Pro-angiogenic and antibacterial copper containing nanoparticles in PLGA/amorphous calcium phosphate bone nanocomposites.

Large bone defects after trauma demand for adequate bone substitutes. Bone void fillers should be antibacterial and pro-angiogenic. One viable option is the use of composite materials like the combination of PLGA and amorphous calcium phosphate (aCaP). Copper stimulates angiogenesis and has antibacterial qualities. Either copper oxide (CuO) nanoparticles (NPs) were therefore added to PLGA/aCaP/CuO in different concentrations (1, 5 and 10 w/w %) or copper-doped tricalcium phosphate NPs (TCP with 2% of copper) were electrospun into PLGA/CuTCP nanocomposites. Bi-layered nanocomposites of PLGA/aCaP with different copper NPs (CuO or TCP) and a second layer of pristine PLGA were fabricated. Two clinical bacterial isolates (Staphylococcus aureus and Staphylococcus epidermidis) were used to assess antibacterial properties of the copper-containing materials. For angiogenesis, the chorioallantoic membrane (CAM) assay of the chicken embryo was performed. The higher the CuO content, the higher were the antibacterial properties, with 10 % CuO reducing bacterial adhesion most effectively. Vessel and cell densities were highest in the 5 % CuO containing scaffolds, while tissue integration was more pronounced at lower CuO content. The PLGA/aCaP/CuO (1 % CuO) behaved similar like PLGA/CuTCP in all angiogenic and antibacterial readouts, based on the same copper fraction. We conclude that CuO NPs or CuTCP NPs are useful components to increase angiogenic properties of nanocomposites and at the same time exhibiting antibacterial characteristics.

Guideline for management of septic arthritis in native joints (SANJO).

This clinical guideline is intended for use by orthopedic surgeons and physicians who care for patients with possible or documented septic arthritis of a native joint (SANJO). It includes evidence and opinion-based recommendations for the diagnosis and management of patients with SANJO.

Joint fluid concentrations of amphotericin B after local application with calcium sulphate-report of 2 cases.

Fungal periprosthetic joint infections (PJI) are difficult to treat, due to important biofilm formation and limited local penetration of systemically administered antifungals. Calcium sulphate (CaSO4 ) might be a promising carrier to increase local concentration of antifungals. We hypothesized that local amphotericin B release from CaSO4 is high enough to significantly contribute to treatment of fungal PJI. We report joint fluid and serum concentrations of amphotericin B after local application with CaSO4 as an implanted resorbable carrier material as adjunct to standard surgical and systemic antifungal treatment in two cases of PJI with Candida spp. Maximal joint fluid amphotericin B concentration was 14.01 mg/L 5 days after the second local administration of liposomal amphotericin in Case One and 25.77 mg/L 14 days after the second local administration in Case Two. Concentrations higher than minimal inhibitory concentrations (MIC) could be measured for 21 days and 17 days after local administration in Case One and Two, respectively. In Case Two, serum concentration of amphotericin B was <0.01 mg/L 3 days after local administration of 450 mg liposomal amphotericin B. No local or systemic adverse reaction was observed. Fungal PJI was successfully eradicated in both cases with a follow-up of 12 months in Case One and 20 months in Case Two. Application of amphotericin B-loaded CaSO4 was associated with joint fluid concentrations higher than minimal inhibitory concentrations for Candida spp. for approximately 3 weeks, with the advantage that the carrier material dissolves spontaneously and does not require secondary removal. Relapse of fungal infections did not occur in these two patients.

Effective Biofilm Eradication on Orthopedic Implants with Methylene Blue Based Antimicrobial Photodynamic Therapy In Vitro.

Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. This in vitro study investigated the effect of methylene blue photodynamic therapy (MB-PDT) on PJI-causing biofilms on different implant materials. MB-PDT (664 nm LED, 15 J/cm2) was tested on different Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Cutibacterium acnes strains in both planktonic form and grown in early and mature biofilms on prosthetic materials (polyethylene, titanium alloys, cobalt-chrome-based alloys, and bone cement). The minimum bactericidal concentration with 100% killing (MBC100%) was determined. Chemical and topographical alterations were investigated on the prosthesis surfaces after MB-PDT. Results showed a MBC100% of 0.5-5 µg/mL for planktonic bacteria and 50-100 µg/mL for bacteria in biofilms-independent of the tested strain, the orthopedic material, or the maturity of the biofilm. Material testing showed no relevant surface modification. MB-PDT effectively eradicated common PJI pathogens on arthroplasty materials without damage to the materials, suggesting that MB-PDT could be used as a novel treatment method, replacing current, more invasive approaches and potentially shortening the antibiotic treatment in PJI. This would improve quality of life and reduce morbidity, mortality, and high health-care costs.

Wound fluid ceftriaxone concentrations after local application with calcium sulphate as carrier material in the treatment of orthopaedic device-associated hip infections.

AIMS: There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI. METHODS: A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. CONCLUSION: Our study highlights new clinical data of locally administered ceftriaxone with CaSO4 as carrier material. The near-constant release of ceftriaxone from CaSO4 observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds.Cite this article: Bone Joint Res 2022;11(11):835-842.

Asymptomatic Periprosthetic Joint Infection of the Hip with High-Virulence Pathogens: Report of Two Cases.

Periprosthetic joint infection (PJI) may be a life-threatening condition, particularly when caused by pathogens with high virulence, capable of developing secondary bloodstream infection. We report two cases of chronic PJI of the hip, one with Staphylococcus aureus in a 27-year-old female with severe anorexia, the other one with Staphylococcus lugdunensis in a 74-year-old female suffering from morbid obesity. Both infections did not cause relevant symptoms over time despite the absence of suppressive antibiotic treatment. To our knowledge, there are no similar cases described in the literature. While it remains difficult to recommend postponing treatment in such cases, this option may be an alternative to suppressive antibiotic therapy.

Microbiological Characterization of Cutibacterium acnes Strains Isolated from Prosthetic Joint Infections.

Aims: This study aimed to characterize 79 Cutibacterium acnes strains isolated from prosthetic joint infections (PJIs) originated from eight European hospitals. Methods: Isolates were phylotyped according to the single-locus sequence typing (SLST) scheme. We evaluated the ability of the biofilm formation of C. acnes strains isolated from PJIs and 84 isolates recovered from healthy skin. Antibiotic susceptibility testing of planktonic and biofilm cells of PJI isolates and skin isolates was performed. Results: Most of the isolates from PJIs belonged to the SLST class H/phylotype IB (34.2%), followed by class D/phylotype IA1 (21.5%), class A/phylotype IA1 (18.9%), and class K/phylotype II (13.9%). All tested isolates were biofilm producers; no difference in biofilm formation was observed between the healthy skin group and the PJI group of strains. Planktonic and sessile cells of C. acnes remained highly susceptible to a broad spectrum of antibiotics, including beta-lactams, clindamycin, fluoroquinolones, linezolid, rifampin, and vancomycin. The minimal inhibitory concentrations (MICs) for planktonic and biofilm states coincided in most cases. However, the minimal biofilm eradication concentration (MBEC) was high for all antimicrobial drugs tested (>32 mg/L), except for rifampin (2 mg/L). Conclusions: C. acnes strains isolated from healthy skin were able to produce biofilm to the same extent as isolates recovered from PJIs. All C. acnes strains in planktonic and sessile states were susceptible to most antibiotics commonly used for PJI treatment, although rifampin was the only antimicrobial agent able to eradicate C. acnes embedded in biofilm.

Treatment and Outcomes of Clostridioides difficile Infection in Switzerland: A Two-Center Retrospective Cohort Study.

