The effect of different antibiotic combinations in calcium sulfate cement on the growth of Cutibacterium acnes and Staphylococcus periprosthetic shoulder infection isolates.

BACKGROUND: Periprosthetic joint infections (PJI) of the shoulder are a devastating complication of shoulder arthroplasty and are commonly caused by Staphylococcus and Cutibacterium acnes. Absorbable calcium sulfate (CS) beads are sometimes used for delivering antibiotics in PJI. This study evaluates the in vitro effect of different combinations of gentamicin, vancomycin, and ertapenem in beads made from CS cement on the growth of C acnes and coagulase-negative Staphylococcus (CNS) strains. METHODS: Three strains of C acnes and 5 strains of CNS from clinically proven shoulder PJI were cultured and plated with CS beads containing combinations of vancomycin, gentamicin, and ertapenem. Plates with C acnes were incubated anaerobically while plates with Staphylococcus were incubated aerobically at 37 °C. Zones of inhibition were measured at intervals of 3 and 7 days using a modified Kirby Bauer technique, and beads were moved to plates containing freshly streaked bacteria every seventh day. This process was run in triplicate over the course of 56 days. Statistical analysis was conducted using SPSS v. 28 with repeated measures analysis of variance (ANOVA) and pairwise comparisons with Tukey correction. RESULTS: In experiments with C acnes, beads containing ertapenem + vancomycin and vancomycin alone formed the largest zones of inhibition over time (P < .001). In experiments with Staphylococcus, beads containing vancomycin alone formed the largest zones of inhibition over time for all 5 strains (P < .001). Zones of inhibition were 1.4x larger for C acnes than for Staphylococcus with beads containing vancomycin alone. For both C acnes and Staphylococcus, beads containing ertapenem had the strongest initial effect, preventing all bacterial growth in C acnes and almost all growth for Staphylococcus during the first week but dropping substantially by the second week. Beads containing gentamicin alone consistently created smaller zones of inhibition than beads containing vancomycin alone, with vancomycin producing zones 5.3x larger than gentamicin in C acnes and 1.3x larger in Staphylococcus (P < .001). DISCUSSION: These data suggest that for both C acnes and Staphylococcal species, CS beads impregnated with vancomycin were most effective at producing a robust antibiotic effect. Additionally, ertapenem may be a viable supplement in order to create a more potent initial antibiotic effect but is not as effective as vancomycin when used alone. Gentamicin alone was not effective in maintaining consistent and long-term antibiotic effects. These results indicate that amongst the antibiotics currently commercially available to be used with CS, vancomycin is consistently superior to gentamicin in the setting of C. acnes and CNS.

Biofilm Microenvironment Activated Antibiotic Adjuvant for Implant-Associated Infections by Systematic Iron Metabolism Interference.

Hematoma, a risk factor of implant-associated infections (IAIs), creates a Fe-rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)-loaded layered double hydroxide (LDH)-based nanomedicine (DFP@Ga-LDH) that targets the Fe-rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga-LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga-LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe-associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga-LDH functions as a nano-adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga-LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga-LDH-Cefi. Antimicrobial and biosafety efficacies of DFP@Ga-LDH-Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma-created Fe-rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano-adjuvants as antibacterial agents.

Effect of Taiwan's Diabetes Shared Care Program on the risk of periprosthetic joint infection after total joint arthroplasty in patients with type 2 diabetes mellitus: an eight-year population-based study.

