Inhibition of Angiotensin Converting Enzyme Impairs Anti-staphylococcal Immune Function in a Preclinical Model of Implant Infection.

Background: Evidence suggests the renin-angiotensin system (RAS) plays key immunomodulatory roles. In particular, angiotensin-converting enzyme (ACE) has been shown to play a role in antimicrobial host defense. ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) are some of the most commonly prescribed medications, especially in patients undergoing invasive surgery. Thus, the current study assessed the immunomodulatory effect of RAS-modulation in a preclinical model of implant infection. Methods:In vitro antimicrobial effects of ACEi and ARBs were first assessed. C57BL/6J mice subsequently received either an ACEi (lisinopril; 16 mg/kg/day), an ARB (losartan; 30 mg/kg/day), or no treatment. Conditioned mice blood was then utilized to quantify respiratory burst function as well as Staphylococcus aureus Xen36 burden ex vivo in each treatment group. S. aureus infectious burden for each treatment group was then assessed in vivo using a validated mouse model of implant infection. Real-time quantitation of infectious burden via bioluminescent imaging over the course of 28 days post-procedure was assessed. Host response via monocyte and neutrophil infiltration within paraspinal and spleen tissue was quantified by immunohistochemistry for F4/80 and myeloperoxidase, respectively. Results: Blood from mice treated with an ACEi demonstrated a decreased ability to eradicate bacteria when mixed with Xen36 as significantly higher levels of colony forming units (CFU) and biofilm formation was appreciated ex vivo (p < 0.05). Mice treated with an ACEi showed a higher infection burden in vivo at all times (p < 0.05) and significantly higher CFUs of bacteria on both implant and paraspinal tissue at the time of sacrifice (p < 0.05 for each comparison). There was also significantly decreased infiltration and respiratory burst function of immune effector cells in the ACEi group (p < 0.05). Conclusion: ACEi, but not ARB, treatment resulted in increased S. aureus burden and impaired immune response in a preclinical model of implant infection. These results suggest that perioperative ACEi use may represent a previously unappreciated risk factor for surgical site infection. Given the relative interchangeability of ACEi and ARB from a cardiovascular standpoint, this risk factor may be modifiable.

Topical vancomycin for treatment of methicillin-resistant Staphylococcus epidermidis infection in a rat spinal implant model.

STUDY DESIGN: Basic science. OBJECTIVE: Investigate the ability of local applicaiton of vancomycin, either in powder form or suspended within poly(lactic-co-glycolic acid) microspheres (MS), to treat infection using a rat spinal model. Surgical site infections (SSIs) are a serious complication after spine surgery and are associated with high morbidity and mortality and often caused my coagulase negative staphylococci. A comprehensive approach to reduce SSIs has been recommended including the use of topical vancomycin. Animal and human studies have shown improved control of infection with local compared to systemic antibiotics. METHODS: K-wires seeded with methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) were treated with vancomycin powder, carboxymethylcellulose sodium salt (CMC) (microsphere carrier), vancomycin powder, blank MS or vancomycin-loaded MS for 24 or 48 h in vitro after which bacteria were enumerated. In addition, a spinal instrumentation model was developed in rats with a bacterial seeded K-wire implanted into the right side of L4 and L5. Rats underwent no treatment or were treated locally with either vancomycin powder, blank MS or vancomycin-loaded MS. After 8 weeks, the K-wire, bone, soft tissue and wire fastener were cultured and results analyzed. RESULTS: Vancomycin powder and vancomycin-loaded MS resulted in significantly fewer bacteria remaining in vitro than did CMC. Vancomycin powder- treated animals' cultures were significantly lower than all other groups (P < 0.0001) with negative culture results, except for one animal. The vancomycin-loaded MS-treated animals had lower bone bacterial counts than the controls (P < 0.0279); blank MS-treated animals had no differences in bacterial densities when compared to non-treated animals. CONCLUSION: Vancomycin powder and vancomycin-loaded MS were active against MRSE in vitro, in a rat MRSE implant model; however, vancomycin MS were inferior to the topical vancomycin powder. Vancomycin powder prevented MRSE infection in a rat spinal implant infection model.

