Aim. Although there are no treatment guidelines for Propionibacterium acnes (PA) bone and joint infections (Corvec et al Acta Orthopedica 2016), these infections can be treated with a combination of fluoroquinolones and rifampicin. Rifampicin resistance have already been reported either in in vitro selected mutants or clinical isolates (Furustrand et al JAC 2013, Anaerobe 2015). Minimal inhibitory concentrations of levofloxacin (LVX) ranging from 0,12 to 0.5mg/L are regularly observed but resistance has not yet been investigated. We investigated the in vitro emergence of LVX resistance and characterized the mutations involved in gyrA gene. Method. The strain of PA ATCC11827 (MIC LVF = 0.25 mg/L) was used. The frequency of mutation was determined after inoculation of 108 PA on blood agar containing concentrations of 2 to 128 times the MIC incubated for 7 days in anaerobiosis at 35 ° C. The emergence of high-level of resistance was also studied from the low-level mutants after a second exposure. For the resistant mutants, the gyrA and parC genes were sequenced and compared to the PA reference sequences. Results. The mutation frequency was 3.8 cfu × 10–8 (8×MIC) and 1.6 cfu × 10–7 (4×MIC), respectively. A low or high-level resistance to LVX was observed. MICs varied between 0.75 and> 32 mg/L and were stable after three subcultures. 87 mutants were studied including 40 with a mutation in gyrA gene. 10 different genotypes could be demonstrated with either high-level resistance: G99 (n = 4), G99 D (n = 3), D100N (n = 1), S101 L (n = 14), S101W N = 5) or low-level resistance D100H (n=1), D100G (n=1), A102P (n=5), D105 H (n = 4), D105 G (n = 2). Substitution 101 always leads to a high level of resistance. No mutation was found in parC gene. Conclusions. To our knowledge, this is the first description of the emergence of LVX resistance in PA. The MIC increases from sensitivity to low or high-level resistance. This resistance is stable and associated exclusively with mutations in the gyrA gene. Six different positions give rise to ten different genotypes. The passage from a low to a high-level resistance is done mainly by the selection of the mutation at position 101. Finally, some mutants do not exhibit mutations in QRDRs, suggesting the existence of an efflux system

Aim. Antimicrobial resistance (AMR) aggravates an already difficult treatment of periprosthetic joint infections (PJI). The prevalence of drug-resistant pathogens varies across countries and increases over time. Regular monitoring of bacteriological analyses should be performed. Due to many factors influencing the AMR, the correct choice of antimicrobial management remains arguable. The primary purpose of this retrospective study was to identify and compare causative bacteria and to compare the incidence of antibiotic resistance between the septic revision total knee arthroplasty (TKA) and septic revision total hip arthroplasty (THA). Method. A review of all revision TKAs and revision THAs, undertaken between 2007 and 2020 in a tertiary referral centre, was performed. Included were cases meeting the consensus criteria for PJI, in which an organism has been identified. There were no major differences in tissue sampling between revision TKAs and revision THAs over time. Results. A total of 228 bacterial strains, isolated after revision TKA and THA, were analysed for their resistance to 20 different antibiotics. There was a statistically significant higher occurrence of Gram-negative bacteria (p=0.002) and Enterococcus species (p=0.026) identified after revision THAs compared to TKA. The comparison of antibiotic resistance between revision TKAs and revision THAs was statistically significant in 9 of 20 analysed antibiotics. Pathogens isolated after revision THA were much more resistant compared to pathogens isolated after revision TKA. Resistance in revision THAs was significantly higher to oxacillin (p=0.03), ciprofloxacin (p<0.001), levofloxacin (p<0.001), moxifloxacin (p=0.005), clindamycin (p<0.001), co-trimoxazole (p<0.001), imipenem (p=0.01), rifampicin (p=0.005) and tetracycline (p=0.009). There was no significantly higher resistance of pathogens isolated after revision TKAs detected. No statistically significant difference in antibiotic resistance of Gram-negative bacteria between revision TKA and revision THA was observed. Conclusions. The occurrence and the resistance of bacteria to antibiotics differs significantly between revision TKAs and revision THAs. This has implications on of the choice of empirical antibiotic in revision surgery as well as prophylactic antibiotic in primary surgery, depending on the joint that is to be replaced

Aim. Local antibiotic treatment for bone and joint infections offers direct delivery of high concentrations of antibiotics with reduced systemic exposure and favourable safety profile. However, the possibility of prolonged release of antibiotics at sub-therapeutic levels creates concern about the possible development of antimicrobial resistance. We investigated patients with recurrent bone and joint infection for evidence of antimicrobial resistance emerging from the use of local antibiotics. Method. 125 patients with recurrent infection (prosthetic joint infection, fracture related infection and osteomyelitis) in the UK between 2007 and 2021 were identified. Electronic patient records (including operative notes, pathology results and prescriptions) were reviewed to extract site of infection, date of surgery, the use of local antibiotics, culture results, empiric and definitive antibiotic therapy. All antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary guidelines (BSAC and EUCAST). Results. Local antibiotics were used in 74/125 (59.2%) of patients. Agents used were Gentamicin 53/125 (42.4%), Tobramycin 18/125 (14.4%), and vancomycin in 19/125 (15.2%). Combined gentamicin and vancomycin usage was seen in 16/125 patients (12.8%). Gentamicin non-sensitivity was common in this cohort with frequent aminoglycoside use. At index procedure, a Gentamicin non-sensitive organism was cultured in 51/125 patients (40.8%). At re-operation this proportion was lower: 40/125 (32%). There was no statistically significant difference in the rate of Gentamicin resistance at reoperation comparing patients who previously received local aminoglycosides with those who had not (21/71, 29.8% vs 19/54, 35.2% p=0.6, chi-squared test). In 48/125 (38.4%) of patients, the same species was isolated during the index and recurrence surgery. We identified 7 cases with new aminoglycoside resistance arising at the second procedure. In 2/7 – S. aureus and E. faecalis - aminoglycoside resistance was the only change in antimicrobial sensitivity. In 5/7, there were at least 2 additional changes in observed antimicrobial sensitivity. 3/74 (4%) of cases who initially received local aminoglycoside cultured organisms with aminoglycoside resistance at recurrence. 4/51 (7.8%) of those who did not receive local or systemic aminoglycoside at index surgery cultured resistant organisms (chi square 0.82; p=0.365). Conclusions. As a group, patients whose treatment for orthopaedic infection included local antibiotics did not exhibit higher rates of specific antimicrobial resistance compared with those not treated with local antibiotics. However we did identify cases where Gram positive bacteria developed aminoglycoside resistance regardless of their initial antimicrobial therapy. This should be considered in antimicrobial choice during surgery for recurrence

