Article

Regional Antibiotic Delivery for the Treatment of Experimental Prosthetic Graft Infections

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Abstract

To evaluate the efficacy of antibiotic-impregnated polymethylmethacrylate (PMMA) beads in eradication of an arterial prosthetic graft methicillin-resistant Staphylococcus aureus (MRSA) biofilm in an experimental animal model. Forty rats underwent subcutaneous implantation of a MRSA-colonized arterial polytetrafluoroethylene (PTFE) 1 x 1 cm wafer on the back. The effect of regional antibiosis produced by antibiotic PMMA bead placement adjacent to the infected PTFE wafer was determined using four 10-animal study groups: control (no antibiotic), PMMA bead with no antibiotic, PMMA bead with 10% vancomycin, and PMMA bead with 10% daptomycin. After 3 d, the PTFE wafers were explanted and quantitative biofilm cultures, expressed as colony-forming units (CFU) per graft wafer, performed using real-time polymerase chain reaction to assess MRSA eradication. No systemic antibiotic was administered. Bioassays of antibiotic bead bacteriocidal were performed by measuring zone of inhibition diameters on MRSA colonized agar culture plates prior to and following graft explantation. All animal tolerated implantation of the MRSA-infected PTFE wafer and survived the 3 d until graft explantation. Quantitative biofilm cultures demonstrated a significant decrease (P < 0.01) in MRSA CFUs present on the PTFE wafer surfaces in the presence of both the vancomycin- and daptomycin-impregnated beads compared to controls and plain PMMA beads. Both vancomycin and daptomycin PMMA beads retained antibacterial activity after 3 d of implantation with decrease in zones of inhibition of 15% and 45%, respectively. Regional antibiotic delivery using an antibiotic-impregnated PMMA bead reduced the bacterial biofilm concentration in experimental subcutaneous pocket model of vascular surgical site infection. The delivery of antibiotics via a PMMA bead may be a useful adjunct in the treatment of vascular surgical site infection.

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... In addition, numerous antibiotics have been investigated, such as rifampicin, cefazolin, tobramycin, or gentamycin, sometimes with different carriers to encourage a prolonged antimicrobial effect. Silver-coated prostheses and antibiotic-impregnated polymethylmethacrylate beads have also been investigated [25]. ...
... If bacteria attach to the surface of medical implants such as vascular prostheses and begin to produce an extracellular, slime-like matrix, the embedded biofilm organisms will be protected against the host defense mechanisms and antimicrobial agents. Due to the strong bactericidal effect of daptomycin and the realization that this antibiotic also works particularly well against gram-positive biofilm organisms [25], we evaluated the effects of local daptomycin application. We took note of previous findings that suggested a prolongation of the effect of various antibiotics by using a fibrin sealant [11]. ...
... We feel that it should be normal in clinical practice to soak vascular prostheses in antibiotic solutions prior to implantation, and given the proliferation of wellknown problem pathogens, the antibiotic used should be daptomycin. Similar results have been found with the use of beads impregnated with daptomycin [25]. Moreover, the protective effect could be more than doubled with the use of fibrin sealant as a carrier substance. ...
Article
Infections after prosthetic replacement of the aorta remain a serious and life-threatening complication. The only appropriate treatment is the surgical removal of the infected prosthesis. Accordingly, there is a need for new procedures to prevent the infection of vascular prostheses. This in vitro experiment investigated the effect of the pretreatment of vascular prostheses with antibiotics (daptomycin or baneocin) and the effect of antibiotics combined with fibrin sealant as possible prophylaxis of perioperative graft infection. Untreated prostheses served as controls. Pretreated prostheses of double woven velour vascular grafts were contaminated with Staphylococcus epidermidis, and colony-forming units were counted each day (CFU/mL). The period of sterility differed significantly as a function of the pretreatment. Uncoated prostheses were immediately non-sterile and exhibited 2.63 ± 0.61 × 10(5) CFU/mL. Baneocin pretreatment resulted in sterility for 1.7 ± 0.6 (95% confidence interval (CI) 1.0-2.4) d before we detected 2.14 ± 0.57 × 10(5) CFU/mL on the prostheses. Pretreatment with daptomycin yielded 2.9 ± 0.4 (CI 2.6-3.2) and fibrin sealant/baneocin compound yielded 3.1 ± 0.3 (CI 2.9-3.3) d of sterility, after which 1.81 ± 0.86 × 10(5) CFU/mL and 1.04 ± 0.77 × 10(5) CFU/mL were recorded. Finally, pretreatment with fibrin sealant/daptomycin led to sterility for 7.1 ± 0.3 (CI 6.9-7.3) d, after which 0.77 ± 0.60 × 10(5) CFU/mL were observed on the prostheses. The risk of vascular graft infection is reduced by pretreating the prostheses with antibiotics. The antibiotic/fibrin compound exhibited an effect of delayed antibiotic release. Vascular prostheses should therefore be pretreated with antibiotic solution to reduce bacterial adhesion. This procedure might be an effective prophylaxis for perioperative vascular graft infection and provides suitable protection for the prosthetic material.
