Significance of infection markers and ... - Hogrefe eContent

VASA 2009; 38: 365–373 © 2009 by Verlag Hans Huber, Hogrefe AG, Bern

T. E. Bisdas et al., Volume 38, Issue 4, November 2009 DOI 10.1024/0301–1526.38.4.365

Original communication 365

Significance of infection markers and microbiological findings during tissue processing of cryopreserved arterial homografts for the early postoperative course T. E. Bisdas1, F. Mattner2, 3, E. Ott3, M. A. Pichlmaier1, M. Wilhelmi1, A. Haverich1 and O. Teebken1 1

Hannover Medical School, Dept. of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover, Germany University of Schleswig Holstein, Campus Luebeck, Institute of Microbiology and Hygiene, Luebeck, Germany 3 Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, Hannover, Germany 2

Summary

Zusammenfassung

Background: To evaluate homograft implantation for the urgent treatment of vascular infections on the basis of the course of infection using microbiological findings in perioperatively obtained specimens and during homograft processing. Patients and methods: 85 patients were treated with cryopreserved homografts from 2004–2007. The microbiological findings of the decontamination process of homografts in the tissue bank were evaluated. The perioperative infection profile (microorganisms, CRP, leukocytes, body temperature) of the patients was analysed. Results: Complete microbiological and clinical follow-up for the postoperative course was available for 35 patients, who were treated with homografts from the same tissue bank and finally included into this study. 55 cryopreserved homografts were implanted. 35 / 55 (64 %) homografts were positive for microorganisms before decontamination. 3 / 35 (9 %) homografts remained positive after the decontamination. 33 patients were operated for prosthetic graft infection and 2 for an infiltration of a large vessel from neighbouring malignant disease. The most common infection agent was Staphylococcus aureus. Thirty-day mortality was 20 % (7 / 35). Only in 4 / 35 (11 %) patients were the microorganisms of the intraoperative swabs also detected during the postoperative course. The microorganisms were ORSA, Enterococcus faecium, Enterobacter aerogenes and Burkholderia cepacia. The patient with ORSA infection died on POD 11 from multiple organ failure and all other patients recovered. None of the postoperative swabs showed the homograft predecontamination microorganisms. Interestingly, a significant association (P = 0.003) between C-reactive protein increase two weeks after surgery and donor-recipient ABO mismatch was found. Conclusions: The implantation of homografts following the established decontamination is an alternative urgent therapeutic option in vascular infections with encouraging outcomes. The absence of the predecontamination focus in the postoperative specimens of patients, suggests that the postoperative course and outcomes show no strong relation to potential homograft contamination prior to the decontamination process.

