Cutibacterium acnes biofilm formation is influenced by bone microenvironment, implant surfaces and bacterial internalization.

BACKGROUND: The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections. METHODS: In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments. RESULTS: We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk. CONCLUSION: Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain.

Cannabidiol-drug interaction in cancer patients: A retrospective study in a real-life setting.

Cannabidiol (CBD) consumption in cancer patients is growing and there is a need to investigate how to detect cannabidiol-drug interactions (CDIs). However, CDIs and the clinical relevance between CBD, anticancer treatment, supportive care and conventional drugs is poorly studied especially in real-life settings. In 1 oncology day-hospital, a cross-sectional study in 363 cancer patients treated with chemotherapy revealed 20 patients (5.5%) who consumed CBD. In this study we aimed to explore the prevalence and clinical relevance of CDIs among these 20 patients. CDI detection used the Food and Drug Administration Drugs.com database and clinical relevance was assessed accordingly. Ninety CDIs with 34 medicines were detected (4.6 CDI/patient). The main clinical risks were central nervous system depression and hepatoxicity. The main CDIs were assessed as moderate and anticancer treatment do not seem to add to the risk. CBD discontinuation appears to be the most consistent management. Future studies should explore the clinical relevance of drug interactions with CBD in cancer patients.

Prevalence of cannabidiol (CBD) consumption and cancer patients' expectations in one oncology day-hospital: A cross-sectional study and questionnaire validation.

INTRODUCTION: The growing interest of cannabidiol (CBD) in medical care prompted French health authorities to explore the potential of CBD in cancer-related severe symptoms. This study aimed to assess the prevalence of CBD use among cancer patients with potential associated factors and to measure the cancer patient's health literacy (HL) on CBD consumption. METHODS: In a prospective study in oncology day-care hospital including patients from 29 October to 20 December 2021, we collected demographic, biological, and oncological characteristics. Patient CBD HL was measured by the hetero-questionnaire 8-item-CBD HL scale (HLS-8-CBD) whose conception has been validated by a psychometric analysis. RESULTS: Among 363 participants, 20 patients (5.5%) reported CBD use. Factors associated with CBD use were: age <60 years (odd ratio = 7.80[1.36-13.32], p < 10-4 versus ≥60 years), smoking history (OR = 5.53[1.81-16.88], p < 0.01), and no smoking cessation (OR = 5.07[1.66-15.46], p < 0.01). CBD use was also associated with a better CBD total HL score than non-users (p-value = 0.02). CONCLUSION: Identification of factors associated with CBD use and a relatively high patient CBD HL in CBD users showed that CBD use in cancer patients care represented a new concern and should enhance health professionals to consider CBD with its associated drug-related problems.

Safety and Survival Outcomes in Lung Cancer Patients Receiving Carboplatin: Impact of Uncapped Dosage.

The prescription of carboplatin is commonly based on the Calvert formula, and low serum creatinine values can lead to an overestimation of the glomerular filtration rate and of the carboplatin dose. Limited data recommend to cap carboplatin dose at 800 mg, but the risk of suboptimal carboplatin dose is concerning. This study compared hematologic toxicity occurrence and survival outcomes in lung cancer patients receiving carboplatin > or <800 mg based on the Calvert formula (target area under the curve = 5 mg/mL min). Our results show more severe cytopenia in patients receiving carboplatin >800 mg with significant difference for all grades of thrombocytopenia in the uncapped group (37% patients vs. 3%, p = 0.02). For metastatic non-small-cell lung cancer patients, we also observed hematologic toxicity in the uncapped group with more severe anemia (30% of patients vs. 0%, p = 0.03) and all grades of thrombocytopenia (39 vs. 0%, p = 0.02) than the capped group. Concerning the secondary endpoint, we obtained a trend of lower progression-free survival and overall survival in patients receiving carboplatin >800 mg, but no significant difference appears for the both survival criteria. This study aims to improve the determination of carboplatin dosage to know the real impact of carboplatin capping and to find the optimum balance between excessive toxicity and substandard therapeutics outcomes.

Collagen-Based Medical Device as a Stem Cell Carrier for Regenerative Medicine.

