Prevention of prosthetic vascular graft infection by rifampicin impregnation of a protein-sealed Dacron graft in combination with parenteral cephalosporin.

Antibiotic-impregnated prosthetic vascular grafts have been shown to be highly resistant to bacterial contamination in animal models. The aim of this study was to assess if graft infection in an animal model challenged with local bacterial contamination could be reduced further by the use of rifampicin soaking of a protein-sealed Dacron graft in addition to the prophylaxis provided by perioperative intravenous cephalosporin. Of 20 Merino sheep given cefoxitin intravenously before the induction of anaesthesia, ten had a rifampicin treated Dacron graft implanted into the common carotid artery (group 1), and ten received an untreated Dacron graft (group 2). Before wound closure the grafts were inoculated with 1 ml of 10(8) colony forming units per ml of Staphylococcus aureus. After three weeks the grafts were removed and cultured. Group 1 sheep had fewer graft infections (two of 10) compared to group 2 (six of eight survivors), this difference being statistically significant (p = 0.03; Fisher exact test). It is concluded that rifampicin treatment of protein-sealed Dacron grafts combined with intravenous cefoxitin provides more protection from contaminating Staphylococcus aureus than intravenous cefoxitin alone in this animal model.     

The prophylactic efficacy of rifampicin-soaked graft in combination with systemic vancomycin in the prevention of prosthetic vascular graft infection: an experimental study

OBJECTIVE: To investigate the prophylactic efficacy of systemic, topical, or combined antibiotic usage in the prevention of late prosthetic vascular graft infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and the differential adherence of S. epidermidis to Dacron and ePTFE grafts in a rat model. MATERIALS AND METHODS: Graft infections were established in the back subcutaneous tissue of 120 adult male Wistar rats by implantation of 1-cm(2) Dacron/ePTFE prosthesis followed by topical inoculation with 2 x 10(7) CFU of clinical isolate of MRSE. Each of the series included one group with no graft contamination and no antibiotic prophylaxis (uncontaminated control), one contaminated group that did not receive any antibiotic prophylaxis (untreated control), one contaminated group in which perioperative intraperitoneal prophylaxis with vancomycin (10 mg/kg) was administered, two contaminated groups that received rifampicin-soaked (5 mg/1 ml) or vancomycin-soaked (1 mg/1 ml) grafts, and one contaminated group that received a combination of rifampicin-soaked (5 mg/1 ml) graft with perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were removed sterilely 7 days after implantation and evaluated by using sonication and quantitative blood agar culture. RESULTS: MRSE had significantly greater adherence to Dacron than ePTFE grafts in the untreated contaminated groups (P < 0.001). Rifampicin had better efficacy than vancomycin in topical application, but the difference was not statistically significant (P > 0.05). Intraperitoneal vancomycin showed a significantly higher efficacy than topical vancomycin or rifampicin (P < 0.001). The best results were provided by a combination of intraperitoneal vancomycin in rifampicin-soaked graft groups (P < 0.001). CONCLUSIONS: The combination of rifampicin and intraperitoneal vancomycin seems to be the best choice for the prophylaxis of late prosthetic vascular graft infections caused by MRSE.     

Prophylaxis against Staphylococcus epidermidies vascular graft infection with rifampicin-soaked,gelatin-sealed Dacron

An animal model was used to assess the efficacy of rifampicin-impregnated, gelatin-sealed Dacron in the prevention of vascular graft infections caused by Staphylococcus epidermidis. Under a general anaesthetic an interposition graft was placed into sheep carotid artery. On completion of the operation 1 ml of normal saline containing 10⁸ colony forming units (cfu) of a slime-producing S. epidermidis was inoculated directly onto the graft. After 3 weeks the graft was harvested. Swabs were taken of perigraft tissues, and of external and internal aspects of the graft. A 3–5-mm segment of the graft was incubated in broth medium and a second segment was ground for 5 min and incubated in broth medium. The presence of abscess formation and anastomotic disruption was assessed. Ten sheep received a gelatin-sealed Dacron graft (control), while nine received the same graft impregnated with rifampicin at a concentration of 1.2 mg/ml (treated). Eight of 10 control grafts were infected, with 30 of 50 possible cultures positive, compared with four of nine treatment grafts infected (P = 0.13) and 13 of 45 cultures positive (P = 0.004). The control group had four abscesses and two anastomotic disruptions; the treatment group had no abscesses (P = 0.05) or anastomotic disruptions (P = 0.26). Other organisms were isolated from nine of the 12 infected grafts, most commonly Staphylococcus aureus. There was no development of resistance to rifampicin. Rifampicin-impregnated, gelatin-sealed Dacron is successful at reducing the incidence of S. epidermidis vascular graft infection.     