Objectives: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, often complicated by severe infection and recurrence with increased morbidity and mortality. Data from large cohorts in Switzerland are scarce. We aimed to describe diagnostic assays, treatment, outcomes, and risk factors for CDI in a large cohort of patients in Switzerland. Methods: We conducted a retrospective cohort study of CDI episodes diagnosed in patients from two tertiary care hospitals in Switzerland. During a 3-month follow-up, we used a composite outcome combining clinical cure at day 10, recurrence at week 8, or death, to evaluate a patient's response. Unfavorable outcomes consisted in the occurrence of any of these events. Results: From January 2014 to December 2018, we included 826 hospitalized patients with documented CDI. Overall, 299 patients (36.2%) had a severe infection. Metronidazole was used in 566 patients (83.7%), compared to 82 patients (12.1%) treated with vancomycin and 28 patients (4.1%) treated with fidaxomicin. Overall mortality at week 8 was at 15.3% (112/733). Eighty-six patients (12.7%) presented with clinical failure at day 10, and 78 (14.9%) presented with recurrence within 8 weeks; 269 (39.8%) met the composite outcome of death, clinical failure, or recurrence. The Charlson Comorbidity Index score (p < 0.001), leukocytes > 15 G/L (p = 0.008), and the use of metronidazole (p = 0.012) or vancomycin (p = 0.049) were factors associated with the composite outcome. Conclusions: Our study provides valuable insights on CDI treatment and outcomes in Switzerland, highlights the heterogeneity in practices among centers, and underlines the need for the active monitoring of clinical practices and their impact on clinical outcomes through large multicentric cohorts.

Antimicrobial susceptibility testing is crucial when treating Finegoldia magna infections.

Finegoldia magna is an anaerobic gram-positive bacterium that can cause invasive human infections. Recently, a 52-year-old patient suffering from a periprosthetic joint infection (PJI) due to F. magna was treated with cefepime on hemodialysis; however, treatment failed due to relapse caused by antibiotic-resistant strains. Reports on the antimicrobial susceptibility of F. magna clinical isolates are rare. We collected 57 clinical F. magna isolates from Zurich, Switzerland, between September 2019 and July 2020 and tested their antimicrobial susceptibility to investigate the local resistance pattern. Antimicrobial susceptibility testing (AST) was evaluated for nine antibiotics (benzylpenicillin, amoxicillin/clavulanic acid, cefuroxime, cefepime, levofloxacin, rifampicin, metronidazole, doxycycline, and clindamycin) by E-test according to CLSI guidelines. All F. magna strains were susceptible to benzylpenicillin, amoxicillin/clavulanic acid, and metronidazole, while 75% to clindamycin. F. magna isolates showed MIC values lower than species-unrelated breakpoints for cefuroxime, levofloxacin, and cefepime in 93%, 56%, and 32% of the cases, respectively. MIC values for rifampicin and doxycycline were lower than locally determined ECOFFs in 98% and 72% of the cases, respectively. In summary, we recommend the use of benzylpenicillin, amoxicillin/clavulanic acid, or metronidazole without prior AST as first-line treatment option against F. magna PJI infections. If cefuroxime, cefepime, levofloxacin, rifampicin, doxycycline, or clindamycin are used, AST is mandatory.

Fast and Sensitive Multiplex Real-Time Quantitative PCR to Detect Cutibacterium Periprosthetic Joint Infections.

Diagnosis of Cutibacterium periprosthetic joint infections (PJIs) is challenging due to a long cultivation time of up to 14 days. Faster culture-independent diagnosis would improve patient care with early and accurate treatment. Specific primers and probes were designed for Cutibacterium acnes, Cutibacterium avidum, and Cutibacterium granulosum and evaluated in a multiplex TaqMan real-time quantitative PCR (qPCR) format on 57 skin swabs and 20 culture-negative cerebrospinal fluid samples. The multiplex qPCR was tested in a PJI cohort of 41 sonication fluid samples from removed implants infected with different pathogens. All five culture-positive Cutibacterium PJIs were detected with the corresponding Cutibacterium-specific probe (100% positive percent agreement). The multiplex qPCR additionally detected C. avidum in two PJI sonication fluid samples that were diagnosed as Staphylococcus species infections according to culture (95% negative percent agreement). The new multiplex qPCR can provide a Cutibacterium PJI diagnosis within 1 day, allowing early and accurate antibiotic treatment. A prospective diagnostic trial in PJI with a high number of Cutibacterium species infections (shoulder PJI) is needed for further evaluation.

Calcium sulfate matrix as local antibiotic carrier in the mastoid.

