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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.

Orthopedic device-related infection (ODRI), including both fracture-related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio-economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial-coated orthopedic devices, antimicrobial-loaded bone cements and void fillers, and dual osteo-inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drug-device combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience-driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:271-287, 2019.

Background Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. Methods In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher’s exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. Results We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment—though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10). Conclusions We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.

The most preferred treatment for acute periprosthetic joint infection (PJI) is surgical debridement, antibiotics and retention of the implant (DAIR). The reported success of DAIR varies greatly and depends on a complex interplay of several host-related factors, duration of symptoms, the microorganism(s) causing the infection, its susceptibility to antibiotics and many others. Thus, there is a great clinical need to predict failure of the "classical" DAIR procedure so that this surgical option is offered to those most likely to succeed, but also to identify those patients who may benefit from more intensified antibiotic treatment regimens or new and innovative treatment strategies. In this review article, the current recommendations for DAIR will be discussed, a summary of independent risk factors for DAIR failure will be provided and the advantages and limitations of the clinical use of preoperative risk scores in early acute (post-surgical) and late acute (hematogenous) PJIs will be presented. In addition, the potential of implementing machine learning (artificial intelligence) in identifying patients who are at highest risk for failure of DAIR will be addressed. The ultimate goal is to maximally tailor and individualize treatment strategies and to avoid treatment generalization.

The most preferred treatment for acute periprosthetic joint infection (PJI) is surgical debridement, antibiotics and retention of the implant (DAIR). The reported success of DAIR varies greatly and depends on a complex interplay of several host-related factors, duration of symptoms, the microorganism(s) causing the infection, its susceptibility to antibiotics and many others. Thus, there is a great clinical need to predict failure of the “classical” DAIR procedure so that this surgical option is offered to those most likely to succeed, but also to identify those patients who may benefit from more intensified antibiotic treatment regimens or new and innovative treatment strategies. In this review article, the current recommendations for DAIR will be discussed, a summary of independent risk factors for DAIR failure will be provided and the advantages and limitations of the clinical use of preoperative risk scores in early acute (post-surgical) and late acute (hematogenous) PJIs will be presented. In addition, the potential of implementing machine learning (artificial intelligence) in identifying patients who are at highest risk for failure of DAIR will be addressed. The ultimate goal is to maximally tailor and individualize treatment strategies and to avoid treatment generalization.

In vitro occurrence of levofloxacin (LVX) resistance in C. acnes and characterization of its molecular background were investigated. The mutation frequency was determined by inoculation of 10 8 cfu of C. acnes ATCC 11827 (LVX MIC = 0.25 mg/L) on LVX-containing agar plates. The progressive emergence of resistance was studied by a second exposure to increasing LVX concentrations. For mutants, the QRDR regions including the gyrA and parC genes were sequenced and compared to both C. acnes ATCC 11827 and C. acnes KPA171202 reference sequences (NC006085). The importance of the efflux pump system in resistance was investigated by using inhibitors on selected resistant mutants with no mutation in the QRDR. C. acnes growth was observed on LVX-containing plates with mutation frequencies of 3. 8 cfu × 10 −8 (8 × MIC) and 1.6 cfu × 10 −7 (4 × MIC). LVX resistance emerged progressively after one-step or two-step assays. In LVX-resistant isolates, the MIC ranged from 0.75 to >32 mg/L. Mutations were detected exclusively in the gyrA gene. Ten genotypes were identified: G99 C, G99 D, D100N, D100 H, D100 G, S101L, S101W, A102 P, D105 H and A105 G. Mutants S101L and S101W were always associated with a high level of resistance. Mutants with no mutation in the QRDR were more susceptible when incubated with an efflux pump inhibitor (phenyl-arginine β-naphthylamide) only, suggesting, for the first time, the expression of such a system in C. acnes LVX-resistant mutants.

