination and prolonged wound discharge, with a relative risk of 2.5. The culturing of removed bone had a positive predictive value of 81% to 90%. Other factors associated with prolonged wound discharge were rheumatoid arthritis (relative risk, 6.4), use of cement (relative risk, 1.6), and increased blood loss (relative risk, 1.5).

The increasing gentamicin resistance among bacteria in septic joint arthroplasty has stimulated interest in adding a second antibiotic into gentamicin-loaded bone cement. A first aim of this in vitro study is to investigate whether addition of fusidic acid or clindamycin to gentamicin-loaded bone cement has an additional antimicrobial effect against a collection of 38 clinical isolates, including 16 gentamicin-resistant strains. A modified Kirby-Bauer test, involving measurement of the inhibition zone around antibiotic-loaded bone cement discs on agar plates, was used to investigate whether adding a second antibiotic has an additional antimicrobial effect. Second, a selected number of strains was used to study their survival in an interfacial gap made in the different bone cements to mimic the gap between bone and cement as existing near a prosthesis. Gentamicin-loaded bone cement had an antimicrobial activity against 58% of the 38 bacterial strains included in this study, while 68% of the strains were affected by bone cement loaded with a combination of gentamicin and clindamycin. Bone cement loaded with the combination of gentamicin and fusidic acid had antimicrobial activity against 87% of the bacterial strains. In the prosthesis-related gap model, there was a clear trend toward less bacterial survival for gentamicin-loaded bone cement after adding clindamycin or fusidic acid. Addition of clindamycin or fusidic acid into gentamicin-loaded bone cement yields an additional antimicrobial effect. The combination gentamicin and fusidic acid was effective against a higher number of clinical isolates than the combination of gentamicin with clindamycin, including gentamicin-resistant strains., (.(c)2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.)

The formation of staphylococcal biofilms on experimental bone cements, loaded with 0.5 or 1.0 g of active gentamicin and an additional equivalent amount of gentamicin, clindamycin, or fusidic acid was investigated. The biofilms were formed in a modified Robbins device over a 3-day time span and the influence of the additional antibiotics was quantified by expressing the number of colony forming units relative to the corresponding bone cement containing only gentamicin. Combinations of gentamicin with either fusidic acid or clindamycin reduced growth of clinical isolates of both gentamicin-sensitive Staphylococcus aureus and gentamicin-resistant coagulase-negative staphylococci to approximately 28%. To determine whether adding a second antibiotic has influence on the gentamicin release, cement blocks were placed in phosphate buffer and aliquots were taken at designated sampling intervals. The influence of the additional antibiotics was quantified by expressing the percentage released of the total amount of antibiotic incorporated in the different bone cements. After 3 days, all bone cements had released similar percentages of gentamicin, whereas more clindamycin and fusidic acid were released after doubling their concentration in the bone cements. In conclusion, bone cements loaded with combinations of gentamicin and clindamycin or fusidic acid are more effective in preventing biofilm formation than bone cements with gentamicin as a single drug. In addition, the presence of clindamycin or fusidic acid in gentamicin-loaded bone cement has no influence on the total gentamicin release.

Unlabelled: All surgical procedures have the risk of microbial contamination. However, procedures in which prosthetic materials are involved have a high risk for future infectious problems because of the protection offered by the biofilm mode of growth. Studies of perioperative contamination have been done on involved surgical instruments, but whether these instruments transmit contamination to the prosthesis or future site of the prosthesis is not known. The aim of this study was to detect possible bacterial contamination in total hip arthroplasty through instruments that are used at the direct site of implantation during the primary procedure. Samples of the broaches used for preparing the acetabulum and femur, and samples of the reamed acetabular and femoral bone, were collected during 67 consecutive primary total hip arthroplasties in 67 patients. Broach samples were taken at the start and end of every reaming procedure. Four hundred two samples were taken, of which 26 were found to be positive for microorganisms. In 20 patients, at least one of these positive samples had been in direct contact with the actual prosthesis site, indicating that at least 30% of the involved patients had a possible bacterial contamination when leaving the operating theater., Level of Evidence: Diagnostic study, Level I-1 (testing of previously developed diagnostic criteria in series of consecutive patients--with universally applied reference gold standard). See the Guidelines for Authors for a complete description of levels of evidence.