... PMMA containing antibiotics has been presented as an alternative treatment modality; successful results have been reported with aggressive debridement, repeated irrigations, and PMMA soaked with 500 mg gentamicin and 2.4 g tobramycin (25). Keeling et al. showed that PMMA soaked with vancomycin and daptomycin decreased biofilm formation (26). ...
Article
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Purpose: Bone and soft tissue infections are among the least desired complications after orthopaedic surgery. This study analysed the in vivo effects of the local application of nano-silver particles (AgNPs) [1nm = 1 billionth of a meter] in soft tissue infections. Materials-Method: An experimental osteomyelitis model was formed by inoculating both tibias of 24 rats with methicillin-resistant Staphylococcus aureus. The rats were followed without treatment for 21 days. Blood samples and tibial x-rays at day 21 confirmed the development of infection. Then, the rats were divided randomly into two groups. One group (12 rats) underwent surgical debridement and received 21 days of teicoplanin therapy. The second group had the same treatment, with the addition of local nano-silver. All of the rats were sacrificed at day 42. Blood and wound swab samples were taken and the culture results were analysed. Results: No differences were observed between the groups in healing values at pathological examination, or in changes in the number of colonies at days 21 and 42. No differences in white blood cell count (WBC) were observed between the groups before and after the treatment. Conclusion: Although in vitro studies suggest the effectiveness of AgNPs on pathogens, we found that the application of nano-silver did not make any difference when used in addition to the classical osteomyelitis treatment with antibiotics and local surgical debridement. We believe that additional in vivo studies using repeated nano-silver application could be beneficial.
... Next to standardized pre-and peri-surgical prevention measures against VGIs (pre-screening for multidrug resistant organisms, control of infection parameters, antimicrobial prophylaxis), also regional antibiotic release from vascular grafts (pre-soaking of the graft with antibiotics) could play an effective role (Keeling et al., 2009;Kuehn et al., 2010;Bisdas et al., 2012). ...
Article
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Objectives: Increasing resistance of microorganisms and particularly tolerance of bacterial biofilms against antibiotics require the need for alternative antimicrobial substances. S. aureus is the most frequent pathogen causing vascular graft infections. In order to evaluate the antimicrobial efficacy, quantification of the bacterial biofilms is necessary. Aim of the present study was the validation of an in vitro model for quantification of bacterial biofilm on vascular graft surfaces using three different assays. Methods: Standardized discs of vascular graft material (Dacron or PTFE) or polystyrene (PS) as control surface with 0.25 cm² surface area were inoculated with 10⁻³ diluted overnight culture of three biofilm-producing S. aureus isolates (BEB-029, BEB-295, SH1000) in 96-well PS culture plates. After incubation for 4 and 18 h, the biofilm was determined by three different methods: (a) mitochondrial ATP concentration as measure of bacterial viability (ATP), (b) crystal violet staining (Cry), and (c) vital cell count by calculation of colony-forming units (CFU). The experiments were performed three times. Quadruplicates were used for each isolate, time point, and method. In parallel, bacterial biofilms were documented via scanning electron microscopy. Results: All three methods could quantify biofilms on the PS control. Time needed was 0:40, 13:10, and 14:30 h for ATP, Cry, and CFU, respectively. The Cry assay could not be used for vascular graft surfaces due to high unspecific background staining. However, ATP assay and CFU count showed comparable results on vascular graft material and control. The correlations between ATP and CFU assay differed according to the surface and incubation time and were significant only after 4 h on Dacron (BEB-029, p = 0.013) and on PS (BEB-029, p < 0.001). Between ATP and Cry assay on PS, a significant correlation could be detected after 4 h (BEB-295, p = 0.027) and after 18 h (all three strains, p < 0.026). The reproducibility of the ATP-assay presented as inter-assay-variance of 2.1 and as intra-assay variance of 8.1 on polystyrene. Conclusion: The in-vitro model reproducibly quantifies biofilm on standardized vascular graft surfaces with ATP assay as detection system. The ATP assay allows accelerated microbial quantification, however the correlation with the CFU assay may be strain- and surface-dependent.
... The position inside the magnet bore was checked by using a self-gated cine FLASH sequence (repetition time/ echo time, 85.0/1.7 milliseconds; flip angle, 15 ; field of view, 35 Â 35 mm 2 ; section thickness, 0.5 mm; acquisition matrix, 296 Â 296). Subsequently, blood flow measurements were performed using a section-selective, balanced two-point velocityeencoded phase-contrast MRI sequence, which is based on a respiration and ECG-triggered FLASH gradient echo (Flowmap, Bruker BioSpin) (repetition time/echo time, 15.0 /2.6 milliseconds; flip angle, 30 ; field of vision, 35 Â 35 mm 2 ; section thickness, 0.8 mm; acquisition matrix, 296 Â 296; number of averages: 6) with three parallel sections (placed above and below the catheter as well as on site). After MRI measurements, the MR-PET mouse bed was transferred from the MRI scanner to the PET without changing the position of the mouse. ...