Bedeutung von Infektionsparameter und mikrobiologischen Befunden während der Homograft-Prozessierung für den frühen postoperativen Verlauf Hintergrund: Erfassung und Beurteilung des Krankheitsverlaufes nach einer Homograftimplantation zur Therapie einer Gefäß- oder Protheseninfektion in Abhängigkeit von den perioperativ in vivo erhobenen mikrobiologischen Befunden und während der Homograft-Prozessierung in vitro. Patienten und Methoden: Fünfundachtzig Patienten wurden von 2004 bis 2007 mit kryokonservierten Homografts therapiert. Die mikrobiologischen Befunde aus dem Dekontaminationsprozess der Homografts in der Gewebebank wurden ausgewertet. Das perioperative Infektionsprofil (Mikroorganismen, CRP, Leukozyten, Körpertemperatur) der Patienten wurde erfasst. Ergebnisse: Fünfunddreißig Patienten, für die ein komplettes mikrobiologisches und klinisches Follow-up erstellt werden konnte, wurden in die Studie einbezogen. Fünfundfünfzig Homografts wurden implantiert, bei 35 / 55 (64 %) der Homografts wurden vor der Dekontamination Bakterien nachgewiesen, bei 3 / 35 (9 %) der Homografts auch nach der Dekontamination. Dreiunddreißig Patienten wurden wegen einer Gefäßprotheseninfektion und zwei aufgrund einer tumorösen Gefäßinfiltration behandelt. Am häufigsten wurde Staphylococcus aureus nachgewiesen. Die 30-Tage-Mortalität betrug 20 % (7 / 35). In nur 4 / 35 (11 %) der Patienten fanden sich die in den intraoperativen Proben gefundenen Mikroorganismen auch in der postoperativen Phase wieder. Folgende Keime wurden nachgewiesen: ORSA, Enterococcus faecium, Enterobacter aerogenes and Burkholderia cepacia. Der eine Patient mit der ORSA-Infektion starb am 11. postoperativen Tag an Multiorganversagen, die anderen drei überlebten. In keinem Fall wurde postoperativ ein vor der Dekontamination im Homograft nachgewiesener Keim detektiert. Interessant ist eine signifikante Assoziation (P = 0.003) zwischen dem CRP-Anstieg zwei Wochen nach dem operativen Eingriff und einem Spender / Empfänger ABO-Missmatch. Schlussfolgerungen: Kryokonservierte Homografts sind eine wichtige Alternative in der chirurgischen Behandlung von Gefäß-(Prothesen)infektionen. Das Fehlen von vor dem Dekontaminationsprozess noch nachgewiesenen Keimen in den postoperativ gewonnenen Patientenproben spricht dafür, dass das Dekontaminationsprotokoll effektiv ist und dass es dadurch keinen Zusammenhang zwischen Krankheitsverlauf und potentieller Kontamination der Homografts vor der Prozessierung gibt.

Key words: Cryopreservation, decontamination, graft infection, homograft, human allograft, microbiology, vascular infection

T. E. Bisdas et al., Volume 38, Issue 4, November 2009


366 Original communication

Introduction Homografts have been under evaluation with controversial results for the past 40 years [3]. A difficult technical task remains the reestablishment of arterial perfusion in contaminated fields. Currently, improved methods for cryopreservation and decontamination of homografts have resulted in better graft survival namely with regard to the viscoelastic and inertial properties of the arterial wall [1]. Clinical outcomes and survival rates using homografts in cardiac surgery or for vascular surgical procedures e.g. in graft infections are well documented [12, 17, 18]. However, no studies exist in the English literature correlating the infection profile of the patient with the microbiological findings and the graft decontamination protocol. The aim of this study is (1) to evaluate the decontamination protocol with respect to the microbiological findings of homografts before and after decontamination, (2) to correlate these findings with the data from intraoperative and postoperative specimens and finally (3) to assess the effectiveness of this therapy analysing the blood and clinical status of our patients.

Patients and methods Patients Between January 2004 and December 2007, 85 patients were treated with cryopreserved homografts. Complete microbiological and clinical follow-up of the postoperative course was available for 35 patients (29 male and 6 female), who were treated with homografts from the same tissue bank and finally included into this study. Their mean age was 61 ± 13 years (range: 48–74). The patient demographics are shown in Table I.

Table I: Demographic data, risk profile and indications for surgery of 35 patients at hospital admission Characteristics

Number (%)

Age, years (range)

61 (74-48)

Gender Male

29 (83 )

Female

6 (17)

Indications for surgery Prosthetic graft infection

25 (71)

Perforated mycotic aneurysm

8 (23)

Infiltration of a large vessel from neighbouring malignant disease

2 (6)

Comorbidities Diabetes mellitus type 1

0 (0)

Diabetes mellitus type 2

5 (14)

Arterial hypertension

24 (69)

Heart insufficiency

4 (11)

ORSA/MRSA1 infection / colonisation2

2 (6) / 3 (9)

Coronary artery disease

7 (20)

Renal insufficiency

16 (46)

Hypercholesterolemia

9 (26)

Chronic obstructive pulmonary disease

7 (20)