Aim. In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes of the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries. Therefore, the aim of this study was to analyze the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII. Furthermore, changes of the microbiological spectrum, distribution of mono vs. polymicrobial infections, and changes of the antimicrobial resistance profile in persistent microorganisms were evaluated. Method. A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Overall, 20 patients (6 male/14 female) underwent 82 revisions for PSII (median 3; range 2–12). There were 55/82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test. Results. In total, 74 microorganisms (83.3% gram-positive; 10.8% gram-negative) were identified. The most common microorganisms were Staphylococcus epidermidis (18.9%) and Cutibacterium acnes (18.9%). All S. epidermidis identified were methicillin-resistant (MRSE). Overall, there were 15/55 (27.3%) polymicrobial infections. The microbiological spectrum changed in 57.1% (20/35) between the revision stages over the entire PSII period. In 42.9% (15/35) the microorganism persisted between the revision surgeries stages. Overall, changes of the antibiotic resistance pattern were seen in 17.4% (8/46) of the detected microorganisms comparing index revision and all subsequent re-revisions. Moreover, higher resistance rates were found for moxifloxacin and for ciprofloxacin at first re-revision surgery compared with index PSII revision. Resistances against vancomycin increased from 4.5% (1/23) at index PSII revision to 7.7% (2/26) at first re-revision surgery. Conclusions. Changes of the microbiological spectrum and the resistance pattern can occur in patients with severe PSII who require multiple revision surgeries. It is important to consider these findings in the antimicrobial treatment of PSII. The microbiological analysis of intraoperative tissue samples should be performed at every revision procedure for PSI

Aim. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with serious cases of community-onset skin and musculoskeletal infections (Co-SMSI). Molecular epidemiology analysis of CA-MRSA recovered from skin and soft tissues specimens is lacking in Latin America. This study aimed to identify phenotypic and genotypic features of MRSA isolates recovered from patients presenting Co-SMSI. Methods. Consecutive MRSA isolates recovered from Co-SMSI of patients admitted from March 2022 to January 2023 in a Brazilian teaching hospital were tested for antimicrobial resistance and characterized by their genotypic features. Identification was carried out by automated method and through MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion, broth microdilution and E-test strips for determination of the minimal inhibitory concentration (MIC) according to recommendations from the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Gene mecA characterization and Sccmec typing were performed by multiplex polymerase chain reaction (PCR) assay, and gene lukF detection by single PCR. Patients were prospectively followed up for two months, in order to determine their clinical characteristics and outcomes. Results. Overall, 48 Staphylococcus aureus isolates were obtained from 68 samples recovered from patients with Co-SMSI. Twenty two (42%) were phenotypically characterized as MRSA, although mecA gene was only identified in 20 of those samples. Sccmec was untypable in 12 isolates, Sccmec was type II in 4 isolates and 2 were classified as type IVa. LukF gene was identified in 5 isolates. Antimicrobial resistance profile showed that all isolates were susceptible to linezolid and vancomycin with MIC = 1 and MIC = 2 in 66,7% and 33.3%, respectively. Susceptibility to quinolones was worryingly low and none of the isolates were sensitive to usual doses of ciprofloxacin and levofloxacin, and showed increased rates of resistance to increased exposure to these drugs, as well. Isolates were both susceptible to gentamicin and tetracycline in 85% and resistance to also Sulfamethoxazole/Trimethoprim occurred in only 2 isolates. Mortality rate evaluated within 1 month of the initial evaluation was 10% among MRSA isolates. Conclusions. Our results showed that CA-MRSA isolates causing Co-SMSI demonstrated an alarming pattern of multidrug resistance, including to β-lactam and quinolones, which have been commonly prescribed as empirical therapy for patients with skin, soft tissue and musculoskeletal infections