Article
Staphylococcus aureus causes very serious infections of vascular grafts. Knowledge of the molecular mechanisms of this disease is largely lacking because of the absence of representable models. Therefore, the aim of this study was to set up a mouse model of vascular graft infections that closely mimics the human situation. A catheter was inserted into the right carotid artery of mice, which acted as a vascular graft. Mice were infected i.v. using 8 different S. aureus strains, and development of the infection was followed up. Although all strains had varying abilities to form biofilm in vitro and different levels of virulence in mice, they all caused biofilm formation on the grafts. This graft infection was monitored using magnetic resonance imaging (MRI) and (18)F-fluordeoxyglucose positron emission tomography (FDG-PET). MRI allowed the quantification of blood flow through the arteries, which was decreased in the catheter after infection. FDG-PET revealed high inflammation levels at the site of the catheter after infection. This model closely resembles the situation in patients, which is characterized by a tight interplay between pathogen and host, and can therefore be used for the testing of novel treatment, diagnosis, and prevention strategies. In addition, combining MRI and PET with microscopic techniques provides an appropriate way to characterize the course of these infections and to precisely analyze biofilm development.
... Other experimental techniques yet to be verified in clinical settings have been attempted in animal models, such as the peri-graft implantation of antibiotic-impregnated beads PTFE graft infection (47). Regional administration of antibiotics appeared to decrease biofilm concentration, without major harm to the animal. ...
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Vascular graft infections are a particularly troublesome complication for dialysis patients, many of whom are in an already immunocompromised state. The objective of this review is to detail the risk factors, etiology, diagnosis, perioperative and operative management of vascular graft infections.
... An active approach is based on drug/medical device combination products providing a localized bacterial inhibition effect by functionalizing the device biomaterial and/or coating with antibiotics, antiseptics, and metals (12). Localized delivery of high doses of antibiotics enhances efficacy, prevents systemic toxicity, and reduces bacterial resistance (3,13). ...
Article
A new vancomycin (VCM)-eluting mixed bilayer niosome formulation was evaluated for the control of staphylococcal colonization and biofilm formation on abiotic surfaces, a niosome application not explored to date. Cosurfactant niosomes were prepared using a Span 60/Tween 40/cholesterol blend (1: 1: 2). Tween 40, a polyethoxylated amphiphile, was included to enhance VCM entrapment and confer niosomal surface properties precluding bacterial adhesion. VCM-eluting niosomes showed good quality attributes including relatively high entrapment efficiency (∼50%), association of Tween 40 with vesicles in a constant proportion (∼87%), biphasic release profile suitable for inhibiting early bacterial colonization, and long-term stability at 4°C for a 12-month study period. Niosomes significantly enhanced VCM activity against planktonic bacteria of nine staphylococcal strains. Using microtiter plates as abiotic surface, VCM-eluting niosomes proved superior to VCM in inhibiting biofilm formation, eradicating surface-borne biofilms, inhibiting biofilm growth, and interfering with biofilm induction by VCM subminimal inhibitory concentrations. Data suggest dual functionality of cosurfactant VCM-eluting niosomes as passive colonization inhibiting barrier and active antimicrobial-controlled delivery system, two functions recognized in infection control of abiotic surfaces and medical devices.
... 23 In this context, encouraging results after the use of antibioticimpregnated polymethylmethacrylate beads for the treatment of experimental prosthetic graft infections support this concept. 24 However, considerations for rapid development of antibiotic resistance have been uttered. 25 To field this issue, Friberg et al. demonstrated in 1359 patients, undergoing local implantation of collagen-gentamycin for the prevention of sternal wound infections, no long-term increase in the absolute incidence of aminoglycoside resistance agents. ...
Article
To compare the in vitro efficacy of graft impregnation with nebacetin versus rifampin versus daptomycin against vascular graft infections caused by Staphylococcus epidermidis and Staphylococcus aureus and nebacetin versus rifampin against Pseudomonas aeruginosa and Escherichia coli. Twenty-three Dacron-grafts (1 cm2) for each micro-organism were microbiologically tested and eight grafts per antibiotic underwent viability tests against human umbilical vein endothelial cells (ECs). Fifteen grafts (5/antibiotic agent) underwent 15 min impregnation and contamination with 4 ml bacterial solution (optical density (OD (600 nm)): 0.20 ± 0.02). After 24-h-incubation, all grafts were washed with phosphate-buffered saline and underwent sonification to release viable adherent bacteria. OD (600 nm) of the solution was measured. Afterwards, six 1:10 dilution steps took place and colony-forming units (CFUs) were counted. Nebacetin showed comparable efficacy to daptomycin against Gram-positive bacteria. Both eradicated more efficiently S. epidermidis than rifampin (daptomycin:0, rifampin:5 ± 7.3, nebacetin:0 CFU ml(-1), P = 0.0003). All antibiotics showed comparable antibacterial activity against S. aureus. Nebacetin was more efficient than rifampin to eradicate Gram-negative organisms (P. aeruginosa: rifampin:1308 ± 252, nebacetin:8 ± 8 CFU ml(-1), P = 0.01, E. coli: rifampin:294 ± 159, nebacetin:0.2 ± 0.5 CFU ml(-1), P = 0.001), while only rifampin was toxic against ECs (daptomycin:30.88 ± 5.44, rifampin:5.13 ± 5.08, nebacetin:28.50 ± 3.82 ECs/field, P = 0.0003). Nebacetin showed excellent in vitro antibacterial activity against both Gram-positive and -negative pathogens representing an effective candidate for vascular graft impregnation.