Novel Antibacterial Coating on Orthopedic Wires To Eliminate Pin Tract Infections.

Novel approaches to the prevention of microbial infections after the insertion of orthopedic external fixators are in great demand because of the extremely high incidence rates of such infections, which can reach up to 100% with longer implant residence times. Monolaurin is an antimicrobial agent with a known safety record that is broadly used in the food and cosmetic industries; however, its use in antimicrobial coatings of medical devices has not been studied in much detail. Here, we report the use of monolaurin as an antibacterial coating on external fixators for the first time. Monolaurin-coated Kirschner wires (K-wires) showed excellent antibacterial properties against three different bacterial strains, i.e., methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermidis Approximately 6.0-log reductions of both planktonic and adherent bacteria were achieved using monolaurin-coated K-wires, but monolaurin-coated K-wires did not show any observable cytotoxicity with mouse osteoblast cell cultures. Overall, monolaurin-coated K-wires could be promising as potent antimicrobial materials for orthopedic surgery.

Fosfomycin Addition to Poly(D,L-Lactide) Coating Does Not Affect Prophylaxis Efficacy in Rat Implant-Related Infection Model, But That of Gentamicin Does.

Gentamicin is the preferred antimicrobial agent used in implant coating for the prevention of implant-related infections (IRI). However, the present heavy local and systemic administration of gentamicin can lead to increased resistance, which has made its future use uncertain, together with related preventive technologies. Fosfomycin is an alternative antimicrobial agent that lacks the cross-resistance presented by other classes of antibiotics. We evaluated the efficacy of prophylaxis of 10% fosfomycin-containing poly(D,L-lactide) (PDL) coated K-wires in a rat IRI model and compared it with uncoated (Control 1), PDL-coated (Control 2), and 10% gentamicin-containing PDL-coated groups with a single layer of coating. Stainless steel K-wires were implanted and methicillin-resistant Staphylococcus aureus (ATCC 43300) suspensions (103 CFU/10 µl) were injected into a cavity in the left tibiae. Thereafter, K-wires were removed and cultured in tryptic soy broth and then 5% sheep blood agar mediums. Sliced sections were removed from the tibiae, stained with hematoxylin-eosin, and semi-quantitatively evaluated with X-rays. The addition of fosfomycin into PDL did not affect the X-ray and histopathological evaluation scores; however, the addition of gentamicin lowered them. The addition of gentamicin showed a protective effect after the 28th day of X-ray evaluations. PDL-only coating provided no protection, while adding fosfomycin to PDL offered a 20% level protection and adding gentamicin offered 80%. Furthermore, there were 103 CFU level growths in the gentamicin-added group, while the other groups had 105. Thus, the addition of fosfomycin to PDL does not affect the efficacy of prophylaxis, but the addition of gentamicin does. We therefore do not advise the use of fosfomycin as a single antimicrobial agent in coating for IRI prophylaxis.

In vivo quantification of gentamicin released from an implant coating.

Drug-releasing implants are gaining increasing interest. The present study reports a detailed physicochemical analysis of a polymeric coating based on poly(D,L-lactide) and the incorporated gentamicin combined with an in vitro and in vivo study of the gentamicin release. Differential scanning calorimeter, Fourier transform infrared spectroscopy, gel permeation chromatography and high-performance liquid chromatography showed no effect of the gamma sterilisation on the coating components or an interaction of the polymer and the gentamicin. Microbiological analysis revealed an inhibition of bacterial growth on the implant surface. For the in vivo study, gentamicin-coated wires were implanted into the tibiae of rats and harvested at different time points up to day 42. To monitor the release in vivo, gentamicin was quantified in serum, bone, endosteum, kidney, and on the explanted wires. Gentamicin was detectable over a time period of 42 days in the endosteum, up to seven days in the kidney, up to 4 h in the bone and at the end of the experiment on one of eight wires. The locally released gentamicin caused no histological changes of the kidney. Microbiologically active concentrations of released gentamicin were found in the endosteum up to 4 h after implantation. The combination of different methods supports the individual results, where quantification is complemented by visualisation or antimicrobial activity. This work demonstrates that the coating procedure results in no substantial alteration of the incorporated drug and that the in vitro burst release occurs also in vivo.