Maintenance of mesenchymal stem cells (MSCs) requires a tissue-specific microenvironment (i.e., niche), which is poorly represented by the typical plastic substrate used for two-dimensional growth of MSCs in a tissue culture flask. The objective of this study was to address the potential use of collagen-based medical devices (HEMOCOLLAGENE®, Saint-Maur-des-Fossés, France) as mimetic niche for MSCs with the ability to preserve human MSC stemness in vitro. With a chemical composition similar to type I collagen, HEMOCOLLAGENE® foam presented a porous and interconnected structure (>90%) and a relative low elastic modulus of around 60 kPa. Biological studies revealed an apparently inert microenvironment of HEMOCOLLAGENE® foam, where 80% of cultured human MSCs remained viable, adopted a flattened morphology, and maintained their undifferentiated state with basal secretory activity. Thus, three-dimensional HEMOCOLLAGENE® foams present an in vitro model that mimics the MSC niche with the capacity to support viable and quiescent MSCs within a low stiffness collagen I scaffold simulating Wharton's jelly. These results suggest that haemostatic foam may be a useful and versatile carrier for MSC transplantation for regenerative medicine applications.

Arsenic trioxide exerts antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer.

Immunotherapy is a promising antitumor strategy that can successfully be combined with current anticancer treatment. In this study, arsenic trioxide (As(2)O(3)) was shown to increase the antitumor immune response in CT26 colon tumor-bearing mice through the modulation of regulatory T cell (T(reg)) numbers. As(2)O(3) induced T(reg)-selective depletion in vitro. In vivo, tumor-bearing mice injected with 1 mg/kg As(2)O(3) showed a significant decrease in the T(reg)/CD4 cell ratio and in absolute T(reg) count versus controls. As(2)O(3) exerted antitumor effects only in immunocompetent mice and enhanced adoptive immunotherapy effects. Inhibition of As(2)O(3)-induced T(reg) depletion by the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester and the superoxide dismutase mimic manganese [III] tetrakis-(5, 10, 15, 20)-benzoic acid porphyrin suggested that it was mediated by oxidative and nitrosative stress. The differential effect of As(2)O(3) on T(reg) versus other CD4 cells may be related to differences in the cells' redox status, as indicated by significant differences in 2'7'dichlorodihydrofluorescein diacetate and 4,5-diaminofluorescein diacetate fluorescence levels. In conclusion, these results show for the first time, to our knowledge, that low doses As(2)O(3) can delay solid tumor growth by depleting T(regs) through oxidative and nitrosative bursts, and suggest that As(2)O(3) could be used to enhance the antitumor activity of adoptive immunotherapy strategies in human cancer.

Clinical risk assessment of modelled situations in a pharmaceutical decision support system: a modified e-Delphi exploratory study.

BACKGROUND: Pharmaceutical decision support systems (PDSSs) use reasoning software to match patient data to modelled situations likely to cause drug-related problems (DRPs) or adverse drug events. To aid decision-making, modelled situations must be linked to well-defined systemic clinical risks. AIM: To obtain expert consensus on the level of clinical risk for patients associated with each modelled situation that could be addressed using a PDSS. METHOD: A two-round e-Delphi survey was conducted from February to April 2022, involving 20 experts from four French-speaking countries. Participants had to rate modelled situations on two five-point Likert scales, assessing the likelihood of clinical consequences and their severity. The degree of consensus was determined as the proportion of participants providing risk scores in line with the median. The combined median scores for likelihood and severity provided the level of risk according to the Clinical Risk Situation for Patients (CRiSP) scale, formalized via validated tools. RESULTS: The expert panel achieved consensus (≥ 75% agreement) on 48 out of 52 modelled clinical situations. Among these, 45 were categorized as high or extreme risk. The most common DRP identified was overdosing, accounting for 22% of cases. Furthermore, DRPs involving cardiovascular, psychiatric, and endocrinological drug classes were prevalent, constituting 45, 13, and 9% of cases, respectively. CONCLUSION: Through consensus, our study identified 45 modelled clinical situations associated with high or extreme risks. This study highlights the interest of using PDSSs to prevent harm in patients and, on a large scale, document the impact of the pharmacist in preventing, intercepting and managing iatrogenic drug risk.

