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Collagen implant with gentamicin sulphate reduces surgical site infection in vascular surgery: A prospective cohort study
International Journal of Surgery 12 (2014) 1100e1104
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
Collagen implant with gentamicin sulphate reduces surgical site infection in vascular surgery: A prospective cohort study ~o Costa Almeida*, Luis Reis, Luis Carvalho, Carlos Eduardo Perdiga Carlos Manuel Costa Almeida rio de Coimbra (Covo ~o Martinho do Bispo, 3041-801 Coimbra, Portugal ~es), Quinta dos Vales, Sa Centro Hospitalar e Universita
h i g h l i g h t s SSI in vascular surgery with synthetic grafts can have catastrophic outcome. Topic antibiotics have not been fully studied in vascular surgery. A collagen implant with gentamicin sulphate was used in the groin incision. There is a decrease in SSI rates in vascular surgery when the implant is used. This is a pilot study that can be a starting point for a randomized controlled trial.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 April 2014 Received in revised form 18 August 2014 Accepted 19 August 2014 Available online 30 August 2014
Introduction: Surgical site infection (SSI) is a common complication after vascular surgery. It may cause exposure of the underlying prosthesis causing graft infection, which may require the removal of the vascular graft, increasing amputation and mortality risks. Graft contamination usually occurs during operative procedure or by direct spread from an infected wound. It is therefore advisable to a strong effort in reducing SSI. Topic antibiotics have not been fully studied in vascular surgery, but collagen implant with gentamicin sulphate has shown to reduce SSI in cardiac surgery, orthopaedics, and general surgery procedures. Methods: Sixty (60) non-diabetic and non-obese patients with lower limb ischaemia with indication for femoropopliteal PTFE prosthetic bypass were allocated into 2 groups of 30 patients. A collagen implant impregnated with gentamicin sulphate (Collatamp®) was applied in the groin incision adjacent to the prosthesis in one group, and the other was a control group. The same surgical team operated all patients. Szilagyi classification was used. Results: There was no SSI (0% e 0/30) in the collagen implant with gentamicin sulphate group, contrasting with 6 cases (20% e 6/30) of SSI (grade I and II) in the control group (p ¼ 0.024). In-hospital day's data shows a significant difference between the two groups (p ¼ 0.004) with a mean of 5.66 days for implant group and 8.10 days for control group. There was no SSI grade III. Conclusion: Collagen implant with gentamicin sulphate (Collatamp®) reduces SSI in the groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. Days of hospitalization are also reduced. Decreasing SSI rate and in-hospital days, this implant may also reduce health care costs. Because this is a small pilot study, a multicentre RCT is necessary for validation. © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Surgical site infection Collatamp® Collagen implant Gentamicin Groin Vascular infection
1. Introduction Surgical site infection (SSI) is a common complication after vascular surgery. Some prospective trials report an incidence of SSI between 4% and 25%, but in retrospective studies there is an incidence from 4% up to 43% [1,2]. In 184 consecutive patients from
* Corresponding author. E-mail address: [email protected] (C.E.P. Costa Almeida). http://dx.doi.org/10.1016/j.ijsu.2014.08.397 1743-9191/© 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
several centres in Finland submitted to a range of vascular surgery procedures the SSI rate was reported as 27% [2]. Turtiainen et al. identified a higher rate of infection in patients who underwent infrainguinal surgery [3]. SSI after vascular surgery may cause exposure of the underlying prosthesis causing graft infection, which is the most serious complication in vascular surgery occurring from 1% up to 6% of all vascular procedures [2,4,5]. This infection may require the removal of the vascular graft, increasing amputation and mortality risks [1,2,4].