Development of a hematogenous implant-related infection in a rat model.

BACKGROUND: Implant-related osteomyelitis is a major complication that requires immediate treatment, often involving removal of the implant, prolonging patient recovery and inflating expenses. Current research involving interventions to diminish the prevalence of such measures include investigating prophylactic and therapeutic remedies. A proper and accurate animal model is needed to thoroughly investigate such treatments. The scope of this project was to develop an animal model in which a consistent and measurable infection can be formed on an orthopedic implant when bacteria is introduced via a hematogenous source. METHODS: Titanium Kirschner-wires were implanted into the intramedullary canals of both femurs. Staphylococcus aureus, ranging from10(4) to 10(9) colony forming units, was injected into a tail vessel. After a designated time (3, 7, 14, or 42 days) the femurs were harvested and bacterial numbers determined for both the femur and the implanted K-wire. In addition, histology and micro-computed tomography were used as subjective tools to further characterize the infection. RESULTS: Consistent infection, that is infection of ≥75% of the femurs, wasn't achieved until 10(7) CFU S. aureus was injected. At 10(7) CFU, the femurs contained 4.6x10(6) CFU/g bone tissue at day 3 and 4.8×10(8) CFU/g bone tissue by day 14. The wire showed comparable contamination with 4.8×10(4) CFU/mm(2) at day 3 and 3.7×10(5)/mm(2) by day 14. After 42 days, the bacteria number decreased but was still occupying at 1.9×10(5) CFU/g bone tissue. There were morphological changes to the bone as well. At day 42, there were signs of osteonecrosis and active bone formation when compared to control animals that received a K-wire but were inoculated with saline. CONCLUSIONS: A model for hematogenous osteomyelitis, a common complication associated with implants, has been introduced. A reproducible, preclinical model is essential to evaluate future methods used to mitigate blood-borne bacteria hardware and bone infections.

Combined in vivo optical and µCT imaging to monitor infection, inflammation, and bone anatomy in an orthopaedic implant infection in mice.

Multimodality imaging has emerged as a common technological approach used in both preclinical and clinical research. Advanced techniques that combine in vivo optical and µCT imaging allow the visualization of biological phenomena in an anatomical context. These imaging modalities may be especially useful to study conditions that impact bone. In particular, orthopaedic implant infections are an important problem in clinical orthopaedic surgery. These infections are difficult to treat because bacterial biofilms form on the foreign surgically implanted materials, leading to persistent inflammation, osteomyelitis and eventual osteolysis of the bone surrounding the implant, which ultimately results in implant loosening and failure. Here, a mouse model of an infected orthopaedic prosthetic implant was used that involved the surgical placement of a Kirschner-wire implant into an intramedullary canal in the femur in such a way that the end of the implant extended into the knee joint. In this model, LysEGFP mice, a mouse strain that has EGFP-fluorescent neutrophils, were employed in conjunction with a bioluminescent Staphylococcus aureus strain, which naturally emits light. The bacteria were inoculated into the knee joints of the mice prior to closing the surgical site. In vivo bioluminescent and fluorescent imaging was used to quantify the bacterial burden and neutrophil inflammatory response, respectively. In addition, µCT imaging was performed on the same mice so that the 3D location of the bioluminescent and fluorescent optical signals could be co-registered with the anatomical µCT images. To quantify the changes in the bone over time, the outer bone volume of the distal femurs were measured at specific time points using a semi-automated contour based segmentation process. Taken together, the combination of in vivo bioluminescent/fluorescent imaging with µCT imaging may be especially useful for the noninvasive monitoring of the infection, inflammatory response and anatomical changes in bone over time.