1 ORSA: Oxacillin-resistant Staphylococcus aureus, MRSA: Methicillin-resistant Staphylococcus aureus 2 swab from nose

Homograft preparation All homografts were provided by Deutsche Gesellschaft fuer Gewebetransplantation (DGFG), or her predecessor DSO-G, and were harvested from multi-organ-donors. All donors were tested seronegative for human immunodeficiency virus and antibodies against hepatitis B surface and core antigen, hepatitis C and cytomegalovirus. The grafts were kept in + 4 °C Ringer’s solution and were processed according to DGFG standard operating procedures. Tissues were kept in 250 ml tissue culture medium M199 containing broadspectrum antibiotic cocktail (Mero-

penem, Colistin, Tobramycin, Vancomycin, Amphotericin B) at + 4 °C for 24 h. Before and after decontamination microbiologic tests were performed of various tissue samples. After rinsing with tissue culture medium, tissues were transferred to M199 containing 10 % dimethyl sulfoxide as cryoprotective agent and then were frozen at 1 °C / min to –40 °C. Before the cryopreservation, various tissue samples were examined by an independent pathologist according to an internal protocol of the DGFG comparable to the standards of American Association of Tissue Banks. Only homografts without




pathological changes were implanted. After further cooling to –100 °C the homografts were transferred to permanent storage in vapour phase of liquid nitrogen. Before implantation, grafts were thawed and washed in three consecutive + 40 °C baths of Ringer’s solution in the operating room. Homograft implantation technique Prosthetic graft infection in aorta and peripheral vessels (n = 19): The indications are shown in Table II. From the 14 patients with aortic prosthetic infection, two were treated for an aorto-pulmonary fistula following thoracic aortic replacement. The first patient was treated initially for aortic coarctation using a Dacron patch. Because of a postoperative aneurysm of the aortic isthmus, a stent graft was implanted. 6 months later the patient developed haemoptysis and was operated as follows. The distal aortic arch and the proximal descending aorta were reconstructed with a 12 cm thoracic homograft. The fistula was occluded with 3–0 propylene stitches. The second patient developed a fistula one year after prosthetic thoraco-abdominal aortic replacement. The prosthesis was explanted and replaced by three homografts. In two patients the indication for homograft replacement was an infected aortic Dacron graft following aortic arch replacement with elephant trunk [2]. Five patients were operated for an infected infrarenal Y-graft (aortobiiliac). A total of nine homografts were used and in all cases the abdominal aorta was approached via median laparotomy. Four patients were operated for an aorto-intestinal fistula after repair of an infrarenal abdominal aneurysm with a Dacron bifurcated graft (aorto-biiliac). The surgical technique in all cases is described elsewhere [17, 18].

Ruptured mycotic aneurysm (n = 8): 8 patients received a homograft because of a ruptured mycotic aneurysm (RMA). The indications as well as the primary operations are shown in Table II. In all patients the diagnosis was based on physical examination, patient history and CT images, and positive evidence of microorganisms was confirmed with intraoperative swabs. For a description of the surgical technique see Ref. 17 and 18. Endocarditis (n = 6): Four patients were operated for prosthetic valve endocarditis and two patients for an infection of the Dacron prosthesis after aortic valve reimplantation according to David [5]. All patients had aortic root replacement with reimplantation of the coronary arteries [12]. Neighbouring malignant disease (n = 2): The indications were angiosarcom infiltrating the left pulmonary artery in one patient and an urothelium carcinoma infiltrating the right iliac bifurcation in the second. In the first patient a left intrapericardial pneumonectomy was performed and the right pulmonary artery was substituted with a 10 mm homograft via median sternotomy. In the second patient the tumour was removed and the involved vessel (common iliac artery 2 cm proximal to the bifurcation) was replaced with a homograft. Data collection and statistics Microbiological findings Microbiological findings before and after the decontamination process were provided by DGFG documents. All preoperative swabs from wounds, blood culture and abscess puncture were obtained from patient records and matched with the intraoperative findings as well as with the postoperative blood cultures.