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Currently, the majority of animal models that are used to study biofilm-related infections use planktonic bacterial cells as initial inocula to produce positive signals of infection in biomaterials studies. However, the use of planktonic cells has potentially led to inconsistent results in infection outcomes. In this study, well-established biofilms of methicillin-resistant Staphylococcus aureus were grown and used as initial inocula in an animal model of a Type IIIB open fracture. The goal of the work was to establish, for the first time, a repeatable model of biofilm implant-related osteomyelitis, wherein biofilms were used as initial inocula to test combination biomaterials. Results showed that 100% of animals that were treated with biofilms developed osteomyelitis, whereas 0% of animals not treated with biofilm developed infection. The development of this experimental model may lead to an important shift in biofilm and biomaterials research by showing that when biofilms are used as initial inocula, they may provide additional insights into how biofilm-related infections in the clinic develop and how they can be treated with combination biomaterials to eradicate and/or prevent biofilm formation.
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Prosthetic valve endocarditis (PVE), a rare but major complication after heart valve replacement surgery, has potentially catastrophic consequences despite maximal treatment. Thus, preventive measures are essential. The study aim was to investigate the effect of pretreating heart valve prostheses with the antibiotics baneomycin and daptomycin, with and without surgical sealant fibrin glue as a drug-releasing substance. The biocompatibility of baneocin and daptomycin was also investigated. Samples of polyethylene terephthalate (PTE), as used for the sewing cuffs of prosthetic heart valves, were tested; untreated samples served as controls. All samples were contaminated with Staphylococcus epidermidis, and colony-forming units (CFUs) then counted. Cytotoxicity tests were performed using the MTT-assay to evaluate the effects of baneomycin and daptomycin on cell proliferation and wound healing. Untreated and fibrin glue-coated samples were directly infected with a bacterial count of 2.82 +/- 0.63 x 10(5) CFU/ml and 2.80 +/- 1.07 x 10(5) CFU/ml, on average. Baneocin-impregnated samples were sterile for 1.9 +/- 0.38 days, with a subsequent bacterial count of 2.26 +/- 0.6 x 10(5) CFU/ml, while daptomycin-impregnated samples were sterile for 2.9 +/- 0.38 days, with a subsequent bacterial count of 1.81 +/- 0.53 x 10(5) CFU/ml. Samples coated with a fibrin glue-baneocin mixture were sterile for 3.14 +/- 0.38 days, after which the bacterial count was 0.74 +/- 0.47 x 10(5) CFU/ml. After coating with a fibrin glue-daptomycin mixture, samples were sterile for 7.0 +/- 0.58 days, and the bacterial count was 0.70 +/- 0.56 x 10(5) CFU/ml. In this in-vitro study, the pretreatment of prosthetic heart valves with antibiotics reduced the risk of bacterial adhesion and consequent infection. The combination of antibiotics with fibrin glue prolonged this preventive effect, with baneocin demonstrating a better biocompatibility than daptomycin. On the basis of its antibacterial efficacy, daptomycin appears to be a more suitable antibiotic to prevent early PVE with Gram-positive bacteria. The soaking of prosthetic heart valves in antibiotic solutions prior to implantation, in combination with fibrin glue in cases of suspected endocarditis, can prevent the development of early PVE. This preventive strategy should be investigated for use as a standard procedure in clinical practice.
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One of the most practical strategies that has been undertaken to fight biofilm implant-related infections has been the development of coatings on biomaterial devices that can elute antimicrobials into regions of patients' tissues. To date, the majority of animal studies that have been developed to model infections that accompany the use of these materials have primarily involved an initial inoculum of planktonic bacterial cells from batch cultures. Although valuable, data that have been derived from these experiments may not provide important clinical insight into how bacteria in well-established, mature biofilms impact device-related and other clinical infections when they contaminate a patient site or implanted device. In this review, a discussion is presented on the impact that a shift in biofilm research may have if initial inocula of well-established, mature biofilms are used to model biomaterial device-related infections in animal models.
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Prosthetic vascular grafting is a commonly performed procedure that is central to the management of arterial disease and renal failure. Though rare, vascular graft infections (VGI) are potentially devastating, and carry a high rate of mortality and amputation. Despite extensive research and clinical experience, VGI remain a daunting therapeutic challenge for surgeons and infectious disease specialists. This article reviews the pathogenesis of VGI, in particular the role of biofilms, as well as the current state of clinical management including diagnostic modalities, surgical options for treatment, antimicrobial therapy, and preventive measures.
