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Introduction: Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. I hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods: The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats using a posterior surgical approach. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa (PA) strains: a reference strain (PA14-lux) and a mutant strain that is defective in biofilm formation (flgK-lux). Infection was assessed in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI) and in vitro by quantifying bacterial loads on collected implants surface and in periprosthetic tissues as well as biofilm visualization using the Field emission scanning electron microscopy (FE-SEM). The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGaitTM system in vivo. Results: Bioluminescence detected by IVIS, was focused on the hip region, demonstrating localized-infection, with the ability of PA14-lux to persist in the model compared to flgK-lux defective in biofilm formation. This was corroborated by MRI as the PA14-lux induced relatively larger implant-related abscesses. Biofilm formation at the bone-implant-interface induced by the PA14-lux was visualized using FE-SEM versus defective-biofilm formation by flgK-lux. This could be quantitatively confirmed, by average viable-colony-count of the sonicated implants, 3.77x108CFU/ml versus 3.65x103CFU/ml for PA14-lux and flgK-lux, respectively (p=0.0025; 95%CI: -6.08x108 to -1.45x108). This difference in the ability to persist in the model was reflected significantly on the implant osseointegration with a mean intersection surface 4.1x106μm2 1.99x106 for PA14-lux versus 6.44x106μm2 2.53x106 for flgK-lux and 7.08x106μm2 1.55x106 for non-infected control (p=0.048). Conclusions: To date, the proposed in vivo biofilm-based model is the most clinically representative for GN-PJI since animals can bear weight on the implant and poor osseointegration correlates with biofilm formation. Clinical Relevance: The current model will allow for reliable testing of novel biofilm-targeting therapeutics.

En bakteriell ledinfektion kallas för septisk artrit och utan snabb behandling kan tillståndet leda till irreversibla ledskador och flera allvarliga komplikationer. Snabb diagnostik är viktigt för en god prognos och med nuvarande metod för odling av ledvätska tar det upp till fem dygn för detektion av mikroorganismer. Metoden inkluderar odling på fasta substrat och i blododlingsflaskor. Med en ny metod som använder multiplex PCR (polymerase chain reaction) skulle analystiden kunna minskas till en timme. BioFire Joint Infection (JI) Panel är ett test som kan detektera flera mikroorganismer samtidigt genom amplifiering av DNA. Mikroorganismer detekteras och identifieras genom cellysering, DNA-rening, PCR-reaktioner i två steg och smältanalys. Syftet med arbetet var att utvärdera BioFire JI Panel för detektion av mikroorganismer i ledvätska och jämföra metodens känslighet med standardiserad odling respektive odling i buljong, och svara på frågeställningen hur känslig JI-panelen är jämfört med standardiserad odlingsmetod. Prov konstruerades genom att suspendera målbakterierna Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, Neisseria gonorrhoeae, Haemophilus influenzae, Kingella kingae och Finegoldia magna i natriumklorid. Suspensionerna seriespäddes och odlades ut på fasta substrat, inokulerades i blododlingsflaskor och buljonger samt analyserades med JI-panelen för att identifiera metodernas detektionsgränser. Fasta substrat, blododlingsflaskor och buljonger visade likvärdig känslighet för majoriteten av bakterieisolaten medan JI-panelen generellt visade en sämre eller likvärdig känslighet i jämförelse med standardmetod. Panelen visade potential för detektion av svårodlade bakterier och skulle vara ett bra komplement till nuvarande odlingsmetod. Ytterligare studier hade behövts men den snabba analystiden som möjliggör snabbare behandling framhävde metodens kliniska potential. / Bacterial joint infections are called septic arthritis and without rapid diagnosis and treatment the condition could lead to irreversible joint damage and other serious complications. With the current method for synovial fluid cultivation, which includes both solid substrates and culture vials, detection of microorganisms takes up to five days. With a new method utilizing multiplex polymerase chain reaction (PCR), the time to detection could decrease to an hour. BioFire Joint Infection (JI) Panel can detect multiple microorganisms simultaneously through amplification of DNA. Microorganisms are detected and identified by cell lysis, DNA purification and two consecutive PCR reactions with subsequent melting curve analysis. The aim of the study was to evaluate the BioFire JI Panel for detection of microorganisms in synovial fluid and compare the method’s sensitivity to standard and broth cultivation. Samples were constructed by suspending target bacteria, Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, Neisseria gonorrhoeae, Haemophilus influenzae, Kingella kingae and Finegoldia magna, in sodium chloride. The suspensions were serially diluted and cultivated on solid substrates, in culture vials, broth and analyzed with the JI panel to find the detection limits for each method. Solid substrates, culture vials and broth exhibited similar sensitivity while the JI panel generally had a lower or similar sensitivity compared to standard methods. The panel showed potential detecting difficult to grow bacteria and would be a good complement to current methods. Further studies are required but the quick analysis enabling faster treatment highlighted the clinical potential.