C.E.P. Costa Almeida et al. / International Journal of Surgery 12 (2014) 1100e1104
Graft contamination usually occurs during operative procedure or by direct spread during early postoperative period [5,6]. Groin incision is most likely at risk for SSI and prosthetic graft infection because of surgical division of lymphatic channels, the proximity to the perineum, the relatively superficial localization of vascular grafts in the groin, the development of wound infection adjacent to the prosthesis [7,8], and the presence of skin folds. Infrainguinal vascular surgery is a risk factor for infection [1,3], and a SSI rate of 2.5% has been reported. A mortality rate of 17% and an amputation rate of 41% have been associated with infrainguinal arterial prosthesis infection [4]. SSI is also associated with an increase in health costs [1,2], with a V3320 cost attributable to developing SSI in a 2010 study [3]. It is evident that SSI in an ischaemic patient submitted to femoropopliteal PTFE prosthetic bypass can have catastrophic outcome because of graft infection that can lead to limb amputation or even patient death. It is therefore advisable to a strong focus on primary prevention of infection, particularly for surgical procedures involving prosthesis [9]. Systemic prophylactic antibiotics for 24 h was the only measure found to reduce SSI and prosthetic graft infection in several trials [5,6,10]. Although topic antibiotics have not been fully studied in vascular surgery, collagen implant with gentamicin sulphate has shown to reduce SSI in cardiac surgery [11,12], orthopaedics [13], and general surgery procedures [13e16]. Study the impact of collagen implant impregnated with gentamicin sulphate e Collatamp® e on the SSI rate of groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass is the objective of this study. 2. Methods Sixty (N ¼ 60) non-diabetic and non-obese (BMI < 30) patients with lower limb ischaemia (grade IIb, III and IV) with indication for femoropopliteal bypass above or below knee were allocated in an alternate method by the surgical team into 2 groups of 30 patients. These eligible criteria were applied during ambulatory consultant and in the emergency department. The study was enrolled in one single centre with limited population. It began in 2006 and ended in 2013, with a 30-day follow-up for each participant. A collagen implant impregnated with gentamicin sulphate (Collatamp®) was applied in the groin incision adjacent to the prosthesis in the subfascial plane in one group (Fig. 1), and the other was a control group who had no implant applied. In both groups a 24 h protocol of systemic prophylactic antibiotic with 3 doses of piperacilin plus tazobactan initiating 1 h before skin incision was administrated. Skin was prepared with iodopovidone solution. Polytetrafluoroethylene (PTFE) supported prosthesis were used, and all patients were operated by the same surgical team. The SSI rate for the first 30-day of follow-up was compared between the two groups. Szilagyi classification [17] was used, and the following broad criteria
1101
were used for SSI diagnosis: local excessive pain, local erythema and oedema, pus drainage, suture dehiscence. The surgical team was responsible for the follow-up. Data collected for patients' characterization included: age, gender, ischaemic grade, above or below knee bypass, right or left lower limb. Because a higher ischaemic grade and a below knee bypass can have both negative influence in SSI, participants were allocated in an alternate method and these data were compared between groups to confirm their similarity. SSI rate and hospital stay for both groups were analysed. A comparison of parameters with vs. without Collatamp® was carried. The statistical analysis was carried by means of SPSS for Windows (version 20.0 SPSS Inc. USA). The continuous variables were presented as means and medians, while standard deviations and quartiles were chosen as measure of dispersion. Regarding their normal distribution, the continuous variables were tested by means of the ShapiroeWilk-test. While some of the tested variables did not feature any normal distribution (p < 0.05), a normal distribution could be calculated for other variables (p 0.05). Thus, for the comparison of the samples, tests for normally distributed samples and non-parametric tests for non-normally distributed samples were applied. For the comparison of 2 independent, normally distributed samples, the t-test was applied. Before that, the homogeneity of the variances was tested by means of the Levene-test. Due to the proven homogeneity of the variances, Student t-test was carried out. For non-normally distributed samples the ManneWhitney-UTest was applied as a non-parametric procedure. The categorized data, on the other hand, was evaluated by means of the exact Fisher tests, whereby all necessary requirements for these tests were fulfilled. With all carried out tests, a two-sided significance-test was carried out. A p-value of <0.05 was assumed as statistically significance for all statistical tests.
3. Results During study period no participant was excluded. Surgery length was about 90 mine120 min depending if it was above or below knee bypass respectively. Data were compared between implant and control groups concluding for the similarity of both.
3.1. Age pattern The mean of age for all 60 patients was 67.93 years old. The group with the implant had a mean of 68.53 y and the control group 67.33 y. There was no difference concerning age (p ¼ 0.635) between the two groups.
Fig. 1. The implant was applied in the groin incision (in the subfascial plane) adjacent to the prosthesis covering the anastomosis. Saline solution was used to moister the implant and facilitate its use.
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C.E.P. Costa Almeida et al. / International Journal of Surgery 12 (2014) 1100e1104
3.2. Gender In both groups 83.3% of the patients were males, and 16.7% were females. After Chi-Square Test there was no difference between the groups concerning the gender (p ¼ 1.000).
Table 1 Right or left and above or bellow knee bypass with vs. without Collatamp®. There is no statistical difference (p > 0.05). Data collected (% within Collatamp)
Collatamp No
Yes
Bypass
60% 40% 40% 60%
53.3% 46.7% 60% 40%
3.3. Ischaemic grade Lower limb
Ischaemic grades IIb, III and IV were included in this one prospective analysis. In the control group ischaemic grades IIb, III and IV represented 66.7%, 23.3% and 10.0% of patients respectively. In the implant group 80.0% of patients were grade IIb, 10.0% were grade III, and 10.0% grade IV (Graphic 1). Comparing both groups it was also evident that there was no difference between them concerning ischaemic grade (p ¼ 0.375).