There were intraoperative swabs from all operative fields. The postoperative blood cultures were taken from all patients. The results from this matching were correlated with the variation of leukocytes and C reactive protein (CRP) during the postoperative course. Infection profile The criteria of the Centers for Disease Control and Prevention (CDC) were used for the definition of evidence of infection in the pre- and postoperative swabs, as well as of primary sepsis, which had developed after implantation of the homograft [11]. Daily body temperature of patient, leukocytes and CRP were recorded daily at 07:00 am from the first postoperative day until the day of discharge. ABO compatibility of patients We matched blood groups from tissue donors with the blood group from our study patients. HLA typing was not performed. Data analysis and statistical methods Clinical follow-up lasted from the first postoperative day (POD) until the day of discharge for a median period of hospitalisation of 20.5 ± 12.2 days (range: 8.3–32.7). Data of all homograft recipients was collected prospectively, including the 35 consecutive patients. The analysis was performed using Microsoft Excel and Epi Info (Version 3.5) software. All continuous data is presented as mean and range. Fisher’s exact test were used to examine potential association between second increase of CRP, mortality and ABO incompatibility, as well as between mortality, each comorbidity and preoperative ASA score. Statistical significance was defined as P < 0.05.




Table II: Indications for replacement of the infected prosthesis / vessel with a homograft

Primary operation

Indication

Number

Implantation of a stent for treatment of restenosis 6 months after patchplasty for aortic coarctation

Pulmonary – graft fistula

Replacement of thoracoabdominal aorta

1 1

Aortic arch replacement using elephant trunk technique

Infection of the old graft

2

Y – graft (aorto – biiliac)

5

A. femoralis communis – A. poplitea I graft bypass

2

A. iliaca communis – A. femoralis communis graft bypass

2

A. profunda femoris patchplasty

1 Intestine – graft fistula

Infrarenal Y - graft (aorto – biiliac)

1

graft – duodenum

2

graft – jejunum

1

graft – sigmoid colon

1

Explorative abdominal laparotomy

RMA1 of abdominal aorta

2

Destruction of vertebral body (LKW 4–5)

RMA of abdominal aorta

1

Spondyloscitis with RMA of abdominal aorta

2

Open-surgical occlusion of arterial duct

RMA of aorta ascendens

1

Aortobiprofundal Y-graft

RMA of profunda femoris artery

1

Treatment of thyroid gland cancer

RMA of brachiocephalic trunk

1

RMA: ruptured mycotic aneurysm

Results Hospital mortality Thirty-day mortality was 20% (7/35 patients). Five patients died on POD 1, one patient on POD 7, one patient on POD 11. Two patients (5.7 %) died during hospitalisation after POD 30, resulting in an in-hospital mortality of 25.7 %. All patients died from multi organ failure, and only one patient was examined postmortem. Due to the absence of any

macroscopic degeneration, no information was provided regarding the histological status of homografts. No statistically significant association was obtained between mortality rates and comorbidities (P > 0.05) as well as preoperative ASA score > 2 (P = 1.00).

Microbiological findings in homografts before and after decontamination Fifty-five homografts were implanted. 35 / 55 (64 %) were positive to one or more microorganisms (Table III) before the decontamination process, 18 homografts were negative and in 2 homografts pre-decontamination results were not available. After the decontamination process 32 / 35 homografts had no evidence of bacteria, 18 / 18 homografts remained




negative and 3 / 35 homografts continued to be tested positive. One homograft was positive for Staphylococcus epidermidis and Candida tropicalis before and after the decontamination. One was positive for Klebsiella oxytoca and Staphylococcus epidermidis before the process and with Propionibacterium spp thereafter. In the third, the microbiological agents were Escherichia coli and Actinobacter baumannii before the decontamination and Propionibacterium spp after the decontamination. Figure 1 shows the final matching of the microbiological findings with regard to the decontamination process. Microbiological findings from pre-, intra- and postoperative specimens Preoperative swabs were taken from eight patients with open wounds, from the drainage fluid in one patient and blood samples were drawn from all patients. Table IV presents the detected microorganisms and their frequency in pre-, intra- and postoperative specimens. Unsuccessful elimination of the initial focus was found in 4 patients (Table V). In the first patient an infected graft (A. iliaca communis – A. femoralis communis bypass) was replaced. The second patient was treated for an infected aortic Dacron graft after replacement of the ascending aorta and aortic arch with elephant trunk due to acute type A dissection. The third and the fourth patients were operated for an infected infrarenal Y-graft (aorto-biliac). The most common microorganisms in the intraoperative swabs were Staphylococcus aureus and the MRSA / ORSA type (10 / 38 patients). Infection profile of patients A complete data set covering the initial 30 days was available for 33 patients. During the postopera-

