Use of rifampin-soaked gelatin-sealed polyester grafts for in situ treatment of primary aortic and vascular prosthetic infections

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.     

Expanded application of in situ replacement for prosthetic graft infection

PURPOSE: The purpose of this study was to analyze the outcome of an individualized treatment algorithm for prosthetic graft infection, including the application of in situ graft replacement, based on clinical presentation, extent of graft infection, and microbiology. METHODS: There was a retrospective review (1991-2000) of 119 patients with 68 aortoiliofemoral or 51 extracavitary (infrainguinal, 19; axillofemoral, 16; femorofemoral, 16) prosthetic graft infections presenting more than 3 months (range, 3-136 months) after implantation/revision. The treatment algorithm consisted of graft excision with or without ex situ bypass grafts for patients presenting with sepsis or graft-enteric erosion, whereas in situ replacement (autogenous vein, rifampin-bonded polyester, polytetrafluoroethylene [PTFE]) was used in patients with less virulent gram-positive graft infection, in particular infections caused by Staphylococcus epidermidis. Outcomes (death, limb loss, recurrent infection) were correlated with treatment type and infecting organism. RESULTS: In situ replacement was used in 52% of aortoiliofemoral (autogenous vein, 10; rifampin-bonded polyester, 6; PTFE, 9) and 80% of extracavitary (autogenous vein, 26; PTFE, 9; rifampin, 6) graft infections. Total graft excision with ex situ bypass was performed in 34 patients, including 21 patients with graft-enteric erosion/fistula, with a 21% operative mortality and 9% amputation rate. In situ graft replacement was used to treat 76 graft infections with a 30-day operative mortality rate of 4% and an amputation rate of 2%. Graft excision alone was performed in nine patients with one 30-day death. Gram-positive cocci were the prevalent infecting organisms of both intracavitary (59% of isolates) and extracavitary (76% of isolates) graft infections. S epidermidis was the infecting organism in 40% of patients, accounting for the expanded application of in situ prosthetic replacement using a rifampin-bonded polyester or PTFE prosthesis. During the mean follow-up interval of 26 months, recurrent graft infection developed in 3% (1 of 34) of patients after conventional treatment, 3% (1 of 36) patients after in situ vein replacement, and 10% (4 of 40) patients after in situ prosthetic graft replacement (P >.05). Failure of in situ replacement procedures was the result of virulent and antibiotic-resistant bacterial strains. CONCLUSIONS: In situ replacement was a safe and durable option in most (64%) patients presenting with prosthetic graft infection. In situ replacement with a rifampin-bonded graft was effective for S epidermidis graft infection, but when the entire prosthesis is involved with either a biofilm or invasive perigraft infection, in situ autogenous vein replacement is preferred. Virulent graft infections presenting with sepsis, anastomotic dehiscence, or graft enteric fistula should continue to be treated with total graft excision, and if feasible, staged ex situ bypass graft.     

Treatment of vascular graft infection by in situ replacement with a rifampin-bonded gelatin-sealed Dacron graft

Purpose: The purpose of this study was to treat an established prosthetic vascular graft infection by in situ replacement with a rifampin-bonded gelatin-sealed Dacron graft in an animal model.Methods: The infrarenal aorta of 18 dogs was replaced with a gelatin-sealed graft contaminated in vitro by soaking it in a solution with Staphylococcus epidermidis. One week later, animals were randomized into three groups. In group I (control, (n = 6), the dogs did not undergo repeat operations. The dogs in groups II and III underwent repeat operation. In these animals the infected grafts were removed for bacteriologic analysis and replaced in situ with one of two types of grafts: group II (n = 6) received an untreated, gelatin-sealed graft; group III (n = 6) received a rifampin-bonded, gelatin-sealed graft. Antibiotic bonding was obtained by soaking grafts for 15 minutes in a 60 mg/ml saline solution of rifampin at 37° C. All 18 dogs received no systemic adjunct antibiotic therapy. Control grafts and replacement grafts were removed 4 weeks after the initial implantation for bacteriologic analysis. When harvested, all the grafts were cut into two fragments, and quantitative bacterial cultures were obtained from all the fragments. Results were expressed as colony-forming units (CFU)/cm² of graft material.Results: All 18 initially implanted grafts and all the untreated replacement grafts were grossly infected at the time of removal, whereas all the rifampin-bonded replacement grafts had normal incorporation. None of the rifampin-bonded grafts grew bacteria, whereas all the initially implanted and all the untreated replacement grafts were infected (p < 0.01). Bacterial counts from the infected fragments were similar in control grafts (2.6 ± 1.9 × 10⁶ CFU/cm²), in initially implanted grafts of groups II (9 ± 1.1 × 10⁵ CFU/cm²) and III (1.3 ± 1.5 × 10⁶ CFU/cm²), and in untreated replacement grafts of group II (1.7 ± 2.5 × 10⁶ CFU/cm²). Blood culture results and culture results of liver, spleen, kidney, and lung specimens at the time of sacrifice were negative.Conclusion: This study demonstrates that rifampin-bonded gelatin-sealed Dacron grafts are resistant to infection when used for in situ replacement of an infected graft in the dog. (J VASC SURG 1994;19:739-44.)     

