Prevention of Staphylococcus aureus graft infection by a new gelatin-sealed vascular graft prebonded with antibiotics

OBJECTIVE: The aim of this study was to evaluate the efficacy of a new gelatin-sealed graft prebonded with two antibiotics in resisting infection with Staphylococcus aureus (S aureus) A980142 after direct bacterial application in a dog model. METHODS: Twelve 6.0-mm polyester grafts were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into two groups. A test group (n = 6) received experimental antibiotic-bonded gelatin-sealed knitted polyester grafts, loaded with two antibiotics, rifampin and tobramycin. A control group (n = 6) received commercial gelatin-sealed knitted polyester grafts. At the end of graft implantation, 50 mul of a 1.8 x 10(4) CFU/mL S aureus solution were instilled directly over the graft. One week after implantation, grafts were harvested with sterile technique. Quantitative cultures were obtained from all the harvested grafts. The results were expressed as colony-forming units per cm(2) of surface of the graft. Bacteriological study was also performed on various tissue samples. The chi(2) test was used to compare the culture proven infection of control and antibiotics-bonded grafts. RESULTS: Mean inoculum size was similar in the two groups of dogs. Five of the six control grafts grew S aureus A980142 at the time of graft removal, whereas none of the six antibiotic-bonded gelatin-sealed grafts were infected (P = .0192). None of the organ samples were infected in the group implanted with antibiotic-bonded grafts, whereas 15/34 samples grew S. aureus in the control group. CONCLUSION: These results indicate that this gelatin sealed graft prebonded with two antibiotics resists infection caused by S aureus graft contamination in a dog model.     

Infectibility of endovascular stents following antibiotic prophylaxis or after arterial wall incorporation.

BACKGROUND: Case reports of endovascular stent infection have been accumulating in the last several years. We sought to determine if prophylactic antibiotics would prevent stent/artery complex infections in a swine model if given before a bacterial challenge at the time of stent placement and 4 weeks following deployment. We also investigated whether arterial wall incorporation protected the stent against infection without antibiotic prophylaxis. METHODS: Balloon expandable Palmaz stents were placed in the iliac arteries of 42 swine. At the same time, angioplasty was performed on the contralateral iliac artery as a control. In group A, prophylactic cefazolin was given to 12 swine at the time of stent deployment followed by an intraaortic bacterial challenge of Staphylococcus aureus. In group B, 10 swine received prophylactic cefazolin followed by intravenous S aureus 4 weeks after iliac stenting and angioplasty. In group C, 3 months following iliac stent placement and angioplasty an intravenous bacterial challenge was administered with S aureus. All swine were euthanized, and the iliac stent/artery complex and the contralateral angioplastied iliac artery were harvested and sent for culture and pathology. Experimental groups were compared with results from our previously published swine infection model using the Fisher's exact test. P values were considered significant if less than 0.05. RESULTS: Group A: Two of the 12 (17%) stent/artery complexes in the antibiotic treatment group had positive cultures. This compares with 7 of 10 (70%) in the control group (P = 0.016). In addition, there was one infection in an angioplastied vessel contralateral to one of the two stent infections. Molecular strain typing verified that the positive cultures were the same strain that was used to challenge the animals. No vessel thrombosis occurred in the stented arteries even in the presence of infection. Group B: One of 10 (10%) stented iliac arteries had a culture positive infection. This compares with 7 of 14 (50%) positive cultures in the control group (P = 0.04). In addition, one angioplastied vessel did have mild S aureus growth on culture. Both positive cultures were verified to be the same as the injected strain by molecular strain typing. There were no thrombosed or occluded vessels. Group C: One of 15 patent stents had growth of S aureus on culture and evidence of acute inflammation on histopathologic examination. The stent infection rate of 1 of 15 (7%) patent stents in this study was significantly less than the infection rates with bacterial challenge at placement (7 of 10, 70%; P < 0.01) and at 1 month postplacement (7 of 14, 50%; P = 0.0142). Five stents occluded without evidence of infectious cause. CONCLUSIONS: The results of this study support a recommendation that antibiotic prophylaxis should be used at the time of arterial stent placement and early after placement at times of anticipated bacteremia, but indefinite prophylaxis may be unnecessary due to arterial wall incorporation of the stent.     