Table III: Microorganisms cultured from 55 homografts and their frequencies before decontamination Microorganisms1

No. of homografts n=55 (%)

No microorganisms

26 (47%)

Staphylococcus epidermidis

12 (24%)

Staphylococcus aureus

4 (8%)

Staphylococcus capitis

4 (8%)

Staphylococcus spp.

4 (8%)

Acinetobacter baumannii

3 (6%)

Escherichia coli

2 (4%)

Klebsiella pneumoniae pneumoniae

2 (4%)

Propionibacterium spp.

2 (4%)

Candida albicans

1 (2%)

Candida glabrata

1 (2%)

Candida guilliermondii

1 (2%)

Candida tropicalis

1 (2%)

Enterobacter cloacae

1 (2%)

Enterococcus faecalis

1 (2%)

Klebsiella oxytoca

1 (2%)

Lactobacillus spp.

1 (2%)

Staphylococcus lugdunensis

1 (2%)

Streptococcus constellatus

1 (2%)

Staphylococcus haemolyticus

1 (2%)

Streptococcus mitis

1 (2%)

1

18 homografts had more than one microorganism in their microbiological swab.

tive course the median peak body temperature was 37.8 °C (range: 37.1–38.5). In the first five POD all patients (n = 33) exhibited the expected postoperative simultaneous increase of leukocyte count and CRP. Unexpected was a secondary increase of CRP (SI-CRP) between POD 6 and POD 10 in 22 / 32 patients (Figure 2). At that time there was no evidence of infection due to sterile microbiological specimens and no parallel increase of leukocytes. No significant association was found between SI-CRP and mortality (P = 0.09) and between SI-CRP and ASA score > 2 (P = 1.00).

ABO compatibility between homograft donor and recipient We reviewed the ABO blood group compatibility between patients and donors of the homografts. Considering the fact that some patients received more than one homograft, we accepted ABO compatibility only if all homografts had the same blood group as the respective patient. There were only 10 patients with such a perfect match. A significant association between the ABO incompatibility and SI-CRP was found with a risk ratio of 2.52 (95 % CI: 1.166–5.484, P = 0.003).




Discussion Prosthetic vascular graft infections still remain a serious problem. The majority of graft infections are probably caused by inoculation of bacteria at the time of surgery, despite perioperative antibiotics [17]. Mycotic aneurysms are a great surgical challenge as well. They account for 0.8 % of aneurysms operated on, require an aggressive antimicrobial therapy and immediate surgical repair [9]. Furthermore, aortoenteric and aortopulmonary / bronchial fistula are associated with significant mortality. The prognosis remains poor with overall survival reported to be near 44 % regardless of the method of repair employed [8, 18]. Despite absence of randomised trials and level I evidence, many vascular surgeons prefer human allografts to deal with the difficult problem of mycotic aneurysms or prosthetic graft infection [17, 18]. Homografts have been used for aortic valve replacement in cardiac surgery patients with excellent clinical outcomes [12]. However, published results are difficult to transfer to vascular surgery due to the small number of patients and the heterogenous patient population. Despite the fact that homografts have been utilised for many decades, the association between decontamination protocol, microbiological findings and postoperative outcomes in cardiovascular infections is neither well defined nor has it been addressed previously in detail. Thus, our results show that the decontamination process is an appropriate and encouraging method due to the absence of the pre-decontamination microorganisms not only after decontamination in the majority of cases, but also in the postoperative specimens. Three homografts were tested positive for bacteria after the decontami-

Figure 1: Relationship of microbiological findings before and after homograft decontamination (source: DSO-G) 1

Percentages differ from 100 since for two homografts microbiological results were not available before the decontamination, however their microbiological swabs were negative after the decontamination.