BACKGROUND: Periprosthetic joint infection (PJI) is a significant post-arthroplasty complication for diabetic patients, with uncontrolled diabetes identified as a PJI risk factor. Taiwan's Diabetes Shared Care Program (DSCP) was established for holistic diabetes care. AIM: To evaluate the DSCP's impact on PJI incidence and patients' medical costs. METHODS: Data were analysed from Taiwan's National Health Insurance Research Database from 2010 to 2020, focusing on type 2 diabetes mellitus (DM) patients who had undergone arthroplasty. The study group involved DSCP participants, while a comparison group comprised non-participants with matched propensity scores for age, sex, and comorbidities. The primary outcome was the PJI incidence difference between the groups; the secondary outcome was the medical expense difference. FINDINGS: The study group consisted of 11,908 type 2 DM patients who had arthroplasty and joined the DSCP; PJI occurred in 128 patients. Among non-participants, 184 patients had PJI. The PJI incidence difference between the groups was statistically significant (1.07% vs 1.55%). The study group's medical costs were notably lower, regardless of PJI incidence. Multivariate regression showed higher PJI risk in patients in comparison group, aged >70 years, male, or who had obesity, anaemia. CONCLUSION: The study indicates that DSCP involvement reduces PJI risks and decreases annual medical costs for diabetic patients after arthroplasty. Consequently, the DSCP is a recommendable option for such patients who are preparing for total joint arthroplasty.

Healing beyond the joint: Addressing mental health in periprosthetic joint infection in a prospective longitudinal study.

OBJECTIVE: Periprosthetic joint infection (PJI) is a devastating complication following joint replacement surgeries. While the somatic impacts of PJI have been extensively explored, the influence on mental health remains understudied. This study aimed to longitudinally assess the psychological burden, quality of life, and expectations in individuals undergoing treatment for PJI. METHODS: A prospective study was conducted at a German trauma center between January 2020 and December 2022. Patients diagnosed with PJI (n = 29, mean age 71.4 ± 8.8 years) were assessed at five timepoints, within one week before revision surgery, one month, three, six, and twelve months postoperatively. Outcomes included the ICD-10 symptom-rating (ISR), German Short-Form 36 (SF-36), European Quality of Life 5 Dimensions (EQ-5D), and an expectation questionnaire. RESULTS: Psychological scores exhibited significant upward trends over time. The ISR score increased from 0.55 preoperatively to 0.87 at the 12-month follow-up (p = 0.002), surpassing the clinically relevant threshold. Depression and anxiety scores peaked at 6 months (1.6, p = 0.005) and 12 months (1.12, p = 0.001), respectively. Quality of life, measured by SF-36, showed stable physical component summary scores but declining mental component summary scores. Patients' expectations of returning to normal health consistently decreased (p = 0.009). CONCLUSION: Patients undergoing treatment for PJI experience significant psychological burden, with implications for quality of life and expectations of recovery. The findings underscore the importance of addressing psychological well-being in the management of PJI and emphasize the need for comprehensive care strategies that encompass both somatic and psychological dimensions.

Vitamin D deficiency and driveline infection in patients with a left ventricular assist device implant.

Driveline infection is a frequent complication in recipients of durable left ventricular assist devices (LVAD), but its cause is largely unclear. Since vitamin D supplementation can reduce the risk of infections, we aimed at investigating the association of vitamin D deficiency with driveline infection. In 154 patients with continuous flow LVAD implants, we assessed 2-year risk of driveline infection according to vitamin D status (circulating 25-hydroxyvitamin D < 25 nmol/L or ⩾25 nmol/L). Of the study cohort, 34% (n = 53) had 25-hydroxyvitamin D concentrations <25 nmol/L. Kaplan-Meir estimates of 2-year freedom from driveline infection were in the vitamin D deficient and vitamin D non-deficient groups 49.7% and 74.2%, respectively (p = 0.017). Covariate-adjusted hazard ratio of driveline infection for the vitamin D deficient versus non-deficient group was 2.51 [95% CI: 1.11-5.69; p = 0.028). Circulating concentrations of endocrine regulators of calcium and phosphorus metabolism such as parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor-23 were not significantly associated with the risk of driveline infection (p-values > 0.15). In total, our data indicate that in LVAD recipients deficient vitamin D status is a predictor of driveline infection, but future studies are needed to investigate whether these associations are causal.

Late summer is a risk factor for periprosthetic joint infection after total joint arthroplasty: A retrospective cohort study.

