Primary graft infections

Primary graft infections William H. Edwards, Jr., M.D., Raymond S. Martin III, M.D., Judith M. Jenkins, 1LN., M.S.N., William H. Edwards, Sr., M.D., and Joseph L. Mtflherin, Jr., M.D., Nashville, Tenn. An amputation rate of 8% to 52% and a mortality rate of 13% to 58% make vascular prosthetic graft infections the most dreaded complication facing a vascular surgeon. In I978 a randomized prospective double-blind study reported a statistically significant decrease in wound infections in patients treated with prophylactic antibiotics whereas the graft infection difference only approached statistical significance. The present study reviews 2614 arterial prosthetic grafts implanted from January 1975 through June 1986. Twenty-four patients were identified as having a prosthetic graft infection, yielding an overall infection rate of 0.92%. Staphylococcus aureus was the most common organism, occurring in one third of the cases. The most common graft material was polytetrafluoroethylene (PTFE) (33%) followed by Dacron (29%), composite PTFE and Dacron (20%), and umbilical vein grafts (9%). Diabetes was a common factor in one third o f the patients. Symptoms of infection were present in 15 patients (63%) within 3 months of operation, with 11 patients showing symptoms within 30 days. The longest interval between operation and onset of symptoms was 48 months. Prophylactic antibiotics were administered to 22 of the24 patients, but in only 7 of the 22 (29.5%) were they given according to our usual practice. All patients required removal of the infected prosthesis, with limb loss in 17% and death in 17%. (J VAsc SURG 1987;6:235-9.)

Infection of a vascular prosthesis is one of the most dreaded complications that faces a vascular surgeon. The incidence of this problem has been reported in the recent literature to range from 0.8% to 2.6%. 19 Even more devastating are the high mortality rates, ranging from 13% to 58% 1~'7'9-11and the high rate of subsequent amputations, ranging from 8% to 52%* that occur after this complication. Nine years ago, a prospective double-blind trial of prophylactic antibiotics in vascular surgical patients was reported. 13 Although this study showed a statistically significant decrease in wound infections in patients treated with prophylactic antibiotics, the graft infection difference between the treated and control groups only approached statistical significance. The present study was undertaken to review our experience with arterial prosthetic grafts that became infected after implantation and to review factors that might lead to lower graft infection rates.

M A T E R I A L AND M E T H O D S From January 1975 through June 1986, 2614 arterial prosthetic grafts were implanted in the aortic, iliac, femoral, and popliteal-tibial positions. All brachiocephalic, visceral artery, vascular access, and patch prostheses are excluded. The Infectious Disease Database was used to identify any patient on the vascular surgical service with any positive wound culture (graft infections are not specifically coded). This yielded approximately 200 patients whose charts were reviewed for identification of Szilagyi grade III graft infections on the basis of purulent or culturepositive perigraft fluid.1 All graft enteric erosions and graft enteric fistulas were excluded from study. In addition, the operative time was obtained for 100 consecutive aortobifemoral bypass grafts and femoropopliteal/tibial bypass grafts performed during 1985 and 1986 with prosthetic material or composite graft and autogenous tissue. Statistical analysis was performed by means of the Mann-Whitney test.

From the Departmentof Surgery,St. ThomasHospital and the Section of Surgical Sciences,Vanderbilt UniversityMedical Center (Drs. Edwards, Jr., Martin, Edwards, Sr., and Mulherin), and the Edwards-EveClinicAssociation(Ms.Jenkins). Presented at the EleventhAnnualMeetingof the SouthernAssociation for Vascular Surgery,Scottsdale,Ariz., Jan. 28-31, 1987. Reprintrequests:WilliamH. Edwards,Sr.,M.D., Suite205, 4230 Harding Rd,, Nashville,TN 37205. *References1, 2, 4, 7, 9, 10, 12.

RESULTS Twenty-four patients (21 men and three women) were identified, giving an overall graft infection rate of 0.92%. The average age of patients at the time of graft implantation was 61.6 years (range 30 to 75 years). Atherosclerotic disease was the indication for operation in all patients. Risk factors for infection (Table I) were found in 19 patients (79%). Post235

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Edwards et al.

Table I. Risk factors for infection

Table II. Graft insertion sites _No.

Wound with infection Diabetes Distal ulcer or gangrene Multiple limb revascularization

%

8 8 5 5

33 33 20 20

4 3

16.6 12.5

(>2) Graft thrombosis Emergency operation

Femoropopliteal Femorotibial Aortobifemoral* Primary femoral artery replacement Extra-anatomic bypass Total

No.