Using national data to describe characteristics and determine acceptance factors of pharmacists' interventions: a six-year longitudinal study.

BACKGROUND: In France, hospital pharmacists perform medication order reviews during patients' hospital stays. This activity can be centralized in the pharmacy or carried out directly in the ward, in collaboration with the healthcare team. During this review, pharmacists can make recommendations to optimize therapeutics. Since 2006, they can document their interventions, via the national Act-IP© observatory. AIM: To determine the characteristics of pharmacists' interventions and their acceptance by physicians in French hospitals. METHOD: A 6-year observational study of pharmacists' interventions documented on the Act-IP© French observatory between 2009 and 2014 was performed. Multiple logistic regression was undertaken to determine the predictors of physicians' acceptance of interventions. RESULTS: A total of 194,684 pharmacists' interventions were documented and concerned mainly "dosage adjustment" (25.6%). These interventions were mostly related to drugs from the central nervous system (23.7%). Seventy percent of pharmacists' interventions were accepted by physicians. Acceptance rate was higher when conducted by a pharmacist regularly practicing in the ward (ORa = 1.60, CI 95 [1.57-1.64]). Physicians' acceptance was significantly associated with (1) ward specialty: emergency (ORa = 1.24, CI 95 [1.14-1.35]); (2) type of intervention: "drug discontinuation", "drug switch" (ORa = 1.15, CI 95 [1.12-1.19]) and "addition of a new drug" (ORa = 1.15, CI 95 [1.12-1.19]); (3) drug group: antineoplastic and immunomodulators (ORa = 3.67, CI 95 [3.44-3.92]). CONCLUSION: This 6-year longitudinal study highlights the role of clinical pharmacists, and particularly the impact of those integrated into wards. This was found to improve intervention acceptance, potentially through collaboration with physicians in pursuit of patient care and drug safety.

Impact of Pharmacists-Led Interventions in Primary Care for Adults with Type 2 Diabetes on HbA1c Levels: A Systematic Review and Meta-Analysis.

Type 2 diabetes mellitus (T2D) is responsible for an important premature mortality. Pharmacists involved in community-based pharmaceutical care services could help patients with diabetes through education and management as they participate in their regular and long-term care. This meta-analysis aimed to evaluate the association between interventions led by pharmacists in the primary care setting and mean change in HbA1c levels. Randomized controlled trials and quasi-experimental studies with a control group were included. Standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were calculated to compare the mean change in HbA1c values between baseline and end of the intervention in each group. Subgroup analyses were performed to explore heterogeneity. Twelve articles were included. The results showed that pharmacist's interventions significantly reduced HbA1c compared to usual care with an overall SMD of −0.67 (95% CI = [−0.87; −0.48], p < 0.0001). Even if no significant difference between subgroups were found, the reduction of HbA1c seemed more important when baseline HbA1c was ≥8.5%, the intervention occurred monthly, in a primary care center and in countries with a lower human development index. Our results suggest that pharmacists-led interventions in the primary care setting can improve glycemic control for adults with T2D.

Development and validation of a ready-to-use score to prioritise medication reconciliation at patient admission in an orthopaedic and trauma department.