To explore whether season is a risk factor of periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) and explain it with the theory of traditional Chinese medicine. This was a retrospective cohort study. Only patients who suffered from PJI within 1 month after TJA were included in the study. Occurrence of PJI was the outcome of this study. Chi-squared test and t test was used to assess differences for baseline characteristics. Chi-square test was used to analyze whether season was related to the occurrence of PJI. Logistic regression was used to evaluate the association between season and occurrence of PJI. The incidence of PJI in summer is significantly higher than that in winter, whether after total knee arthroplasty (Chi-square value = 6.455, P = .011) or total hip arthroplasty (Chi-square value = 6.141, P = .013). Summer was an independent risk factor for PJI (OR = 4.373, 95% confidence interval = 1.899-10.673, P = .004). To be more exact, compared to nonlate summer (19.51%), and PJI is mainly concentrated in late summer (80.49%). Late summer was an independent risk factor of PJI after TJA. The infection rate of PJI after TJA in late summer is higher than other seasons. A more thorough preoperative disinfection procedure is needed in late summer.

Palliative arthroscopic debridement with continuous irrigation for infected total knee arthroplasty in high mortality risk patients.

PURPOSE: This study aimed to evaluate the infection control rate of palliative arthroscopic debridement, antibiotics, and implant retention (DAIR) for the high mortality risk or terminal cancer stage patients. METHODS: From March 2018 to August 2021, 21 patients met the following inclusion criteria: old age of more than 80, diagnosed as a terminal stage of cancer, high risk of mortality and morbidity representing as Charlson comorbidity index (CCI) ≥ 5, low daily activity with disabled extremity, and re-infection after two-stage revision. Each patient underwent arthroscopic DAIR and additional continuous irrigation for 48 hours. The need for subsequent re-arthroscopic DAIR or two-stage revision was determined by the post-operative trends of C-reactive protein (CRP) levels. Infection control was defined as continuing controlled status of infection based on clinical and laboratory results by one or two times of arthroscopic DAIR within initial two months. Treatment failure was defined as more than three times arthroscopic debridement, two-stage revision surgery, or expired due to uncontrolled infection. RESULTS: Arthroscopic DAIR controlled the infection in 19 (90.5%) of the 21 cases. The other knee underwent a total of three times of re-arthroscopic DAIR and the other one underwent two-stage revision. Although five patients expired during the follow-up period due to worsening medical problems or terminal cancer, there were no deaths from uncontrolled infection, sepsis, or surgery-related complications. CONCLUSIONS: Arthroscopic debridement with continuous irrigation for the infection TKA with high mortality risk or terminal cancer patients showed a 90.5% infection control rate. For high-risk patients, arthroscopic debridement with continuous irrigation can be an alternative treatment to improve the quality of life during survival.

Moderate-to-Severe Malnutrition Identified by the Controlling Nutritional Status (CONUT) Score Is Significantly Associated with Treatment Failure of Periprosthetic Joint Infection.