%

8 8 5 1

33 33 21 4 9

2 24

*Two patients required urgent femoropopliteal bypass at same hospitalization.

operative wound infection and diabetes were the most frequent predisposing factors. Preoperative cultures of distal ulcers were obtained in three cases and in only one case was the graft infection identical. Fig. 1 presents the infection rate per year as a function of the number of grafts inserted and Table II presents the sites of insertion. In three cases, other operations were added in addition to the vascular bypass (lumbar sympathectomy, inguinal hernia repair, and cholecystectomy); in two of the aortobifemoral bypass cases, urgent femoropopliteal bypass was required. In five cases, use of a previously inserted aortofemoral graft as a donor vessel for distal bypass resulted in infection of both the distal bypass and at least one limb o f the aortofemoral graft. Two deaths and one hip disarticulation for ischemia and infection ensued from this complication. There were no intraabdominal graft infections in the 2614 cases. In 20 cases the groin was the primary site of infection. Four patients had a graft infection at the distal insertion site. In all cases of graft infection during the period under study, the operation involved a groin incision. The most common graft material involved was polytetrafluoroethylene (PTFE) (33%), followed by Dacron (29%), and then human umbilical vein grafts (9%). The remainder of the infections involved composite PTFE and Dacron (20%) or composite synthetic graft and vein (9%). Staphylococcus aureus was the most common offending organism, occurring in one third o f the cases (Table III). Symptoms of infection became apparent in 15 of the cases less than 3 months after operation, with 11 cases occurring in the first 30 days. Five more infections occurred before 6 months and four occurred after 6 months. The longest interval between operation and onset of infection was 48 months. The most common symptom of infection was purulent wound drainage (48%). This was followed by acute and chronic bleeding (26%), fever (17%), false aneurysm (12.5%), and

was randomly assigned to a control group for study and in the other case the medical record was incomplete. In only 7 of the 22 remaining cases were the prophylactic antibiotics administered according to the recommendations of the hospital Infectious Disease Department. Cefazolin doses at the anesthetic induction were repeated every 4 hours during the operation and continued every 6 hours for a total of 24 hours, xs,14The mean operative time was calculated for both the infected aortofemoral bypass patients and femoropopliteal/tibial patients. The mean operative time for the past 100 consecutive aortobifemoral bypass patients and femoropopliteal/tibial bypass patients was likewise calculated. The two groups were then compared for a difference in operative time with the Mann-Whitney test of significance. The infected aortobifemoral bypass patients had a mean operative time of 245 _+ 58 minutes compared with the population of 100 consecutive aortobifemoral bypass patients whose mean time was 196 _+ 55 minutes (p < 0.05). Likewise, the group of femoropopliteal/tibial bypass patients was compared with 100 consecutive patients with similar operations; means were 168 _+ 63 minutes and 132 _+ 57 minutes, respectively (p < 0.02). All patients eventually required removal of the infected graft with autogenous tissue repair of the native vessel, autogenous tissue bypass through the infected bed, or bypass through clean tissue planes with prosthetic material. Table IV reviews the results obtained, revealing a mortality rate of 17% and an amputation rate of 17%. Three of the four deaths were due to uncontrolled sepsis and one was due to an acute superior mesenteric infarction. The high death rate after the infection of femorodistal bypass grafts was the result of proximal spread along a previously placed aortofemoral graft, which acted as the donor vessel for the distal bypass.

pain (8%).

DISCUSSION Use o f prophylactic antibiotics. The routine use of prophylactic antibiotics in vascular surgery has

Confirmation of prophylactic antibiotic administration was obtained in 22 of 24 cases. One case

Volume 6 Number 3 September 1987

Primary graJ~ infections

237

2.5

2.0

CL 1.5 0

1.0

E 0.5

75

76

77

78

79

80

81

82

8:5

84

85

86

Year of Implantation

Fig, 1. Graft infections per year. contributed to decreasing the graft infection rate. In the randomized study conducted in which prophylactic antibiotics were compared with placebo, a significant decrease in postoperative wound infection in the treated group was found) 3 The study was halted before the graft infection rate reached significance (p = 0.062). It was believed that the continued exposure of patients to placebo was not warranted to prove that graft infections might be reduced. Many authors consider wound infections to be a predisposing factor to deep graft infection and in fact this was the case in one third of our patients in the present

Table Ill. Culture results No. of patients Staphylococcus aureus No growth

7 5

% 29 21

Proteus mirabilis

3

13

Mixed gram positive and gram negative Anaerobes

3

13

2

8

Staphylococcus epidermidis Pseudomonas aeruginosa

1 1

4 4

Serra~ sp.