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.     

Prophylaxis against Staphylococcus aureus vascular graft infection with mupirocin-soaked, collagen-sealed dacron

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infections. The effect of mupirocin-soaked Dacron was compared with the effect of rifampin-soaked, collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus. Graft infections were established in the back subcutaneous tissue of 195 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses followed by topical inoculation with 5 x 10(7) colony-forming units of S. aureus. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups in which perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg) was administered, four contaminated groups that received mupirocin- or rifampin-soaked graft, and four contaminated groups that received mupirocin- or rifampin-soaked graft and perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg). The grafts were sterilely removed 7 days after implantation and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed that the efficacy of mupirocin against both strains was significantly different from that of the untreated control. In addition, mupirocin was more effective than rifampin against the methicillin-resistant strain. Finally, only the combination of mupirocin and amoxicillin clavulanate produced complete suppression of growth of all strains.     

Bacterial resistance of refrigerated and cryopreserved aortic allografts in an experimental virulent infection model

PURPOSE: The bacterial resistance of refrigerated and cryopreserved aortic allografts in a highly virulent infection in a dog model was studied. METHODS: The infrarenal aorta of 12 dogs was replaced with either a cryopreserved aortic allograft (group I, n = 6) or a refrigerated aortic allograft (group II, n = 6) in infected sites. Allografts were harvested from dogs and stored for 1 week, either by cryopreservation (-140 degrees C) or refrigerated method (4 degrees C), in a preservation medium. At the time of implantation, induction of infection was achieved with an infected piece of knitted Dacron placed just beneath the allograft. The Dacron was contaminated in vitro by soaking it in a solution with Staphylococcus aureus PR209. All 12 dogs received no adjunct antibiotic or antithrombotic therapy. Four weeks after implantation, the animals were killed to recover the grafts for bacteriological and histological analyses. Bacterial results were expressed as colony-forming units (CFU)/cm2 of graft material. RESULTS: In group I, only one allograft grew bacteria at 2. 16 x 10(6 )CFU/cm2, with a blood culture positive for S aureus. In group II, one dog died at 3 weeks from a false septic aneurysm rupture, all the allografts were infected (P <.05) with a mean bacterial count of 9.41 +/- 6.8 x 10(4) CFU/cm2, and three blood cultures were positive for S aureus. The patency of the grafts was analyzed at the time of recovery. Three laminar thrombi without occlusion were present in group I; none were present in group II. A better preserved endothelium in group I was revealed by means of histologic analysis staining with factor VIII antibody before implantation. After 4 weeks of implantation in the infected site, infected allografts presented polynuclear infiltrates in the media with a high degree of inflammatory reaction, and endothelial recovery was more significant in group I, with numerous young plump cells. CONCLUSION: This study demonstrates that cryopreserved allografts implanted in infected sites in a dog model can produce greater bacterial resistance.     

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.     

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.     

Stent graft repair of visceral artery aneurysms

PURPOSE: The purpose of this study was to compare the efficacy of rifampin-bonded gelatin-sealed and silver acetate/collagen-coated knitted polyester prostheses for the prevention of bacteremic graft infection in an animal model. METHODS: Eighteen 6.0-mm polyester grafts (length, 5.0 cm) were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into four groups as a function of type of prosthesis implanted. The dogs in groups I (n = 3) and II (n = 3) received control gelatin-sealed or collagen-coated polyester prostheses, respectively. In group III (n = 6), the dogs received rifampin-bonded gelatin-sealed polyester prostheses. In group IV (n = 6), the dogs received silver/collagen-coated polyester prostheses. Two days after implantation, the grafts were challenged with 6 x 10(9) Staphylococcus aureus intravenously. One week after implantation, the grafts were harvested with sterile technique. Quantitative cultures were obtained from all the harvested grafts. The results were expressed as colony-forming units per cm(2) of graft material. Bacteriologic study was also performed on various tissue samples. The chi(2) test was used to compare the culture proven infection of control and antimicrobial grafts. RESULTS: All the control grafts were infected with S aureus at the time of removal. Five of the six silver/collagen-coated grafts were infected, whereas none of the six rifampin-bonded gelatin-sealed grafts grew S aureus (P <.01). There was no significant difference in the number of positive culture results of organ samples between the different groups of dogs. CONCLUSION: These results indicate that rifampin-bonded gelatin-sealed polyester grafts are significantly more resistant to bacteremic infection than are silver/collagen-coated polyester grafts in a highly challenging model.     