Bacteriophage mediated killing of Staphylococcus aureus in vitro on orthopaedic K wires in presence of linezolid prevents implant colonization.

BACKGROUND: Infections of bone and joint tissues following arthroplasty surgeries remain a major challenge in orthopaedic settings. Methicillin resistant Staphylococcus aureus (MRSA) is recognised as an established pathogen in such infections. Combination therapy using linezolid and bacteriophage impregnated in biopolymer was investigated in the present study as an alternative strategy to prevent MRSA colonisation on the orthopaedic implant surface. METHODOLOGY: Coating of stainless steel orthopaedic grade K-wires was achieved using hydroxypropylmethlycellulose (HPMC) mixed with phage alone, linezolid alone and phage and linezolid together. The potential of these agents to inhibit adhesion of S.aureus (MRSA) 43300 on K-wires was assessed. Coated and naked wires were analysed by scanning electron microscopy (SEM) and fluorescent staining. RESULT: Significant reduction in bacterial adhesion was achieved on phage/linezolid wires in comparison to naked as well as HPMC coated wires. However, maximum reduction in bacterial adherence (∼4 log cycles) was observed on the wires coated with phage-linezolid combination. The frequency of emergence of resistant mutants was also negligible in presence of both the agents. CONCLUSION: This study provides evidence to confirm that local delivery system employing linezolid (a potent protein synthesis inhibitor) along with a broad spectrum lytic bacteriophage (capable of self-multiplication) is able to attack the adhered as well as surrounding bacteria present near the implant site. Unlike other antibiotic based therapies, this combination has the potential to significantly restrict the emergence of resistant mutants, thus paving the way for effective treatment of MRSA associated infection of medical implants.

Remission rate of implant-related infections following revision surgery after fractures.

PURPOSE: In contrast to a large amount of epidemiological data regarding the incidence of implant infections after fracture management, surprisingly few have been published concerning the success of their treatment. METHODS: This was a single-centre cohort study at Geneva University Hospitals from 2000 to 2012 investigating the remission rates of orthopaedic implant infections after fracture repair and associated variables. RESULTS: A total of 139 episodes were included: There were 51 women (37%) and 28 immunosuppressed (20%) patients with a median age and American Society of Anaesthesiologists (ASA) score of 51 years and 2 points, respectively. The infected implants were plates (n = 75, 54 %), nails (24, 17%), wires (20), screws (10), cerclage cables or wires (3), hip screws (4) or material for spondylodesis (3). A pathogen was identified in 135 (97%) cases, including Staphylococcus aureus (73, 52%), coagulase-negative staphylococci (20), streptococci (7) and 19 Gram-negative rods. All patients underwent antibiotic treatment, and 128 (92%) remained in remission at a median follow-up time of 2.6 years (range one to 13 years). In multivariate logistic regression analysis, the plate infections were significantly associated with lower remission rates [65/75, 87%, odds ratio (OR) 0.1, 95% confidence interval (CI) 0.01-0.90]. No associations were found for gender, age, immune status, ASA score, additional surgical interventions (OR 0.4, 95% CI 0.1-4.1) or duration of antibiotic treatment (OR 1.0, 95% CI 0.98-1.01). CONCLUSIONS: Among all infected and removed orthopaedic implants, plates were associated with slightly lower remission rates, while the overall treatment success exceeded 90%. The duration of antibiotic therapy did not alter the outcome.

Material and biofilm load of K wires in toe surgery: titanium versus stainless steel.