A common location for radius fracture is the proximal radial head. With the arm in neutral position, the fracture usually happens in the anterolateral quadrant (Lacheta et al., 2019). If traditional surgeries are not enough to induce bone stabilization and vascularization, or the fracture can be defined grade III or grade IV (Mason classification), a radial head prosthesis can be the optimal compromise between bone saving and recovering the “terrible triad”. A commercially available design of radial head prosthesis such as Antea (Adler Ortho, Milan, Italy) is characterized by flexibility in selecting the best matching size for patients and induced osteointegration thanks to the Ti-Por. ®. radial stem realized by 3D printing with laser technique (Figure 1). As demonstrated, Ti-Por. ®. push-out resistance increased 45% between 8 −12 weeks after implantation, hence confirming the ideal bone-osteointegration. Additional features of Antea are: bipolarity, modularity, TiN coating, radiolucency, hypoallergenic, 10° self-aligning. The osteointegration is of paramount importance for radius, in fact the literature is unfortunately reporting several clinical cases for which the fracture of the prosthesis happened after bone-resorption. Even if related to an uncommon activity, the combination of mechanical resistance provided by the prosthesis and the stabilization due to the osteointegration should cover also accidental movements. Based upon Lacheta et al. (2019), after axial compression-load until radii failure, all native specimens survived a compression-load of 500N, while the failure happened for a mean compression force of 2560N. The aim of this research study was to test the mechanical resistance of a radial head prosthesis obtained by 3D printing. In detail, a finite element analysis (FEA) was used to understand the mechanical resistance of the core of the prosthesis and the potential bone fracture induced in the radius with simulated bone- resorption (Figure 2a). The critical level was estimated at the height for which the thickness of the core is the minimum (Figure 2b). Considered boundary conditions:. - Full-length prosthesis plus radius out of the cement block equal to 60mm (Figure 2a);. - Bone inside the cement equal to 60mm (Figure 2b);. - Load inclined 10° epiphysiary component (Figure 2c);. - Radius with physiological or osteoporotic bone conditions;. - Load (concentrated in the sphere simulating full transmission from the articulation) of 500N or 1300N or 2560N. Figure 3 shows the results in terms of maximum stress on the core of the prosthesis and the risk of fracture (Schileo et al., 2008). According to the obtained results, the radial head prosthesis shows promising mechanical resistance despite of the simulated bone-resorption for all applied loads except for 2560N. The estimated mechanical limit for the material in use is 200MPa. The risk of fracture is in agreement with the experimental findings (Lacheta et al. (2019)), in fact bone starts to fail for the minimum reported failure load, but only for osteoporotic conditions. The presented FEA aimed at investigating the behavior of a femoral head prostheses made by 3D printing with simulated bone-resorption. The prosthesis shows to be a skilled solution even during accidental loads. For any figures or tables, please contact the authors directly

Aim. There is an ongoing controversy whether the observed benefit of infection risk reduction by ALBC outweighs the risk of possible antimicrobial resistance development. Methods. The scientific & clinical literature in PubMed, Medline and Embase has been systematically reviewed with the keywords “antibiotic resistance”, “antibiotic loaded bone cement”, “local antibiotics”, “bacterial colonization” and “joint infection”. In total 28 relevant publications were found with the majority of them reporting laboratory results. Only 7 papers focused on clinical septic situations & patient data. Results. Although rare as consequence of the initially high drug concentrations in situ, experimental and clinical studies demonstrated survival of resistant bacteria on ALBC with subsequent bacterial re-colonisation of the biomaterial. This was most notable for coagulase-negative staphylococci (CoNS). Bacterial survival in presence of ALBC represents a selection process of already pre-existing high-level resistant mutants and not antibiotic resistance induction. The use of antibiotic combinations with gentamicin in bone cement is associated with a markedly lower risk of survival of resistant bacteria. This is particularly important in patients at high infection risks and in septic revision cases. There is no clinical evidence for a widespread increase of clinically important gentamicin resistancies in the orthopaedic ward because of routine use of ALBC. On an individual basis, the benefit of a lower infection probability with combined systemic & local antibiotic application should outweigh the risk of selecting pre-existing resistant bacteria. Each prevented infection case means that a complex and extended antibiotic therapy with risk of antibiotic resistance development over time has been avoided for a patient. In those cases where pre-existing resistant bacteria have survived the prophylactic exposure to antibiotics in bone cement, they remain in vast majority still susceptible to the clinically important antibiotics used for treatment of prosthetic joint infections. Conclusions. The benefit of a lower infection probability with ALBC should outweigh the risk of selecting resistant bacteria against the particular antibiotic used in bone cement. A trend towards broad resistance development which may complicate treatment of infection cases was not found

Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product

Introduction. Support of appositional bone ingrowth and resistance to bacterial adhesion and biofilm formation are preferred properties for biomaterials used in spinal fusion surgery. Although polyetheretherketone (PEEK) is a widely used interbody spacer material, it exhibits poor osteoconductive and bacteriostatic properties. In contrast, monolithic silicon nitride (Si. 3. N. 4. ) has shown enhanced osteogenic and antimicrobial behavior. Therefore, it was hypothesized that incorporation of Si. 3. N. 4. into a PEEK matrix might improve upon PEEK's inherently poor ability to bond with bone and also impart resistance to biofilm formation. Methods. A PEEK polymer was melted and compounded with three different silicon nitride powders at 15% (by volume, vol.%), including: (i) α-Si. 3. N. 4. ; (ii) a liquid phase sintered (LPS) ß-Si. 3. N. 4. ; and (iii) a melt-derived SiYAlON mixture. These three ceramic powders exhibited different solubilities, polymorphic structures, and/or chemical compositions. Osteoconductivity was assessed by seeding specimens with 5 × 10. 5. /ml of SaOS-2 osteosarcoma cells within an osteogenic media for 7 days. Antibacterial behavior was determined by inoculating samples with 1 × 10. 7. CFU/ml of Staphylococcus epidermidis (S. epi.) in a 1 × 10. 8. /ml brain heart infusion (BHI) agar culture for 24 h. After staining with PureBlu™ Hoechst 33342 or with DAPI and CFDA for SaOS-2 cell adhesion or bacterial presence, respectively, samples were examined with a confocal fluorescence microscope using a 488 nm Krypton/Argon laser source. Images were also acquired using a FEG-SEM in secondary and backscattered modes on gold sputter-coated specimens (∼20–30Å). Hydroxyapatite (HAp) deposition was measured using a laser microscope. Raman spectra were collected for samples in backscattering mode using a triple monochromator using a 532 nm excitation source (Nd:YVO. 4. diode-pumped solid-state laser). Results. PEEK composites with 15 vol.% α-Si. 3. N. 4. , LPS ß-Si. 3. N. 4. , or the SiYAlON mixture showed significantly greater SaOS-2 cell proliferation (>600%, p<0.003, cf., Fig. 1(a)) and HAp deposition (>100%, p<0.003, cf., Fig. 1(b)) relative to monolithic PEEK. The largest increase in cell proliferation was observed with the SiYAlON composite, while the greatest amount of HAp was found on the LPS ß-Si. 3. N. 4. composite. Following exposure to S. epidermidis, the composite containing the LPS β-Si. 3. N. 4. powder showed one order of magnitude reduction in adherent live bacteria (p<0.003, cf., Fig. 1(c)) as compared to the PEEK monolith. It is interesting to note that the composite containing α-Si. 3. N. 4. exhibited the worst bacterial resistance (i.e., ∼100% higher than monolithic PEEK), suggesting that the bacteriostatic effectiveness of Si. 3. N. 4. bioceramics is apparently dependent upon the presence of selective sintering additives, viz. yttria and alumina. Conclusions. The addition of 15 wt.% of specific Si. 3. N. 4. powders to PEEK showed enhanced SaOS-2 cell adhesion, proliferation, and HAp deposition when compared to monolithic PEEK. These same composites also showed resistance to S. epi. adhesion and biofilm formation.. Although improvements in osteoconductivity have been previously observed by compounding or coating PEEK with HAp, titanium, or tantalum, these approaches did not provide anti-microbial properties. Compounding PEEK with Si. 3. N. 4. represents a significant advancement due to its ability to provide both improved bone apposition and resistance to biofilm formation. For any figures or tables, please contact the authors directly