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.     

Anastomotic tensile strength following in situ replacement of an infected abdominal aortic graft

The tensile strength and histologic features of anastomotic bonding were studied prior to and following in situ replacement of aortic vascular prostheses infected by Staphylococcus epidermidis. Sterile (n = 6) and infected (n = 19) Dacron grafts were used to replace the abdominal aorta of 25 dogs. After five weeks, grafts were explanted, and peak tensile force (measured in kilograms) required for anastomotic disruption was measured using a linear gain tensiometer. Anastomotic tensile strength (mean +/- SEM) of infected grafts (5.4 +/- 0.5 kg) was decreased when compared with that of sterile, control grafts (9.0 +/- 0.9 kg). The decreased anastomotic tensile strength of infected grafts was the result of an inflammatory aortitis adjacent to the suture line. Only grafts infected with the study strain of bacteria demonstrated signs of infection. In 19 dogs, the graft infection was treated by graft excision, antibiotic administration, and in situ graft replacement (Dacron or polytetrafluoroethylene prostheses). After five weeks and 12 weeks, anastomotic tensile strength of polytetrafluoroethylene (10.6 +/- 0.6 kg) and Dacron (10.8 +/- 0.5 kg) replacement grafts was similar to that of uninfected control grafts. In situ replacement of vascular prostheses infected by S epidermidis can result in graft healing with normal anastomotic bonding.     

Evaluation of three techniques for documenting Staphylococcus epidermidis vascular prosthetic graft infections

Staphylococcus epidermidis (S. epidermidis) vascular prosthetic graft infections are notoriously hard to detect. Three different techniques of determining whether vascular prosthetic grafts were infected using a dog model were evaluated. Aortic angiograms were compared with nuclear magnetic resonance (NMR) imaging and systemic norepinephrine (NE) kinetics to determine if either newer technique would be more reliable than standard angiograms. Twelve dogs were randomized to control (n = 6) or infected groups (n = 6). All dogs had a 5 cm section of their infrarenal aorta replaced with knitted Dacron vascular prosthetic graft. The grafts in the infected group were contaminated by soaking them in a broth containing S. epidermidis. NE production and clearance rates were calculated for all animals after an infusion of 3H-NE using the steady-state radionuclide tracer methodology. One week following graft insertion, dogs were reanesthetized, and the 3H-NE infusion and measurements were repeated. Standard angiograms and NMR imaging were also performed. Once all tests were performed, the prosthetic grafts were removed for cultures. Comparisons between the initial and final norepinephrine measurements for each group were made using the nonparametric Wilcoxon two-sample test, while comparisons between the groups were made by chi square or the Student's t test. Angiogram results were similar for control and infected animals. Angiograms missed disruption of the proximal anastomosis found in three of the six infected dogs at graft removal. None of the six control animals, while five of the six infected animals, had localized areas of high signal intensity on NMR imaging (P less than 0.01) suggesting abscess formation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Infection of vascular prostheses caused by bacterial biofilms