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Background The in vitro antibacterial effect of bacteriophages (BPH) as impregnation agents was tested for prevention of vascular graft infections. Methods Pathogen-specific BPHs for S. epidermidis, S. aureus, P. aeruginosa and E. coli were tested. In each case 7 segments of prosthesis tissue sized 1 cm2 were impregnated for each group (15 min), a further 7 segments were used as a positive control and 4 as a negative control and 5 segments were observed under scanning electron microscopy (SEM). After 24 h incubation (37°C) segments were washed 3 times in 20 ml PBS. Viable adherent bacteria were released by sonification and the optical density (OD) of the bacterial solutions was measured. A total of 6 dilution steps of 1:10 of the solution was made and incubated for 24 h (37°C) on agar plates. Colony formed units (CFU) after the 4th and 6th dilution were counted. Results Impregnation with BPHs against S. epidermidis and E. coli showed a statistically significant reduction of OD, CFU-4 and CFU-6. For S. aureus and P. aeruginosa, all parameters were comparable to the positive control group. The microbiological findings were confirmed by SEM bio-films. Conclusions The pathogen-specific BPHs tested were effective in prevention of in vitro graft infections caused by S. epidermidis and E. coli but not by S. aureus and P. aeruginosa.
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The majority of animal studies that have been used to model biofilm-related infections that accompany the use of biomedical devices have primarily involved an initial inoculum of planktonic bacterial cells from batch cultures. Although valuable, data that has been derived from these experiments may not provide important clinical insight into how bacteria in well-established, mature biofilms impact device-related and other clinical infections when they initially contaminate a patient site or implanted device. In this chapter, a discussion is presented on the impact that a shift in biofilm research may have if initial inocula of well-established, mature biofilms are used to model device-related infections in animal models. © 2014 Springer Science+Business Media New York. All rights are reserved.
Chapter
Advancements in peripheral vascular surgical interventions have permitted higher limb salvage rates and better quality of life for many patients. Overall, postoperative complications for peripheral interventions are varied among operative procedures and practice patterns. When complications do occur, detection and definitive treatment is key, as these complications, if left unrecognized, can be devastating and result in significant morbidity and mortality. A clear understanding of the surgical procedures performed and the underlying vascular pathology that had been treated is critical to understanding and identifying vascular surgical complications. Likewise, knowledge of the clinical findings and diagnostic algorithms required to verify presence of a surgical complication is required. With a clear understanding of the surgical complications that can occur, as well as their identification, diagnostic verification, and definitive treatment, a healthcare team can successfully provide the entirety of vascular care to a given patient population. This will allow successful outcomes in even the most challenging cases. In this chapter we will review the major categories of complications that arise in patients undergoing surgical interventions for peripheral arterial disease.
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Advancements in peripheral vascular surgical interventions have permitted higher limb salvage rates and better quality of life for many patients. Overall, postoperative complications for peripheral interventions are varied among operative procedures and practice patterns. When complications do occur, detection and definitive treatment is key, as these complications, if left unrecognized, can be devastating and result in significant morbidity and mortality. A clear understanding of the surgical procedures performed and the underlying vascular pathology that had been treated is critical to understanding and identifying vascular surgical complications. Likewise, knowledge of the clinical findings and diagnostic algorithms required to verify presence of a surgical complication is required. With a clear understanding of the surgical complications that can occur, as well as their identification, diagnostic verification, and definitive treatment, a healthcare team can successfully provide the entirety of vascular care to a given patient population. This will allow successful outcomes in even the most challenging cases. In this chapter we will review the major categories of complications that arise in patients undergoing surgical interventions for peripheral arterial disease.
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The purpose was to determine the early and late mortality and morbidity rates associated with infrainguinal arterial prosthetic graft infection (IAPGI) and to identify optimal methods of management. The study included 53 men and 14 women (mean age, 61 years) in whom a total of 68 IAPGIs developed in the years 1959 to 1993. IAPGI involved 58 femoropopliteal grafts (85%), six femorodistal grafts (9%), and four other grafts or synthetic patches (6%). Graft material was dacron in 36 (53%), polytetrafluoroethylene in 28 (41%), and human umbilical vein in four (6%). Sixteen IAPGIs (24%) involved limbs that had required amputations before IAPGI was diagnosed. Twenty-six (38%) of the 68 grafts were thrombosed, and 14 (88%) of the 16 amputees had occluded grafts. Staphylococcal organisms were isolated from 34 (58%) of the 59 IAPGIs for which culture data were available. The median intervals until IAPGI was diagnosed were 3 months after implantation and 1 month after the last procedure involving the original graft. Initial management consisted of local measures only in 13 (19%), partial removal or in situ graft replacement in 15 (22%), and total graft excision in 40 (59%). Total excision was performed in 15 (94%) of the 16 patients with prior amputations and in only 25 (48%) of the 52 intact limbs. The overall postoperative mortality rate was 18%; seven (58%) of the 12 early deaths were related to sepsis, and all 12 occurred within the group of 51 patients (24%) for whom limb salvage was still being attempted (p = 0.056). IAPGI ultimately led to amputations in 21 (40%) of 52 intact limbs within the first year. Twenty-three (82%) of the 28 IAPGIs managed with incomplete graft removal required subsequent operations for continued sepsis, compared with five (13%) of the 40 treated with complete excision (p < 0.001). The cumulative 5-year survival rate (77%) for 53 patients who survived operation was less than that (89%) for the normal, age-matched U.S. male population. IAPGI is associated with substantial early mortality and amputation rates. Complete excision of infected graft material results in a significant reduction in the incidence of recurrent sepsis.