Introduction. Highly crosslinked, ultra-high molecular weight polyethylene (HXLPE) acetabular liners inherently have a risk of fatigue failure associated with femoral neck impingement. One of the potential reasons for liner failure was reported as crosslinking formulations of polyethylene, increasing the brittleness and structural rigidity. In addition, the acetabular component designs greatly affect the mechanical loading scenario, such as the offset (lateralized) liners with protruded rim above the metal shells, which commonly induce a weak resistance to rim impingement. The purpose of the present study was to compare the influence of the liner offset length on the impingement resistance in the annealed (first generation) and vitamin E-blended (second-generation) HXLPE liners with a commercial design. Materials and Methods. The materials tested were the 95-kGy irradiated annealed GUR1020, and the 300-kGy irradiated vitamin E-blended GUR1050 HXLPE offset liners, which were referred to as “20_95” and “50E_300”, respectively. These liners had 2, 3, 4-mm rim offset, 2.45-mm rim thickness, and 36-mm internal diameter. Their rims were protruded above the metal rim at 2, 3, 4mm. Rim impingement testing was performed using an electrodynamic axial-torsional machine. The cyclic impingement load of 25–250N was applied on the rims through the necks of the femoral stems at 1Hz. The rotational torque was simultaneously generated by swinging the stem necks on the rims at 1Hz and its rotational angle was set at the range of 0–10˚. The percent crystallinity was analyzed on the as-received (intact) and impinged HXLPE acetabular rims by confocal Raman microspectroscopy. Results. The number of cycles to failure was dependent on the offset length (2, 3, 4-mm) in 20_95 and 50E_300 liners. Our results showed that the shorter the rim offset, the shorter the number of cycles to failure. In both HXLPEs, accumulation of impingement damages significantly decreased crystallinity in their near-surfaces, indicating the occurrence of crystallographic breakdown. In each offset length tested, the fracture always occurred much earlier in 50E_300 than 20_95. However, the magnitudes of the microstructural changes at the time of failure were much less in 50E_300 than 20_95. Conclusions. Although it is known that vitamin E blend into HXLPE can improve the fatigue resistance of HXLPE, the impingement resistance of 50E_300 was lower than vitamin-E free 20_95, indicating a larger negative contribution of high-dose radiation (300kGy) over a positive contribution of the vitamin E blend in 50E_300. Our results implied that the reduction of the protruded rim length in the offset liners may increase the neck-rim contact stresses at the time of impingement, causing a decrease in the fatigue durability. Therefore, if HXLPE offset liner is used, surgeons should take special care in maximizing the volume of the protruded lip section

Aim. Bone and joint infections are frequent in African countries and their prevention and treatment remain a great challenge. This study aimed to determine the bacterial ecology and sensitivity of isolates to locally available antibiotics in orthopedic unit of a tertiary care hospital in Cameroun. Method. During a 12 months period, all the patients presenting with osteomyelitis or septic arthritis irrespective of the mechanism and the location were enrolled in this study. Intraoperative samples (biopsies) were taken and sent for microbiological analysis, and all strains isolated were tested for antibiotic sensitivity according to conventional methods. Results. on the 52 bacteriological analysis performed, 48 were positive. The most isolated germs were staphylococcus aureus (41.9 % of isolates), pseudomonas aeruginosa (14.5 %), Escherichia coli (14.5 %) and Klebsiella pneumonia (12.9 %). The antibiotic sensitivity pattern revealed worrying resistance rates for common and affordable antibiotics: ampicillin (94 %), amoxicillin + clavulanic acid (63.9 %), ceftazidim (65.5%), ticarcillin + clavulanate (57.4%), gentamycin (49 %), ciprofloxacin (40 %), cefuroxim (40 %), tobramycin (38.5 %). The strains of Staphylococcus aureus showed resistance to penicillin G (83%), oxacillin (25%), lincomycin (27%) and vancomycin (7%). The overall highest sensitivity rates were observed with amikacin (92 %) and imipenem (90.1%), which for many patients were the only effective locally available antibiotics. The daily cost of treatment with those two antibiotics is close to the guaranteed minimum wage in our country. Conclusions. The alarming rate of multidrug-resistant bacteria makes the long antibiotic treatment of bone infections unaffordable (in a context of lack of social insurance) for most of our patients. We advocate strong national policies for bacteriological surveillance and antibiotic misuse de-escalation to prevent antibiotic resistance