Table IV: Detected microorganisms and their frequencies in the pre-, intraand postoperative swabs Microorganisms Staphylococcus aureus Oxacillin-resistant Staphylococcus aureus Enterococcus faecalis Enterococcus faecium Escherichia coli Bacteroides spp. Burkholderia cepacia Candida albicans Enterobacter cloacae Enterobacter aerogenes Lactobacillus rhamnosus Pseudomonas aeruginosa Salmonella typhimurium Stenotrophomonas maltophilia 1

No. of patients1 n=35 (%) 6 (16) 4 (11) 3 (7) 3 (7) 2 (5) 1 (2) 1 (2) 1 (2) 1 (2) 1 (2) 1 (2) 1 (2) 1 (2) 1 (2)

In 4 patients 2 microorganisms were detected in the microbiological swab. 5 patients died on POD 1 without postoperative swab. In 2 patients the swabs were free of microorganisms and in 2 patients neither intra- nor postoperative swabs were taken.




Median peak values of CRP after 6th POD (n=22)

CRP (mg/L)

250 200 150 100 50 0 POD

Figure 2: Median peak values of CRP between POD 6–10 in 22 / 32 patients (mean ± SD) 1 1 th 6 day: 79 g/l (29–129), 7th day: 105 g/l (43–167), 8th day: 137 g/l (65–209), 9th day: 130 g/l (38–222), 10th day: 80 g/l (1–159)

nation. The fact, that in all cases we had no evidence of post- or predecontamination foci in the postoperative specimens of patients, suggests that the postoperative course and outcomes show no strong relation to potential homograft contamination prior to the decontamination process, under the condition of perioperative broad spectrum antibiotic prophylaxis. The comparison of the pre- or intraoperative swabs with the postoperative samples of blood cultures showed encouraging results with respect to the surgical procedure and the effectiveness of homografts to eliminate the primary focus. According to Table V in 4 / 38 (10.5 %) patients the initial microorganism was re-detected in the blood culture or in the wound after the operation. The microorganisms were ORSA, Enterococcus faecium, Enterobacter aerogenes and Burkholderia cepacia. In one of four patients (25 %) with preoperative ORSA infection we detected the microorganism postoperatively again and the patient died on POD11 from multi organ failure. All other patients recovered. As found

by other groups, the most common infection agent was Staphylococcus aureus [6, 15]. Our thirty-day mortality was 20 % and is higher than in other groups [17–19]. Lavigne et al. in their comparison of the treatment of prosthetic vascular infection with and without cryopreserved homograft had a 13.6 % mortality [13]. Vogt et al., who investigated fistulae which originated from aortic aneurysms or infected prosthetic grafts, presented only 9 % mortality [18]. These differences may be due to the heterogeneity of indications, the patients’ comorbidities and patient selection (Table I). The insignificant association between mortality and preoperative ASA score could be due to the small size of our cohort. The analysis of the infection profile confirmed the expected increase of leukocytes and CRP during the first five POD that is related to the infection itself and surgical stress [14]. Interestingly, we detected a new increase of CRP between the 5th and 10th POD with a median peak value of 132 g / dl (65–209 mg / L) in 22 / 32 patients without parallel evidence