The prevalence and role of malnutrition in periprosthetic joint infection (PJI) remain unclear. This study aimed to use measurable nutritional screening tools to assess the prevalence of malnutrition in PJI patients during two-stage exchange arthroplasty and to explore the association between malnutrition and treatment failure. Our study retrospectively included 183 PJI cases who underwent 1st stage exchange arthroplasty and had available nutritional parameters, of which 167 proceeded with 2nd stage reimplantation. The recently proposed Musculoskeletal Infection Society (MSIS) Outcome Reporting Tool was used to determine clinical outcomes. The Controlling Nutritional Status (CONUT), Nutritional Risk Index (NRI), and Naples Prognostic Score (NPS) were used to identify malnutrition at 1st and 2nd stage exchange, respectively. Multivariate logistic regression analyses were performed to determine the association between malnutrition and treatment failure. Restricted cubic spline models were further used to explore the dose−response association. Additionally, risk factors for moderate-to-severe malnutrition were evaluated. Malnourished patients identified by CONUT, NPS, and NRI accounted for 48.1% (88/183), 98.9% (181/183), and 55.7% (102/183) of patients at 1st stage, and 9.0% (15/167), 41.9% (70/167), and 43.1% (72/167) at 2nd stage, indicating a significant improvement in nutritional status. We found that poorer nutritional status was a predictor of treatment failure, with CONUT performing best as a predictive tool. Moderate-to-severe malnutrition at 1st stage identified by CONUT was significantly related to treatment failure directly caused by PJI (odds ratio [OR] = 5.86), while the OR was raised to 12.15 at 2nd stage (OR = 12.15). The linear dose−response associations between them were also confirmed (P for nonlinearity at both 1st and 2nd stage > 0.05). As for total treatment failure, moderate-to-severe malnutrition as determined by CONUT was associated with a 1.96-fold and 8.99-fold elevated risk at the 1st and 2nd stages, respectively. Age ≥ 68 years (OR = 5.35) and an increased number of previous surgeries (OR = 2.04) may be risk factors for moderate-to-severe malnutrition. Overall, the prevalence of malnutrition in PJI patients is very high. Given the strong association between moderate-to-severe malnutrition identified by CONUT and PJI treatment failure, COUNT could be a promising tool to evaluate the nutritional status of PJI patients to optimize treatment outcomes.

Effect of functional relaxation on the quality of life in patients with periprosthetic joint infection: Protocol for a randomised controlled trial.

INTRODUCTION: Periprosthetic joint infection (PJI) is a devastating complication in orthopaedic and trauma surgery, which puts a high burden on the patients involving recurrent hospitalisation, prolonged courses of antibiotic medication, severe pain and long periods of immobility as well as high levels of psychological distress. Thus, this multicentre study aims at implementing body-oriented psychotherapy in clinical practice and evaluating its therapeutic effect on the quality of life. METHODS AND ANALYSIS: A prospective, parallel two-armed randomised controlled trial with approximately n=270 patients with verified PJI treated surgically with a one-staged exchange, or a two-staged exchange will be conducted. Functional relaxation (FR) therapy will be implemented as a group therapy. FR originally belongs to the psychodynamically based body-oriented psychotherapy. Intervention techniques consist of minute movements of small joints, which are performed during relaxed expiration accompanied by an exploration of differences of body feelings. A group will include 3-8 patients, led by a specialist physiotherapist certified in FR once a week. The participants are consecutively admitted to the class and participate in 12 sessions. The control group will consist of patients receiving an unspecific 'placebo relaxation' intervention for the same duration. The primary efficacy endpoint is the mental component summary and physical component summary of quality of life assessed by the 36-Item Short Form Health Survey (SF-36) after 6 months. Secondary outcomes include SF-36 scores after 12 months, consumption of pain medication, mobility measured by the Parker mobility score and the physical activity measured by daily steps with an accelerometer (actibelt). ETHICS AND DISSEMINATION: Approval from the Ethical Committee of the University Hospital Regensburg was received (file number: 21-2226-101). Written, informed consent to participate will be obtained from all participants. Results will be made available in the form of peer-reviewed publications and presentation in congresses. TRIAL REGISTRATION NUMBER: DRKS00028881; German Clinical Trials Register.

Calcium sulfate beads made with antibacterial essential oil-water emulsions exhibit growth inhibition against Staphylococcus aureus in agar pour plates.