1

4

Enterobacter cloaca

1

4

Total

24

study. 7,932

Once the decision has been made to use prophylactic antibiotics, we believe that it is equally important that they be administered appropriately. Principles important to their use include an agent effective against most potential pathogens, administration at the time of anesthetic induction, and recurrent doses to maintain serum levels throughout the operative procedure. ~4Kaiser et al.~4"~sreported that deviations from these principles can lead to a higher wound infection rate. Investigation of an increasing wound infection rate on the vascular surgical service in the past uncovered minor deviations from these principles. A cephalosporin of shorter half-life was being substituted and probably led to inadequate serum levels on prolonged procedures. ~ At the same time a random review of charts revealed that the time between "on call" cephalosporin and the surgical procedure had increased from 91 to 131 minutes. In addition, 15% of the patients surveyed had in excess of 3 hours between the administration of the antibiotic prophylaxis and the onset of the surgical procedure. ~4,~s In the present study, prophylactic anti-

biotics were appropriately administered in only 29.5% of the patients in whom a graft infection occurred. Preparation o f the operative site. Skin cleansing and disinfection is an integral part of every surgical procedure. This becomes even more important when operations are performed in the groins. All patients received the standard antiseptic scrub and preparation with povidone-iodine solutions the night before surgery. In the previous study of antibiotic prophylaxis, a significant difference in wound infection rate between hexachlorophene-ethanol skin preparation (10.3%) and the patients receiving a povidoneiodine preparation (2.8%) was seen. In addition, there was an even more marked difference in the wound infection rate in the patients who received hexachlorophene-ethanol skin preparation when they were broken down into placebo and antibiotictreated groups. The placebo group had an extremely high wound infection rate of 18.9% vs. the treated

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Edwards et al.

Table IV. Results of primary graft infections Site of insertion

No.

Aortic/aortoiliac Aortofemoral Femoropopliteal/tibial Extra-anatomic Total

769 1060 583 202 2614

Infections 0 5 17 2 24

(0.47%) (2.9%) (0.99%) (0.92%)

group with no wound infections, suggesting an even greater protection of prophylactic antibiotics.IS If the groin is the "dirtiest" area in which vascular surgeons perform operations and prophylactic antibiotics seem to be more effective when the wound infection rate is higher, then their proper use takes on even greater importance when an operation in the groin is contemplated. Several authors have noted a disproportionate infection rate when a groin incision is involved in the implantation of a vascular prosthesis. 1-4,6,9,11Most of these infections probably result from the inability to prepare and drape this area, as well as the moisture and constant motion that occur postoperatively. It is important to avoid skin contamination of the graft and the use of plastic skin drapes on all cases involving the abdomen and groins is standard practice with the higher incidence of infections found in the femoropopliteal/tibial group. We began to use circumferential plastic leg drapes in all distal bypass procedures in which it was known that a synthetic graft was required. Role o f local and remote w o u n d contamination. Arteriography performed in the same groin as the vascular prosthesis implantation has been thought by some authors to contribute to a higher rate of groin wound complications. 6 Routine use of translumbar aortography for investigation of aortoiliac atherosclerotic disease and needle femoral arteriography when there is suspicion of distal disease avoids this problem. Personal performance of these procedures assures adequate visualization of the arterial tree. These procedures are performed by members of a vascular team of attending physicians and residents. When catheter studies are carried out from the groin, every attempt is made to perform the operative procedure the next day. Remote site infections have been thought to be important in the genesis of wound infections and perioperative bacteremia. .6 There are anecdotal reports in the literature of remote site infections (primarily urinary) causing graft infections. Accordingly, the active investigation of even minimal pyuria pre-

No amputation 0 2 12 2 16

(40%) (70%) (100%) (66%)

Amputation

Deaths

0 2 (40%) 2 (12%) 0 4 (17%)

0 1 (20%) 3 (18%) 0 4 (17%)

operatively and institution of antibiotic treatment as soon as cultures are obtained should be standard. If an infection is confirmed, then therapeutic antibiotics are used and adjusted according to the organism and sensitivity. The effect o f operative time. Surgical wound infection rates have previously been correlated with duration of operation and in at least one report, it was thought that the length of operation was a reflection of operative technique. 9,1r Expeditious completion of surgical procedures with two dissection and anastomotic teams operating simultaneously when the case involves two groins or a groin and a leg will keep open wound times to a minimum. In the present study, a statistically significant difference was found between the operative times in the respective infected aortobifemoral and femoropopliteal/tibial patients compared with a group of patients that are comparable except for date of operation. The two groups may not be completely comparable as the skills of the surgeons involved have probably improved during the 11.5 years of the study and that may have contributed to a shorter operative time in the past 100 patients. Lorentzen et al.9 reported median operative times of 310 minutes for infected bifurcated grafts and a corresponding time in femoral peripheral reconstructions of 295 minutes with infection rates of 2.6% for a group of patients in Denmark. Shorter operative times through the use of the two-team approach have contributed to maintenance of a low graft infection rate in the patients reported herein. The effect o f secondary operations. Groins in which a previous graft implantation was performed afford special challenges. It is essential in all surgical procedures to use Halstedian principles of operative technique. Never is this more important than in groins in which operations have been repeated, where there is dense scar tissue, increased bleeding, lymphatic leak, and frequently nonfunctioning graft material already implanted. In the present study, 20% of patients had had more than two revascularizations of their distal extremity. In addition, six patients suf-