Rifampin and Triclosan but not silver is effective in preventing bacterial infection of vascular dacron graft material.

OBJECTIVES: To evaluate the efficacy of silver- or Triclosan-coated prosthetic material compared to Rifampin bonded Dacron concerning their resistance to infection following subcutaneous implantation and contamination with Staphylococcus aureus. DESIGN: Animal experimental study in mice. MATERIAL AND METHODS: Thirty-six C3H/HcN mice (Charles River Lab., Sulzfeld, Germany) with a weight between 24 and 27 g were randomised into six groups counting six animals each. Group I: control, gel-sealed dacron graft, group II: gel-sealed dacron graft and local contamination, group III: Intergard-Silver-prosthesis and contamination, group IV: silver/gel-sealed dacron prosthesis (test graft) and contamination, group V: Rifampin-bonded gel-sealed graft and contamination, group VI: Triclosan/collagen-coated dacron graft and contamination. Dacron graft material 0.8x1 cm was subcutaneously implanted in mice. Local contamination with 2x10(7)/0.2 ml S. aureus ATCC 25923 was carried out in groups II to VI. On day 14 the animals were killed and the grafts were explanted. The microscopic, histologic and microbiological evaluation of the graft material and the perigraft tissue was performed. RESULTS: In control group I no case of infection was detected. In group II, 6 of 6 animals showed infection. In group III (Intergard-Silver) and group IV (silver/gel-test graft) were 6 of 6, in group V (Rifampin) only 1 of 6 grafts and in group VI (Triclosan) 4 of 6 grafts were infected. The difference between the low rate of infection in group V (Rifampin) in comparison to the completely infected groups III and IV (Silver) as well as the control group II was significant. Treatment of grafts with Triclosan could prevent infection only in 1/3 of the cases in group IV. CONCLUSION: Silver coating failed to prevent graft infection material. A potential antimicrobial property was evident for Triclosan whereas Rifampin-bonded grafts exhibit a significantly reduced infection rate. Thus, silver-coated vascular grafts cannot ensure protection from vascular graft infection.     

Graft infectivity of rifampin and silver-bonded polyester grafts to MRSA contamination

The purpose of this study was to evaluate the ability of vascular polyester grafts with antibacterial properties to resist colonization following surface contamination by methicillin-resistant Staphylococcus aureus (MRSA) in an experimental canine model or aortic graft infection. Twenty-four pathogen-free dogs underwent replacement of the infrarenal aorta with either a rifampin-soaked (30 mg/mL) or silver-impregnated (Ag-acetate) woven polyester graft. Following implantation, the external graft surface was inoculated with 2 mL of 10(7) colony-forming units/mL (CFU) of MRSA. Preoperative antibiotic prophylaxis consisted of a single intravenous dose of 500 mg of sodium cefazolin. Four grafts of each type were explanted at 3, 7, and 14 days after implantation. Quantitative cultures (CFU/specimen) of perigraft fluid (1 mL), graft material (1 cm segment), and adjacent aorta (1 cm segment) were performed. Differences between grafts are expressed as % mean log reduction in recoverable CFU compared to the inoculation solution concentration of 10(7) CFUs. At 3 days, explanted rifampin-soaked grafts exhibited no MRSA growth (4 of 4 grafts) and a > or =97% mean log reduction of MRSA CFUs from the adjacent aorta and perigraft fluid (PGF). At 3 days, all silver-bonded grafts exhibited signs of infection and a mean log CFU reduction of MRSA ranging from 68% (absolute range 10(1)-10(3) recoverable CFU) for the graft, 79% (absolute range 10(1)-10(3) recoverable CFU) for the aorta, and 86% (absolute range 10(1)-10(4) recoverable CFU) for PGF. The 7-day rifampin group had an average log reduction in MRSA CFU of 72% (graft), 58% (PGF), 75% (aorta). Quantitative cultures of 14-day rifampin grafted demonstrated continued bacterial growth suppression with mean MRSA CFU log reductions of 82%, graft; 72%, PGF; 89%, aorta. Silver-bonded grafts demonstrated <50% mean CFU reduction in MRSA growth at 7 days (absolute range 10(5)-10(7) recoverable CFU) and 14 days (absolute range 10(3)-10(7) recoverable CFU). No animal died from sepsis or anastomotic hemorrhage. Neither rifampin- nor silver-bonded grafts demonstrated prolonged resistance to surface MRSA contamination. Rifampin-soaked polyester grafts exhibited a marked but transient resistance MRSA colonization likely the result of high antibiotic concentration in the perigraft tissue. While both types of grafts failed to eradicate the MRSA infection future research with silver-bonded grafts that have an additional antibiotic attached may have a place in the treatment of MRSA infection.     