Felix Greimel,1 Christine Scheuerer,1 Andre Gessner,2 Michaela Simon,2 Thomas Kalteis,1 Joachim Grifka,1 Achim Benditz,1 Hans-Robert Springorum,1 JensSchaumburger1 1Department of Orthopedics, University Medical Center Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach, 2Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Bavaria, Germany Abstract: The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus, whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections. Keywords: moxifloxacin, rifampin, flucloxacillin, implant-associated infection, prosthetic infection, Staphylococcus aureus

This review presents the clinical background to abdominal wall reconstruction, the different types of surgical meshes employed and known mechanisms of infection. It is shown that there are major physico-chemical differences between available meshes, which, in combination with the location of the mesh, the surgical technique applied and hernia type involved influence the infection potential. (c) 2007 Elsevier Ltd. All rights reserved.

Wear of metal-on-metal (cobaltchromium, CoCr particles) and metal-on-polyethylene (ultra-high-molecular-weight polyethylene, UHMWPE particles) bearing surfaces in hip prostheses is a major problem in orthopedics. This study aimed to compare the influence of CoCr and UHMWPE particles on the persistence of infection. Bioluminescent Staphylococcus aureus Xen36 were injected in air pouches prepared in subcutaneous tissue of immuno-competent BALB/c mice (control), as a model for the joint space, in the absence or presence of CoCr or UHMWPE particles. Bioluminescence was monitored longitudinally up to 21 days, corrected for absorption and reflection by the particles and expressed relative to the bioluminescence found in the presence of staphylococci only. After termination, air pouch fluid and air pouch membrane were cultured and histologically analyzed. Bioluminescence was initially lower in mice exposed to UHMWPE particles with staphylococci than in mice injected with staphylococci only, possibly because UHMWPE particles initially stimulated a higher macrophage presence in murine air pouch membranes. For mice exposed to CoCr particles with staphylococci, bioluminescence was observed to be higher in two out of six animals compared to the presence of staphylococci alone. In the majority of mice, infection risk in the absence or presence of CoCr and UHMWPE particles appeared similar, assuming that the longevity of an elevated bioluminescence is indicative of a higher infection risk. However, the presence of CoCr particles yielded a higher bioluminescence in two out of six mice, possibly because the macrophage degradative function was hampered by the presence of CoCr particles. (C) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:341347, 2012

Background and purpose Joint replacement with metal-on-metal (MOM) bearings have gained popularity in the last decades in young and active patients. However, the possible effects of MOM wear debris and its corrosion products are still the subject of debate. Alongside the potential disadvantages such as toxicity, the influences of metal particles and metal ions on infection risk are unclear. Methods We reviewed the available literature on the influence of degradation products of MOM bearings in total hip arthroplasties on infection risk. Results Wear products were found to influence the risk of infection by hampering the immune system, by inhibiting or accelerating bacterial growth, and by a possible antibiotic resistance and heavy metal co-selection mechanism. Interpretation Whether or not the combined effects of MOM wear products make MOM bearings less or more prone to infection requires investigation in the near future.

Methods We reviewed the available literature on the influence of degradation products of MOM bearings in total hip arthroplasties on infection risk.Results Wear products were found to influence the risk of infection by hampering the immune system, by inhibiting or accelerating bacterial growth, and by a possible antibiotic resistance and heavy metal co-selection mechanism.Interpretation Whether or not the combined effects of MOM wear products make MOM bearings less or more prone to infection requires investigation in the near future.

Summary Objectives The treatment of Candida implant-associated infections remains challenging. We investigated the antifungal activity against planktonic and biofilm Candida albicans in a foreign-body infection model. Methods Teflon cages were subcutaneously implanted in guinea pigs, infected with C. albicans (ATCC 90028). Animals were treated intraperitoneally 12 h after infection for 4 days once daily with saline, fluconazole (16 mg/kg), amphotericin B (2.5 mg/kg), caspofungin (2.5 mg/kg) or anidulafungin (20 mg/kg). Planktonic Candida was quantified, the clearance rate and cure rate determined. Results In untreated animals, planktonic Candida was cleared from cage fluid in 25% (infected with 4.5 × 10 3 CFU/cage), 8% (infected with 4.8 × 10 4 CFU/cage) and 0% (infected with 6.2 × 10 5 CFU/cage). Candida biofilm persisted on all explanted cages. Compared to untreated controls, caspofungin reduced the number of planktonic C. albicans to 0.22 and 0.0 CFU/ml, respectively, and anidulafungin to 0.11 and 0.13 CFU/ml, respectively. Fluconazole cured 2/12 cages (17%), amphotericin B and anidulafungin 1/12 cages (8%) and caspofungin 3/12 cages (25%). Conclusion Echinocandins showed superior activity against planktonic C. albicans . Caspofungin showed the highest cure rate of C. albicans biofilm. However, no antifungal exceeded 25% cure rate, demonstrating the difficulty of eradicating Candida biofilms from implants.