OBJECTIVE: Medication reconciliation (MR) is recognised as an important tool in preventing medication errors such as unintentional discrepancies (UDs). The aim of this study was to identify independent predictive factors of UDs during MR at patient admission to an orthopaedic and trauma department. The secondary objective was to build and validate a ready-to-use score to prioritise patients. METHOD: A retrospective study was performed on 3.5 years of pharmacist-led MR in the orthopaedic and trauma department of a large university teaching hospital. Independent predictors of UD were identified by multivariable logistic regression. A priority score to identify patients at risk of at least one UD was constructed from the odds ratios of the risk factors, and validated in a separate cohort. Performance was assessed with sensitivity, specificity, C-statistic and Hosmer-Lemeshow goodness-of-fit. RESULTS: In total, 888 patients were included and 387 UDs were identified, mainly drug omissions (65.1%). Five independent predictors of UD were identified: age >75 years (OR 2.05, 95% CI 1.41 to 3.00; p<0.001), admission during school holidays (OR 1.69, 95% CI 1.17 to 2.44; p=0.005), female gender (OR 2.20, 95% CI 1.53 to 3.16; p<0.001), emergency hospitalisation (OR 2.05, 95% CI 1.45 to 2.92; p<0.001), and ≥5 medications on the best possible medication history (BPMH) (OR 3.29, 95% CI 2.20 to 4.94; p<0.001). Based on these predictors, a priority score ranging from 0 to 10 was built and internally and externally validated (C statistic 0.72, 95% CI 0.67 to 0.76). CONCLUSIONS: This study confirms the high prevalence of UD in patients admitted to orthopaedic and trauma surgery departments. Five independent predictive factors of UD during MR were identified (female gender, emergency hospitalisation, hospitalisation during school holidays, age ≥75 years, and ≥5 medicines on the BPMH). The developed risk score will help to prioritise MR among patients at risk of medication error and is ready-to-use in other orthopaedic and trauma departments.

Association between proton pump inhibitors and severe hematological toxicity in patients receiving pemetrexed-based anticancer treatment: The prospective IPPEM study.

OBJECTIVE: Pemetrexed is associated with hematological toxicity. Drug-drug interactions (DDIs) between methotrexate and proton pump inhibitors (PPIs) induce a higher risk of hematological toxicity due to the inhibition of methotrexate excretion by PPIs. As pemetrexed and methotrexate are both excreted by human organic anion transporter 3 (hOAT3), this study investigates the hypothetical DDI between pemetrexed and PPIs in lung cancer patients. The primary objective was the occurrence of severe (grade ≥ 3) hematological toxicity. The secondary objectives were to describe the type of hematological toxicity and associated clinical consequences (NCT03537833). MATERIALS AND METHODS: PPI consumption was collected for each patient receiving pemetrexed-based anticancer chemotherapy from May 2018 to October 2020 in a prospective multicentric observational and nonrandomized study. Multivariate Cox regression and propensity score (PS) adjustment, PS matching and inverse weighting on PS (IPTW) methods were used. RESULTS: PPI consumption (55 among 156 included patients) was associated with a significantly higher risk of severe hematological toxicity in the multivariable Cox regression model (hazard ratio HR = 2.51, 95% confidence interval [1.47-4.26]; p = 0.005). Similar results were found with PS adjustment (HR = 1.91 CI95% [1.14-3.20]; p = 0.002), PS-matching (HR = 1.93 CI95% [1.08-3.45]; p = 0.02) and IPTW method (HR = 2.06 CI95% [1.27-3.35]; p = 0.004). Severe neutropenia and anemia occurred in 32.7% and 14.1% of patients, respectively. This resulted in 48 anticancer chemotherapy postponements and 24 dose adjustments, 26 growth factor prescriptions, 24 red blood cell transfusions, and 20 hospitalizations. CONCLUSIONS: The results strongly suggest an association between PPI consumption and pemetrexed-related severe hematological toxicity. Deprescription of PPIs when feasible should be considered to prevent this DDI.

Bystander effect of vinorelbine alters antitumor immune response.

The bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells. In this study, we showed that it could also affect immune cells surrounding the tumor and interfere with the antitumor immune response. We observed that the exposure of human lung cancer cells A549 to vinorelbine induced a BE on neighboring human peripheral blood mononuclear cells (PBMCs) in vitro and on mice splenocytes in vivo. In vitro, the number of PBMCs killed because of their coculture with vinorelbine-pretreated A549 cells was 33% higher than those killed by A549 control cells (p = 0.003). In addition, we showed that when vinorelbine-pretreated A549 cells were injected into immunocompetent mice, splenocyte proliferation ex vivo toward tumor cells decreased by 27% compared with that seen in mice injected with untreated A549 cells (p = 0.03). Finally, in vivo experiment in A549 tumor bearing nude mice showed that adoptive transfer of A549 immune splenocytes was not able to delay tumor growth when vinorelbine-pretreated A549 cells were used for immunization. Inhibition of the BE by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and the superoxide dismutase mimic, mangafodipir, suggested that it was mediated by oxidative and nitrosative stress. In conclusion, exposure of cancer cells to vinorelbine alters the antitumor immune response through a BE mediated by cellular oxidative and nitrosative stress. Our results offer new prospects for using oxidative stress modulators to restore the antitumor immune response in patients treated with anticancer agents.