DEVELOPMENT OF A STAPHYLOCOCCUS EPIDERMIDIS VASCULAR GRAFT INFECTION MODEL IN SHEEP

Staphylococcus epidermidis is an increasingly recognized causative organism of vascular graft infections. To increase our understanding of this problem we have tried to establish Staph. epidermidis vascular graft infection in sheep by direct inoculation. A 2 cm long, 5 mm diameter polytetrafluoroethylene (PTFE) or a gelatin sealed Dacron vascular graft was inserted into the left carotid artery, At the completion of the operation 1 mL of normal saline containing either 10⁴, 10⁶, or 10⁸ colony forming units (cfu) of a slime producing Staph. epidermidis was inoculated directly onto the graft. After 3 weeks the grafts were harvested in a sterile fashion. Swabs were taken of the perigraft tissues and the external and internal aspects of the grafts; a 3–5 mm segment of the graft was incubated in broth medium and a second segment was ground for 5 min and then incubated in broth medium. Note was made of the presence of abscess formation, anastomotic failure or thrombosis. Thirteen sheep received a PTFE graft and 14 received a gelatin sealed Dacron graft. Three sheep died immediately postoperatively. The rate of infection was 40% at 10⁴. 67% at 10⁶ and 80% at 10⁸ cfu Staph. epidermidis. In only four cases were all five cultures positive. In nine cases two or less cultures were positive, the majority of these being the broth cultures. Nine other organisms were isolated from nine mixed infections. Nine out of 13 PTFE and seven out of 11 Dacron grafts were infected. The rate of graft infection grew with increasing concentration of inoculum. Retrieval of bacteria was greatest when the graft was cultured directly, especially with physical disruption. Infection with additional organisms was common. There was no difference in the infection rate between gelatin sealed Dacron and PTFE.     

Vascular prosthetic infection with Staphylococcus epidermidis: experimental study of pathogenesis and therapy

To determine whether a slime-producing strain of Staphylococcus epidermidis was capable of producing acute infection of a prosthetic vascular graft, 5 cm segments of knitted Dacron were implanted in the infrarenal aortic position of dogs in three groups of animals. These included a control group (no graft contamination), a contaminated group that received a graft soaked in an S. epidermidis solution (untreated group), and a contaminated group in which perioperative antibiotics (three doses of cefamandole, 100 mg/kg) were administered (prophylaxis group). In all the animals reexploration and graft removal were performed at 10 days, with replacement of the defect being achieved with a new uncontaminated graft. These animals underwent exploration a third time after an additional 10-day period. S. epidermidis was not grown from the control animals (n = 7) but was cultured in 44% of the prophylaxis group (n = 9) and 88% of the untreated group (n = 16) during at least one of the operative procedures (chi 2 = 15.859; p less than 0.001). The pathologic features of acute S. epidermidis infection were best seen in the untreated animals and included anastomotic disruption (56%), periaortic hematoma, and lymphadenopathy (94%). Microscopic examination of the aortic tissues revealed extensive infiltrates of leukocytes, macrophages, and foreign body giant cells with aortic necrosis. These features were less prominent in the prophylaxis animals. We conclude that S. epidermidis is capable of producing acute graft infection with perigraft inflammation and anastomotic disruption. The administration of perioperative antibiotics reduced but did not abolish these effects of bacterial contamination of prosthetic vascular grafts.     