Calcium sulfate bone void filler beads are fully absorbable in the body, and are often used in complicated orthopedic infection cases to release a relatively high dose of antibiotics locally to the body site over time. However, the antibiotic resistance crisis and/or inability to treat chronic biofilm infections remains to be a formidable and increasing health threat. In this report, we tested the hypothesis that plant essential oils (PEOs) with anti-staphylococcal qualities could inhibit the growth of Staphylococcus aureus (a major etiological agent of periprosthetic joint infection) in agar pour plates when infused in calcium sulfate beads. To begin, we conducted a screen of 57 single plant PEOs for anti-staphylococcal activity via disk diffusions assays. We observed that 55/57 of the PEOs had significant growth inhibitory activity compared to the null hypothesis, and 41/57 PEOs exhibited activity similar-to-or-higher-than a vancomycin minimum inhibitory control. When PEOs were infused in beads, we observed that 17/57 PEOs tested exhibited significant bacterial growth inhibition when encased in S. aureus-seeded agar compared to a null hypothesis of six millimeters (bead size). However, none of the PEO-beads had activity similar to a vancomycin bead control made according to a clinically relevant formula. To the best of our knowledge, this is the first report and screen of PEOs for growth inhibitory activity when infused in lab-made calcium sulfate beads. These data indicate that antibacterial PEOs warrant further investigations, and may be useful in developing new treatment strategies for periprosthetic joint infection.

The cost of CIED infectious complications treatment in Poland from the perspective of Polish hospitals.

INTRODUCTION: Cardiac implantable electronic devices (CIED) are a recognized form of therapy in cardiology. Apart from the benefits, the use of CIEDs is also associated with the risk of complications, and the most important ones influencing treatment results and prognosis are infectious complications. AIM: This study aimed to calculate the cost of treatment of CIED-related infections, including transvenous lead extraction and device reimplantation, from the perspective of a Polish hospital. METHODS: A retrospective analysis of hospitalization costs of patients referred to transvenous lead extraction (TLE) for CIED infection was performed. The study covers cases from three Polish reference centers specializing in the comprehensive treatment of cardiac electrotherapy complications. RESULTS: It was shown that the average cost of treating a CIED infection is 34 000 PLN (8010 EUR) and is the highest in the cardiac resynchronization therapy with defibrillator function (CRT-D) group, where it amounts to almost 50 000 PLN (11 440 EUR). Thus, treatment of CIED infections is associated with an average loss of 3000 PLN for the healthcare provider and the length of hospitalization has a major influence on final outcomes. CONCLUSIONS: The hospital cost of treatment of CIED-related infections was high and related mainly to the type of device and length of hospitalization. Despite the low utilization of costly extraction tools, the hospitalization was still likely to be unprofitable.

Adaptive antimicrobial resistance, a description of microbial variants, and their relevance to periprosthetic joint infection.

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: Bone Joint J 2022;104-B(5):575-580.

Rifampicin-induced fever during treatment against staphylococcal biofilm in a patient with periprosthetic joint infection.

Periprosthetic joint infection (PJI) after total knee arthroplasty remains a challenging complication. The treatment options for PJI include different procedures; however, regardless of the strategy, antibiotics are required. The combination of different antibiotics increased the rates of PJI eradication. For almost 3 decades, rifampicin has been used as part of antibiotic therapy for PJI. Drug fever, a febrile response that coincides with the onset of drug administration and disappears after drug discontinuation in the absence of other underlying conditions that could cause fever, is frequently misdiagnosed. We present the case of a 72-year-old man with PJI 6 months after total knee arthroplasty. Two-stage revision surgery was followed by culture-directed antibiotic treatment (ciprofloxacin and rifampicin) against Staphylococcus aureus isolated from the periprosthetic tissue. On the fifth day of antibiotic treatment, the patient became febrile and, in the next 5 days, he had an intermittent fever of up to 40°C, although he showed clinical improvement. The patient was normotensive without a maculopapular rash, urticaria or clotting abnormalities. A drug fever was suspected, and rifampicin was discontinued. A re-challenge test was performed, and the fever recurred. Antibiotic treatment with ciprofloxacin was continued and, after 12 months of follow-up, the patient was doing well. Clinicians should be aware that fever could be a clinical presentation of drug fever. If it occurs during an infection, drug fever could necessitate additional diagnostic procedures for further evaluation, inadequate antibiotic therapy and prolonged hospitalisation.

Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model.

Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR).

Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus: a Preclinical Study.