Targeting ADAM-17/notch signaling abrogates the development of systemic sclerosis in a murine model.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by the fibrosis of various organs, vascular hyperreactivity, and immunologic dysregulation. Since Notch signaling is known to affect fibroblast homeostasis, angiogenesis, and lymphocyte development, we undertook this study to investigate the role of the Notch pathway in human and murine SSc. METHODS: SSc was induced in BALB/c mice by subcutaneous injections of HOCl every day for 6 weeks. Notch activation was analyzed in tissues from mice with SSc and from patients with scleroderma. Mice with SSc were either treated or not treated with the γ-secretase inhibitor DAPT, a specific inhibitor of the Notch pathway, and the severity of the disease was evaluated. RESULTS: As previously described, mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase I antibodies. The Notch pathway was hyperactivated in the skin, lung, fibroblasts, and splenocytes of diseased mice and in skin biopsy samples from patients with scleroderma. ADAM-17, a proteinase involved in Notch activation, was overexpressed in the skin of mice and patients in response to the local production of reactive oxygen species. In HOCl-injected mice, DAPT significantly reduced the development of skin and lung fibrosis, decreased skin fibroblast proliferation and ex vivo serum-induced endothelial H(2)O(2) production, and abrogated the production of anti-DNA topoisomerase I antibodies. CONCLUSION: Our results show the pivotal role of the ADAM-17/Notch pathway in SSc following activation by reactive oxygen species. The inhibition of this pathway may represent a new treatment of this life-threatening disease.

Clinical Relevance of Pharmacist Intervention: Development of a Named Entity Recognition Model on Unstructured Comments.

We developed a clinical named entity recognition model to predict clinical relevance of pharmacist interventions (PIs) by identifying and labelling expressions from unstructured comments of PIs. Three labels, drug, kidney and dosage, had a great inter-annotator agreement (>60%) and could be used as reference labelization. These labels also showed a high precision (>70%) and a variable recall (50-90 %).

Comparison of Two Cutibacterium acnes Biofilm Models.

The study of biofilms in vitro is complex and often limited by technical problems due to simplified models. Here, we compared C. acnes biofilm formation, from species involved in bone and prosthesis infection, in a static model with a dynamic model. Using similar parameters, the percentage of live bacteria within the biofilm was higher in dynamic than in static approach. In both models, bacterial internalization in osteoblast-like cells, playing the role of stress factor, affected this proportion but in opposite ways: increase of live bacteria proportion in the static model (×2.04 ± 0.53) and of dead bacteria proportion (×3.5 ± 1.03) in the dynamic model. This work highlights the huge importance in the selection of a relevant biofilm model in accordance with the environmental or clinical context to effectively improve the understanding of biofilms and the development of better antibiofilm strategies.

Staphylococcus aureus Strain-Dependent Biofilm Formation in Bone-Like Environment.

Staphylococcus aureus species is an important threat for hospital healthcare because of frequent colonization of indwelling medical devices such as bone and joint prostheses through biofilm formations, leading to therapeutic failure. Furthermore, bacteria within biofilm are less sensitive to the host immune system responses and to potential antibiotic treatments. We suggested that the periprosthetic bone environment is stressful for bacteria, influencing biofilm development. To provide insights into S. aureus biofilm properties of three strains [including one methicillin-resistant S. aureus (MRSA)] under this specific environment, we assessed several parameters related to bone conditions and expected to affect biofilm characteristics. We reported that the three strains harbored different behaviors in response to the lack of oxygen, casamino acids and glucose starvation, and high concentration of magnesium. Each strain presented different biofilm biomass and live adherent cells proportion, or matrix production and composition. However, the three strains shared common responses in a bone-like environment: a similar production of extracellular DNA and engagement of the SOS response. This study is a step toward a better understanding of periprosthetic joint infections and highlights targets, which could be common among S. aureus strains and for future antibiofilm strategies.