Linezolid alone and in combination with rifampicin prevents experimental vascular graft infection due to methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis

BACKGROUND: In this report we describe the in vivo antibacterial activity of linezolid in an experimental graft infection model in rats and compare it with teicoplanin. The objective of this study was also to determine the effects of the interaction of linezolid when it was combined with rifampicin and test this effect against strains of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. MATERIALS AND METHODS: Graft infections were established in the subcutaneous tissue of 130 Wistar rats by implantation of Dacron grafts followed by a topical inoculation with 2 x 10(7) CFU of clinical isolates of MRSA and MRSE. The study included a control group and six groups for each of the staphylococcal strains: an inoculated group that did not receive any antibiotic prophylaxis, two inoculated groups that received intraperitoneal prophylaxis with teicoplanin or linezolid alone, an inoculated group that received rifampicin-soaked grafts, and two inoculated groups that received a combination prophylaxis consisting of intraperitoneal teicoplanin or linezolid and rifampicin-soaked grafts. RESULTS: There was a reduction in the quantitative bacterial graft cultures in all prophylaxis groups when compared with inoculated control groups. There was not a statistically significant difference between linezolid and teicoplanin prophylaxis groups. The best results were obtained by a combination of rifampicin-soaked grafts with linezolid or teicoplanin. CONCLUSIONS: We found no evidence to suggest that linezolid differs from teicoplanin regarding effectiveness in the prevention of prosthetic vascular graft infection. Linezolid plus rifampicin and teicoplanin plus rifampicin are demonstrated to be valuable prophylactic regimens.     

Efficacy of muscle flaps in the treatment of prosthetic vascular graft infections

Prosthetic vascular graft infection requires graft removal and often leads to limb loss. To determine whether vascularized muscle flaps could alter the course of graft infection, 18 mongrel dogs (18-29 kg) were randomized to one of three groups and underwent unilateral carotid artery bypass with 6-mm X 4-cm PTFE grafts. At implantation, the grafts were inoculated with Staphylococcus aureus, 2 x 10(7) organisms/wound. On Day 3, dogs with patent grafts underwent wound debridement, irrigation, and closure, and the treatment to which they had been randomized was carried out. Group A (n = 4, controls) received only dicloxacillin, 500 mg po bid, beginning on Day 4. Group B (n = 5) underwent transfer of a vascularized sternocephalicus muscle flap around the infected graft, but received no antibiotics. Group C (n = 5) underwent muscle transfer as in Group B and were given dicloxacillin as in Group A. Dogs were followed until anastomotic disruption occurred or for 60 days. Quantitative bacterial cultures were taken from sternocephalicus muscle and wound fluid at the time of debridement and at sacrifice. All dogs that received antibiotics without flaps or flaps without antibiotics (Groups A and B) experienced anastomotic disruption. Dogs that received both antibiotics and flaps (Group C) had a significantly lower incidence of hemorrhage (20%, P less than 0.05). At sacrifice, fewer bacterial colonies were cultured from muscle flaps of Group C as opposed to Group A dogs (0.05 +/- 0.02 x 10(5) vs 0.79 +/- 0.31 x 10(5), P less than 0.05). Muscle flaps with antibiotic therapy may prove to be effective treatment for infected prosthetic vascular grafts.     

Temporin A as a prophylactic agent against methicillin sodium-susceptible and methicillin sodium-resistant Staphylococcus epidermidis vascular graft infection

OBJECTIVE: The purpose of this study was to investigate the efficacy of temporin A as a prophylactic agent in a rat model of vascular graft infection from methicillin sodium-susceptible and methicillin sodium-resistant Staphylococcus epidermidis. METHODS: The prospective, randomized, controlled animal study set in a research laboratory in a university hospital used 280 adult male Wistar rats (weight range, 280 to 350 g). Graft infections were established in the back subcutaneous tissue of rats with implantation of 1-cm(2) sterile Dacron grafts followed by topical inoculation with 2 x 10(7) colony-forming units of S epidermidis. The study for each staphylococcal strain included: one control group (no graft contamination), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received temporin A-soaked graft, two contaminated groups that received perioperative intraperitoneal cefazolin (30 mg/kg) or vancomycin hydrochloride prophylaxis (10 mg/kg), and two contaminated groups that received temporin A-soaked graft and perioperative intraperitoneal cefazolin (30 mg/kg) or vancomycin hydrochloride (10 mg/kg) prophylaxis. All grafts were explanted at 7 days after implantation. The main outcome measure was quantification of bacterial contamination. RESULTS: Overall, the perioperative prophylaxis based on soaked grafts was not significantly different to that of parenteral vancomycin hydrochloride. Only the combination between temporin A and vancomycin hydrochloride produced a complete bacterial inhibition for both strains. CONCLUSION: Temporin A showed a similar antibacterial in vitro activity against the two different strains. The in vivo results suggest its potential use in providing prophylaxis to direct graft contamination when used in combination with parenteral vancomycin hydrochloride.     