We describe the use of calcium sulfate beads as antibiotic carrier in a patient, who suffered from chronic mastoiditis with consecutive otogenic meningitis due to Burkholderia cenocepacia. Our findings suggest a possible role of calcium sulfate matrix as a local antibiotic carrier in the mastoid in complicated mastoiditis cases.

Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for the presence of persisters across clinical presentations.

OBJECTIVES: Difficult-to-treat infections caused by antibiotic-susceptible strains have been linked to the occurrence of persisters, a subpopulation of dormant bacteria that tolerate antibiotic exposure despite lacking genetic resistance. These persisters can be identified phenotypically by plating on nutrient agar because of their altered growth dynamics, resulting in colony-size heterogeneity. The occurrence of within-patient bacterial phenotypic heterogeneity in various infections and clinical determinants of persister formation remains unknown. METHODS: We plated bacteria derived from 132 patient samples of difficult-to-treat infections directly on nutrient-rich agar and monitored colony growth by time-lapse imaging. We retained 36 Staphylococcus aureus monocultures for further analysis. We investigated clinical factors associated with increased colony growth-delay with regression analyses. We corroborated the clinical findings using in vitro grown static biofilms exposed to distinct antibiotics. RESULTS: The extent of phenotypic heterogeneity of patient-derived S. aureus varied substantially between patients (from no delay to a maximum of 57.6 hours). Increased heterogeneity coincided with increased median colony growth-delay. Multivariable regression showed that rifampicin treatment was significantly associated with increased median growth-delay (13.3 hours; 95% CI 7.13-19.6 hours; p < 0.001). S. aureus grown in biofilms and exposed to high concentrations of rifampicin or a combination of rifampicin with clindamycin or levofloxacin exhibited prolonged growth-delay (p < 0.05 for 11 of 12 comparisons), correlating with a strain-dependent increase in antibiotic tolerance. DISCUSSION: Colony-size heterogeneity upon direct sampling of difficult-to-treat S. aureus infections was frequently observed. Hence, future studies are needed to assess the potential benefit of phenotypic heterogeneity quantification for staphylococcal infection prognosis and treatment guidelines.

The Role of 99mTc-antigranulocyte SPECT/CT In Community-Acquired Diabetic Foot Osteomyelitis: A Clinical Experience.

BACKGROUND: Magnetic resonance imaging (MRI) is the actual gold standard for the radiological diagnosis of diabetic foot osteomyelitis (DFO). MATERIALS AND METHODS: MRI is not always available and many patients have contraindications. We evaluated the clinical value of 99mTc-antigranulocyte SPECT/CT (AGS) in eight DFO patients who underwent MRI before. RESULTS: The goal was to have a better clinical view on the extent of bone infection and to ameliorate the surgical approach for DFO. However, this additional scintigraphy did not change anything in the clinical approach. CONCLUSION: We shared our experience with AGS for clinical management of complex DFO cases.

Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases.

PURPOSE: The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. METHODS: We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. RESULTS: A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. CONCLUSION: Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

The role of biofilm formation in the pathogenesis and antimicrobial susceptibility of Cutibacterium acnes.

Cutibacterium acnes (previously known as Propionibacterium acnes) is frequently found on lipid-rich parts of the human skin. While C. acnes is most known for its role in the development and progression of the skin disease acne, it is also involved in many other types of infections, often involving implanted medical devices. C. acnes readily forms biofilms in vitro and there is growing evidence that biofilm formation by this Gram-positive, facultative anaerobic micro-organism plays an important role in vivo and is also involved in treatment failure. In this brief review we present an overview on what is known about C. acnes biofilms (including their role in pathogenesis and reduced susceptibility to antibiotics), discuss model systems that can be used to study these biofilms in vitro and in vivo and give an overview of interspecies interactions occurring in polymicrobial communities containing C. acnes.