Introduction. Ideally, a patient receiving a unicondylar knee replacement will have fully functional anterior and posterior cruciate ligaments. When at least one of the cruciate ligaments is not fully functional, femoral and tibial implant contact position can potentially increase along the anterior-posterior (AP) axis. Where unicondylar implant wear testing typically uses AP resistance assuming fully functional cruciate ligaments, the authors used reduced AP resistance intended to simulate deficient cruciate ligaments. Methods. Optetrak Logic® Uni (Exactech Inc, Gainesville, FL USA) unicondylar test specimens featuring an all-UHMWPE tibial component and a cobalt chromium femoral component were used in this study. The system has a semi-constrained articular geometry. Testing was conducted at an independent testing facility (EndoLab GMBH, Thansau, Rosenheim, Germany). A four-station knee simulator was used (EndoLab knee simulator) with two unicondylar knee implants per station, giving a total of eight test specimens. Two different tibial fixation designs (keeled and peg) with identical articulating surfaces were tested. Tibial test specimens were 6 mm in thickness. Unloaded soak controls were stored in distilled water at 37°C. The test was conducted according to ISO 14243–1: 2009 [1]. Test specimens were immersed in calf serum (PAA GmBH, Cölbe, LOT B00111-5126) with a protein content of 20 g/l. Custom polyurethane molds allowed for individual component measurement. Per the ISO 14243-1, a 7% medial offset was incorporated into the set-up. The unicondylar knee implants were set at neutral position in extension. Tibial rotational restraint was 0.36 Nm/° and zero when the test specimen was within ± 6° of the reference position. This test was conducted with an AP resistance of 9.3N/mm to maximize AP displacement and simulate deficient cruciate ligaments. Typical unicondylar knee wear testing is conducted with an AP resistance of 44N/mm, which assumes functional cruciate ligaments. Results. Wear data was separated by component design (keeled and peg) as well as for medial and lateral placement [Table 1]. There was no significant difference between lateral components but there was for medial components. This difference could be due to the small sample size. Contact area of the UHMWPE tibial components was elliptical, with the longer portion along the AP axis. Mean wear rates were comparable to historical unicondylar knee systems tested at the same laboratory using the standard AP resistance (i.e., 44 N/mm). Discussion/Conclusion. This study demonstrated using an AP resistance 9.3 N/mm to simulate the presence of deficient cruciate ligaments in a unicondylar knee wear test produced similar wear rates and greater AP displacement when compared to testing using an AP resistance of 44 N/mm, which assumes functioning ligaments. This being said, design and material information about historical unicondylar knee systems tested are not known, so a direct comparison cannot be made. Performing unicondylar knee wear tests with reduced AP resistance could provide realistic wear information for devices implanted in patients without fully functioning cruciate ligaments

The main objective of joint arthroplasty is to improve activities of daily living of the patient. However, normal daily activities may lead to separation of articular surfaces of an artificial joint, possibly as a result of a combined impact and sliding motion. Therefore, the properties of articular surfaces define the durability of implant materials. Modification of bearing surfaces with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) increases the hydration of the surfaces and decreases the wear of the substrates. Hence, a PMPC layer can potentially cushion the impact and improve the resistance of cross-linked polyethylene (CLPE). This study aimed to explore the fatigue and wear resistance of PMPC-grafted hydrated CLPE under impact-to-wear conditions using a pin-on-disk tester. The surfaces of a CLPE disk (3- or 6-mm thick) were modified with PMPC by photoinduced polymerization and were sterilized using gamma rays. The wear resistance of PMPC-grafted CLPE disks against a Co-Cr-Mo alloy pin was evaluated and compared to that of untreated disks. The disks were fixed to the tester with a metal plate (Ti-6Al-4V alloy) that had a central hole. The test was performed for 2 × 10. 6. cycles of repetitive impact and unidirectional sliding with the maximum load of 150 N, sliding distance of 10 mm, and frequency of 1 Hz [Fig. 1]. Gravimetric wear was determined by weighing the disks, and soak controls were used to compensate for fluid absorption. Volumetric changes in the surfaces of the disks were evaluated using a three-dimensional non-contact optical profiler. The average gravimetric wear (mg) after 2 × 10. 6. cycles was 0.000/0.120 for CLPE (3/6 mm) and −0.073/–0.137 for PMPC-CLPE (3/6 mm). The weight gain of the PMPC-CLPE disks was due to their greater fluid absorption compared to that of the soak controls under the impact-to-wear conditions, as judged from the fact that during the load-soak in the lubricant this gain was observed for all the disks irrespectively of PMPC grafting. PMPC-grafting decreased the gravimetric wear of CLPE (p < 0.01) in the 6-mm group, whereas the thickness of the CLPE disks had no substantial effect on the wear resistance [Fig. 2]. In all cases, three-dimensional measurements detected a remarkable volumetric penetration in the impact-sliding surfaces and an extrusion of CLPE from the backside surfaces into the hole in the metal plate. Both the volumetric penetration and backside extrusion were smaller in the 6-mm group. The PMPC grafting had no discernible effect on these volumetric changes [Fig. 3]. Even after 2 × 10. 6. cycles of impact loads, mechanical fracture or delamination of the impact-sliding or backside surfaces were hardly observed in all the groups. The results of this study revealed that: (1) PMPC-grafting of CLPE surfaces decreased the gravimetric wear irrespectively of the disk thickness; and (2) thinner CLPE increased the risk of volumetric changes, including penetration in the impact-sliding surface and extrusion of the backside surface. In conclusion, PMPC grafting can potentially improve the wear resistance of the bearing surface of biomaterials even under impact-to-wear conditions, increasing the longevity of artificial joints