PTFE graft treated with silver norfloxacin (AgNF): drug retention and resistance to bacterial challenge

Norfloxacin (NF) and silver norfloxacin (AgNF) were used to coat polytetrafluoroethylene (PTFE) vascular prostheses by using triododecylmethylammonium chloride as a cationic surfactant. The relative retention of the drug on the graft after subjecting it to the biological environment for 3 weeks and antibacterial activity against coagulase-positive Staphylococcus aureus and Escherichia coli were determined. In addition, the ability of AgNF-coated PTFE grafts to sterilize perigraft tissue after mixed bacterial contamination was studied and compared with control PTFE grafts in 10 dogs. At the end of 21 days, 15 and 18% of AgNF were retained on the grafts tested in in vitro and in vivo experiments, respectively. During the same time AgNF-coated grafts from in vitro experiments exhibited significant antibacterial activity (25 mm zone of inhibition (z.i.)), but antibacterial activity was negligible (10 mm z.i.) in the grafts from in vivo experiments. NF retention on the grafts could not be determined because of spectral interference by blood. The antibacterial activity of NF-coated grafts significantly declined after 24 hr in in vivo experiments, hence further evaluation of NF-coated grafts was not done. Seven perigraft sites surrounding AgNF-coated grafts were sterile, but only one perigraft site surrounding control grafts was sterile (P less than 0.05). Cultures from six of nine perigraft infections surrounding control grafts yielded heavy bacterial growth. There was only one wound infection at the site of AgNF graft while there were seven severe wound infections at control graft sites. AgNF-coated grafts exhibited prolonged antibacterial activity compared to NF-coated grafts and offered significant protection against infection from local bacterial contamination.     

Colonisation of prosthetic grafts by immunocompetent cells in a sheep model

The present study examined the distribution of immunocompetent cells in synthetic vascular grafts in an experimental sheep model. Sixty-two adult Merino sheep underwent synthetic patch closure of a longitudinal arteriotomy in the left common carotid artery. The synthetic patch materials used were gelatin sealed Dacron (n=10), fluoropassivated Dacron (n=10), Fluoropassiv (n=12), polyurethane (n=10), expanded polytetrafluoroethylene (n=10) and carbon-lined expanded polytetrafluoroethylene (n=10). The sheep were sacrificed after four weeks when the prosthetic patches were harvested and fixed in 10% neutral buffered formalin. Transverse sections were taken along the graft and paraffin embedded. Serial sections were stained with cell type specific antibodies to identify T-lymphocytes (CD3(+)), dendritic cells (S-100(+)), endothelial cells (von Willebrand factor(+)) and smooth muscle cells (smooth muscle alpha-actin(+)). All six graft types contained CD3(+) and S-100(+) cells in the neointima, within the synthetic matrix and in the perigraft layer. Three different tissue responses to synthetic materials were observed and the grafts were classified accordingly into three groups: (1) gelatin sealed Dacron, fluoropassivated Dacron and Fluoropassiv; (2) expanded polytetrafluoroethylene and carbon-lined expanded polytetrafluoroethylene; (3) polyurethane. The three synthetic materials in Group 1 showed almost identical reactions with least accumulation of immunocompetent cells within the synthetic material but greater accumulation of immuno-inflammatory infiltrates in the perigraft vascular tissue. In this group, new vessels penetrated into the synthetic material and there was prominent formation of foreign body (giant) cells. Group 2 showed greater accumulation of immunocompetent cells within the synthetic material itself but only sparse immuno-inflammatory infiltrates in the perigraft tissue. Group 3 showed a high degree of inflammatory response within both the synthetic material and the perigraft vascular tissue. These observations demonstrate that immunocompetent cells colonise the synthetic matrix of grafts and accumulate in the perigraft tissue, but inflammatory responses vary in different graft types.     