Although several studies have shown promising clinical outcomes of phage therapy in patients with orthopedic device-related infections, questions remain regarding the optimal application protocol, systemic effects, and the impact of the immune response. This study provides a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection (FRI) caused by Staphylococcus aureus. In a prevention setting, phage in saline (without any biomaterial-based carrier) was highly effective in the prevention of FRI, compared to systemic antibiotic prophylaxis alone. In the subsequent study involving treatment of established infection, daily administration of phage in saline through a subcutaneous access tube was compared to a single intraoperative application of a phage-loaded hydrogel and a control group receiving antibiotics only. In this setting, although a possible trend of bacterial load reduction on the implant was observed with the phage-loaded hydrogel, no superior effect of phage therapy was found compared to antibiotic treatment alone. The application of phage in saline through a subcutaneous access tube was, however, complicated by superinfection and the development of neutralizing antibodies. The latter was not found in the animals that received the phage-loaded hydrogel, which may indicate that encapsulation of phages into a carrier such as a hydrogel limits their exposure to the adaptive immune system. These studies show phage therapy can be useful in targeting orthopedic device-related infection, however, further research and improvements of these application methods are required for this complex clinical setting. IMPORTANCE Because of the growing spread of antimicrobial resistance, the use of alternative prevention and treatment strategies is gaining interest. Although the therapeutic potential of bacteriophages has been demonstrated in a number of case reports and series over the past decade, many unanswered questions remain regarding the optimal application protocol. Furthermore, a major concern during phage therapy is the induction of phage neutralizing antibodies. This study aimed at providing a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection caused by Staphylococcus aureus. Phage therapy was applied as prophylaxis in a first phase, and as treatment of an established infection in a second phase. The development of phage neutralizing antibodies was evaluated in the treatment study. This study demonstrates that phage therapy can be useful in targeting orthopedic device-related infection, especially as prophylaxis; however, further research and improvements of these application methods are required.

Usefulness of therapeutic drug monitoring in estimating the duration of dalbavancin optimal target attainment in staphylococcal osteoarticular infections: a proof-of-concept.

Dalbavancin is increasingly used for the treatment of staphylococcal osteoarticular infections (OIs). Some population pharmacokinetic studies suggest that a regimen of two 1500 mg doses 1 week apart could ensure effective treatment for several weeks. Here we aim to provide clinicians with a proof-of-concept of the potential role that therapeutic drug monitoring may have in giving real-time feedback of the estimated duration of optimal treatment of staphylococcal OIs with dalbavancin in each single patient.

Modular knee arthrodesis secures limb, mobility, improves quality of life, and leads to high infection control in periprosthetic knee infection, when revision knee arthroplasty is not an option.

INTRODUCTION: This study compared the outcome of knee arthrodesis versus hinged total knee arthroplasty (TKA) in patients suffering from periprosthetic joint infection (PJI). METHODS: 104 patients with PJI were treated using a two-stage exchange of failed TKA. In case of non reconstructable bone loss or loss of extension mechanism, a modular intramedullary arthrodesis nail was used for reimplantation [Knee Arthrodesis Module (KAM); n = 52]. The control group was retrospectively matched treated using a hinged revision TKA [Rotating Hinge Knee (RHK); n = 52]. PJI remission rates, functional outcome (WOMAC; KSS) and quality of life (SF-12), as well as comorbidities and pain were evaluated. RESULTS: Mean age was 72.5 years. Charlson Comorbidity Index was higher in the KAM group (3.3 vs. 2.8). PJI remission rate was 89.4% (88.5% vs. 90.4%, respectively). In case of reinfection, implant retention was mostly possible in the RHK group (7.7%), whereas amputations were mostly performed in the KAM group (9.6%). Significant pain reduction (VAS 7.9-2.8) was achieved in both groups. Walking distance was significantly reduced in the KAM groups versus the RHK group (504 vs. 1064 m). WOMAC and KSS function scores were significantly reduced in the KAM group (25 vs. 40 and 35 vs. 64). Only moderate reduction in quality of life in the KAM group was observed (SF-12 physical: 34 vs. 40; SF-12 mental: 51 vs. 56) respectively. CONCLUSIONS: Arthrodesis using a modular intramedullary nail is an alternative for limb salvage, pain reduction, and preservation of quality of life and everyday mobility, when revision TKA is not an option. This study presents the largest number of case, comparing the outcome after performing an arthrodesis versus hinged TKA after septic failed TKA.