Höft- och knäprotesoperationer är idag en vanlig operation vid artros i höft- och knäled. Trotsminutiösa infektionsförebyggande förberedelser inför operationen drabbas ändå en delpatienter av postoperativa infektioner. Vid ortopedisk proteskirurgi är postoperativainfektioner ett direkt hot mot den nya inopererade leden och kan leda till långabehandlingstider som påverkar patientens livskvalitet under lång tid. Syftet med studien var att utforska patienters möjlighet till delaktighet i tidig upptäckt avpostoperativ infektion utifrån given information vid operation för höft- eller knäprotes. Semi-strukturerade intervjuer genomfördes med tio patienter med diagnostiserad postoperativinfektion efter höft- eller knäprotesoperation. Transkriberade intervjuer analyserades medinnehållsanalys. Journaler granskades för att beskriva patientens tidigare sjukdomar. Resultatet visade att första tecknen på infektion kan beskrivas med temat: Vad är normalt ochvad är inte normalt. Två kategorier beskriver patienternas Möjlighet till delaktighet ochHinder till delaktighet i det infektionsförebyggande arbete före, under och efter operation. Det handlade om hur patienten hade förstått eller inte förstått given information, vilketkategoriserades som subkategorier. Personcentrerad vård kan vara ett redskap för att stärka patienternas förutsättningar tilldelaktighet och ökar möjligheterna för att förhindra att vårdskador så som postoperativainfektioner uppstår. / Surgery with prosthetic joint replacement of the hip and knee in patients with osteoarthritis is a common procedure. Despite meticulous preparation prior to surgery, surgical site infections develop in some patients. A surgical site infection is a direct threat to the new implanted joint and can lead to long treatments that affect quality of life over time. The aim of this study was to explore patients´ participation in early detection of a surgical site infection based on the information given in conjunction to surgery for hip and knee replacement. Semi structured interviews were conducted with ten patients diagnosed with surgical site infection after hip or knee replacement surgery. Transcribed interviews were analyzed using content analysis. Medical records were reviewed to describe the patients´ comorbidity. The result showed that the first signs of infection can be described with the theme; What is normal and what is not normal? Two categories describe patients´ Possibility of participation and Barriers to participation in infection prevention before and after surgery. It was all about How the patient had understood or not understood the given information which was categorized as subcategories. Person-centered care can be a tool that enables patients´ possibilities to participate in their care and increases the possibilities to prevent adverse events such as surgical site infections.