Above knee Below knee Right Left
p
0.795 0.196
3.4. Above or below knee bypass In the implant group 53.3% of patients were submitted to an above knee bypass, and 46.7% to a below knee bypass. The distribution in the control group was similar, with 60.0% of patients and 40.0% submitted to an above and below knee bypass respectively (Table 1). Again, there was no statistical difference between them (p ¼ 0.795). 3.5. Right or left lower limb In the implant group 60.0% and 40.0% of patients were operated to the right and left lower limb respectively. In the control group 40.0% of patients were operated to the right, and 60.0% to the left lower limb (Table 1). There was one patient that was operated first to the right and two years later to the left lower limb. No difference was found between the two groups (p ¼ 0.196). After concluding for the similarity of both cases and control groups surgical site infection and hospital stay were compared between them. Szilagyi classification was applied during follow-up by the surgical team. There were no allergic reactions in all 30 patients with the implant. 3.6. Surgical site infection In the implant group there was a SSI rate of 0% (0/30 patients) comparing to 20.0% in the control group (6/30 patients) (Graphic 2). This difference was statistically significant (p ¼ 0.024). Of those 6 cases of SSI in the control group, 4 were grade I (13.3%), and 2 were grade II (6.7%) according to Szilagyi classification [17]. There were
Graphic 1. Ischaemic grade distribution in both groups (p ¼ 0.375).
Graphic 2. SSI distribution. There was no SSI with collagen implant with gentamicin sulphate, but 20% of patients without the implant had SSI. This is significant (p ¼ 0.024).
no grade III infections (Graphic 3). All SSI grades I and II were solved with systemic antibiotic. 3.7. Hospital stay Hospital stay was analysed in postoperative in-hospital days. If no implant was applied there was a minimum of 4 and a maximum of 20 postoperative days, mean of 8.10 days. However, if a collagen implant with gentamicin sulphate was applied, a mean of 5.66 postoperative days (minimum of 3 and maximum of 11 days) was found (Graphic 4). These results are statistically significant (p ¼ 0.004). 4. Discussion SSI after vascular surgery may cause exposure of the underlying prosthesis causing graft infection. In fact, bacteria dissemination from an infected wound is the most frequent cause of vascular graft infection [5]. With an amputation rate of 8%e52% and a mortality rate of 13%e58% [7], vascular prosthetic graft infection is the most serious complication in vascular surgery occurring from 1% up to 6% of all vascular procedures [4,5]. Vascular infections and prosthesis infections are both limb- and life-threatening [6]. Staphylococcus and gram-negative bacteria are the main cause of SSI in vascular surgery [1,5,10,18], and because of that antibiotic shall be active against these germs. Infectious diseases are increasing because of bacteria resistance to antibiotics. Knowing local standard of resistance is crucial for a correct prophylaxis and treatment [6]. Systemic prophylactic antibiotic for 24 h is the only measure shown to reduce SSI, and there is no advantage to prolong this [1,5,10] or to add anti-MRSA agents to prophylactic regimen [6,18]. The use of piperacilin plus tazobactan for prophylaxis probably was not the best choice since it is used in treatment. However it is active against staphylococcus and gram-negatives,
C.E.P. Costa Almeida et al. / International Journal of Surgery 12 (2014) 1100e1104
Graphic 3. Slizagyi classification of SSI.
Graphic 4. In-hospital days: with vs. without Collatamp®. Patients with the implant had significantly shorter hospital stay (5.66 days) than patients without the implant (8.10 days). This difference is statistically significant (p ¼ 0.004).
and since a grade III infection can have catastrophic outcome a high spectrum antibiotic could have advantages. Topic antibiotics have not been fully studied in vascular surgery, although collagen implant with gentamicin sulphate has shown to decrease SSI in cardiac surgery [11,12], orthopaedics [13] and several general surgery procedures [13e16]. With topic application of collagen implant with gentamicin sulphate (active against staphylococcus and gram-negative germs) a local concentration high above minimum inhibitory concentration (mic) is reached, and without toxic effects since there is no systemic absorption [11,16,19e21]. Because fall-off in local gentamicin concentration is rapid enough to prevent long-term sub-inhibitory concentrations it reduces risk of antibiotic resistance, and there is no evidence of resistance with longterm use [2,13,19e21]. Additionally, using collagen as a carrier has effects on healing and haemostasis, and it is a well-tolerated implant without side effects [2,13,14,20,21]. These are the reasons that justify our choice as anti-infectious prophylactic drug. The implant was applied in the groin adjacent to the prosthesis covering the anastomosis to take advantage of the haemostatic properties (Fig. 1). Ischaemia grades IIb, III and IV were included. Grade IV could have had a negative impact in the results, maybe prolonging inhospital stay and increasing infection risk. However both groups were similar concerning ischaemic grade (p ¼ 0.375) with three grade IV ischaemic patients in each group. In the Lee et al. paper the