Effects of exogenous endothelin-1 application on liver perfusion in native and transplanted porcine livers

PURPOSE: This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-1 (ET) plasma concentrations on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). METHODS: A standardized gradual increment in systemic ET plasma concentration (0-58 pg/ml) was induced by continuous ET-1 infusion into the portal vein in both groups (A: n = 10, B: n = 10). Control animals received only saline (n = 5, each group). Hepatic microcirculation (HMC) was quantified by thermodiffusion electrodes, hepatic artery flow (HAF), and portal venous flow (PVF) by Doppler flowmetry. RESULTS: No changes in ET or perfusion parameters were observed in controls. The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A from 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 +/- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Baseline HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml/100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/- 32 ml/100 g/min. No significant alteration in systemic circulation was noted at the ET concentrations investigated. CONCLUSIONS: Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominantly by reduction of portal venous flow, while the effect of ET on HAF was less pronounced. Characteristics of flow impairment in transplanted and native livers were analogous after short cold ischemic graft storage (6 h).     

Local application of vancomycin for prophylaxis of graft infection: Release of vancomycin from antibiotic-bonded dacron grafts,toxicity in endothelial cell culture,and efficacy against graft infection in an animal model

Methicillin-resistant strains ofStaphylococcus epidermidis cause an increasing number of prosthetic infections. This prompted us to test the uptake of vancomycin in various graft materials in vitro, its influence on graft healing, and its efficacy against graft infection in pigs. Incubation of six different Dacron graft materials in a vancomycin solution (20 gm/L) was performed. Grafts were then placed in plasma, and samples were taken over 72 hours to determine vancomycin levels. Release of vancomycin ranged from 775 µg/cm² to 3691 µg/cm² after 1 hour of incubation. Gelatin-covered grafts increased release of vancomycin fourfold when incubation time was extended to 24 hours; uncovered grafts or the collagen-covered graft did not. Graft healing was not complicated when a vancomycin-bonded, gelatin-impregnated Dacron graft was implanted to replace the common femoral artery in pigs. Four weeks after implantation, histologic examination revealed normal development of neointima and perigraft scar tissue in the vancomycin-treated (n=4) and untreated (n=5) grafts. To test the efficacy of local vancomycin against graft infection, grafts were implanted in the groin of pigs and contaminated with 2 × 10⁷ colony-forming units ofStaphylococcus aureus. Four weeks after implantation, all grafts were infected in the untreated group (n=6), with abscess, nonincorporated graft, and detection ofS. aureus from the graft. In the treatment group (n=6) vancomycin was added to the contaminated grafts. As a carrier for the vancomycin, we used a resorbable gelatin-glycerol foam. All grafts healed without infection. The difference between the treated and untreated groups is statistically significant (p<0.05). We conclude that it may be effective to prevent graft infection with local application of vancomycin if an in situ replacement of infected graft (infected by gram-positive bacteria) is necessary or if there is a high risk of infection by methicillin-resistant staphylococci.     

In situ replacement of vascular prostheses infected by bacterial biofilms

Late prosthetic graft infections are commonly the result of coagulase-negative staphylococci that survive within a biofilm on prosthetic surfaces and provoke perigraft inflammation. The indolent nature and microbiologic characteristics of bacterial biofilm infections coupled with the morbidity of graft excision and extraanatomic bypass grafting prompted us to use in situ graft replacement in 15 patients admitted to the hospital with 17 infected graft segments at a mean (+/- SEM) time interval of 70 +/- 16 months after graft implantation (n = 6) or revision (n = 9). Since 1986, 17 grafts (14 aortofemoral, 2 axillofemoral, and 1 femoropopliteal) infected by bacterial biofilms have been treated. Signs on admission included femoral pseudoaneurysm (n = 7), perigraft abscess (n = 6), or graft-cutaneous sinus tract (n = 4). No patient exhibited septicemia. At operation graft incorporation was absent and Gram's stain of perigraft exudate showed polymorphonuclear leukocytes but no bacteria. Culture of explanted graft material isolated coagulase-negative staphylococci (n = 12), Staphylococcus aureus (n = 1), and no growth (n = 2). All patients were successfully treated by a regimen that included parenteral antibiotics, removal of involved graft material, excision of inflamed perigraft tissue, and in situ replacement with an expanded polytetrafluoroethylene prosthesis. No deaths, graft thromboses, or deep wound infections occurred after operation. Recurrent graft infection did not develop during a follow-up interval that ranged from 5 to 50 months (mean, 21 months). Diagnosis of vascular prosthesis infection caused by bacterial biofilms can be based on signs at admission and operative findings. Complications of this perigraft infection can be eradicated by antibiotic administration, local debridement, and in situ graft replacement.     