Prosthetic joint infection (PJI) is an emergent concern given the wide usage of prosthetic joints in old and young population to assist with activities of daily living. While the public health burden of PJI appears to be relatively low compared with other potentially fatal infections such as blood stream infections, PJI is associated with excess morbidity and steep healthcare costs. Appropriate and timely diagnosis and management are crucial in preventing poor clinical outcomes and restoring adequate function in patients with PJI. There is lack of studies using robust epidemiologic methods to evaluate effectiveness of existing treatment protocols for PJI. We conducted retrospective studies using the Veterans Affairs (VA) database using data from 123 VA hospitals between 2003 and 2012. We also abstracted clinical data from VA medical records to achieve the objectives of this research. The effectiveness of an antibiotic — rifampin and a surgical management – exchange arthroplasty was assessed in separate studies. These treatments were adjudicated based on their effectiveness in prevention of PJI recurrence and two-year postoperative mortality, respectively. Seven hundred thirty-one of the 2838 patients with first episode of PJI were treated with surgery and medical management for Staphylococcus aureus PJI and were retained in the thesis dataset. In the first study, we compared 300 patients treated with rifampin for the first 42 days of treatment period to 364 patients treated with antibiotics other than rifampin during the 42 days (unexposed). Overall, 255 patients (38.4%) were observed to have a treatment failure defined as recurrence of S. aureus PJI with or without a repeat surgery or death in the 90 days after surgery for the PJI. The rifampin-treated and unexposed groups did not differ on time to treatment failure (p=0.92). It was noted that patients treated with a less invasive surgery that resulted in retention of the infection prosthesis with removal of infected tissue and rifampin treatment had lower risk for treatment failure compared to patients with similar surgery but not treated with rifampin (HR=0.79, 95%CI 0.52-1.20). We also observed that patients who had surgery for removal of the infected prosthesis and were treated with rifampin had significantly greater risk for treatment failure compared to those treated with the prosthesis removal surgery but no rifampin. In our second study we further analyzed this research question in depth using advanced epidemiologic methods to attenuate any bias in our previous findings. We noted that the groups did not differ in their risk for treatment failure after matching patients on their probability of receiving rifampin treatment (HR=1.08, 95%CI 0.71-1.65). In addition, we observed that patients whose treatment decision with rifampin was determined by the rifampin prescription rate in the treating facility substantially benefited with use of rifampin antibiotic for S. aureus PJI. In the third study we assessed the effectiveness of a surgery — exchange arthroplasty (involves removal of infected prosthesis and insertion of new prosthesis) to reduce the risk of death two years after surgery in a sample of 566 S. aureus PJI patients. Patients with this procedure were compared to patients treated with retention of their infected prosthesis and removal of infected tissue (DAIR). Overall, 90 patients (15.9%) died in the 2 years after surgery. Of these, 14 (9.9%) died after exchange surgery while 76 (17.9%) died after the DAIR procedure. We observed that the exchange surgery reduced the risk for death by almost 60% compared to the DAIR (OR=0.42, 95%CI 0.19-0.89). In conclusion, epidemiological studies conducted as part of this thesis identified considerable burden of treatment failure (38.4%) and all-cause mortality (15.9%) among veterans treated for S. aureus PJI. Rifampin combination antibiotic regimen was not observed to be effective in reducing the burden of the infection, in comparison to other antibiotics. Exchange arthroplasty reduced the risk for death in old veteran patients compared to a less invasive but potentially life-threatening procedure such as DAIR. Choice of treatment should be made on a case-by-case basis for patients with S. aureus PJI after thorough consideration of patient characteristics.