1103
presence of a non-healing wound in the extremity being revascularized was not a significant risk factor for SSI [22]. On the other hand being grade IV patients the group with higher risk of SSI and graft infection (comparing to IIb and III) after vascular surgery, more patients will be needed in a multicentre randomized controlled trial (RCT) so that solid conclusions could be made. Having a small number of patients including grade IV patients is in fact a weakness point of this pilot study. Concerning age, gender, above or below knee bypass, right or left lower limb, there was no statistical difference between both groups (p > 0.05). There was no SSI (0%) in the implant group, contrasting with 6 cases (20%) of SSI in the control group. This difference was significant with p ¼ 0.024. SSI rate in the control group match other studies data [1,2]. According do Szilagyi classification there was 4 (13.3%) grade I infections (dermis), 2 (6.7%) grade II infections (subcutaneous) and none (0%) grade III (arterial implant). By decreasing SSI, collagen implant with gentamicin sulphate is expected to decrease graft infection, however a follow-up of one year should be accomplished so that we can take any conclusion on grade III infections. A multicentre RCT will need to evaluate graft infection, which is the ultimate objective of using the implant. Analysis of in-hospital day's data shows a significant difference between the two groups (p ¼ 0.004) with a mean of 5.66 days for implant group and 8.10 days for control group. Maximum inhospital days for control group were 20 because of a grade IV ischaemic patient, but there was no difference between groups concerning ischaemia grade (p ¼ 0.375). Since this implant decreases SSI rate and in-hospital days, its use may reduce health care cost in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. A major disadvantage of this one-centre study is not being a double-blinded one. We studied 30 patients in each group because it is a one-centre study with limited population. For these reasons a double-blinded multicentre RCT must be engaged for validation of these results. According to Gorbach guidelines the ideal anti-infectious agent should prevent postoperative infectious morbidity and mortality, should reduce the duration and cost of surgical care, should have no adverse effects on the patient, and should have no adverse effects on the microbial flora of the patient or the hospital [13,23]. 5. Conclusion Reduction of SSI rate in groin incision must be an objective for all surgeons performing femoropopliteal PTFE prosthetic bypass. Collagen implant with gentamicin sulphate reduces SSI in the groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. Days of hospitalization are also reduced by the topic use of collagen implant with gentamicin sulphate. Decreasing SSI rate and in-hospital days, this implant may also reduce health care costs. However, because this is a small pilot study, a multicentre RCT is necessary for validation of these results, and so that its use can be routinely advised. Ethics This work was ethically approved, and informed consent was obtained from patients. Funding No sources of funding.
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C.E.P. Costa Almeida et al. / International Journal of Surgery 12 (2014) 1100e1104
Author contribution CE Costa Almeida e study design, data collections and analysis, writing. L Reis e data collections and analysis, review. L Carvalho e data collections, review. CM Costa Almeida e study design, data collections, review. Conflicts of interest The authors declare no conflicts of interest. References [1] J. Turtiainen, E. Saimanen, T. Partio, J. Karkkainen, V. Kiviniemi, K. Makinen, Surgical wound infections after vascular surgery: prospective multicenter observational study, Scand. J. Surg. 99 (2010) 167e172. [2] S.T. Hussain, Local application of gentamicin-containing collagen implant in prophylaxis and treatment of surgical site infection following vascular surgery, Int. J. Surg. 10 (2012) S5eS9. [3] J. Turtianinen, E. Saimanen, T. Partio, J. Karkkainen, V. Kiviniemi, K. Makinen, et al., Surgical wound infection after vascular surgery: prospective multicentre observational study, Scand. J. Surg. 99 (2010) 167e172. [4] Shinji Hirai, Yoshiharu Hamanaka, Norimasa Mitsui, Masahiko Morifuji, Miwa Sutoh, Surgical treatment of methicillin-resistant staphylococcus aureus infection following infrainguinal arterial reconstruction, Ann. Thorac. Cardiovasc. Surg. 11 (2005) 139e141. [5] Andrew H. Stewart, Paul S. Eyers, Jonothan J. Earnshaw, Prevention of infection in peripheral arterial reconstruction: a systematic review and metaanalysis, J. Vasc. Surg. 46 (2007) 148e155. [6] Shervanthi Homer-Vanniasinkam, Surgical site and vascular infections: treatment and prophylaxis, Int. J. Infect. Dis. 11 (S1) (2007) S17eS22. [7] G. Salzmann, Perioperative infection prophylaxis in vascular surgery e a randomized prospective study, Thorac. Cardiovasc. Surg. 31 (4) (1983) 239e242. [8] Cagatay Engin, Hakan Posacioglu, Fatih Ayik, Anil Ziya Apaydin, Management of vascular infection in the groin, Tex. Heart Inst. J. 32 (2005) 529e534.