BACKGROUND: Recurrence rates for toe deformity correction are high and primarily are attributable to scar contractures. These contractures may result from subclinical infection. QUESTIONS/PURPOSES: We hypothesized that (1) recurrence of toe deformities and residual pain are related to low-grade infections from biofilm formation on percutaneous K wires, (2) biofilm formation is lower on titanium (Ti) K wires compared with stainless steel (SS) K wires, and (3) clinical outcome is superior with the use of Ti K wires compared with SS K wires. METHODS: In this prospective nonrandomized, comparative study, we investigated 135 lesser toe deformities (61 patients; 49 women; mean ± SD age, 60 ± 15 years) temporarily fixed with K wires between August 2010 and March 2011 (81 SS, 54 Ti). K wires were removed after 6 weeks. The presence of biofilm-related infections was analyzed by sonication. RESULTS: High bacterial loads (> 500 colony-forming units [CFU]/mL) were detected on all six toes requiring revision before 6 months. Increased bacterial load was associated with pain and swelling but not recurrence of the deformity. More SS K wires had greater than 100 CFU/mL bacteria than Ti K wires. For K wires with a bacterial count greater than 100 CFU/mL, toes with Ti K wires had a lower recurrence rate, less pain, and less swelling than toes with SS K wires. CONCLUSIONS: Ti K wires showed superior clinical outcomes to SS K wires. This appears to be attributable to reduced infection rates. Although additional study is needed, we currently recommend the use of Ti K wires for the transfixation of toe deformities. LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Sequential release kinetics of two (gentamicin and BMP-2) or three (gentamicin, IGF-I and BMP-2) substances from a one-component polymeric coating on implants.

The local application of antibiotics in combination with timely controlled growth factor delivery might be beneficial for the prevention of infections and to stimulate bone healing. Therefore, in this study a variable sequential drug delivery system with three distinctly different release profiles was developed: i) a burst release of gentamicin, ii) a burst release of IGF-I followed by a sustained release, and iii) a slow sustained release of BMP-2 out of an implant coating. Only one polymer [poly(D,L-lactide)], incorporating gentamicin, IGF-I or BMP-2, was used for two- or three-layer coatings of K-wires. To control the release kinetics, the polymer concentrations in the solvent were varied. The activity of early released gentamicin from a two-layer coating was confirmed microbiologically and BMP-2 stimulated the metabolic activity and alkaline phosphatase activity of C2C12 cells after 2 weeks. From the three-layer coated wires, IGF-I continuously stimulated the cell proliferation, whereas BMP-2 enhanced ALP between 1 and 3 weeks. The sequential release of growth factors revealed an additive effect on the metabolic activity and ALP of primary osteoblast-like cells compared to the single coated controls. The controlled delivery of different factors from one implant might prevent infections and subsequently stimulate the different phases of bone healing.

Protective role of IL-1ß against post-arthroplasty Staphylococcus aureus infection.

MyD88 is an adapter molecule that is used by both IL-1R and TLR family members to initiate downstream signaling and promote immune responses. Given that IL-1ß is induced after Staphylococcus aureus infections and TLR2 is activated by S. aureus lipopeptides, we hypothesized that IL-1ß and TLR2 contribute to MyD88-dependent protective immune responses against post-arthroplasty S. aureus infections. To test this hypothesis, we used a mouse model of a post-arthroplasty S. aureus infection to compare the bacterial burden, biofilm formation and neutrophil recruitment in IL-1ß-deficient, TLR2-deficient and wild-type (wt) mice. By using in vivo bioluminescence imaging, we found that the bacterial burden in IL-1ß-deficient mice was 26-fold higher at 1 day after infection and remained 3- to 10-fold greater than wt mice through day 42. In contrast, the bacterial burden in TLR2-deficient mice did not differ from wt mice. In addition, implants harvested from IL-1ß-deficient mice had more biofilm formation and 14-fold higher adherent bacteria compared with those from wt mice. Finally, IL-1ß-deficient mice had ∼50% decreased neutrophil recruitment to the infected postoperative joints than wt mice. Taken together, these findings suggest a mechanism by which IL-1ß induces neutrophil recruitment to help control the bacterial burden and the ensuing biofilm formation in a post-surgical joint.