A canine model was developed to study the efficacy of graft replacement as treatment for vascular prosthesis infections from Staphylococcus epidermidis. Infrarenal aortic graft infections were established in 18 dogs by implantation of Dacron prostheses colonized in vitro with a slime-producing strain of S. epidermidis to form an adherent bacteria-laden biofilm (5 X 10(6) colony-forming units/cm2 graft). Study animals developed a graft infection with anatomic and microbiologic characteristics typical of late prosthetic graft infections in humans (sterile perigraft exudate, absent graft incorporation, and normal serum leukocyte count and sedimentation rate). The S. epidermidis study strain was isolated from 14 of 18 explanted grafts (78%) by mechanical disruption of the graft surface biofilm and culture in broth media. Four dogs with sterile graft cultures had histologic evidence of bacterial infection. The established prosthetic surface biofilm infection was treated by graft excision, parenteral cefazolin, and graft replacement with a Dacron or polytetrafluoroethylene (PTFE) vascular prosthesis. One month after graft replacement, no PTFE graft had signs of infection, but perigraft exudate and inflammation involved three of nine Dacron grafts (33%). The study strain was recovered from four of nine PTFE grafts (44%) and two of nine Dacron (22%) replacement grafts (p greater than 0.05). Prosthetic replacement of Dacron prostheses infected by S. epidermidis as a bacteria-laden surface biofilm can result in early graft healing, but persistent colonization of one third of replacement grafts signify that recurrent clinical infection remains a risk.     

Diagnosis and management of aortic graft infection.

This report summarizes the currently available methods of diagnosing and treating aortic graft infections. These infections tend to present in subtle ways; therefore, no single diagnostic test is appropriate for all patients. Available imaging techniques have a wide spectrum of sensitivity and specificity. Complementary tests may be necessary to confirm the diagnosis, determine the extent of infection, and assist with operative planning. Once localized, the infectious organism should be cultured. Treatment should be highly individualized and determined by the virulence of the infectious organism, the extent of infection, and the medical status of the patient. Whereas graft excision and extra-anatomic revascularization remains the "gold standard" for treatment of aortic graft infection, the use of in situ replacement with autogenous vein has been shown to be an excellent alternative. In very limited circumstances, in situ replacement with allograft or rifampin-bonded prosthesis may be acceptable.     

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.     

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.     

Treatment of vascular graft infection by in situ replacement with cryopreserved aortic allografts: An experimental study

Purpose: The purposes of this study were to prove the efficacy of cryopreserved aortic allografts to treat an established vascular graft infection by in situ replacement in an animal model and to evaluate the role of the antibiotics normally used to decontaminate the allografts. Methods: Twenty-three dogs underwent infrarenal aortic replacement with a gelatin-sealed knitted polyester graft contaminated in vitro by staphylococcus epidermidis RP-62. One week later, the 18 surviving animals underwent reoperation for graft removal and were randomized into three groups for in situ replacement: group I (control, n = 6) received a new gelatin-sealed graft; group II (n = 6) received a non–antibiotic-treated cryopreserved allograft; and group III (n = 6) received an antibiotic-treated cryopreserved allograft. Control grafts and allografts were removed 4 weeks after the initial intervention for quantitative bacteriologic analysis and histologic analysis. Bacteriologic results were expressed as colony-forming units per square centimeter of graft material. Qualitative bacteriologic analysis was also obtained from perigraft fluid and tissue. Results: All of the initially implanted grafts and all of the control grafts (group I) were infected at the time of removal. In group II, three out of six allografts were not totally incorporated, whereas in group III incorporation was always complete, with a significantly decreased inflammatory reaction. All of the antibiotic-treated allografts were sterile, whereas three untreated allografts grew bacteria. Conclusions: In this model, cryopreserved aortic allografts were more resistant to reinfection than synthetic grafts after in situ replacement of an infected prosthetic graft. However, the antibiotic loading of the cryopreserved aortic allograft appears to be essential to obtain optimal therapeutic effects. (J Vasc Surg 1998;27:689-98.)     

Identification of Staphylococcus epidermidis vascular graft infections: a comparison of culture techniques