[9] J.B. Ricco, O. Assadian, Antimicrobial silver grafts for prevention and treatment of vascular graft infection, Semin. Vasc. Surg. 24 (4) (2011) 234e241. [10] W.H. Edwards Jr., R.S. Martin 3rd, J.M. Jenkins, W.H. Edwards Sr., J.L. Mulherin, Primary graft infections, J. Vasc. Surg. 6 (1987) 235e239. € Friberg, R. Svedjeholm, B. So €derquist, H. Granfeldt, T. Vikerfors, J. Ka €llman, [11] O. Local gentamicin reduces sternal wound infection after cardiac surgery: a randomized controlled trial, Ann. Thorac. Surg. 79 (2005) 153e162. [12] A.M. Eklund, M. Valtonenb, K.A. Werkkala, Prophylaxis of sternal wound infections with gentamicin-collagen implant: randomized controlled study in cardiac surgery, J. Hosp. Infect. 59 (2005) 108e112. [13] H.J.T. Rutten, P.H.A. Nijhuis, Prevention of wound infection in elective colorectal surgery by local application of a gentamicin-containing collagen sponge, Eur. J. Surg. 578 (1997) 31e35. [14] G. Gomez, T. Guerrero, M.C. Lluck, F.J. Delgado, Effectiveness of collagengentamicin implant for treatment of “Dirty” abdominal wounds, World J. Surg. 23 (1999) 123e127. [15] A.F.J. De Bruin, M.P. Gosselink, N.A.T. Wijffels, P. Coene, E. van der Harst, Local gentamicin reduces perineal wound infection after radiotherapy and abdominoperineal resection, Tech. Coloproctol. 12 (4) (2008) 303e307. [16] M. Rao, W. Zawislak, R. Kennedy, R. Gilliland, A prospective randomised study comparing two treatment modalities for chronic pilonidal sinus with a 5-year follow-up, Int. J. Colorectal Dis. 25 (3) (2010) 395e400. [17] D. Szilagyi, R. Smith, J. Elliot, M. Vrandecic, Infection in arterial reconstruction with synthetic grafts, Ann. Surg. 176 (3) (1972) 321e332. [18] S. Patrick, C. James, A. Ali, S. Lawson, E. Mary, A. Modak, Vascular surgical antibiotic prophylaxis study (VSAPS), Vasc. Endovascular Surg. 44 (7) (2010) 521e528. [19] Z. Ruszczak, W. Friess, Collagen as a carrier for on-site delivery of antibacterial drugs, Adv. Drug. Deliv. Rev. 55 (12) (2003) 1679e1698. [20] A. Formiga, J. Neves, A. Paulino, A. Fernandes, M.L. Rocha, L. Mata, A. Sousa, nio Alves Pereira, Tratamento das úlceras de perna com implantes de colage com gentamicina (estudo preliminary), in: Proceedings Eurosurgery, 2000. [21] Carlos E. Costa Almeida, Luis S. Reis, Luis F. Carvalho, Carlos M. Costa Almeida, Treatment of venous ulcers with Cronocol® implants e analysis of 10 cases, Rev. Port. Cir. 21 (2012) 13e20. [22] E.S. Lee, S.M. Santilli, M.M. Olson, M.A. Kuskowski, J.T. Lee, Wound infection after infrainguinal bypass operations: multivariate analysis of putative risk factors, Surg. Infect. Larchmt 1 (4) (2000 Winter) 257e263. [23] S.L. Gorbach, R.E. Condon, R.E. Conte Jr., A.B. Kaiser, W.J. Ledger, R.L. Nichols, General guidelines for the evaluation of new anti-infective drugs for prophylaxis of surgical infections, Clin. Infect. Dis. 15 (1) (1992) 313e338.