Prosthetic joint infection (PJI) poses a significant risk to implanted patients, requiring multiple surgeries with high rates of reinfection. The primary cause of such infections is otherwise innocuous bacterial species present on the skin that have survived sterilization protocols. Antibiotic drugs have significantly reduced efficacy due to the lack of vasculature in the newly implanted site, allowing microbes to form biofilms with even greater resistance. Graphene oxide (GO) is known to have good biocompatibility while providing drugless antimicrobial properties. The focus of this study is on the development and characterization of a robust coating for titanium alloy implants to promote bone regeneration while inhibiting microbial biofilm adhesion to the implant surface. The novelty of this study is the use of proprietary coal-derived graphene oxide (c-GO) in a biomedical application. c-GO has been demonstrated to have a greater number of functional oxygen groups to promote cell adhesion, while also maintaining thinner layers than possible with graphite exfoliation methods. As an alternative to powerful antimicrobial drugs, it was hypothesized that an advanced coating of graphene-oxide would provide a defensive, passively antimicrobial layer to a titanium implant. While GO is typically quite expensive, the newly developed process provides an economical and environmentally friendly method of producing GO from coal (c-GO). The result is a coating that is inexpensive and capable of halving the biofilm formation of MRSA on titanium-alloy surgical screws in addition to providing improved bone cell adhesion and hard tissue compatibility. / Master of Science / Any time a patient receives implantation surgery, there is a chance of microbes entering the body. These are typically naturally occurring skin flora, harmless but opportunistic. On the surface of implants within the body, these bacteria can form colonies called biofilms, leading to severe and potentially deadly infections, called prosthetic joint infection (PJI). PJI often requires multiple surgeries to remedy, but rates of reinfection are relatively high. As with any surgery, patients are given antibiotic drugs, but implants to not receive blood flow as the body normally would, reducing the effectiveness of antibiotics. Once biofilms are formed, the bacteria become even hardier and resistant even to powerful antibiotics. Graphene oxide (GO) is a carbon material known to have good biocompatibility (i.e., non-toxic) while providing antimicrobial properties. The focus of this study is on the development and characterization of a robust coating for titanium alloy implants to promote bone healing while reducing microbial biofilm colonization on the implant's surface. The novelty of this study is the use of proprietary coal-derived graphene oxide (c-GO) in a biomedical application. c-GO has been demonstrated to have a different chemical makeup than graphite-derived GO, which may improve its efficacy as an antimicrobial coating. As an alternative to powerful antimicrobial drugs, it was hypothesized that a coating of graphene-oxide would provide a defensive, passively antimicrobial layer to a titanium implant. While GO is typically quite expensive, the newly developed one-pot process provides an economical and environmentally friendly method of producing GO from coal (c-GO). The result is a coating that is inexpensive and capable of halving the biofilm formation of MRSA on titanium-alloy surgical screws in addition to providing improved bone cell adhesion and hard tissue compatibility.

Abstract Prosthetic joint infection (PJI) is one of the most devastating complications of hip or knee arthroplasty. Treatment options for PJI include prosthesis retention, prosthesis exchange and salvage procedures (e.g., arthrodesis or amputation). The purpose of this retrospective study is to assess the impact of shortening antibiotic treatment durations in PJIs treated with debridement, antibiotics and implant retention (DAIR) and to evaluate the predictors of DAIR treatment failure for PJIs. A second aim is to evaluate the outcomes and reimplantation microbiologies of PJIs treated with two-stage revision. The main data consist of 197 patients with PJI treated in Oulu University Hospital, Finland, between February 2001 and August 2009. Patients were identified retrospectively using the hospital’s patient databases. The study shows that, if antibiotic treatments for PJI are completed as planned, then DAIR treatment success rates (88%) are excellent. Prolonging antibiotic treatment over three months in total knee arthroplasty PJIs or over two months in total hip arthroplasty PJIs does not seem to offer any additional benefits. The failure of DAIR in the treatment of PJI is independently associated with high leucocyte counts at admission and with ineffective empirical antibiotics. Rifampin combination therapy, especially the combination of rifampin and ciprofloxacin, is significantly associated with successful DAIR treatments of staphylococcal PJIs. Our study also shows that a six-week course of antibiotics between stages is sufficient for treating PJIs with two-stage revision. Positive