Culture of prosthetic material is routinely used to exclude or implicate infection in the pathogenesis of late-appearing graft complications. In a canine model of aortic graft infection caused by a bacterial biofilm, the influence of culture media (blood agar and tryptic soy broth) and mechanical surface biofilm disruption (tissue grinding and ultrasonic oscillation) on microorganism recovery was determined. Dacron prostheses colonized in vitro with Staphylococcus epidermidis were implanted in the infrarenal aortas of 36 dogs. After 3 weeks an infection with anatomic characteristics of late graft infection in humans was present. Explantation (+/- surface biofilm disruption) of infected grafts showed broth culture was superior (p less than 0.001) to agar media in confirming infection. The recovery rate of S. epidermidis was 30% with agar media, was 72% with broth media alone, and was 83% with broth media plus biofilm disruption. In situ replacement of infected grafts plus parenteral antibiotics resulted in early (1 month) healing of 31 grafts without signs of infection. All replacement grafts were sterile when cultured in broth media alone, but the addition of biofilm disruption isolated the study strain from eight (22%) of 36 grafts (p less than 0.01). Biofilm disruption by tissue grinding or sonication increased bacteria recovery equally. When biofilm bacterial concentration was less than 100 colony-forming units/cm2 of graft, only culture in broth media reliably recovered microorganisms. In the absence of perigraft inflammation, microbiologic recovery techniques that identify bacterial biofilms are necessary to exclude infection in studies concerning the pathogenesis of late graft complications or the treatment of S. epidermidis prosthetic infections.     

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.     

Efficacy and duration of antistaphylococcal activity comparing three antibiotics bonded to Dacron vascular grafts with a collagen release system.

Type 1 collagen, minimally cross-linked, was used to bind one of three antibiotics (amikacin, chloramphenicol, or rifampin) to double-velour Dacron grafts to develop a prosthesis resistant to infection. Six millimeter disks of graft were placed in separate flasks (specific for each antibiotic) containing albumin in saline and continuously agitated. At daily intervals the solution was changed, and paired graft samples were removed and placed on a blood agar plate confluently streaked with bacteria. The initial zone of inhibition (centimeters squared), the time to 50% reduction of initial inhibition zone, and the overall duration of antibacterial activity were recorded on an exponential model. Grafts bonded with amikacin and chloramphenicol had an overall duration of activity of only 2 and 1 day, respectively, against Staphylococcus aureus. The collagen bonded rifampin grafts had an initial zone of 14.76 cm,2 took 3.92 days to reach 50% of initial inhibition, and had an overall duration of activity of 22.4 days. This was significantly better than grafts preclotted with 1.0 ml of rifampin (60 mg/ml) and 9 ml of blood (10.92 cm,2 1.06 days, and 5.6 days). When tested against a slime-producing Staphylococcus epidermidis (American Type Culture Collection No. 35983), the graft bonded with rifampin had inhibitory activity of up to 27.77 days with a 50% of activity eluted at 4.78 days, significantly better than the preclotted rifampin graft without collagen bonding. These data suggest that rifampin bonded by collagen can protect a vascular graft against infection from S. aureus and S. epidermidis for up to 3 weeks after implantation.     

Antibacterial activity,antibiotic retention,and infection resistance of a rifampin-impregnated gelatin-sealed Dacron graft

Purpose: A gelatin-sealed porous Dacron graft impregnated with rifampin was evaluated in a two-part study of its use in preventing prosthetic infection.Methods: The graft was impregnated by soaking it for 15 minutes in rifampin (1 mg/ml). In part 1 its antibacterial activity and rifampin retention over time were determined. Infrarenal aortic replacement was performed in pigs, and the rifampin concentration of the graft, serum, and perigraft space was assayed up to 96 hours after surgery. In part 2, infection resistance was tested in pigs in which the retroperitoneum was contaminated with Staphylococcus aureus after graft replacement. The postoperative infection rate was compared in three groups: pigs given gelatin-sealed grafts without rifampin (controls), pigs receiving nonimpregnated grafts and intravenous rifampin (15 mg/kg) for 3 days after surgery, and those given the rifampin grafts.Results: Rifampin was present in the grafts for up to 72 hours after surgery and in the perigraft fluid for 24 hours but was never detected in the serum. The grafts had inhibitory activity in vitro against S. aureus and the biofilm phase of Staphylococcus epidermidis for up to 3 days and against Escherichia coli for 2 days. Pigs given intravenous rifampin had a significantly lower infection rate than had control pigs (7/12 vs 13/13; p = 0.02); those receiving the rifampin graft had a lower rate (2/13) than had either the control pigs (p < 0.001) or those given intravenous rifampin (p < 0.04).Conclusions: This simple method of graft impregnation resulted in antibiotic retention for 3 days and appeared to be superior to intravenous antibiotic administration in preventing perioperative graft infection. (J VASC SURG 1994;19:675-82.)     

Evaluation of muscle flaps in the treatment of infected aortic grafts.