[Prophylactics of pyo-inflammatory complications in the wire area during treatment by the method of transosseous compressive-distractive osteosynthesis with probiotic "Sporobacterin liquid"].

Prophylactics of surgical infections is one of the principal problems in using any surgical method, the method of transosseous osteosynthesis included. Preventive treatment is considered to be one of possible ways to decrease the number of pyo-inflammatory complications. However, unjustified antibiotic therapy gives a negative effect and is often followed by side reactions and complications. This experimental investigation presents grounds for using the method of prophylactics of pyo-inflammatory complications in the area of wires in treatment by the method of extrafocal compressive-distractive osteosynthesis with a new generation probiotic "Sporobacterin liquid".

Study of the efficacy of coated Vicryl plus antibacterial suture in an animal model of orthopedic surgery.

PURPOSE: To evaluate the efficacy in vitro and in vivo of a new antibacterial suture, polyglactin 910 suture with triclosan, compared with a traditional braided suture, polyglactin (Vicryl), in a validated animal model of orthopedic infection. Our primary goal was to compare the microbiologic effectiveness of the two sutures. The secondary goal was to evaluate histopathologic signs of an inflammatory response. METHODS: We used 20 Sprague-Dawley rats. Samples of Staphylococcus epidermidis were diluted to a 0.5 McFarland concentration (100,000 colony-forming units/mL). A surgical steel suture was placed in the spinous process of the rats, and the deep zone of the incision was contaminated bilaterally. Wounds were closed with one of the sutures. After 16 days, the animals were sacrificed, and the surgical wounds were reopened, with cultures being performed of both the zone adjacent to the implant and the deep region of the wound. We also studied the histopathologic features of the tissue adjacent to the implant. RESULTS: No clinical signs of infection were observed. The culture of the zone adjacent to the implant was positive in nine animals in the polyglactin group vs. three in the polyglactin 910 with triclosan group (p = 0.005). Culture of the deep zone of the wound was positive in ten animals in the polyglactin group vs. six in the polyglactin 910 with triclosan group (p = 0.03). We found predominant polymorphonuclear neutrophil populations in four samples in the polyglactin group vs. two in the polyglactin 910 with triclosan group. CONCLUSIONS: Under simulated conditions of severe intraoperative contamination, the antibacterial suture reduced the number of positive cultures after surgery by 66.6%. Judging from the available clinical information, its use might contribute to reducing the number of infected implants by 25.8%. Human studies are needed to determine the clinical implications of these results.

A simple practical protocol for care of metal-skin interface of external fixation.

Patients treated with external fixation for limb reconsturciton or fracture stabilization equire regular and prolongedperiod of pin-tract care involving frequent visits to clinic and dressing traditionally carried out by trained nurses or medical assistants. A simple method of do-it-yourself dressing was introduced in our institution and this study was undertaken to evaluate the effectiveness of the protocol. Sixty patients (40 trauma-related problems and 20 congenital or developmental disorders) were enrolled into the study. Following application of external fixation, the patients and/or their caretakers were taught on how to do pin-site dressing using normal saline or drinking water as cleansing solution on daily basis. Patients were discharged on the second or third post-operative day and were followed-up every two weeks for an average 182 days (range 66 to 379 days) with special attention on identifying pin-tract infection. A simple grading system for pin-tract infections was proposed. Of 40 patients with trauma-related problems. 65% were post-traumatic infections. There were 788 metal-skin interfaces (239 half-pin fixations and 549 tensioned wire fixations. A total 143 metal-skin interface infections (18.1%) involving half-pin sites (41.3%) and tensioned wire sites (58.7%) was noted. Majority were grade I infections (79.7%), 18.8% grade II and only 1.4% grade III. Most infections (81%)were caused by Staphylococcus aureus. Grade I infections were successfully treated with frequent dressing, grade II by adjunctive oral antibiotic but grade III infections required removal of fixator. All eventually healed. Do yourself non-sterile dressing of metal-skin interfaces is a cost-effective method of pin-site care with a low infection rate. The infections were sucessfully treated using guidelines according to the proposed classification of pin-tract infections.