Tobramycin-adhesive in preventing and treating PTFE vascular graft infections

The present study was designed to determine the effectiveness of N-butyl-2-cyanoacrylate as a vehicle to deliver antibiotics locally to contaminated vascular graft sites and to grafts with established infections. Phase I--Contaminated wound model: Sixteen dogs had a 1-cm section of infrarenal aorta replaced with a PTFE graft. Prior to placement, the graft was immersed in solutions of Escherichia coli 3 X 10(8) CFU/ml and then Staphylococcus aureus 3 X 10(8) CFU/ml. After anastomosis, 1 cc of each solution was placed directly over the graft. Eleven dogs served as controls and 5 as treatment dogs. Parenteral cefonecid was given preoperatively and daily until sacrifice. Treatment animals had the anastomoses and graft sealed with a suspension of N-butyl-2-cyanoacrylate and 1.2 g tobramycin powder (antibiotic glue, ANGL) after contamination. All dogs were reoperated on the third postoperative day. Results: Eleven of 11 control dogs had positive cultures for S. aureus and 9 of 11 had positive cultures for E. coli. Seven of 11 had pseudoaneurysms, 1 exsanguinated. None of the 4 treatment dogs had positive cultures (P = 0.0002), pseudo-aneurysms (P = 0.017), or local signs of sepsis. Phase II--Infected graft model: The 10 surviving infected control dogs served as the established graft infection model. These dogs were randomized into two groups; Group 1 control (N = 5) had the graft replaced; Group 2 treatment (N = 5) had the graft replaced and ANGL treatment. Dogs were sacrificed after 2 weeks. Results: Graft cultures were positive in all 4 control dogs and negative in the 4 treatment dogs (P = 0.005). One dog in each group was eliminated secondary to failure to obtain graft culture. The data show that ANGL can be effective in the prevention and treatment of prosthetic graft infection.     

Efficacy of vancomycin, teicoplanin and fusidic acid as prophylactic agents in prevention of vascular graft infection: an experimental study in rat.

OBJECTIVES: To compare the efficacy of a single prophylactic dose of intra-peritoneal vancomycin and teicoplanin with anti-biotic treated Dacron grafts (vancomycin, teicoplanin, 10 or 40% fusidic acid-soaked grafts) in preventing vascular graft infections in a rat model. DESIGN: Prospective, randomized, controlled animal study. MATERIALS AND METHODS: The graft infections were established in the subcutaneous tissues of 80 female Sprague-Dawley rats by the implantation of Dacron prostheses followed by the topical inoculation with methicillin-resistant Staphylococcus aureus. The study groups were as follows: (1) uncontaminated control group, (2) untreated contaminated group, (3) contaminated group with intra-peritoneal vancomycin, (4) contaminated group with intra-peritoneal teicoplanin, (5) contaminated group received vancomycin-soaked Dacron graft, (6) contaminated group received teicoplanin-soaked Dacron graft, (7) contaminated group received 40% fusidic acid-soaked Dacron graft, and (8) contaminated group received 10% fusidic acid-soaked Dacron graft prophylaxis. The grafts were removed after 7 days and evaluated by a quantitative culture analysis. RESULTS: No infection was detected in controls. The untreated contaminated group had a high bacteria count (6.0 x 10(4) CFU/cm2 Dacron graft). Groups that received intra-peritoneal vancomycin or teicoplanin had less bacterial growth (4.8 x 10(3) and 3.9 x 10(3)CFU/cm2 Dacron graft, respectively). Similarly, the group that received 10% fusidic acid-soaked graft showed less bacterial growth (3.6 x 10(3) CFU/cm2 Dacron graft). The groups with vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts showed no evidence of infection. Statistical analyses demonstrated that intra-peritoneal prophylactic antibiotic treatment was less effective in inhibiting bacterial growth than high concentration antimicrobial-soaking of grafts. CONCLUSION: The use of vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts was effective in preventing primary prosthetic vascular graft infection.     

Prophylactic antibiotics prevent bacterial biofilm graft infection.