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To assess the use of antibiotic-loaded polymethyl methacrylate beads in the management of chronic osteomyelitis of different aetiologies: infected osteosynthesis, infected open fractures, and haematogenous osteomyelitis. Records of 49 patients with chronic osteomyelitis who were treated at Department of Orthopaedics, Kasturba Medical College, from 1995 to 1999 were studied retrospectively. The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiographic features. Of the 49 patients, 4 had haematogenous osteomyelitis, which later proved to be tuberculosis, and were thus excluded. Antibiotic-loaded acrylic beads were implanted in the remaining patients after thorough debridement. The implant was removed primarily in 16 patients with infected osteosynthesis, who then underwent decompression and sequestrectomy. All wounds were closed primarily. Peri-operative antibiotics were given for 7 days. Beads were removed at the end of 3 weeks followed by bone grafting in 26 patients. Patients were followed up for an average period of 3.7 years. The infective organisms were sensitive to gentamycin in 26 cases and resistant in 19 cases; 14 cases were sensitive to cefuroxime, 11 to cloxacillin, 8 to ampicillin, and 5 to cotrimoxazole. Seven cases were resistant to all antibiotics tested. Of the 19 patients with gentamycin-resistant infection, only one had a poor result. No adverse systemic side-effects such as ototoxicity or nephrotoxicity were seen. Infection did not recur in 39 patients, but 6 patients had low-grade persistent infection at the last follow-up visit. In chronic infections, especially those following osteosynthesis, antibiotic beads are a valuable adjuvant. The most valuable advantage is that the wound can be closed primarily, thereby reducing the incidence of nosocomial infections and requirement of nursing care.
Article
Background With increasing experience, we have encountered patients with complex aortofemoral prosthetic infections in whom extra-anatomic bypass (EAB) is not an option.Hypothesis Autogenous superficial femoropopliteal vein (SFPV) aortic reconstruction provides a limb-saving and lifesaving alternative with acceptable morbidity and mortality.Design Retrospective review.Setting University-based county, private, and Veterans Affairs hospitals.Patients Seventeen patients with infected aortofemoral bypasses in whom conventional EAB was impossible because of infection of previously placed EAB, massive groin and/or thigh sepsis, or both.Main Outcome Measures Morbidity and mortality.Results Multiple previous operations were common (mean, 4 per patient) and included EAB (n=11), replacement aortofemoral bypass (n=4), prosthetic femoropopliteal bypass (n=7), and thoracobifemoral bypass (n=1); all bypasses became infected. Overall, 11 patients had sepsis at the time of presentation. Of the patients with massive groin infection, 7 had extensive deep infections involving most of the proximal thighs or retroperitoneum, 4 had enterocutaneous fistulae, and 2 had necrotizing fasciitis of the lower abdomen and thigh. Polymicrobial infections were common (n=9). Four patients (24%) died in the perioperative period, 8 (47%) suffered major complications, and 4 (24%) underwent major amputations. Mortality in this group of patients was 3 times that of all other patients undergoing autogenous SFPV aortic reconstruction for prosthetic infection (8%). Amputation rates were also increased (24% vs 6%). The mean ± SD follow-up time is 23 ± 21 months. All patients maintained patent SFPV reconstructions.Conclusions In the setting of complex aortofemoral prosthetic infections, autogenous SFPV aortic reconstruction is a useful option for patients in whom EAB is impossible and limb loss and/or death would be inevitable without revascularization.
Article
A recent experience with infrainguinal graft infections was reviewed in an effort to identify factors related to limb loss and mortality. The records of 32 patients who had operative treatment of 33 episodes of infrainguinal graft infection between 1978 and 1985 were reviewed to evaluate the effects of 20 factors possibly affecting outcome. The amputation rate was 79%. Of the 20 factors studied, only the presence of overt limb sepsis was associated with the need for amputation, with 100% of patients having limb sepsis requiring amputation vs. 72% of patients without limb sepsis (p = 0.03). The in-hospital mortality rate was 22%. Eighty-six percent of the deaths were due to ongoing sepsis. Again, a single factor was associated with death. Five of the 12 patients (42%) in whom preservation of axial flow was attempted died in contrast to only 2 of 20 patients (10%) who did not have attempted arterial reconstruction (p = 0.04). Limb salvage did not occur in any of the patients in whom preservation of axial flow was attempted and nine required above-knee amputation. Thirteen of the remaining 20 patients had occluded femoral vessels either because of operative ligation (nine) or previous thrombosis (four). Above-knee amputations healed in all but one of these 13 patients. Determined attempts at increasing limb preservation were associated with no improvement in amputation rate or level and were accompanied by an unacceptably high mortality rate. Aggressive control of sepsis through the early amputation of septic limbs after graft removal may improve survival without further detriment to limb preservation.