of ongoing or recurrent infections. These findings are most likely explained by a possible immunological reaction against the homograft. Cochran et al. presented an experimental model, which came to the conclusion that cryopreservation does not alter the antigenic expression and recommended that at least ABO compatibility should be maintained in all patients undergoing aortic homograft implantation [4]. Fischlein et al. demonstrated after insertion of ABO incompatible homografts in 16 patients an immunologic reaction which was reversible without immunosuppressant treatment [7]. Our proposition, that there is a significant association between the additional SI-CRP and the ABO mismatch between donor and recipient, was confirmed (p = 0.003). Homografts are able to evoke a reduced proliferative response of immunecompetent cells in vitro due to the reduction or absence of endothelial cells [10]. These cells are capable of triggering immune responses by expressing HLA class II. Nevertheless, after the cryopreservation procedure Hoekstra et al. [10] were able to show immune responses against homografts and found an effect of HLA class II matching. This can be explained by the presence of other class II bearing cells, different from endothelium, e.g., dendritic cells or even fibroblasts in the homograft [10]. Simon et al. made an interesting observation when discovering an increased MHC molecule expression in human cardiac allografts after stimulation with IFN-γ [16]. Cytokines, locally released during inflammatory processes or rejection, might induce the up-regulation of MHC-class-II molecules in vivo, thereby increasing the immunogenicity and antigenicity of the graft endothelium and potentially initiating a host reaction against homograft [19]. Additional research



excluded

excluded

no microorganisms detected 2

before decontamination process 1

ND3 Patient 4

Staphylococcus spp.

Candida albicans

Candida glabrata

oxacillin-resistant Staphylococcus aureus

ND ND

ND ND

Candida tropicalis Candida tropicalis

Staphylococcus epidermidis Patient 3

Staphylococcus epidermidis Staphylococcus epidermidis Patient 2

Acetinobacter baumanii

Escherichia coli Patient 1

ND

Burkholderia cepacia

3

Enterobacter aerogens

B.cepacia

Enterococcus faecium

ND

Staphylococcus epidermidis

OS-SSI, BSI (POD 11)

Superficial incisional secondary SSI (POD 8)

BSI (POD 13) B.cepacia

BSI (POD 3)

excluded

excluded Deep incisional secondary SSI, ORSA ORSA2

ORSA

Assessment of donor relatedness Postoperative infection type (day of examination) Post operative blood culture Postoperative contamination of the surgical site Intra operative contamination of the surgical site Microbiological status after decontamination Homograft contamination1 Patient

Table V: Course of microbiological findings in four patients with ongoing infection according to CDC criteria and positive postoperative swabs. (SSI = surgical site infection; BSI = bloodstream infection, OS-SSI = organ/space surgical site infection)


is required in this direction and the cross-matching between homograft and recipient could help to select sensitized patients. Another option remains the use of immunosuppressive agents, although one has to balance their potential benefits with their adherent side-effects [10, 16]. There are several limitations to our study. Despite the intended prospective design, some aspects were evaluated after completion in a subgroup analysis, particularly the relationship between ABO match and the infection profile. Since only the DGFG was able to provide the complete microbiological workup for the decontamination process we included only the data of those homografts that were obtained from their tissue banks (44.7 %). The observation period included only the hospital stay without long-term results. A comparative analysis of our data regarding the postoperative course is difficult because of the variety of surgical procedures prior to the infection and, indeed, those performed to cure the graft infection, the different indications for surgery and implantation sites. Particularly the involvement of cardiac/aortic procedures with the use of extracorporeal circulation will bother the vascular surgeon. However, from a statisticians’ point of view this item is not relevant with respect to secondary increase of CRP and leukocytes. Furthermore, we did neither control the HLA compatibility between donor and recipient nor D-allel and Rhesus factor, but only the ABO blood group. A distinguishable immunologic monitoring was not performed, but is planned for the future. Finally, we are not able to present a control group, e.g. data from patients who were treated with silver coated Dacron graft, since such a therapy is not part of our treatment algorithm for vascular infections.




Conflicts of interest

8

There are no conflicts of interest existing.