reimplantation cultures do not seem to be associated with significantly worse outcomes. / Tiivistelmä Tekonivelinfektio on yksi vakavimmista lonkan ja polven tekonivelleikkauksen komplikaatioista. Tekonivelinfektion hoitovaihtoehtoja ovat tekonivelen säästävä hoito, tekonivelen vaihto ja ns. salvage-toimenpiteet (esimerkiksi jäykistys tai amputaatio). Tämän retrospektiivisen tutkimuksen tavoitteena oli selvittää lyhennetyn mikrobilääkehoidon toimivuutta tekonivelinfektion säästävässä hoidossa. Lisäksi pyrittiin löytämään tekonivelinfektion hoidon epäonnistumiselle altistavia tekijöitä. Tavoitteena oli myös selvittää hoidon tuloksia silloin, kun hoidetaan tekonivelinfektiota kaksivaiheisella revisiolla, sekä tutkia revision toisessa vaiheessa otettavien mikrobinäytteiden merkitystä hoidon onnistumiselle. Tutkimusaineisto koostui 197 potilaasta, joilta hoidettiin tekonivelinfektiota Oulun yliopistollisessa sairaalassa helmikuun 2001 ja huhtikuun 2009 välisenä aikana. Potilastiedot saatiin sairaalan hoitotietojärjestelmästä. Tutkimuksessa todettiin, että lyhyemmällä hoitoajalla voidaan saavuttaa erinomaiset hoitotulokset (88 %) tekonivelinfektion säästävässä hoidossa, jos suunniteltu antibioottihoitoaika voidaan toteuttaa. Yli kahden kuukauden (lonkan tekonivelinfektio) ja kolmen kuukauden (polven tekonivelinfektio) hoitoajasta ei näytä olevan hyötyä säästävässä hoidossa. Lisäksi todettiin, että sairaalaantulovaiheessa mitattu veren leukosyyttiarvo > 10×109/l ja tehoton empiirinen antibiootti ovat itsenäisesti hoidon epäonnistumiselle altistavia tekijöitä. Rifampisiini-yhdistelmähoidon, erityisesti rifampisiini yhdistettynä siprofloksasiiniin, todettiin olevan merkittävästi yhteydessä hoidon onnistumiseen silloin, kun hoidetaan stafylokokki-infektiota tekonivelen säästävällä hoidolla. Tutkimuksemme osoitti myös, että kuuden viikon antibioottihoito on riittävä hoidettaessa tekonivelinfektiota kaksivaiheisella revisiolla. Positiivinen mikrobiviljelynäyte toisen vaiheen leikkauksessa ei näytä olevan yhteydessä huonompaan hoitotulokseen.

La survenue d’une infection péri prothétique (IPP) est la principale complication de la chirurgie prothétique articulaire, depuis son invention par Robert et Jean Judet en 1947. Comme le nombre de prothèses articulaires posées chaque année augmente de façon importante, ces infections sont de plus en plus fréquentes et l’optimisation de leur prise en charge est un enjeu important sur le plan médical et économique.Les modèles animaux d’IPP permettent de comprendre les mécanismes éthio-pathogéniques et tester de nouvelles thérapeutiques. Une analyse critique de la littérature a été effectuée en évaluant chaque modèle selon son type d’inoculation qui influence les taux et la sévérité de l’infection expérimentale obtenue.Un modèle expérimental d’IPP chez le lapin obtenu par remplacement partiel du genou et inoculation locale a été utilisé pour tester l’efficacité de nouvelles thérapeutiques au cours d’infections à deux bactéries multi résistantes qui posent des problèmes en thérapeutique humaine.Dans un 1er temps nous avons évalué l’efficacité de la ceftaroline (CPT) céphalosporine bactéricide in vivo contre le Staphylococcus aureus résistant à la méticilline (SARM) en la comparant à la vancomycine en association ou non à la rifampicine. 5.107UFC (Unités Formant Colonies) de SARM (Concentration Minimale Inhibitrice (CMI) de 0,38, 0,006, et 1 mg/l pour CPT, RIF, et VAN, respectivement) était injecté dans le genou. Les animaux infectés ont été randomisés et recevaient : aucun traitement (contrôles), CPT (60 mg/kg im), VAN (60 mg/kg im), CPT plus RIF (10 mg/kg im), ou VAN plus RIF débutant 7 jours après l'inoculation et durant 7 jours. L’efficacité des traitements a été évaluée sur la quantité de bactéries persistantes dans l’os (tibia proximal) après traitement. Ce travail a montré que la CPT et la VAN étaient efficace en monothérapie mais que seule l’association avec la rifampicine permettait de stériliser la quasi totalité des animaux. La CPT apparaît donc comme un traitement potentiellement efficace dans cette infection.Dans un 2ème temps nous avons étudié l'efficacité de la colistine (COL) dans le ciment, seule ou en combinaison avec des injections intramusculaires (im) de COL et/ou de méropénème (MRP) dans des infections à Klebsiella pneumoniae résistantes aux carbapénèmes (KPC). Un modèle proche de celui décrit pour le SARM a été utilisé. La souche KPC99YC est une souche clinique, résistante à la gentamicine (CMI 8mg/l) intermédiaire à l'imipénème (CMI 4mg/l), et sensible à la COL (CMI 0,25mg/l). L’inoculum était de 1.109UFC. Sept jours après l'infection, les prothèses étaient remplacées par espaceur sans antibiotique (contrôle), ou par espaceur imprégné