Aim. There is a theoretical advantage for immediate postoperative start of rifampicin after debridement, antibiotics and implant retention (DAIR). Anti-biofilm treatment may be mostly needed during the first postoperative days in order to prevent new biofilm formation. However, there are concerns with regard to development of rifampicin resistance if rifampicin is started too early. Rifampicin monotherapy will rapidly result in rifampicin resistance, but this may not occur when prescribed as part of combination antimicrobial therapy and after thorough surgical debridement. We hypothesized that in this setting the probability of development of rifampicin resistance is very low. We evaluated the frequency of development of rifampicin resistance in patients with acute staphylococcal PJI who were treated with DAIR followed by immediate postoperative start of rifampicin in combination with a betalactam or glycopeptide. Method. During 2003–2014, all patients with an acute staphylococcal PJI were treated with five days of high-dose rifampicin (600mg bid) in combination with at least 6 weeks of betalactam or glycopeptide antibiotics, both started immediately postoperative after DAIR. Clinical outcome and development of rifampicin resistance in patients who failed were monitored. Susceptibility testing for rifampicin was performed by Vitek 2 (Biomerieux). Until 2014, Clinical and Laboratory Standards Institute (CLSI) criteria for rifampicin resistance were applied (S ≤ 1), from 2014 EUCAST criteria (S ≤ 0.06) were applied. Results. Forty-one patients with acute staphylococcal hip (22) of knee (19) PJI were included. Comorbidities were rheumatoid arthritis (22%), diabetes (10%), a tumor prosthesis due to malignancy (34%) and corticosteroid use (27%). Fifteen patients (37%) developed a failure after DAIR. Eight failures were caused by the same staphylococcal species as the initial PJI (six Staphylococcus aureus, two Coagulase-negative staphylococci). In all failures, rifampicin susceptibility of the isolate had not changed. One patient was started on chronic suppressive treatment (not including rifampicin) and had a prosthetic joint removal 18 months later. In this patient, one out of five positive cultures with S. aureus from the removed prosthesis showed a rifampicin resistant strain. In all failures, mean duration between the initial DAIR and failure was 208 days (range 7–636 days). Conclusions. Immediate postoperative start of high-dose rifampicin in combination with betalactam or glycopeptide did not result in rifampicin resistant staphylococci among patient who had a failure with the same staphylococci. These results strongly indicate that immediate postoperative start of rifampicin is safe. Larger studies are needed to prove the clinical benefit of this strategy

Aim. Fracture-related infection (FRI) is a serious complication after trauma. More often resistant micro-organisms are cultured. Gentamicin covers a wide variety of causative agents for FRI. A bio-absorbable antibiotic carrier, Cerament-G®, combines dead space management with local release of gentamicin in a one-stage approach. The achieved tissue concentrations of locally applied antibiotics are 4–8 thousand times higher than after systemic administration. Does Cerament-G® have antimicrobial activity towards bacteria that are not susceptible to systemic gentamicin administration. Method. The four most often cultured bacterial species found in FRI were used; Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterobacter cloacae. For each species, four different isolates were obtained, each with a different susceptibility for gentamicin. This susceptibility, expressed in the minimal inhibitory concentration (MIC), varied from completely susceptible (MIC 0,064 mg/L – 4mg/L), minimal resistance (4mg/L – 16mg/L), moderate resistance (8 mg/L – 96 mg/L) to high resistance (24 mg/L - >1024 mg/L), depending on each different organism. Antimicrobial activity of Cerament-G. ®. was determent by a Kirby-Bauer test, according to the EUCAST disc protocol. Each test was done in five-fold for each of the 16 cultured isolates, four of each species. The zone of inhibition (ZOI), obtained by the test, was compared between each bacterial isolate and within each of the four separate species. Results. Cerament-G. ®. shows antimicrobial activity against S. aureus, S. epidermidis, P. aeruginosa and E. cloacae. ZOI-values varied from 11 to 44 mm. It was negatively correlated with the MIC; the higher the MIC, the less the antimicrobial effect of Cerament-G. ®. Between bacterial isolates with the same MIC, within the same species, there was no significant difference in ZOI between the five-fold repetitions of the test, indicating an accurate test. The ZOI of the different bacterial isolates (with different MIC's), belonging to the same bacterial species, differed significantly. Of all 16 isolates, only the S. aureus with a MIC of >1024 mg/L did not show antimicrobial activity of Cerament-G. ®. ; ZOI =0mm. Conclusions. This study shows that Cerament-G. ®. has antimicrobial activity against bacterial isolates, resistant to gentamicin when systemically treated. This confirms that the cut-off point for systemic application is not very useful for the local use of Cerament-G. ®. and emphasizes the need for optimization and change of current antibiotic protocols to increase the durability and sustainability of antibiotic FRI treatment

Introduction. The fatigue strength of ultrahigh molecular weight polyethylene (UHMWPE) in total joint implants is crucial to its long term success in high demand applications, such as in the knee, and is typically determined by measuring the crack propagation resistance in razor-notched specimens under cyclic load [1]. This only tells part of the story: that is, how well the material resists crack propagation once a crack is present. A second, equally important component of fatigue strength is how well the material resists crack formation. Previous studies cyclically loaded a cantilevered post until failure [2], postulating that the post would break very quickly after crack initiation. Parran et. al. proposed a novel method to measure the crack initiation time by holding a sample in constant tension until a crack was visually observed [3]. We hypothesize that the crack initiation times of various UHMWPEs will follow similar trends as the more omnipresent crack propagation resistance tests. Materials and Methods. The following UHMWPE formulations were tested: (i) virgin, (ii) gamma sterilized in vacuum, (iii) 91 kGy gamma irradiated, and (iv) 91 kGy gamma irradiated and subsequently melted. GUR1020 and GUR1050 bar stock of varying irradiation doses were machined into compact tension specimens [4] with a notch depth of 17 mm and a blunt notch root radius of 0.25 mm, mimicking a geometry of a joint replacement component. Specimens were held in constant tension until failure; 3 to 5 different loads between 1 kN and 2.25 kN (n=3 samples per load per material) were tested. A video camera was focused on the face of the notch and took a picture every 10 seconds. The photos were reviewed to manually determine the crack initiation time (Fig 1). The time it took for the sample to completely fail – that is, shear into two separate pieces – was also recorded. Results. For all materials tested, the crack initiation time (Fig 2a,b) and the time to failure (Fig 2c,d) decreased as the applied load increased. The crack initiation time increased for the gamma sterilized materials when compared to the virgin materials while the time to failure decreased. The highly crosslinked, 91 kGy materials had crack initiation times and times to failure that were less than that of the virgin material. Post irradiation melting greatly diminished the fatigue strength of the material, yielding the lowest crack initiation time and time to failure. Discussion. The test yielded results consistent with current knowledge: that is, high-dose irradiation yields a slight drop in fatigue strength, and post-irradiation melting greatly reduces strength. This test was simple to set up and run and can be a good tool to determine the relative fatigue strengths of UHMWPE formulations for orthopaedic applications. For figures/tables, please contact authors directly.