References 1

2

3

4

5

6

7

Bia D, Pessana F, Amentano R, Pèrez H, Graf S, Zòcalo Y, et al. Cryopreservation procedure does not modify human carotid homografts mechanical properties: an isobaric and dynamic analysis. Cell and Tissue Banking 2006; 7: 183–94. Borst HG, Walterbusch G, Schaps D. Extensive aortic replacement using ‘‘elephant trunk’’ prosthesis. J Thorac Cardiovasc Surg 1983; 31: 37–40. Callow A.D. Arterial Homografts. Eur J Vasc Endovasc Surg 1996; 12: 272–81. Cochran RP, Kunzelman KS. Cryopreservation does not alter antigenic expression of aortic allografts J Surg Research 1989; 46: 597–9. David TE, Feindel CM. An aortic valve-sparing operation for patients with aortic incompetence and aneurysm of the ascending aorta. J Thorac Cardiovasc Surg 1992; 103: 617–21. Fiorani P, Speziale F, Calisti A, Misuraca M, Zaccangini D, Rizzo L, Giannoni MF. Endovascular graft infections: preliminary results of an international enquiry. J Endovasc Ther 2003; 10: 919–27. Fischlein T, Schütz A, Haushofer M, Frey R, Uhlig A, Detter C, Reichart B. Immunologic reaction and viability of cryopreserved homografts. Ann Thorac Surg 1995; 60: 122–6.

9

10

11

12

13

14

15

Goshtasby P, Henriksen D, Lynd C, Fielding P. Recurrent aortoenteric fistula: case report and review. Curr Surg 2005; 62: 638– 43. Harding GEJ, Lawlor DK. Ruptured mycotic abdominal aortic aneurysm secondary to Mycobacterium bovis after intravesical treatment with Bacillus Calmette-Guérin. J Vasc Surg 2007; 46: 131–4. Hoekstra FM, Witvliet M, Knoop CY, Wassenaar C, Bogers AJ. Weimar W, Claas FH. Immunogenic human leukocyte antigen class II antigens on human cardiac valves induce specific alloantibodies Ann Thorac Surg 1998; 66: 2022–6. Horan TC, Andrus M, Dudeck M. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36: 309–32. Kirklin JK, Smith D, Novick W, Naftel DC, Kirklin JW, Pacifico AD, et al. Long-term function of cryopreserved aortic homografts. J Thorac Cardiovasc Surg 1993; 106: 154–66. Lavigne J-P, Postal A, Kohl P, Limet R. Prosthetic vascular infection complicated or not by aortoenteric fistula: Comparison of treatment with and without cryopreserved allograft (homograft). Eur J Vasc Endovasc Surg 2003; 25: 416–23. Meisner M, Rauschmeyer C, Schmidt J, Feyrer R, Cesnjevar R, Bredle D, Tschaikowsky K. Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications Intensive Care Med 2002; 28: 1094–102. Shindo S, Ogata K, Kubota K, Kojima A, Kobayashi M, Toda Y, et al. Vascular prosthetic im-

16

17

18

19

plantation is associated with prolonged inflammation following aortic aneurysm surgery J Artif Organs 2003; 6: 173–8. Simon E, Zavazava N, Steinhoff G, Müller-Ruchholtz, Haverich A. Immunogenicity of human cardiac valve allografts. In: Yankah AC, Yacoub MH, Hetzet R (eds.) Cardiac Valve Allografts: science and practice. 1st ed. New York: Springer Publishing; 1997: 87–97. Teebken O, Pichlmaier M, Brand S, Haverich A. Cryopreserved arterial allografts for in situ reconstruction arterial vessels Eur J Vasc Endovasc Surg 2004; 27: 597–602. Vogt PR, Pfammatter T, Schlumpf R, Genoni M, Künzli A, Candinas D, et al. In situ repair of aortobronchial, aortoesophogeal and aortoenteric fistulae with cryopreserved aortic homografts. J Vasc Surg 1997; 26: 11–7. Vogt PR, Von Segesser LK, Goffin Y, Pasic M, Turina MI. Cryopreserved arterial homografts for in situ reconstruction of mycotic aneurysms and prosthetic graft infection. Eur J Cardiothorac Surg 1995; 9: 502–6.

Correspondence address Prof. Dr. Omke Teebken Hannover Medical School Dept. of Cardiac Thoracic, Transplantation and Vascular Surgery, OE 6210 Carl-Neuberg-Strasse 1 D-30625 Hannover Germany E-mail: [email protected]

Submitted: 13.3.2009 Accepted: 12.5.2009