Clinical and Organizational Impacts of Medical Ordering Settings on Patient Pathway and Community Pharmacy Dispensing Process: The Prospective ORDHOSPIVILLE Study.

During the dispensing process of medical orders (MOs), community pharmacists (CPs) can manage drug-related problems (DRPs) by performing pharmacist interventions (PIs). There is little evidence that the PI rate is higher with MOs from hospitals (MOHs) than ambulatory (MOAs) settings, and their impact on the patient and community pharmacy is unknown. The primary objective of this study was to compare the MOH and MOA PI rates. The secondary objective was to describe PIs and their clinical and organizational impacts on patient and community pharmacy workflow. A total of 120 CPs participated in a prospective study. Each CP included 10 MOH and 10 MOA between January and June 2020. DRP and PI description and clinical and organizational impacts between MOH and MOA were assessed and compared. We analyzed 2325 MOs. PIs were significantly more frequent in MOH than in MOA (9.7% versus 4.7%; p < 0.001). The most reported PI was the difficulty of contacting hospital prescribers (n = 45; 52.2%). MOHs were associated with a longer dispensing process time and a greater impact on patient pathway and community pharmacy workflow than MOAs. Lack of communication between hospital and primary care settings partly explains the results. Implementation of clinical pharmacy activities at patient discharge could alleviate these impacts.

Interaction of implant infection-related commensal bacteria with mesenchymal stem cells: a comparison between Cutibacterium acnes and Staphylococcus aureus.

Staphylococcus aureus and Cutibacterium acnes are involved in several tissue infections and can encounter mesenchymal stem cells (MSCs) during their role in tissue regenerative process. C. acnes and S. aureus internalization by three types of MSCs derived from bone marrow, dental pulp and Wharton's jelly; and bacterial biofilm production were compared. Internalization rates ranged between 1.7-6.3% and 0.8-2.7% for C. acnes and S. aureus, respectively. While C. acnes strains exhibited limited cytotoxic effect on MSCs, S. aureus were more virulent with marked effect starting after only 3 h of interaction. Both bacteria were able to produce biofilms with respectively aggregated and monolayered structures for C. acnes and S. aureus. The increase in C. acnes capacity to develop biofilm following MSCs' internalization was not linked to the significant increase in number of live bacteria, except for bone marrow-MSCs/C. acnes CIP 53.117 with 79% live bacteria compared to the 36% before internalization. On the other hand, internalization of S. aureus had no impact on its ability to form biofilms composed mainly of living bacteria. The present study underlined the complexity of MSCs-bacteria cross-interaction and brought insights into understanding the MSCs behavior in response to bacterial infection in tissue regeneration context.

Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies.

The need for bone and joint prostheses is currently growing due to population aging, leading to an increase in prosthetic joint infection cases. Biofilms represent an adaptive and quite common bacterial response to several stress factors which confer an important protection to bacteria. Biofilm formation starts with bacterial adhesion on a surface, such as an orthopedic prosthesis, further reinforced by matrix synthesis. The biofilm formation and structure depend on the immediate environment of the bacteria. In the case of infection, the periprosthetic joint environment represents a particular interface between bacteria, host cells, and the implant, favoring biofilm initiation and maturation. Treating such an infection represents a huge challenge because of the biofilm-specific high tolerance to antibiotics and its ability to evade the immune system. It is crucial to understand these mechanisms in order to find new and adapted strategies to prevent and eradicate implant-associated infections. Therefore, adapted models mimicking the infectious site are of utmost importance to recreate a relevant environment in order to test potential antibiofilm molecules. In periprosthetic joint infections, Staphylococcus aureus is mainly involved because of its high adaptation to the human physiology. The current review deals with the mechanisms involved in the antibiotic resistance and tolerance of Staphylococcus aureus in the particular periprosthetic joint infection context, and exposes different strategies to manage these infections.