One of the major drawbacks in the use of biomedical materials is the occurrence of biomaterials centered infections. After implantation, the host interacts with a biomaterial by forming a conditioning film on its surface and an immune reaction towards the foreign material. When microorganisms can reach the biomaterials surface they can adhere to it. Adhesion of microorganisms to an implant is mediated by their physico-chemical surface properties and the properties of the biomaterials surface itself. Subsequent surface growth of the microorganisms will lead to a mature biofilm and infection, which is difficult to eradicate by antibiotics. The purpose of this review is to give an overview of the mechanisms involved in biomaterials centered infection and the possible methods to prevent these infections. (C) 2002 Kluwer Academic Publishers.

One of the major drawbacks in the use of biomedical materials is the occurrence of biomaterials centered infections. After implantation, the host interacts with a biomaterial by forming a conditioning film on its surface and an immune reaction towards the foreign material. When microorganisms can reach the biomaterials surface they can adhere to it. Adhesion of microorganisms to an implant is mediated by their physico-chemical surface properties and the properties of the biomaterials surface itself. Subsequent surface growth of the microorganisms will lead to a mature biofilm and infection, which is difficult to eradicate by antibiotics. The purpose of this review is to give an overview of the mechanisms involved in biomaterials centered infection and the possible methods to prevent these infections. (C) 2002 Kluwer Academic Publishers.

The conventional therapeutic approach to bone infection associated with osteosynthesis is based on the idea that microbial eradication is most readily achieved by removal of the foreign material together with adequate antimicrobial therapy. This strategy usually requires implantation of external fixation devices with additional discomfort to the patient. We report our experience with conservative medical and antimicrobial therapy without removal of the osteosynthesis until adequate bone callus deposition is documented by bone radiography scan. Twenty patients with infections associated with intramedullary nailing (9 patients), screws and plate (9 patients) or screws (2 patients) were treated between 1995 to 2000. Osteosynthesis implantation sites were tibia (7 patients), femur (6 patients), femur and tibia (1 patient), humerus (1 patient), others (5 patients). Diagnosis of infection was based on clinical-microbiological evidence and confirmed by 99Tc-labeled leukocyte scan studies. Offending pathogens were Staphylococcus aureus 17 cases, Staphylococcus aureus + Escherichia coli, Staphylococcus epidermidis, unknown, 1 case each. Most infections were initially treated with intravenous or intramuscular teicoplanin +/- ciprofloxacin or rifampin followed by oral antimicrobial therapy usually with ciprofloxacin or minocycline plus rifampin. Mean duration of antimicrobial therapy was 27.7 weeks (range 12-64 weeks). All patients (100%) were cured, and none complained of side-effects requiring antibiotic therapy discontinuation. We conclude that conservative medical therapy is feasible for osteosynthesis-associated bone infection.

The activity of dalbavancin, a representative of the lipoglycopeptide antibiotics, alone and in combination with rifampicin, was investigated against meticillin-resistant Staphylococcus aureus (MRSA) in a foreign-body infection model in guinea pigs. The MIC, MBC and time-kill profile of dalbavancin were determined for MRSA ATCC 43300 in the logarithmic (MBC(log)) and stationary (MBC(stat)) growth phases. The pharmacokinetic profile of dalbavancin was determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal dalbavancin (40, 60 or 80 mg/kg as a single dose), rifampicin (12.5 mg/kg/12 h for 4 days) and their combination was assessed against planktonic and biofilm MRSA. The MIC of dalbavancin was 0.078 mg/L; MBC(log) and MBC(stat) were both >128× MIC. In time-kill studies, bacterial reduction of 3log(10)CFU/mL was achieved after 48 h at ≥32× MIC (logarithmic growth) and at ≥1× MIC (stationary growth). Dalbavancin was neither synergistic nor antagonistic with rifampicin, and prevented the emergence of rifampicin resistance in vitro. The half-life of dalbavancin in cage fluid was 35.8-45.4 h and the concentration remained above the MIC of MRSA during 7 days after a single dose. Dalbavancin reduced planktonic MRSA in cage fluid at high dose (60 mg/kg and 80 mg/kg) but failed to eradicate biofilm MRSA from cages. In combination with rifampicin, dalbavancin at 80 mg/kg cured 36% of infected cages, and emergence of rifampicin resistance was completely prevented. Dalbavancin at 80 mg/kg and in combination with rifampicin eradicated approximately one-third of cage-associated MRSA infections and prevented emergence of rifampicin resistance.