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
Collagen implant with gentamicin sulphate reduces surgical site infection in vascular surgery: A prospective cohort study ~o Costa Almeida*, Luis Reis, Luis Carvalho, Carlos Eduardo Perdiga Carlos Manuel Costa Almeida rio de Coimbra (Covo ~o Martinho do Bispo, 3041-801 Coimbra, Portugal ~es), Quinta dos Vales, Sa Centro Hospitalar e Universita
h i g h l i g h t s SSI in vascular surgery with synthetic grafts can have catastrophic outcome. Topic antibiotics have not been fully studied in vascular surgery. A collagen implant with gentamicin sulphate was used in the groin incision. There is a decrease in SSI rates in vascular surgery when the implant is used. This is a pilot study that can be a starting point for a randomized controlled trial.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 April 2014 Received in revised form 18 August 2014 Accepted 19 August 2014 Available online 30 August 2014
Introduction: Surgical site infection (SSI) is a common complication after vascular surgery. It may cause exposure of the underlying prosthesis causing graft infection, which may require the removal of the vascular graft, increasing amputation and mortality risks. Graft contamination usually occurs during operative procedure or by direct spread from an infected wound. It is therefore advisable to a strong effort in reducing SSI. Topic antibiotics have not been fully studied in vascular surgery, but collagen implant with gentamicin sulphate has shown to reduce SSI in cardiac surgery, orthopaedics, and general surgery procedures. Methods: Sixty (60) non-diabetic and non-obese patients with lower limb ischaemia with indication for femoropopliteal PTFE prosthetic bypass were allocated into 2 groups of 30 patients. A collagen implant impregnated with gentamicin sulphate (Collatamp®) was applied in the groin incision adjacent to the prosthesis in one group, and the other was a control group. The same surgical team operated all patients. Szilagyi classification was used. Results: There was no SSI (0% e 0/30) in the collagen implant with gentamicin sulphate group, contrasting with 6 cases (20% e 6/30) of SSI (grade I and II) in the control group (p ¼ 0.024). In-hospital day's data shows a significant difference between the two groups (p ¼ 0.004) with a mean of 5.66 days for implant group and 8.10 days for control group. There was no SSI grade III. Conclusion: Collagen implant with gentamicin sulphate (Collatamp®) reduces SSI in the groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. Days of hospitalization are also reduced. Decreasing SSI rate and in-hospital days, this implant may also reduce health care costs. Because this is a small pilot study, a multicentre RCT is necessary for validation. © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Surgical site infection Collatamp® Collagen implant Gentamicin Groin Vascular infection
1. Introduction Surgical site infection (SSI) is a common complication after vascular surgery. Some prospective trials report an incidence of SSI between 4% and 25%, but in retrospective studies there is an incidence from 4% up to 43% [1,2]. In 184 consecutive patients from
* Corresponding author. E-mail address: [email protected] (C.E.P. Costa Almeida). http://dx.doi.org/10.1016/j.ijsu.2014.08.397 1743-9191/© 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
several centres in Finland submitted to a range of vascular surgery procedures the SSI rate was reported as 27% [2]. Turtiainen et al. identified a higher rate of infection in patients who underwent infrainguinal surgery [3]. SSI after vascular surgery may cause exposure of the underlying prosthesis causing graft infection, which is the most serious complication in vascular surgery occurring from 1% up to 6% of all vascular procedures [2,4,5]. This infection may require the removal of the vascular graft, increasing amputation and mortality risks [1,2,4].
C.E.P. Costa Almeida et al. / International Journal of Surgery 12 (2014) 1100e1104
Graft contamination usually occurs during operative procedure or by direct spread during early postoperative period [5,6]. Groin incision is most likely at risk for SSI and prosthetic graft infection because of surgical division of lymphatic channels, the proximity to the perineum, the relatively superficial localization of vascular grafts in the groin, the development of wound infection adjacent to the prosthesis [7,8], and the presence of skin folds. Infrainguinal vascular surgery is a risk factor for infection [1,3], and a SSI rate of 2.5% has been reported. A mortality rate of 17% and an amputation rate of 41% have been associated with infrainguinal arterial prosthesis infection [4]. SSI is also associated with an increase in health costs [1,2], with a V3320 cost attributable to developing SSI in a 2010 study [3]. It is evident that SSI in an ischaemic patient submitted to femoropopliteal PTFE prosthetic bypass can have catastrophic outcome because of graft infection that can lead to limb amputation or even patient death. It is therefore advisable to a strong focus on primary prevention of infection, particularly for surgical procedures involving prosthesis [9]. Systemic prophylactic antibiotics for 24 h was the only measure found to reduce SSI and prosthetic graft infection in several trials [5,6,10]. Although topic antibiotics have not been fully studied in vascular surgery, collagen implant with gentamicin sulphate has shown to reduce SSI in cardiac surgery [11,12], orthopaedics [13], and general surgery procedures [13e16]. Study the impact of collagen implant impregnated with gentamicin sulphate e Collatamp® e on the SSI rate of groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass is the objective of this study. 2. Methods Sixty (N ¼ 60) non-diabetic and non-obese (BMI < 30) patients with lower limb ischaemia (grade IIb, III and IV) with indication for femoropopliteal bypass above or below knee were allocated in an alternate method by the surgical team into 2 groups of 30 patients. These eligible criteria were applied during ambulatory consultant and in the emergency department. The study was enrolled in one single centre with limited population. It began in 2006 and ended in 2013, with a 30-day follow-up for each participant. A collagen implant impregnated with gentamicin sulphate (Collatamp®) was applied in the groin incision adjacent to the prosthesis in the subfascial plane in one group (Fig. 1), and the other was a control group who had no implant applied. In both groups a 24 h protocol of systemic prophylactic antibiotic with 3 doses of piperacilin plus tazobactan initiating 1 h before skin incision was administrated. Skin was prepared with iodopovidone solution. Polytetrafluoroethylene (PTFE) supported prosthesis were used, and all patients were operated by the same surgical team. The SSI rate for the first 30-day of follow-up was compared between the two groups. Szilagyi classification [17] was used, and the following broad criteria
1101
were used for SSI diagnosis: local excessive pain, local erythema and oedema, pus drainage, suture dehiscence. The surgical team was responsible for the follow-up. Data collected for patients' characterization included: age, gender, ischaemic grade, above or below knee bypass, right or left lower limb. Because a higher ischaemic grade and a below knee bypass can have both negative influence in SSI, participants were allocated in an alternate method and these data were compared between groups to confirm their similarity. SSI rate and hospital stay for both groups were analysed. A comparison of parameters with vs. without Collatamp® was carried. The statistical analysis was carried by means of SPSS for Windows (version 20.0 SPSS Inc. USA). The continuous variables were presented as means and medians, while standard deviations and quartiles were chosen as measure of dispersion. Regarding their normal distribution, the continuous variables were tested by means of the ShapiroeWilk-test. While some of the tested variables did not feature any normal distribution (p < 0.05), a normal distribution could be calculated for other variables (p 0.05). Thus, for the comparison of the samples, tests for normally distributed samples and non-parametric tests for non-normally distributed samples were applied. For the comparison of 2 independent, normally distributed samples, the t-test was applied. Before that, the homogeneity of the variances was tested by means of the Levene-test. Due to the proven homogeneity of the variances, Student t-test was carried out. For non-normally distributed samples the ManneWhitney-UTest was applied as a non-parametric procedure. The categorized data, on the other hand, was evaluated by means of the exact Fisher tests, whereby all necessary requirements for these tests were fulfilled. With all carried out tests, a two-sided significance-test was carried out. A p-value of <0.05 was assumed as statistically significance for all statistical tests.