de COL (3 MUI de COL/40g de ciment), ou par espaceur sans antibiotique et injections de COL (12 mg/kg im), ou l’association des deux, ou injections de COL avec espaceur en ciment imprégné de COL associé ou non à des injections de MRP (80 mg/kg im). Le traitement durait 7 jours. Tous les lapins témoins étaient infectés à J15, avec une moyenne de densité bactérienne de 6,17 [5,69, 7,04] CFU/g d'os. Contrairement à la COL locale, la COL systémique seule ou combinée avec le MRP était plus efficace que le contrôle sur le nombre de bactéries dans l'os à la fin du traitement. L’association COL locale + systémique était significativement plus efficace que le groupe témoin sur le dénombrement bactérien. D’ailleurs, c'était le seul schéma efficace sur le nombre de lapins avec un os stérile et à la limite de significativité par rapport au traitement systémique seul. Une souche résistante à la COL a été détectée dans le traitement local seul mais pas avec l’association de COL locale et systémique.Les modes d’inoculation directs sont les plus efficaces pour reproduire une IPP aigue. Les études expérimentales permettent de tester des traitements innovants en particulier pour les infections à bactéries multi résistantes. / The occurrence of prosthetic joint infection (PJI) is the main complication of joint prosthetic surgery since its invention by Robert and Jean Judet in 1947. Since the number of articular prostheses placed each year increases significantly, these infections are more and more frequent and the optimization of their management is an important medical and economic stake.The animal models of PJI make it possible to understand the ethiopathogenic mechanisms and to test new therapeutics. A critical analysis of the literature was carried out by evaluating each model according to its type of inoculation which influences the rates and the severity of the experimental infection obtained.An experimental model of PJI in rabbits obtained by partial replacement of the knee and local inoculation was used to test the efficacy of new therapeutics during infections with two multi-resistant bacteria which pose problems in human therapeutics.In a first step we evaluated the efficacy of ceftaroline (CPT) cephalosporin bactericidal in vivo against methicillin-resistant Staphylococcus aureus (MRSA) by comparing it with vancomycin (VAN) in combination with or without rifampin (RIF). 5.107UFC MRSA (Minimum Inhibitory Concentration (MIC) of 0.38, 0.006, and 1 mg/l for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomized to receive no treatment (control), CPT (60 mg/kg im), VAN (60 mg/kg im), CPT plus RIF (10 mg/kg im) or VAN plus RIF, 7 days after inoculation and for 7 days. The efficacy of treatments was evaluated on the amount of persistent bacteria in the bone (proximal tibia) after treatment. This work has shown that CPT and VAN were effective as monotherapy, but only the combination with RIF allowed the sterilization of almost all animals. CPT appears to be a potentially effective treatment in this infection.In a second step we studied the efficacy of colistin (COL) in cement, alone or in combination with intramuscular (im) injections of COL and/or meropenem (MRP) in carbapenem-resistant Klebsiella pneumoniae infections (KPC). A model close to that used for MRSA was used. The strain KPC99YC is a clinical strain, resistant to gentamicin (MIC 8mg/L) intermediate to imipenem (MIC 4mg/l), and sensitive to COL (MIC 0,25mg/l). The inoculum was 1,109UFC. Seven days after the infection, the prosthesis were replaced by antibiotic-free spacer (control), or by COL-impregnated spacer (3 MIU of COL/40g of cement), or by antibiotic-free spacer and COL injections (12 mg/kg im), or the combination of the two, or COL injections with COL-impregnated cement spacer associated or not with MRP injections (80 mg/kg im). The treatment lasted 7 days. All control rabbits were infected at D15, with median and interquartile range (IQR) bone bacterial count of 6.17 [5.69, 7.04] CFU/g of bones. In contrast to local COL, systemic COL alone or combined with MRP was more effective than control on bacterial counts in bone at the end of treatment. The combination of COL local + systemic was significantly more effective than control group on bacterial counts. Interestingly it was the only effective regimen on the number of rabbits with sterile bone and at the limit of significance vs systemic treatment alone. One COL-resistant strain was detected in the COL local treatment alone but not with the combination of local and systemic COL.Direct inoculation modes are most effective in reproducing an acute PJI. The experimental studies allow testing innovative treatments in particular for the infections with multi-resistant bacteria.