Artificial knee joints are continuously loaded by higher contact stress than artificial hip joints due to a less conformity and much smaller contact area between the femoral and tibial surfaces. The higher contact stress causes severe surface damage such as pitting or delamination of polyethylene (PE) tibial inserts. To decrease the risks of these surface damages, the oxidation degradation of cross-linked polyethylene (PE) induced by residual free radicals resulting from gamma-ray irradiation for cross-linking or sterilization should be prevented. Vitamin E (VE), as an antioxidant, blended PE (PE(VE)) has been used to solve the problems. In addition, osteolysis induced by PE wear particles, bone cement and metallic debris is recognized as one of the important problems for total knee arthroplasty (TKA). To decrease the generation of PE wear particles, we have developed the bearing surface mimicking the articular cartilage; grafting a biocompatible polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), onto the PE surface having high wear resistance. In this study, we have evaluated the surface, mechanical under severe oxidative condition, and wear properties of PMPC-grafted cross-linked PE(VE) (PMPC-CLPE(VE)) material for artificial knee joints. Untreated and PMPC-grafted 0.1 mass% VE-blended PE (GUR1020E resin) with a gamma-ray irradiation of 100 kGy for cross-linking and 25 kGy for sterilization were prepared (CLPE(VE) and PMPC-CLPE(VE), respectively). Surface properties were evaluated by Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscope (TEM) observations. Surface wettability and frictional property were measured by static water contact angle measurement and ball-on-plate friction test. To evaluate the oxidation degradation resistance, mechanical and physical properties such tensile test, izod impact test, small punch test and cross-link density measurement before and after accelerated aging were measured. Wear properties of the tibial inserts were examined by using knee simulator in the combination of Co-Cr-Mo femoral components according to ISO14243-3. Gravimetric wear, volumetric penetration and the number of generated wear particles were measured. By the FT-IR measurements and TEM observation, P–O peaks attributed to MPC unit and uniform PMPC layer with 100–200 nm thick was observed only on PMPC-CLPE(VE) surface. Static water contact angle of CLPE(VE) was almost 100 degree, while that of PMPC-CLPE(VE) decreased significantly to almost 35 degree. There was no significant difference in the mechanical and physical properties between CLPE(VE) and PMPC-CLPE(VE). Moreover, both the CLPE(VE) and PMPC-CLPE(VE) maintained these properties even after the accelerated aging of 12 weeks [Fig. 1]. Blended VE in CLPE would act as radical scavengers to prevent oxidation degradation. In the knee simulator wear test, the PMPC-CLPE(VE) tibial inserts showed about a half gravimetric wear compared to the CLPE(VE) tibial inserts [Fig. 2]. This would be due to the significant differences observed in wettability of the surface. Water thin film formed on the hydrated PMPC graft layer, would act as significantly efficient lubricant. From these results, the PMPC-CLPE(VE) is expected to be one of the great bearing materials not only preventing surface damages due to higher contact stress and oxidation degradation but also improving wear resistance, and to provide much more lifelong artificial knee joints. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Introduction. Third body wear caused by contaminated bearing environment with debris that may have been generated by a worn or fractured revised bearing coupling, but also originated by generation of metal/cement particles during the primary or revision surgery, may be a relevant issue for the implant life. Objectives. To evaluate the wear behavior of a last generation alumina matrix ceramic composite (AMC) bearing in a worst case scenario consisting of highly contaminated test lubricant with alumina particles in a hip joint simulator study. Methods. AMC (BIOLOX®delta - Group 1) and alumina (BIOLOX®forte - Group 2) liners with an internal diameter of 32mm were articulated against AMC BIOLOX®OPTION heads (all CeramTec GmbH, Plochingen). Coarse alumina particles (D(50):60µm) and fine alumina particles (D(50):0.30µm) with a concentration of 48mg/ml were used as environmental contamination of the first 2mlc and the second 2mlc, respectively. All components were tested according to ISO14242-1(2012) using the EndoLab®hip joint simulator. Each group consisted of 3 couples plus one axially loaded control consisting of a 32mm AMC head on an alumina liner. The test fluid was exchanged every 500'000 cycles. Two different test regimes describing level walking and subluxation of the insert from the femoral head were used as test input. The first regime included 500 standard walking cycles followed by a second block of 5 subluxation cycles. Head subluxation is assumed to increase the number of third-body particles that enter the otherwise closely conforming articular bearing space, when compared to level-walking cycles alone. To maintain the particle suspension in the test fluid, the test fluid of each test chamber was circulated by peristaltic pumps. The wear rate was determined by gravimetric method. The surface of ball heads was subjected to visual inspection every 500'000 cycles by optical and laser microscope. The depth of scratches was measured by the laser microscope. Results. After 2 million load cycles with the test fluid contaminated with coarse alumina particles, no significant wear was detected by the gravimetric method. The qualitative surface inspection by laser microscope individuated an increasing, but low concentration of sparse tiny scratches about 40nm deep on ball head surface at every simulator stop. Nevertheless, after loading the chambers with fine alumina particles, bearing surface wear seemed to increase consistently, since opaque areas appeared after 3 million load cycles, but the wear-rate remained close to the gravimetric measurement detection limit (about 0.1–0.2mg) indicating the still extremely low wear-rate of the tested ceramic couplings. Conclusions. This study confirms the high wear and scratch resistance of AMC used in THA. Even in heavily contaminated environment with hard alumina particles, which may occur after fracture of a ceramic component, gravimetry wasn't able to detect significant wear. The visual inspection by laser microscope exhibited only slight damaged surface characterized by tiny scratches and more opaque areas in the main wear zone as result of using fine alumina particles. Ceramic-on-ceramic is a safe bearing even in the case of revision for ceramic fracture, maintaining the excellent wear resistance of this bearing