3. Results During study period no participant was excluded. Surgery length was about 90 mine120 min depending if it was above or below knee bypass respectively. Data were compared between implant and control groups concluding for the similarity of both.
3.1. Age pattern The mean of age for all 60 patients was 67.93 years old. The group with the implant had a mean of 68.53 y and the control group 67.33 y. There was no difference concerning age (p ¼ 0.635) between the two groups.
Fig. 1. The implant was applied in the groin incision (in the subfascial plane) adjacent to the prosthesis covering the anastomosis. Saline solution was used to moister the implant and facilitate its use.
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3.2. Gender In both groups 83.3% of the patients were males, and 16.7% were females. After Chi-Square Test there was no difference between the groups concerning the gender (p ¼ 1.000).
Table 1 Right or left and above or bellow knee bypass with vs. without Collatamp®. There is no statistical difference (p > 0.05). Data collected (% within Collatamp)
Collatamp No
Yes
Bypass
60% 40% 40% 60%
53.3% 46.7% 60% 40%
3.3. Ischaemic grade Lower limb
Ischaemic grades IIb, III and IV were included in this one prospective analysis. In the control group ischaemic grades IIb, III and IV represented 66.7%, 23.3% and 10.0% of patients respectively. In the implant group 80.0% of patients were grade IIb, 10.0% were grade III, and 10.0% grade IV (Graphic 1). Comparing both groups it was also evident that there was no difference between them concerning ischaemic grade (p ¼ 0.375).
Above knee Below knee Right Left
p
0.795 0.196
3.4. Above or below knee bypass In the implant group 53.3% of patients were submitted to an above knee bypass, and 46.7% to a below knee bypass. The distribution in the control group was similar, with 60.0% of patients and 40.0% submitted to an above and below knee bypass respectively (Table 1). Again, there was no statistical difference between them (p ¼ 0.795). 3.5. Right or left lower limb In the implant group 60.0% and 40.0% of patients were operated to the right and left lower limb respectively. In the control group 40.0% of patients were operated to the right, and 60.0% to the left lower limb (Table 1). There was one patient that was operated first to the right and two years later to the left lower limb. No difference was found between the two groups (p ¼ 0.196). After concluding for the similarity of both cases and control groups surgical site infection and hospital stay were compared between them. Szilagyi classification was applied during follow-up by the surgical team. There were no allergic reactions in all 30 patients with the implant. 3.6. Surgical site infection In the implant group there was a SSI rate of 0% (0/30 patients) comparing to 20.0% in the control group (6/30 patients) (Graphic 2). This difference was statistically significant (p ¼ 0.024). Of those 6 cases of SSI in the control group, 4 were grade I (13.3%), and 2 were grade II (6.7%) according to Szilagyi classification [17]. There were
Graphic 1. Ischaemic grade distribution in both groups (p ¼ 0.375).