Article
With increasing experience, we have encountered patients with complex aortofemoral prosthetic infections in whom extra-anatomic bypass (EAB) is not an option. Autogenous superficial femoropopliteal vein (SFPV) aortic reconstruction provides a limb-saving and lifesaving alternative with acceptable morbidity and mortality. Retrospective review. University-based county, private, and Veterans Affairs hospitals. Seventeen patients with infected aortofemoral bypasses in whom conventional EAB was impossible because of infection of previously placed EAB, massive groin and/or thigh sepsis, or both. Morbidity and mortality. Multiple previous operations were common (mean, 4 per patient) and included EAB (n = 11), replacement aortofemoral bypass (n = 4), prosthetic femoropopliteal bypass (n = 7), and thoracobifemoral bypass (n = 1); all bypasses became infected. Overall, 11 patients had sepsis at the time of presentation. Of the patients with massive groin infection, 7 had extensive deep infections involving most of the proximal thighs or retroperitoneum, 4 had enterocutaneous fistulae, and 2 had necrotizing fasciitis of the lower abdomen and thigh. Polymicrobial infections were common (n = 9). Four patients (24%) died in the perioperative period, 8 (47%) suffered major complications, and 4 (24%) underwent major amputations. Mortality in this group of patients was 3 times that of all other patients undergoing autogenous SFPV aortic reconstruction for prosthetic infection (8%). Amputation rates were also increased (24% vs 6%). The mean+/-SD follow-up time is 23+/-21 months. All patients maintained patent SFPV reconstructions. In the setting of complex aortofemoral prosthetic infections, autogenous SFPV aortic reconstruction is a useful option for patients in whom EAB is impossible and limb loss and/or death would be inevitable without revascularization.
Article
Background: In situ treatment of artery/graft infection has distinct advantages compared to vessel excision and extra-anatomic bypass procedures. Based on animal studies of a rifampin-soaked, gelatin-impregnated polyester graft that demonstrated prolonged in vivo antibacterial activity, this antibiotic-bonded graft was used selectively in patients for in situ treatment of low-grade Gram-positive prosthetic graft infections or primary aortic infections not amenable to excision and ex situ bypass. Methods: In a 5-year period (1995-1999), 27 patients with prosthetic graft infection (aortofemoral, n = 18, femorofemoral, n = 3; axillofemoral, n = 1) or primary aortic infection (mycotic aneurysm, n = 3; infected AAA, n = 2) underwent excision of the infected vessel and in situ replacement with a rifampin soaked (45-60 mg/ml for 15 min) gelatin-impregnated polyester graft. All prosthetic graft infections were low grade in nature, caused Gram-positive bacteria (Staphylococcus epidermidis, 16; Staphylococcus aureus, 5; Streptococcus, 1), and were treated electively. Patients with mycotic aortic aneurysm presented with sepsis and underwent urgent or emergent surgery. Results: Two (8%) patients died-1 as a result of a ruptured Salmonella mycotic aortic aneurysm and the other from methicillin-resistant S. aureus infection following deep vein replacement of an in situ replaced femorofemoral graft. No amputations or late deaths as the result of vascular infection occurred in the 25 surviving patients. Two patients developed recurrent infection caused by a rifampin-resistant S. epidermidis in a replaced aortofemoral graft limb and were successfully treated with graft excision and in situ autogenous vein replacement. Eighteen patients remain alive and clinically free of infection after a mean follow-up interval of 17 months. Conclusions: In situ replacement treatment using a rifampin-bonded prosthetic graft for low-grade staphylococcal arterial infection was safe, durable, and associated with eradication of clinical signs of infection. Failure of this therapy was the result of virulent and antibiotic-resistant bacterial strains.
Article
In spite of new surgical techniques and recently developed antibiotics, there is no satisfactory solution for the treatment of chronic posttraumatic osteomyelitis. The introduction of local antibiotic treatment with gentamicin-PMMA beads according to Klemm has provided new stimuli for the treatment of chronic osteomyelitis. With the development of collagen as an absorbable carrier substance, the disadvantages of the rigid carrier system became evident. Due to the varying surgical techniques and different forms of adjuvant therapy, it is difficult to assess therapeutic methods and compare different studies. Therefore, it seemed appropriate to study the effect of local treatment with different antibiotic carriers in the setting of an animal study. The proven rat model for Staphylococcus aureus-induced osteomyelitis was used to compare the results of monotherapy with cefazolin, gentamicin-PMMA beads, or gentamicin-containing collagen sponge with the combination of local and systemic antibiotic treatment. Single-agent therapy with parenterally administered cefazolin reduced the CFU from 3.7 x 10(6) to 2.9 x 10(4) g(-1) of tibial bone. The effect on osteomyelitis was more pronounced with the local application of antibiotics. The best results were achieved with the gentamicin-containing collagen sponge which reduced the bacterial colony count to 1.4 x 10(2) CFU/g compared with 9.8 x 10(2) CFU/g achieved with gentamicin-PMMA beads. The effect was most marked using a 4-week combination therapy with local application of the gentamicin-containing collagen sponge and systemic administration of cefazolin. In 9 of 11 animals, no bacteria could be detected in the bone. Each of the treatment modalities resulted in a significant therapeutic effect. Due to its ability to quickly release large amounts of gentamicin, the flexible gentamicin-containing collagen sponge proved to be superior to the rigid PMMA system. Although the gentamicin-containing collagen sponge provided high antibiotic concentration at the site of implantation, an additive effect was attained when combined with systemic antibiotic treatment.