INTRODUCTION. Unlike current acetabular cups, this novel ceramic cup has a Ti/HA coating which removes the requirement for assembly into a metal shell which avoiding potential chipping/misalignment and reducing wall thickness [Figure 1]. This study examines the resistance of novel thin-walled, direct to bone fixation ceramic cups to critical impact loads. METHODS. Samples of the smallest (Ø46mm) and largest (Ø70mm) diameter ReCerf. TM. acetabular cups and corresponding femoral head implants were implanted into Sawbones foam blocks considered representative of pelvic cancellous bone. Two different positional configurations were tested and were considered worst case and the extremes of surgical compromise; P1 simulates the cup fully supported by the acetabulum with a high inclination angle (70°) and a vertical impaction axis (worst case loading near the cup rim) and. P2 simulates the cup implanted with a lower inclination (55°) but with the superior section unsupported by acetabulum bone [Figure 2]. For each size, three acetabular cups were tested in each position. The impact fixture was positioned within a drop weight rig above a bed of sand and ≈22mm of pork belly representative of soft tissues damping effect and the implant components aligned to achieve the defined impact point on the cup [Figure 2]. Lateral falls were tested on all available samples applying impact energy of 140J [1] and 3m/s impact velocity [2]. After the lateral fall test, each sample was tested under impact conditions equivalent to a frontal car crash considering a peak impact force of 5.7kN occurring 40ms from initial contact (able to produce acetabular fracture)[3]. RESULTS. None of the testing simulating a lateral fall produced fracture or any other damage to the ceramic acetabular cup. In 7 of the 12 tests, the impact force was sufficient to fracture the foam block representing the periprosthetic bone. The cups showed a good stability within the blocks, with a maximum recorded cup spinning angle relative to the acetabulum of 4.5˚. Subsequent testing simulating a car crash resulted in the fracture of two samples out of 12, one of the largest and one of the smallest ReCerf. TM. cups. In both instances, failure occurred very close to the inner edge. Of the remaining 10 samples no cup fractures were observed. All foam acetabulum blocks were severely damaged and 5 blocks fractured. The maximum recorded cup spinning angle following the car crash impact was 5.8˚. SIGNIFICANCE. Extreme testing scenarios presented here are not a regulatory requirement for manufacturers and have not previously been considered for ceramic acetabular components. Fracture is a possible failure mode of ceramics but this testing has proven that modern ceramics can withstand lateral falls and the large majority can withstand subsequent loading equivalent to head on car-crash; loading under which pelvic bone fracture and significant injury is far more likely to occur than implant fracture

Aim. The incidence of fractured neck of femur (FNOF) is increasing yearly. Many of these patients undergo hip hemiarthroplasty. High dose dual-antibiotic cement (HDDAC) has been shown to reduce rates of deep surgical site infection (SSI) when compared to the current standard low dose single-antibiotic cement (LDSAC) in a quasi-randomised controlled trial. Some concerns exist regarding the use of HDDAC and the development of resistance. We reviewed cases of infection in LDSAC and HDDAC bone cement with regard to causative organism and resistance profile. Method. A retrospective analysis was undertaken of all hemiarthroplasties within our trust from April 2008 to December 2014. We identified all patients in this time period who acquired a deep SSI from the trust SSI surveillance database. The infecting organisms and susceptibility patterns were collated for each cement. Results. We identified 1941 hemiarthroplasties. There were 36 deep surgical site infections representing an infection rate of 3.1% in LDSAC patients and 1.2% in HDDAC patients. A wider variety of organisms were seen in the LDSAC compared to HDDAC. Staphylococcus epidermidis accounted for the majority of infections in both LDSAC and HDDAC patients. Infection with Corynebacterium species and Staphylococcus aureus was eliminated completely in HDDAC. There was minimal change in the proportion of Gram-negative and Gram-positive bacteria. A change in resistance was not demonstrated amongst infections caused by Gram-negative bacteria. In Gram-positive bacteria, resistance to a number of antibiotics increased using HDDAC compared to LDSAC, most notably to clindamycin and gentamicin within the coagulase negative staphylococci. However, levels of resistance remained low to teicoplanin, vancomycin, daptomycin, linezolid and rifampicin. Conclusions. A lower infection rate was seen in HDDAC. Direct comparison demonstrated changes in resistance profiles caused by Gram-positive organisms. 24,000 patients undergo hip hemiarthroplasty annually. Extrapolating our results to this cohort would demonstrate 744 infections in LDSAC and 288 infections in HDDAC. Of these, resistance to both clindamycin and gentamicin would be seen in 180 patients with LDSAC and 177 patients with HDDAC. Overall, this review supports the continued use of HDDAC in FNOF patients. High dose dual antibiotic cement = Copal G+C, Heraeus Medical, UK. Low dose single antibiotic cement = Palacos R+G, Heraeus Medical, UK