Infective endocarditis (IE) usually is studied using animals with catheters inserted into the heart, which causes formation of platelet-fibrin thrombi (vegetations, VGs). We used two rabbit models to study the respective roles of the catheter and the VGs in the development of IE. The influence of the catheter was studied by either removing the catheter before bacterial challenge, or leaving the catheter in place. In all cases, removal of the catheter caused a strong decrease in the frequency of IE. The presence of the catheter stimulated population increase of streptococci within 4 h after challenge. As most catheters were sterile 4 h after challenge, they did not serve as a reservoir of bacteria. To study the requirement of a preformed VG catheters were inserted either 24 h or 30 min before bacterial challenge. In the former model VGs were present, in the latter VGs were not yet formed when bacteria were injected. The frequencies of IE due to 2 S. sanguis and 2 S. epidermidis strains in the 24 h model or 30 min model were similar, indicating that a preformed VG is not necessary for development of IE. Five coagulase-negative stains were shown to vary in their capacity to cause IE in the 30 min model. Variation was not caused by differences in early adhesion br colonization of the aortic valve, but reflects differences in persistence after initial colonization. Like in the 24 h model, persistence of the bacteria was greatly enhanced by the continuous presence of the catheter. Possible mechanisms of the infection-potentiating effect of the catheters are discussed.

Infective endocarditis (IE) usually is studied using animals with catheters inserted into the heart, which causes formation of platelet-fibrin thrombi (vegetations, VGs). We used two rabbit models to study the respective roles of the catheter and the VGs in the development of IE. The influence of the catheter was studied by either removing the catheter before bacterial challenge, or leaving the catheter in place. In all cases, removal of the catheter caused a strong decrease in the frequency of IE. The presence of the catheter stimulated population increase of streptococci within 4 h after challenge. As most catheters were sterile 4 h after challenge, they did not serve as a reservoir of bacteria. To study the requirement of a preformed VG catheters were inserted either 24 h or 30 min before bacterial challenge. In the former model VGs were present, in the latter VGs were not yet formed when bacteria were injected. The frequencies of IE due to 2 S. sanguis and 2 S. epidermidis strains in the 24 h model or 30 min model were similar, indicating that a preformed VG is not necessary for development of IE. Five coagulase-negative stains were shown to vary in their capacity to cause IE in the 30 min model. Variation was not caused by differences in early adhesion br colonization of the aortic valve, but reflects differences in persistence after initial colonization. Like in the 24 h model, persistence of the bacteria was greatly enhanced by the continuous presence of the catheter. Possible mechanisms of the infection-potentiating effect of the catheters are discussed.

Wear of metal-on-metal (cobaltchromium, CoCr particles) and metal-on-polyethylene (ultra-high-molecular-weight polyethylene, UHMWPE particles) bearing surfaces in hip prostheses is a major problem in orthopedics. This study aimed to compare the influence of CoCr and UHMWPE particles on the persistence of infection. Bioluminescent Staphylococcus aureus Xen36 were injected in air pouches prepared in subcutaneous tissue of immuno-competent BALB/c mice (control), as a model for the joint space, in the absence or presence of CoCr or UHMWPE particles. Bioluminescence was monitored longitudinally up to 21 days, corrected for absorption and reflection by the particles and expressed relative to the bioluminescence found in the presence of staphylococci only. After termination, air pouch fluid and air pouch membrane were cultured and histologically analyzed. Bioluminescence was initially lower in mice exposed to UHMWPE particles with staphylococci than in mice injected with staphylococci only, possibly because UHMWPE particles initially stimulated a higher macrophage presence in murine air pouch membranes. For mice exposed to CoCr particles with staphylococci, bioluminescence was observed to be higher in two out of six animals compared to the presence of staphylococci alone. In the majority of mice, infection risk in the absence or presence of CoCr and UHMWPE particles appeared similar, assuming that the longevity of an elevated bioluminescence is indicative of a higher infection risk. However, the presence of CoCr particles yielded a higher bioluminescence in two out of six mice, possibly because the macrophage degradative function was hampered by the presence of CoCr particles. (C) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:341347, 2012