Background The presence or absence of an implant has a major impact on the type of joint infection therapy. Thus, the aim of this study was the examination of potential differences in the spectrum of pathogens in patients with periprosthetic joint infections (PJI) as compared to patients with native joint infections (NJI). Methods In this retrospective study, we evaluated culture-positive synovial fluid samples of 192 consecutive patients obtained from January 2018 to January 2020 in a tertiary care university hospital. For metrically distributed parameters, Mann–Whitney U was used for comparison between groups. In case of nominal data, crosstabs and Chi-squared tests were implemented. Results Overall, 132 patients suffered from periprosthetic joint infections and 60 patients had infections of native joints. The most commonly isolated bacteria were coagulase-negative Staphylococci (CNS, 28%), followed by Staphylococcus aureus (S. aureus, 26.7%), and other bacteria, such as Streptococci (26.3%). We observed a significant dependence between the types of bacteria and the presence of a joint replacement (p < 0.05). Accordingly, detections of CNS occurred 2.5-fold more frequently in prosthetic as compared to native joint infections (33.9% vs. 13.4% p < 0.05). In contrast, S. aureus was observed 3.2-fold more often in NJIs as compared to PJIs (52.2% vs. 16.4%, p < 0.05). Conclusion The pathogen spectra of periprosthetic and native joint infections differ considerably. However, CNS and S. aureus are the predominant microorganisms in both, PJIs and NJIs, which may guide antimicrobial therapy until microbiologic specification of the causative pathogen.

<p>Intra-articular glucocorticoid injection therapy is frequently used to relieve symptoms of arthritis, but there is considerable variation in injection routines among physicians. One issue of debate concerns the importance of synovial fluid aspiration during the injection procedure. In the present randomised controlled study of patients with rheumatoid arthritis (RA), a significantly reduced risk for arthritis relapse was observed when arthrocentesis was included in the intra-articular injection procedure of the knee. </p><p>Furthermore, there is no consensus about the post-injection regimes. Previous studies have shown beneficial effects of post-injection rest of the knee, but also injection routines for other joints often include such recommendations. The present randomised controlled trial showed that 48-hour rest in elastic orthosis after intra-articular injection in the wrist did not improve the outcome. Thus, the effect of post-injection rest varies between different joints. </p><p>The improved treatment result of post-injection rest of the knee is supposed to be caused by retarded steroid resorption from the joint. In order examine the metabolic effects in cartilage, bone and the hypothalamic-piuitary-adrenal (HPA)-axis, resting and mobile RA patients were studied after intra-articular knee injections. Serum levels of the injected glucocorticoid, triamcinolone hexacetonide (THA), were analysed, as well as cartilage oligomeric matrix protein (COMP) as a marker of cartilage turnover, osteocalcin for bone formation and deoxypyridinoline for bone resorption. The HPA-axis was assessed using serum levels of cortisol and adrenocorticotropine hormone. The result showed a short term and reversible suppression of the HPA-axis and bone formation, whereas bone resorption was unaffected. No differences between mobile and resting patients were observed. In both groups reduction of COMP levels were seen, but these were significantly more pronounced in resting patients, suggesting a cartilage-protective effect. The THA levels increased similarly in both groups, indicating that rest did not affect glucocorticoid resorption. </p><p>Consequently, another explanation for the beneficial effects of postinjection rest of knee synovitis should be considered. In the present material the incidence of infectious complications of intra-articular treatment was less than 1/12,000 injections. </p><p>The findings in this thesis can be applied in the clinical practice and should be considered when new guidelines for intra-articular glucocorticoid therapy are created.</p>