Prevention of graft infection by use of prostheses bonded with a rifampin/collagen release system.

The objective of this study was to test the efficacy of bonding rifampin to double-velour Dacron grafts with collagen to prevent graft sepsis. Fifty 6.0 mm Dacron grafts (length 5.0 cm) impregnated with either collagen (control) or collagen plus rifampin (experimental) were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into four groups (each with an experimental and control subdivision) as a function of time between grafting and bacterial challenge. At 2, 7, 10, or 12 days after graft implantation, sequential groups were challenged with 1.2 x 10(8) colony forming units of Staphylococcus aureus (clinical isolate) intravenously suspended in 250 ml normal saline. Three weeks after hematogenous seeding, the grafts were sterilely harvested. One-tailed Fisher's exact test was used to compare the patency and culture-proven infection of control and antibiotic coated grafts as a function of implantation time before bacteremic challenge. In the 2-day group, four of six control grafts were infected compared with zero of six experimental grafts (p less than 0.030). In the 7-day group, five of six control grafts were infected with S. aureus versus zero of six in the experimental group (p less than 0.008). In the 10-day group, one of six experimental grafts was infected, but the control group had only two of six graft infections. In the 12-day group two of six experimental grafts and one of five control grafts were infected. These results indicate that rifampin bonded with collagen to knitted Dacron grafts will protect the graft from bacteremic infection for 7 days after implantation in a highly challenging model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and local antibiotic prophylaxis in the prevention of prosthetic vascular graft infection: an experimental study.

AIM: to determine if local, in addition to systemic antibiotic prophylaxis (compared to that provided by systemic prophylaxis alone) provides additional benefit in terms of reducing graft infection. METHODS: gelatin-sealed Dacron grafts were interposed in the infrarenal aorta of 36 mongrels and inoculated with 1 ml of a S. aureus suspension. Group 1 (control group) received no prophylaxis and were inoculated with 1 ml containing 10(9)cfu/ml. Group 2 (n=6) received systemic prophylaxis (1 g cephamandole) and were inoculated with 10(5) cfu/ml (n=3) or 10(7) cfu/ml (n=3). Group 3 received systemic prophylaxis (1 g cephamandole) and were inoculated with 109 cfu/ml. Group 4 received systemic prophylaxis (2 g cephamandole) and were inoculated with 10(9)cfu/ml. In group 5 and 6 grafts were soaked in a rifampicin solution before use and inoculated with 10(9) cfu/ml. Group 5 received no systemic prophylaxis and group 6 received systemic prophylaxis (1 g cephamandole). Grafts were harvested at 2 weeks, and peritonitis, perigraft abscess, anastomotic disruption and graft occlusion recorded. Swabs were taken of the graft, the perigraft tissues and the peritoneal fluid. Graft segments were incubated in broth medium. RESULTS: inoculation with 10(9) cfu/ml ensured graft infection. Systemic or local prophylaxis alone failed to prevent graft infection. Only systemic and local antibiotic prophylaxis provided significant better results than no prophylaxis at all (p<0.01) and local prophylaxis alone (p<0.05). However, total "graft sterility" was not achieved as bacteriologic analysis of the graft segments showed low bacterial counts (<10 bacteria/graft) in 5 of 6 grafts. CONCLUSION: local and systemic prophylaxis provided more protection as demonstrated by the significant decrease in the incidence of "overt" graft infection. Total "graft sterility" cannot be expected in the case of an overwhelming bacterial challenge.     

Antibiotics-why so many and when should we use them?