The effects of combined gentamicin-hydroxyapatite coating for cementless joint prostheses on the reduction of infection rates in a rabbit infection prophylaxis model.

Infections remain a critical issue in total joint arthroplasty. Addition of antibiotics to bone cement was shown to significantly improve antimicrobial prophylaxis in cemented joint arthroplasty. In cementless joint arthroplasty a comparable prophylaxis by local antibiotics has not been possible yet. The aim of the current study was to investigate the antimicrobial effect of two different gentamicin-hydroxyapatite (HA) coatings for cementless prostheses in a rabbit infection model. Staphylococcus aureus with a dose of 10(7) CFUs was inoculated into the intramedullary canal of the tibia of 30 rabbits followed by the implantation of standard steel HA K-wires (n=10), steel K-wires coated with a gentamicin-HA combination (n=10), and steel K-wires coated with a gentamicin-RGD-HA combination (n=10), respectively. The animals were sacrificed after 28 days and clinical, histological and microbiological assessment on the bone and on the removed K-wire itself by agar plating and DNA-pulsed field gel electrophoresis were carried out to detect infection. There was a statistically significant reduction of infection rates by both gentamicin-coating types (0 infections in both groups) compared to standard HA coating (7 infections in 8 animals; 2 animals were lost due to acute diarrhea) (p<0.001). An excellent correlation between agar plating testing results of the K-wires and of the bone samples was found. Detailed histology showed cortical lysis, abscess and sequester formation in the infected animals. Both gentamicin-coating types showed significant improvement of infection prophylaxis compared to standard HA coating and, therefore, this coating technology could help to improve infection prophylaxis in cementless total joint arthroplasty. In further studies biocompatibility of the coatings has to be assessed.

Evaluation of effectiveness of 10% polyvinylpyrrolidone-iodine solution against infections in wire and pin holes for Ilizarov external fixators.

CONTEXT AND OBJECTIVE: Superficial infection at wire and pin insertions in the skin is a frequent disorder among patients utilizing the Ilizarov method. The objective of this study was to evaluate the effectiveness of daily topical application of 10% polyvinylpyrrolidone-iodine solution against infections of the holes for Kirschner wires and Schanz pins among patients using Ilizarov external fixators, in comparison with cleaning these holes only with 0.9% sterile physiological saline solution. DESIGN AND SETTING: Controlled randomized clinical trial, in the Orthopedics and Traumatology Outpatient Clinic, Hospital São Paulo, and Orthopedics and Traumatology Center of Jundiaí. METHODS: 30 patients were treated using the Ilizarov technique: 15 were instructed to apply 0.9% physiological saline dressing on the wire and pin insertions and 15 to apply 0.9% physiological saline plus 10% polyvinylpyrrolidone-iodine. Patients were evaluated at outpatient return visits for identification of signs and symptoms of superficial infection at wire and pin insertion sites. Samples were collected from cases of purulent exudate secretion, for culturing and clinical tests. RESULTS: The chi-squared and Fischer exact tests were applied, but no statistically significant association between the intervention of topical polyvinylpyrrolidone-iodine solution and the prevention of infections at wire and pin insertions could be found. CONCLUSIONS: Topical 10% polyvinylpyrrolidone-iodine solution applied daily to Kirschner wire and Schanz pin insertions did not reduce the incidence of superficial infection at these holes, in comparison with mechanical removal of dirt using 0.9% physiological saline solution.