One of the major clinical complications in the biomedical application of synthetic materials is the incidence of implant-associated infections. Such infections are very often induced by Staphylococcus aureus. To obtain information on tissue reactions and minimal bacterial challenge needed to create an infection related to untreated implant surfaces, we injected polyurethane tubing segments with a series of Staphylococcus aureus. The segments were subcutaneously implanted in rats. Implantation periods varied from 2, 5 and 10 days to 3 weeks. Specimen were evaluated using light and transmission electron microscopy. At least 0.25 x 10(4) of Staphylococci aureus were needed to clearly recognize that bacteria had been injected in the polyurethane tubing segments. The evidence was indirect, showing high infiltration and activation of neutrophils and macrophages, but not bacteria. Furthermore, 0.25 x 10(6) S. aureus were needed to induce a persistent specific inflammatory reaction with high concentrations of lymphocytes, i.e. mainly plasma-cells, at 3 weeks. The results indicate that this model functioned well to obtain the wanted information. Results are discussed with respect to (a-) specific inflammatory reactions occurring with (bacterial-challenged) biomaterials. Ultimately, our goal is to develop infection-resistant materials, for which the in vivo model developed may be used to qualify the processed materials

One of the major clinical complications in the biomedical application of synthetic materials is the incidence of implant-associated infections. Such infections are very often induced by Staphylococcus aureus. To obtain information on tissue reactions and minimal bacterial challenge needed to create an infection related to untreated implant surfaces, we injected polyurethane tubing segments with a series of Staphylococcus aureus. The segments were subcutaneously implanted in rats. Implantation periods varied from 2, 5 and 10 days to 3 weeks. Specimen were evaluated using light and transmission electron microscopy. At least 0.25 x 10(4) of Staphylococci aureus were needed to clearly recognize that bacteria had been injected in the polyurethane tubing segments. The evidence was indirect, showing high infiltration and activation of neutrophils and macrophages, but not bacteria. Furthermore, 0.25 x 10(6) S. aureus were needed to induce a persistent specific inflammatory reaction with high concentrations of lymphocytes, i.e. mainly plasma-cells, at 3 weeks. The results indicate that this model functioned well to obtain the wanted information. Results are discussed with respect to (a-) specific inflammatory reactions occurring with (bacterial-challenged) biomaterials. Ultimately, our goal is to develop infection-resistant materials, for which the in vivo model developed may be used to qualify the processed materials

Eurosurgery 2000 Meeting -- JUN 21-24, 2000 -- ISTANBUL, TURKEY WOS: 000233300500003 PubMed: 16249165 Wound infection after prosthetic material implantation is a troublesome complication with an incidence of 2% to 10%. The effect of granulocyte colony-stimulating factor (G-CSF) was studied in an experimental methicillin-resistant Staphylococcus aureus (MRSA) graft infection model. Eighty adult mice were used. Under general anesthesia an abdominal incision of 2 cm in length was performed. A subcutaneous cavity of 2 x 2 cm in size was created. Polypropylene mesh pieces of 2 x 1 cm and MRSA solution of 0.1 ml of 10(8) CFU/mL were used. G-CSF was applied systemically or locally in a dosage of 0.02 MU/30 g body weight. There were 8 groups: group I, wound + MRSA; group II, wound + mesh + MRSA; group III, wound + mesh + MRSA + G-CSF (ip, 48 h before operation); group IV, wound + mesh + MRSA + G-CSF (ip, 24 h before operation); group V, wound + mesh + MRSA + G-CSF (locally, into the cavity); group VI, wound + mesh (incubated in G-CSF solution for 4 h) + MRSA; group VII, wound + mesh + MRSA + G-CSF, ip, 24 h from operation; and group VIII (positive control group), wound + mesh + MRSA + Teicoplanin (0.03 mg/30 g body weight, ip, 1/2 h before operation). Three days after, animals were killed and incisions were examined for possible infection or abscess formation and wound failure. Meshes were removed; after vortexing and dilution, samples were incubated with 5% agar media. Results of bacterial incubation were evaluated 24 h and 48 h later. There were symptoms of wound infection and abscess formation in all groups except group VIII. In group VIII, MRSA was isolated in 7 events with a colony count below 10(3). Bacterial counts were above 106 (10(6)-10(8)) in all other groups. Thus, it was observed that wound infection could be created with this model, but G-CSF could not prevent the development of wound infection, whether it was administered systemically or locally. Teicoplanin decreased the number of colony-forming units of MRSA, and prevents wound infection in this MRSA wound infection model.