Article
Purpose: This study was conducted to assess the efficacy of antibiotic-loaded polymethylmethacrylate (PMMA) beads in the management of lower extremity extracavitary prosthetic arterial graft infection. Methods: This was a retrospective review of 34 patients treated for vascular surgical site (VSS) infections involving 36 prosthetic lower extremity arterial bypasses using antibiotic-loaded PMMA beads and culture-specific parenteral antibiotics for 4 to 6 weeks. Sites of graft infection were explored, debrided, and cultured. As determined from the results of Gram's stains of VSS purulence, PMMA powder was polymerized with an antibiotic (vancomycin, daptomycin, or tobramycin/gentamicin, or a combination), molded into a chain of beads, and implanted adjacent to the infected graft after debridement and pulsed-spray antibacterial lavage. All wounds were closed primarily with planned exploration to verify sterilization before a graft preservation or in situ replacement procedure. Treatment outcomes, including wound sterilization, were analyzed based on tissue culture isolates, procedures for persistent infection, and freedom from graft infection. Results: Cultures isolated 42 pathogens, (32 gram-positive, 9 gram-negative, 1 Candida albicans) with methicillin-resistant Staphylococcus aureus (MRSA) cultured from 16 (44%) of 36 surgical site infections. As determined from the initial operative Gram's stain or a prior culture result, vancomycin PMMA beads were implanted in 29 of 36 VSS infections at the first procedure; daptomycin (n = 4) or tobramycin (n = 3) beads were implanted in the rest. Repeat VSS exploration and culture results led to an average of 2.5 antibiotic bead replacements before definitive treatment. A sterile (no growth on tissue culture) VSS was achieved in 87% of cases before a graft preservation (n = 16) or in-situ replacement of an infected graft (n = 20) procedure. No patient deaths occurred. Early and late limb salvage was 100%. Infection recurred in 4 (11%) VSSs during a mean 23-month follow-up period, one within 3 months owing to unrecognized bowel injury associated with in situ replacement of an aortofemoral graft limb. Conclusion: Antibiotic-loaded PMMA beads may be a useful adjunct in the contemporary surgical management of VSS infection involving a prosthetic graft. Wound sterilization was achieved in most VSSs before graft preservation or an in-situ replacement procedure, including infections caused by MRSA, a pathogen isolated in half of the extracavitary prosthetic graft infections. This preliminary trial shows the potential benefit of this new technique, but further study is required to prove efficacy.
Article
The complexity of variables associated with vascular surgical site infections (VSSI) often contribute adversely to reinfection, limb salvage, and mortality rates. This report details our experience with the selective use of a sartorius muscle flaps (SMF) as part of an overall treatment strategy focused on staged surgical debridement (SSD) to control prosthetic graft bed infection prior to a graft preservation or revision plan. From our vascular registry, we identified 422 VSSI of which 89 (21%) had SMF for 24 aorto-bifemoral (ABF), 19 extra-anatomic bypasses (EAB), 34 infrainguinal bypasses, and 12 combined inflow/outflow reconstructions. All 86 patients had Szilagyi grade III prosthetic (Dacron-36, polytetrafluoroethylene [PTFE]-50) graft infections. The treatment algorithm included: SSD, culture-directed parenteral antibiotics, graft preservation (n = 3), or reconstruction (graft excision/EAB, n = 4; rifampin-bonded PTFE, n = 22; autologous conduit, n = 57) based on microbiology and consideration for SMF for extensive soft tissue defects (n = 43) or non-sterilized graft beds (n = 40). Analysis of microbiology, recurrent infection, vascular reconstruction, limb salvage, and mortality was completed over a mean follow-up of 52 months (range: 12 to 132 months). Thirty-day mortality was 2% with two aortic graft infections dying from sepsis. Survival by life table analysis at 1, 3, and 5 years was 94%, 92%, and 90%, respectively. Wound isolates were most commonly gram positive organisms (n = 58, 65%), with gram negative isolates and mixed infections accounting for 19% and 10%, respectively. A single recurrent groin infection was documented at 30 days. Freedom from recurrent infection (n = 6) at 1 and 5 years was 98% and 92% by life tables. Methicillin-resistant Staphylococcus aureus (MRSA) was involved for 50% of reinfections. No amputations were attributable to uncontrolled VSSI and graft patency was 100% in surveillance monitored patients. These results suggest that selective utilization of SMF as part of SSD treatment plan in an attempt to achieve graft bed sterilization can effectively control the complex infectious process allowing for potentially improved outcomes for in situ or preservation graft salvage techniques. Lifelong graft surveillance is recommended.
Mortality and limb loss with infected infrainguinal bypass grafts
  • Kikta