Risk factor analysis for above-knee amputation in patients with periprosthetic joint infection of the knee: a case-control study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication following knee arthroplasty. Therapeutic strategies comprise a combination of surgical and antibiotic treatment modalities and aim to eradicate the infection. Sometimes control of the disease can only be attained by above-knee amputation (AKA). While a vast amount of literature exists illuminating predisposing factors for PJI, risk factors favoring the endpoint AKA in this context are sparsely known. METHODS: The purpose of this investigation was to delineate whether patients with PJI of the knee present specific risk factors for AKA. In a retrospective case-control study 11 cases of PJI treated with AKA were compared to 57 cases treated with limb salvage (LS). The minimum follow-up was 2 years. Comorbidities, signs and symptoms of the current infection, factors related to previous surgeries and the implant, microbiology, as well as therapy related factors were recorded. Comparative analysis was performed using student's t-test, chi-square test or Fisher's exact test. Binary differences were calculated using odds ratio (OR). Reoperation frequency was compared using Mann-Whitney U test. In-depth descriptive analysis of 11 amputees was carried out. RESULTS: A total of 68 cases aged 71 ± 11.2 years were examined, 11 of which underwent AKA and 57 had LS. Severe comorbidities (p = 0.009), alcohol abuse (p = 0.015), and preoperative anemia (p = 0.022) were more frequently associated with AKA. Preoperative anemia was found in all 11 amputees (100%) and in 33 of 57 LS patients (58%) with an average preoperative hemoglobin of 99.9 ± 15.1 g/dl compared to 118.2 ± 19.9 g/dl (p = 0.011). No other parameters differed significantly. AKA patients underwent a median of eight (range 2-24) reoperations, LS patients a median of five (range 2-15). CONCLUSION: Factors potentially influencing the outcome of knee PJI are diverse. The indication of AKA in this context remains a rarity and a case-by-case decision. Patient-intrinsic systemic factors such as alcohol abuse, severe comorbidities and preoperative anemia may elevate the individual risk for AKA in the setting of PJI. We recommend that anemia, being a condition well amenable to therapeutic measures, should be given special consideration in management of PJI patients. TRIAL REGISTRATION: This study was registered with Kantonale Ethikkommission Zürich, (BASEC-No. 2016-01048).

Genomic Analysis of Cutibacterium acnes Strains Isolated from Prosthetic Joint Infections.

Cutibacterium acnes is a common cause of prosthetic joint infections (PJIs). The C. acnes population can be divided into six main phylotypes (IA1, IA2, IB, IC, II and III) that are associated with different clinical conditions and normal skin. A single-locus sequence typing (SLST) scheme can distinguish ten main SLST types: A-E (all IA1), F (IA2), G (IC), H (IB), K (II), L (III). We genome-sequenced and compared 16 strains of C. acnes isolated from healthy skin (n = 4) and PJIs (n = 12), including six PJI cases with a good outcome (four shoulder PJIs, one hip PJI, one knee PJI) and six with infection relapse (three shoulder PJIs, three hip PJIs). The sequenced strains belonged to four different phylotypes (IA1, IA2, IB and II) and seven different SLST types. All five type IB strains (all SLST type H1) were PJI isolates (three hip PJIs, two shoulder PJIs), and four of these caused infection relapse (three hip PJIs, one shoulder PJI). Isolates from PJI cases with a good outcome belonged to three different phylotypes (IA, IB, II). Interestingly, four strains (three strains from PJI cases with good outcome and one strain from healthy skin) contained a linear plasmid; these strains belonged to different SLST types (A1, C1, F4, H1) and were isolated in three different hospitals. This study suggests that type IB strains have the potential to cause infection relapse, in particular regarding hip PJIs. Moreover, our study revealed that strains belonging to the same SLST type can differ in their accessory genome in different geographic locations, indicative of microevolution.

Deep surgical site infections following double-dose perioperative antibiotic prophylaxis in adult obese orthopedic patients.