One of the major drawbacks in the use of biomedical materials is the occurrence of biomaterials centered infections. After implantation, the host interacts with a biomaterial by forming a conditioning film on its surface and an immune reaction towards the foreign material. When microorganisms can reach the biomaterials surface they can adhere to it. Adhesion of microorganisms to an implant is mediated by their physico-chemical surface properties and the properties of the biomaterials surface itself. Subsequent surface growth of the microorganisms will lead to a mature biofilm and infection, which is difficult to eradicate by antibiotics. The purpose of this review is to give an overview of the mechanisms involved in biomaterials centered infection and the possible methods to prevent these infections. (C) 2002 Kluwer Academic Publishers.

Infective endocarditis (IE) usually is studied using animals with catheters inserted into the heart, which causes formation of platelet-fibrin thrombi (vegetations, VGs). We used two rabbit models to study the respective roles of the catheter and the VGs in the development of IE. The influence of the catheter was studied by either removing the catheter before bacterial challenge, or leaving the catheter in place. In all cases, removal of the catheter caused a strong decrease in the frequency of IE. The presence of the catheter stimulated population increase of streptococci within 4 h after challenge. As most catheters were sterile 4 h after challenge, they did not serve as a reservoir of bacteria. To study the requirement of a preformed VG catheters were inserted either 24 h or 30 min before bacterial challenge. In the former model VGs were present, in the latter VGs were not yet formed when bacteria were injected. The frequencies of IE due to 2 S. sanguis and 2 S. epidermidis strains in the 24 h model or 30 min model were similar, indicating that a preformed VG is not necessary for development of IE. Five coagulase-negative stains were shown to vary in their capacity to cause IE in the 30 min model. Variation was not caused by differences in early adhesion br colonization of the aortic valve, but reflects differences in persistence after initial colonization. Like in the 24 h model, persistence of the bacteria was greatly enhanced by the continuous presence of the catheter. Possible mechanisms of the infection-potentiating effect of the catheters are discussed.

Biomaterials are increasingly used for the restoration of human function, but can become infected as a result of peri- or early post-operative bacterial contamination, although biomaterial-associated infections (BAIs) can also initiate at any time from hematogenous spreading of bacteria from an infection elsewhere in the body. Infecting bacteria in BAIs not only seek shelter in their own protective biofilm matrix, but also hide in surrounding tissue. This study compares staphylococcal persistence on and around a degradable and non-degradable surgical mesh through the use of longitudinal bioluminescence imaging in a murine model, including histological evaluation of surrounding tissue after sacrifice. Surgical meshes were first contaminated with bioluminescent Staphylococcus aureus Xen29 and subsequently subcutaneously implanted in mice. Bioluminescent staphylococci persisted on and around non-degradable meshes during the 28-day course of the study, whereas bioluminescence returned to control levels and bacteria disappeared from surrounding tissues once a degradable mesh had fully dissolved. Thus the application of degradable biomaterials yields major advantages with respect to the prevention of BAIs, as dissolution of the implant not only is associated with elimination of the protective biofilm mode of growth of the infecting organisms, but also allows the immune system to clear the surrounding tissue from infecting organisms. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.