Antibiotic prophylaxis in vascular surgery has been proven beneficial to reduce surgical site infections after reconstruction of the aorta, procedures on the leg that involve a groin incision, any procedure that implants a vascular prosthesis or endoluminal stent, and lower extremity amputation for ischemia. Bactericidal antibiotics administered before induction-cefazolin or cefuroxime for 1 to 2 days alone or in combination with vancomycin if a hospital wound surveillance program indicates a high incidence of methicillin-resistant Staphylococcus aureus infection-is recommended. If a patient is felt to be at increased risk for infection and require prosthetic grafting, the use of a rifampin-soaked (1 mg/mL) gelatin- or collagen-impregnated graft may decrease the incidence of wound and graft infection. Antibiotic treatment of established vascular graft infections should begin with broad-spectrum coverage for expected pathogens (S aureus, Staphylococcus epidermidis, Gram-negative bacteria) followed by culture-specific therapy based on antibiotic susceptibility testing. Specific antibiotic usage involves a decision regarding efficacy to expected or isolated pathogens versus its potential side effects and the drug costs. New applications for antibiotics in vascular surgery include the use of specific tetracyclines (doxycycline, azithromycin) as an inhibitor of matrix metalloproteinases to retard aortic aneurysm growth or for their antiinflammatory properties to retard atherogenesis related to Chylamydia pneumoniae.     

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.     

RNAIII-inhibiting Peptide and/or Nisin Inhibit Experimental Vascular Graft Infection with Methicillin-susceptible and Methicillin-resistant Staphylococcus epidermidis

OBJECTIVE: To investigate the efficacy of RNAIII-inhibiting peptide (RIP) and nisin as prophylactic agents in a rat model of vascular graft infection. DESIGN: Prospective, randomized, controlled animal study. MATERIALS: Two hundred and twenty adult male Wistar rats. Staphylococcus epidermidis ATCC 12228 and one clinical isolate of methicillin-resistant S. epidermidis. Drugs: RIP, nisin and rifampin. METHODS: Graft infections were established in the dorsal subcutaneous tissue by implantation of 1 cm(2) sterile Dacron grafts, followed by topical bacterial inoculation: grafts were retrieved at 7 days. The study included a control group (without inoculation) and two series composed of five groups for each staphylococcal strain: one contaminated group that did not receive any antibiotic prophylaxis, three contaminated groups that received grafts soaked with 10 mg/l RIP, 10 mg/l nisin, 10 mg/l rifampin, or RIP+nisin. The main outcome measure was the extent of bacterial at graft harvest. RESULTS: The bacterial counts for methicillin-resistant S. epidermidis on explanted grafts were 6.1+/-2.8x10(2), 7.8+/-3.0x10(3) and 5.5+/-2.9x10(4) for RIP, nisin and rifampin, respectively. RIP and nisin used in combination reduced the bacterial count to <10. The results for S. epidermidis were similar. CONCLUSIONS: RIP and nisin could be used in combination to coat medical devices to prevent drug resistant S. epidermidis infections.     

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.     

Experimental study of a new vascular graft prebonded with antibiotic: healing, toxicity, and antibiotic retention

Despite refinements in surgical techniques, routine antibioprophylaxis, and anesthesiology, vascular prosthetic infections remain a serious complication of reconstructive vascular surgery. The purpose of this study was to evaluate the healing, the toxicity, and the antibiotic delivery of a new vascular graft, preloaded with rifampin and tobramycin. Sixteen dogs underwent infrarenal aortic bypass. They were divided into three groups. In test group 1 (n = 8), dogs received grafts loaded with a standard concentration of antibiotics. In test group 2 (n = 4), dogs received grafts loaded with twice the standard concentration of antibiotics. A control group (n = 4) received a commercial gelatin-sealed graft. Grafts were harvested after different periods of time and submitted to histological evaluation and antibiotic dose determination. Liver and kidney toxicities were evaluated from dosages performed on serum samples taken at different time periods between graft implantation and harvesting. The healing of antibiotic-loaded grafts was similar to that of commercial grafts, without any signs of toxicity. These results suggest resistance to infection of these prebonded grafts in an animal model.     

Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic graft infections.

We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system. The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta. This initial graft was deliberately infected, at the time of operation, with 10(2) organisms of Staphylococcus aureus by direct inoculation. One week later, the dogs were reexplored, the retroperitoneum debrided, and the animals randomized to undergo an end-to-end in situ graft replacement with either one of two types of prosthetic grafts: group I (collagen, n = 36) received control collagen-impregnated knitted Dacron grafts; group II (rifampin, n = 47) received experimental collagen-rifampin-bonded Dacron grafts. Each group of animals was then subdivided to receive one of four treatment protocols: (a) no antibiotic therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000 ml) during operation and two doses of cephalosporin (cefazolin, 500 mg intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1 week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d) treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily). All grafts were sterilely removed between 3 and 4 weeks after implantation. There were no anastomotic disruptions and all grafts were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibiotic binding to polytetrafluoroethylene via glucosaminoglycan-keratin luminal coating

Vascular prosthetic graft infection is one of the most catastrophic problems complicating vascular surgery. The purpose of the present study was to determine the efficacy of binding an antibiotic to a vascular prosthesis via a glucosaminoglycan-keratin luminal coating (GKLC). Ten adult mongrel dogs had polytetrafluoroethylene (PTFE) grafts inserted into the right common carotid artery and PTFE grafts with GKLC bonded with cefoxitin inserted into the left common carotid artery. Before the neck incision was closed, an infusion of 1 X 10(8) Staphylococcus aureus was administered intravenously during a 15-minute period to each dog. Grafts were harvested at 10 different time periods (1, 2, 3, 5, 7, 10, 14, 18, 21, and 28 days). At the time of harvesting, cultures were taken of the lumen of each graft. Washout of antibiotic from the graft lumen was determined by measuring zones of inhibition of disks excised from the antibiotic grafts that were placed on S. aureus plates. Results demonstrated that only 1 of the 10 GKLC-cefoxitin grafts was infected compared with 10 of 10 regular PTFE grafts (p less than 0.003). Regression analysis showed antibiotic elution to occur in an exponential fashion (r = 0.9654) with no detectable antibiotic present after 10 days. GKLC with cefoxitin significantly protects the PTFE graft lumen from infection during bacteremia compared with regular PTFE. The role of antibiotic-bound grafts in relation to the use of intravenous antibiotics will need to be determined by further studies.     

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.     

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.     

Quinupristin/dalfopristin bonding in combination with intraperitoneal antibiotics prevent infection of knitted polyester graft material in a subcutaneous rat pouch model infected with resistant Staphylococcus epidermidis.

OBJECTIVE: to investigate the efficacy of quinupristin/dalfopristin in the prevention of prosthetic graft infection in a rat subcutaneous pouch model. METHODS: graft infections were established in the subcutaneous tissue of 140 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with Staphylococcus epidermidis with intermediate resistance to glycopeptides. The study included one group without contamination, one contaminated group without prophylaxis, one contaminated group that received 50mg/l quinupristin/dalfopristin-soaked graft, one contaminated group that received 10mg/kg intraperitoneal levofloxacin, one contaminated group that received 3mg/kg intraperitoneal doxycycline, and two contaminated groups that received 50mg/l quinupristin/dalfopristin-soaked plus 10mg/kg intraperitoneal levofloxacin or 3mg/kg intraperitoneal doxycycline. Each group included 20 animals. The grafts were removed after 7 days and evaluated by quantitative culture. RESULTS: quinupristin/dalfopristin showed a significantly higher efficacy than levofloxacin and doxycycline, even though quantitative graft cultures for rats that received only quinupristin/dalfopristin-soaked graft showed bacterial growth. Otherwise, the efficacy of levofloxacin was similar to that of doxycycline. Only the group treated with quinupristin/dalfopristin combined with levofloxacin or doxycycline showed no evidence of staphylococcal infection. CONCLUSIONS: quinupristin/dalfopristin as adjunctive topical antibiotic prophylaxis can be useful for the prevention of vascular graft infections caused by staphylococcal strains with high levels of resistance.