Does washing medical devices before and after use decrease bacterial contamination?: An in vitro study.

ABSTRACT: Surface treatment of medical devices may be a way of avoiding the need for replacement of these devices and the comorbidities associated with infection. The aim of this study was to evaluate whether pre- and postcontamination washing of 2 prostheses with different textures can decrease bacterial contamination.The following microorganisms were evaluated: Staphylococcus aureus, Staphylococcus epidermidis, Proteus mirabilis and Enterococcus faecalis. Silicone and expanded polytetrafluoroethylene vascular prostheses were used and divided into 3 groups: prostheses contaminated; prostheses contaminated and treated before contamination; and prostheses contaminated and treated after contamination. Treatments were performed with antibiotic solution, chlorhexidine and lidocaine. After one week of incubation, the prostheses were sown in culture medium, which was incubated for 48 hours. The area of colony formation was evaluated by fractal dimension, an image analysis tool.The antibiotic solution inhibited the growth of S epidermidis and chlorhexidine decrease in 53% the colonization density for S aureus in for both prostheses in the pre-washing. In postcontamination washing, the antibiotic solution inhibited the growth of all bacteria evaluated; there was a 60% decrease in the colonization density of S aureus and absence of colonization for E faecalis with chlorhexidine; and lidocaine inhibited the growth of S aureus in both prostheses.Antibiotic solution showed the highest efficiency in inhibiting bacterial growth, especially for S epidermidis, in both washings. Lidocaine was able to reduce colonization by S aureus in post-contamination washing, showing that it can be used as an alternative adjuvant treatment in these cases.

One-stage versus two-stage revision of the infected knee arthroplasty - a randomized multicenter clinical trial study protocol.

BACKGROUND: A two-stage prosthesis exchange procedure has been the gold standard in surgical treatment of the chronically infected knee arthroplasty so far. This includes 2 surgeries/hospitalizations and an interim period of 2-3 months between surgeries with impaired health, functional status and quality of life of the patients. A one-stage exchange procedure holds many obvious advantages compared to the two-stage approach, but outcomes of a one-stage versus two-stage procedures have never been investigated in a randomized clinical trial. The purpose of this study is primarily to investigate time-adjusted differences in functional status of patients after one-stage versus two-stage revision. Secondary, to report time-adjusted differences in quality of life, complications (including re-revisions due to infection) and mortality. METHODS: This study is a pragmatic, multi-center, randomized, non-inferiority trial comparing one-stage versus two-stage revision of the infected knee arthroplasty. Seven Danish hospitals are currently participating in the study, but additional hospitals can enter the study if adhering to protocol. Ninety-six patients will be included prospectively. Follow-up will be with PROM-questionnaires and clinical controls up to 10 years. The patients who are not able to participate in the randomized trial are followed in a parallel cohort study. PROM'S: Oxford Knee Score and EQ5D + EQ5D VAS questionnaires are completed preoperatively and sent out to the study participants at 6 weeks, 3, 6, 9, 12, 18 and 24 months as well as 5 and 10 years postoperatively. In addition a tailor made cost questionnaire on the non-treating hospital resource use, community health and social service use, travel costs, time off work and informal care are sent out. DISCUSSION: If one of the two treatment alternatives is found superior in both domains of quality of life (both knee-specific and generic) and health economics, that treatment should be promoted. Other outcomes will open informed discussions about treatment strategies for periprosthetic knee infections. TRIAL REGISTRATION: The randomized trial is registered on ClinicalTrials.gov with ID NCT03435679 , initial release date January 31, 2018 and the cohort study is registered with ID NCT04427943 , submitted January 8, 2020 and posted June 11, 2020.