Volume 6 Number 3 September 1987

fered proximal extension of their infection to previously implanted graft material, resulting in significant morbidity and mortality. In many cases it is necessary to use the proximal graft as the donor artery. An alternative approach to the groin is to join the graft onto the native artery distal to the donor graft, thereby avoiding disruption of the perigraft fibrous capsule when the anastomoses are constructed. Treatment o f infected grafts. Prevention is the best treatment of vascular prosthetic graft infections. When an infection occurs, authors disagree on the most appropriate treatment. All patients in the study ultimately required excision of the infected portion of the graft and bypass through clean tissue planes, bypass with autogenous tissue through the infected bed, or repair of the native vessel with autogenous tissue. This treatment led to an overall amputation rate of 17% and a mortality rate of 17%. Sixty-six percent of the patients recovered completely with limb intact. Local wound irrigation has been used if suture lines are not exposed. Prosthetic vascular graft infections are fortunately a rare event. Our infection rate of 0.92% compares favorably with that reported in the literature, which in recent years is approximately 2%. Vascular graft infections, despite their low incidence, remain a significant problem, challenging all vascular surgeons. Detection and treatment require perseverance and ingenuity. Only through continued aggressive prevention will the rate of graft infection be decreased. Prevention of prosthetic graft infections through future research should continue. Emphasis should be placed on chemical sterilization of the contaminated wound with more effective antibiotic prophylaxis, research into control of routes of wound contamination, and modification of the host immune system. REFERENCES 1. Szilagyi DE, Smith RF, Elliott JP, Vrandecic MP. Infection in arterial reconstruction with synthetic grafts. Ann Surg 1972; 176:321-33.

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2. Goldstone J, Moore WS. Infection in vascular prostheses: clinical manifestations and surgical management. Am J Surg 1974;128:225-33. 3. Jamieson GG, DeWeese JA, Rob CG. Infected arterial grafts. Ann Surg 1975;181:850-2. 4. Liekweg WG, Greenfield LJ. Vascular prosthetic infections: collected experience and results of treatment. Surge~, 1977; 81:335-42. 5. Ernst CB, Campbell Jr HC, Daugherty ME, Sachatello CR, Griffen WO. Incidence and significance of intraoperative bacterial cultures during abdominal aortic aneurysmectomy. Ann Surg 1977;185:626-30. 6. Landreneau MD, Raju S. Infections after elective bypass surgery for lower limb ischemia: the influence of preoperative transcutaneous arteriography. Surgery 1981;90:956-61. 7. Bunt TJ. Synthetic vascular graft infections. I. Graft infections. Surgery 1983;93:733-46. 8. Bennion RS, Hiatt JR, Williams RA, Wilson SE. Surgical management of unilateral groin infection after aortofemoral bypass. Surg Gynecol Obstet 1983;156:724-8. 9. Lorentzen JE, Nielsen OM, Arendrup H, et al. Vascular graft infection: an analysis of sixty-two graft infections in 2411 consecutively implanted synthetic vascular grafts. Surgery 1985;98:81-6. 10. Ehrenfeld WK, Wilbur BG, Olcott CN, Stoney RJ. Autogenous tissue reconstruction in the management of infected prosthetic grafts. Surgery 1979;85:82-92. 11. Bouhoutsos J, Chavatzas D, Martin P, Morris T. Infected synthetic arterial grafts. Br J Surg 1974;61:108-11. 12. Reilly LM, Altman H, Lusby RJ, Kersh RA~ Ehrenfeld WK, Stoney RJ. Late results following surgical management of vascular graft infection. J VAsc SURG 1984;1:36-44. 13. Kaiser AB, Clayson KR, Mulherin Jr JL, et al. Antibiotic prophylaxis in vascular surgery. Ann Surg 1978;188:283-9. 14. Kaiser A. Zero infection rate: an achievable irreducible minimum in clean surgery? Infect Control 1986;7:107-9. 15. Kaiser A. Effective and creative surveillance and reporting of surgical wound infections. Infect Control 1982;3:41-3. 16. Edwards LD. The epidemiology of 2056 remote site infections and 1966 surgical wound infections occurring in 1865 patients: a four-year study of 40,923 operations at RushPresbyterian-St. Luke's Hospital, Chicago. Ann Surg 1976; 184:758-66. 17. Cruse PJE, Foord R. A five-year prospective study of 23,649 surgical wounds. Arch Surg 1973;107:206-9.