Bacterial biofilm graft infection is due to prostheses colonization by Staphylococcus epidermidis, a pathogen frequently recovered from perigraft tissues of man during vascular procedures despite the use of asepsis and prophylactic antibiotics. The effect of preoperative intraperitoneal cefazolin, administered at a standard (15 or 30 mg/kg) and high (120 mg/kg) dose, on the prevention of bacterial biofilm infection was studied in a rat model. Seventy-four Dacron grafts, colonized in vitro with S. epidermidis to produce an adherent biofilm (3.19 +/- 0.71 x 10(7) colony-forming units/cm2 graft), were implanted in the dorsal subcutaneous tissue at 0.5, 2, and 4 hr after antibiotic administration. The study strain was a slime-producing clinical isolate with minimum inhibitory concentration (MIC) of 15-30 micrograms/ml to cefazolin. Subcutaneous tissue antibiotic levels were determined at each time interval. One week after implantation, the concentration of bacteria in the surface biofilm by quantitative agar culture was significantly decreased (P less than 0.05) only for grafts implanted when antibiotic tissue levels were greater than or equal to the MIC of the study strain. The result of no growth by biofilm broth culture was significantly achieved (P less than 0.01) only for grafts implanted 0.5 hr after high dose cefazolin, in which the tissue antibiotic level was above the MIC of the study strain. Antibiotics can markedly reduce the bacteria concentration of a prosthetic surface biofilm. The effectiveness of prophylactic antibiotics on the prevention of graft infection is dependent upon maintaining an adequate antibiotic level in the perigraft tissues for the duration of the procedure.     

Prophylactic antibiotics prior to bacteremia decrease endovascular graft infection in dogs

Endovascular placement of vascular stent grafts in the aorta and peripheral vessels has become a prominent tool in the armamentaria of the vascular surgeon. Despite, several reports of stent graft infection, no current guidelines exist regarding the administration of antibiotics prior to episodes of potential bacterial seeding. We sought to clarify the role of prophylactic antibiotics in preventing stent graft infection after the parenteral administration of Staphylococcus aureus (S. aureus) at various intervals following device placement. A stent graft device was constructed from a 4 mm thin-walled polytetrafluoroethylene (PTFE) graft attached to the outside of a balloon expandable 394-Palmaz stent (Johnson and Johnson Interventional Systems, Warren, NJ). It was then inserted into the common iliac artery through an 11F peal-away sheath placed in the femoral artery. Sixty grafts were placed into 30 dogs. There were 5 groups of equal number (groups A-E). In group A, six dogs received intravenous injection of 3 cc x 104 CFU (colony forming units), biotype 31375 S. aureus, 1 day after stent graft implantation. An identically treated group B received antibiotic prophylaxis (1 gm cefazolin 30 minutes prior to bacterial challenge). Group C received bacterial injection 7 days after graft implantation with no antibiotic prophylaxis. Group D received bacterial injection 7 days after graft implantation with antibiotic prophylaxis. A control group E received no antibiotics and was not infected. All infected animals were sacrificed 7 days following bacterial challenge and the stent graft complex cultured. One half of the control group was sacrificed at 7 days and the other half at 14 days. The overall stent graft patency was 90%. Four of the six graft occlusions occurred in group A. Eleven of 12 (92%) dogs cultured S. aureus (biotype 31375) from the explanted stent graft complex. Two localized perforations occurred at the site of the infected complex. In group B, C, and D, no explanted graft complex cultured S. aureus. One graft occluded in group C and D. No stent graft in the control (group E) cultured S. aureus. A stent graft infection model can be consistently produced. In the canine model, the stent graft is more susceptible to infection in the early postoperative period and becomes less susceptible to bacterial seeding at one week after implantation. The authors recommend the use of prophylactic antibiotics in the prevention of endovascular graft infections in the early postoperative period during times when bacterial seeding may occur. They postulate that pseudointima formation during graft incorporation into the vessel wall may be responsible for the resistance to infection.     

Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery

Objective

This study aimed to show the effects of intra-operative diltiazem infusion on flow in arterial and venous grafts in coronary artery bypass graft surgery.

Methods

Hundred fourty patients with a total of 361 grafts [205 (57%) arterial and 156 (43%) venous] underwent isolated coronary surgery. All the grafts were measured by intraoperative transit time flow meter intra-operatively. Group A (n=70) consisted of patients who received diltiazem infusion (dose of 2.5 microgram/kg/min), and Group B (n=70) didn''t receive diltiazem infusion.

Results

Mean graft flow values of left internal mammary artery were 53 ml/min in Group A and 40 ml/min in Group B (P<0.001). Pulsatility index (PI) values of left internal mammary artery for Group A and Group B were 2.6 and 3.0 respectively (P<0.001). No statistically significant difference was found between venous graft parameters.

Conclusion

We recommend an effect of diltiazem infusion in increasing graft flows in coronary artery bypass graft operations.