Standard therapy for abdominal aortic graft infection involving resection of the graft and extraanatomic bypass carries significant morbidity and mortality rates. The present study evaluates the feasibility of combining in situ graft replacement with a highly vascular tissue flap as an alternative to this problem. In 52 pigs a segment of a polytetrafluoroethylene graft was interposed in the infrarenal abdominal aorta. Staphylococcus aureus was used to infect the graft. One week later the animals were divided into six treatment groups. Group 1 (control) had debridement of the retroperitoneum only; group 2 had debridement with replacement of the graft; group 3 consisted of animals with the infected graft left in place and the graft wrapped with a rectus abdominis flap; group 4 is similar to group 3 except the seromuscularis of the jejunum was used to wrap the infected graft; in group 5 the graft was changed, and a rectus abdominis island flap was wrapped around the graft; and finally, group 6 was similar to group 5 except that the flap was obtained from the seromuscularis of the jejunum. Two weeks later, graft patency and infection status were assessed at reoperation. The incidence of graft infection was significantly reduced in groups 5 (0 of 10; p less than 0.01) and 6 (1 of 10; p less than 0.02) compared with group 1 (7 of 10), and the incidence of graft thrombosis was also greatly reduced in groups 5 (2 of 10) and 6 (1 of 10) versus group 1 (10 of 10; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

In situ replacement of infected aortic grafts with rifampicin-bonded prostheses: the Leicester experience (1992 to 1998)

PURPOSE: Prosthetic graft infection after aortic aneurysm surgery is a life-threatening complication. Treatment options include total graft excision and extra-anatomic bypass grafting or in situ replacement of the graft. The latter option is gaining increasing popularity, but the long-term outcome remains uncertain, particularly in light of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We performed a prospective nonrandomized study to assess the outcome after graft excision and in situ replacement with a rifampicin-bonded prosthesis for the treatment of major aortic graft infection. METHODS: In a 6-year period from January 1992 to December 1997, 11 patients (eight men, three women) with major aortic graft infection underwent total graft excision and in situ replacement with a rifampicin-bonded prosthesis. The median age of the patients was 66 years (range, 49 to 78 years). Four patients had a hemorrhage from an aortoenteric fistula, three had a retroperitoneal abscess, two had graft occlusion, one had a perigraft collection shown by means of computed tomography, and one had a ruptured suprarenal false aneurysm. Organisms were cultured from 10 patients. RESULTS: MRSA was isolated in two patients, both of whom had originally undergone repair of a ruptured abdominal aortic aneurysm. Two patients died (18.2%) within 30 days, and three patients (27.6%) had nonfatal complications (peritoneal candidiasis, transient renal impairment, and profound anorexia). Two patients died late in the follow-up period. Seven patients remain alive and clinically free of infection. CONCLUSION: The long-term results after total graft excision and in situ replacement with a rifampicin-bonded prosthesis appear to be favorable. However, MRSA aortic graft infection appears to be associated with a poor prognosis.     

Use of antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary prosthetic vascular graft infections

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.     

Rifampin protection against experimental graft sepsis

The risk of infection in vascular prosthetic conduits appears to be greatest in the perioperative period and the organism most frequently found is Staphylococcus aureus. Previous work suggests that antibiotics must be chemically bonded to the material to resist rapid washout caused by the flow of blood through the graft. The exception to this is rifampin, which remains fixed in Dacron prostheses after passive addition of the agent to aliquots of blood used to clot the interstices of porous Dacron grafts. This characteristic of rifampin is presumed to be caused by its poor water solubility. This potential infection resistance was challenged in a standard model of a canine infrarenal aortic graft by intravenous infusion of S. aureus organisms (10(7)) in the perioperative period. The grafts of five animals were preclotted with 9 ml of autogenous blood plus 1 ml of rifampin (60 mg/ml). A second group had similar procedures with 1 ml of cefazolin (238 mg/ml) substituted for the rifampin, and a control group had 1 ml of saline solution added to the 9 ml aliquot of blood. The animals were killed at 3 weeks and examined for clinically apparent infection. Rings of the graft material were also removed aseptically and cultured. All five grafts preclotted with cefazolin had clinical and culture evidence of infection (S. aureus), as did the grafts of three of the five control dogs. None of the grafts preclotted with rifampin was infected (p less than 0.05). Addition of rifampin to the blood used to clot the graft interstices appears to be a simple way of imparting graft resistance to perioperative sepsis.