BACKGROUND: Obesity is a risk factor for surgical site infections (SSI). Based on retrospective comparisons and pharmacology, many orthopedic centers have adopted weight- or body mass index (BMI)-related antibiotic prophylaxis. METHODS: Double-dose prophylaxis was introduced in March 2017 for patients weighting >80 kg. The period April 2014 to March 2017 ('before') was compared to the period March 2017 to June 2019 ('after') regarding the impact on deep SSIs. RESULTS: A total of 9318 surgeries 'before' were compared to 7455 interventions 'after' the introduction of double-dose prophylaxis. Baseline demographic characteristics (age, sex, BMI, American Society of Anesthesiologists score, and duration of surgery) were similar. In the period 'after', 3088 cases (3088/16 773; 18%) received double-dose prophylaxis. Overall, 82 deep SSIs were observed (0.5%). The pathogens were resistant to the standard cefuroxime prophylaxis in 30 cases (30/82; 37%). Excluding these prophylaxis-resistant cases and all of the five hematogenous SSIs, the remaining 47 SSIs (57%) could have been prevented by the preceding prophylaxis. Double-dosing of parenteral cefuroxime from 1.5 g to 3.0 g in obese patients did not reduce deep SSIs (hazard ratio 0.7, 95% confidence interval 0.3-1.6). In the direct group comparison among obese patients >80 kg, the double-dose prophylaxis equally failed to alter the SSI risk (3088/16 726 non-infections vs 8/47 SSI despite double-dose prophylaxis; Chi-square test, P = 0.78). CONCLUSIONS: In this single-center before-and-after study with almost 17 000 orthopedic surgeries in adult patients, systemic doubling of the perioperative antibiotic prophylaxis in obese patients clinically failed to reduce the overall deep SSI risk.

Establishment of a localized acute implant-associated Staphylococcus aureus bone infection model in sheep.

Orthopedic implant-associated bacterial infections with Staphylococcus aureus constitute a major clinical problem, and large pre-clinical animal models remain scarce. The aim of this study was to establish a standardized method of a localized, acute S. aureus bone infection in the presence of complex implanted devices in a sheep model. Four sheep underwent surgery receiving a complex implanted metallic device with a component stabilizing a bone defect created in the left tibial metaphysis, and an attached component placed in adjacent soft tissue. The bone defect was inoculated with S. aureus strain ATCC25293 (1 × 104 CFU). Twenty one days later, the surgery site was macroscopically evaluated, tissue samples and implants harvested for bacterial cell count quantification and tissue samples histologically analyzed. The animals exhibited clinical signs of localized infection (e.g. swelling, lameness, pain) but did not develop symptoms of sepsis. After euthanasia, macroscopic assessment revealed a localized bone and soft tissue infection at the surgery site. Histologically, an acute inflammation with neutrophils but also signs of bone destruction with necrosis was noted. An ovine model of a localized, acute S. aureus bone infection with complex implants was successfully established and could be used to test novel treatments against orthopedic implant-associated infections.

Cutibacterium avidum resists surgical skin antisepsis in the groin-a potential risk factor for periprosthetic joint infection: a quality control study.

BACKGROUND: The skin commensal Cutibacterium avidum has been recognized as an emerging pathogen for periprosthetic joint infections (PJI). One currently assumes that the early occurring PJIs are a consequence of skin commensals contaminating the peri-implant tissue during surgery. We addressed whether standard skin antisepsis with povidone-iodine/alcohol before total hip arthroplasty (THA) is effective to eliminate colonizing bacteria with focus on C. avidum. METHODS: In a single-center, prospective study, we screened all patients for skin colonizing C. avidum in the groin before THA. Only in the patients positive for C. avidum, we preoperatively repeated skin swabs after the first and third skin antisepsis and antibiotic prophylaxis. We also obtained dermis biopsies for microbiology and fluorescence in situ hybridization (FISH). RESULTS: Fifty-one out of 60 patients (85%) were colonized on the skin with various bacteria, in particular with C. avidum in 12 out of 60. Skin antisepsis eliminated C. avidum in eight of ten (20%) colonized patients undergoing THA. Deeper skin (dermis) biopsies were all culture negative, but FISH detected single positive ribosome-rich C. avidum in one case near sweat glands. CONCLUSION: Standard skin antisepsis was not effective to completely eliminate colonizing C. avidum on the skin in the groin of patients undergoing THA. Colonizing with C. avidum might pose an increased risk for PJI when considering a THA. Novel more effective antisepsis strategies are needed. Trial registration No clinical trial.