Evaluation of effectiveness of 10 percent polyvinylpyrrolidone-iodine solution against infections in wire and pin holes for Ilizarov external fixators

CONTEXTO E OBJETIVO: A incidência de infecção superficial no trajeto dos fios e pinos junto à pele é uma complicação freqüente em pacientes em tratamento pelo método de Ilizarov. Este estudo objetivou avaliar a eficácia da aplicação diária da solução tópica de polivinilpirrolidona-iodo a 10% na interferência de infecção nos orifícios dos fios de Kirschner e pinos de Schanz de pacientes em uso de fixador externo de Ilizarov comparada à limpeza desses orifícios somente com soro fisiológico a 0,9%. TIPO DE ESTUDO E LOCAL: Ensaio clínico randomizado controlado, no Ambulatório de Ortopedia e Traumatologia do Hospital São Paulo e Centro de Ortopedia e Traumatologia de Jundiaí. MÉTODOS: 30 pacientes foram tratados pelo método de Ilizarov: 15 orientados a realizarem o curativo dos orifícios dos fios e pinos com soro fisiológico a 0,9% e 15 com soro fisiológico a 0,9% mais polivinilpirrolidona-iodo tópico a 10%. Os pacientes foram avaliados nos retornos ambulatoriais, para identificação dos sinais e sintomas de infecção superficial nos orifícios dos fios e pinos. Amostras foram obtidas para cultura e antibiograma na presença de exsudato com pus à expressão. RESULTADOS: Aplicado os testes exato de Fisher e qui-quadrado não foi possível encontrar associação estatisticamente significante da intervenção da solução tópica de polivinilpirrolidona-iodo na prevenção de infecções nos trajetos dos fios e pinos.CONCLUSÕES: A solução de polivinilpirrolidona-iodo tópica a 10% quando aplicada diariamente no orifício dos fios de Kirschner e pinos de Schanz à pele não reduz a incidência de infecção superficial nesses trajetos quando comparada com pacientes que realizam a remoção mecânica de sujidades com soro fisiológico a 0,9%.

The role of biofilm formation in percutaneous Kirschner-wire fixation of radial fractures.

This study examines the formation of bacterial biofilms on percutaneous wires used for fracture fixation. Twelve control (clinically uninfected) wires and ten infected wires were collected and examined using broth culture and scanning electron microscopy. Three of the 12 control wires grew Staphylococcus spp. with very low bacterial counts in their percutaneous portions. In the clinically infected wires, six wires in four subjects had positive cultures in their percutaneous portions and four of these also had positive cultures in their deep portions with much higher bacterial counts than the controls. In two patients (four wires) treated with antibiotics, cultures were negative except for the percutaneous portion of one wire. Scanning electron microscopy did not reveal bacterial biofilm formation, but biological deposit without bacteria was noted on most wires. During the 6 weeks of fracture fixation, some bacterial colonization of wires occurred, but bacteria did not form biofilms which may increase bacterial resistance to systemic antibiotics, cause implant loosening and act as a source of late infection.

Collagen and fibronectin binding in experimental staphylococcal osteomyelitis.

A new mouse model of locally induced osteomyelitis was used to study the importance for pathogenicity of the specific binding ability of Staphylococcus aureus to collagen and fibronectin. This method appears to be convenient, reproducible, and suitable for large-scale experiments. In contrast to previous studies in experimental arthritis and endocarditis models, no difference in infection rates was found between the strains deficient in binding to collagen compared with the corresponding adherence-proficient strains. However, fibronectin binding ability in this model, in contrast to the endocarditis model, is thought to enhance the microorganisms' capacity to establish an infection. Infections caused by the fibronectin-binding strain also are thought to be clinically more aggressive than those caused by the nonbinding strain. Specific adherence mechanisms are thought to be operative in the pathogenesis of biomaterial associated osteomyelitis, and an improved understanding of such mechanisms may have an important prophylactic and therapeutic impact.