Graphic 2. SSI distribution. There was no SSI with collagen implant with gentamicin sulphate, but 20% of patients without the implant had SSI. This is significant (p ¼ 0.024).
no grade III infections (Graphic 3). All SSI grades I and II were solved with systemic antibiotic. 3.7. Hospital stay Hospital stay was analysed in postoperative in-hospital days. If no implant was applied there was a minimum of 4 and a maximum of 20 postoperative days, mean of 8.10 days. However, if a collagen implant with gentamicin sulphate was applied, a mean of 5.66 postoperative days (minimum of 3 and maximum of 11 days) was found (Graphic 4). These results are statistically significant (p ¼ 0.004). 4. Discussion SSI after vascular surgery may cause exposure of the underlying prosthesis causing graft infection. In fact, bacteria dissemination from an infected wound is the most frequent cause of vascular graft infection [5]. With an amputation rate of 8%e52% and a mortality rate of 13%e58% [7], vascular prosthetic graft infection is the most serious complication in vascular surgery occurring from 1% up to 6% of all vascular procedures [4,5]. Vascular infections and prosthesis infections are both limb- and life-threatening [6]. Staphylococcus and gram-negative bacteria are the main cause of SSI in vascular surgery [1,5,10,18], and because of that antibiotic shall be active against these germs. Infectious diseases are increasing because of bacteria resistance to antibiotics. Knowing local standard of resistance is crucial for a correct prophylaxis and treatment [6]. Systemic prophylactic antibiotic for 24 h is the only measure shown to reduce SSI, and there is no advantage to prolong this [1,5,10] or to add anti-MRSA agents to prophylactic regimen [6,18]. The use of piperacilin plus tazobactan for prophylaxis probably was not the best choice since it is used in treatment. However it is active against staphylococcus and gram-negatives,
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Graphic 3. Slizagyi classification of SSI.
Graphic 4. In-hospital days: with vs. without Collatamp®. Patients with the implant had significantly shorter hospital stay (5.66 days) than patients without the implant (8.10 days). This difference is statistically significant (p ¼ 0.004).
and since a grade III infection can have catastrophic outcome a high spectrum antibiotic could have advantages. Topic antibiotics have not been fully studied in vascular surgery, although collagen implant with gentamicin sulphate has shown to decrease SSI in cardiac surgery [11,12], orthopaedics [13] and several general surgery procedures [13e16]. With topic application of collagen implant with gentamicin sulphate (active against staphylococcus and gram-negative germs) a local concentration high above minimum inhibitory concentration (mic) is reached, and without toxic effects since there is no systemic absorption [11,16,19e21]. Because fall-off in local gentamicin concentration is rapid enough to prevent long-term sub-inhibitory concentrations it reduces risk of antibiotic resistance, and there is no evidence of resistance with longterm use [2,13,19e21]. Additionally, using collagen as a carrier has effects on healing and haemostasis, and it is a well-tolerated implant without side effects [2,13,14,20,21]. These are the reasons that justify our choice as anti-infectious prophylactic drug. The implant was applied in the groin adjacent to the prosthesis covering the anastomosis to take advantage of the haemostatic properties (Fig. 1). Ischaemia grades IIb, III and IV were included. Grade IV could have had a negative impact in the results, maybe prolonging inhospital stay and increasing infection risk. However both groups were similar concerning ischaemic grade (p ¼ 0.375) with three grade IV ischaemic patients in each group. In the Lee et al. paper the
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presence of a non-healing wound in the extremity being revascularized was not a significant risk factor for SSI [22]. On the other hand being grade IV patients the group with higher risk of SSI and graft infection (comparing to IIb and III) after vascular surgery, more patients will be needed in a multicentre randomized controlled trial (RCT) so that solid conclusions could be made. Having a small number of patients including grade IV patients is in fact a weakness point of this pilot study. Concerning age, gender, above or below knee bypass, right or left lower limb, there was no statistical difference between both groups (p > 0.05). There was no SSI (0%) in the implant group, contrasting with 6 cases (20%) of SSI in the control group. This difference was significant with p ¼ 0.024. SSI rate in the control group match other studies data [1,2]. According do Szilagyi classification there was 4 (13.3%) grade I infections (dermis), 2 (6.7%) grade II infections (subcutaneous) and none (0%) grade III (arterial implant). By decreasing SSI, collagen implant with gentamicin sulphate is expected to decrease graft infection, however a follow-up of one year should be accomplished so that we can take any conclusion on grade III infections. A multicentre RCT will need to evaluate graft infection, which is the ultimate objective of using the implant. Analysis of in-hospital day's data shows a significant difference between the two groups (p ¼ 0.004) with a mean of 5.66 days for implant group and 8.10 days for control group. Maximum inhospital days for control group were 20 because of a grade IV ischaemic patient, but there was no difference between groups concerning ischaemia grade (p ¼ 0.375). Since this implant decreases SSI rate and in-hospital days, its use may reduce health care cost in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. A major disadvantage of this one-centre study is not being a double-blinded one. We studied 30 patients in each group because it is a one-centre study with limited population. For these reasons a double-blinded multicentre RCT must be engaged for validation of these results. According to Gorbach guidelines the ideal anti-infectious agent should prevent postoperative infectious morbidity and mortality, should reduce the duration and cost of surgical care, should have no adverse effects on the patient, and should have no adverse effects on the microbial flora of the patient or the hospital [13,23]. 5. Conclusion Reduction of SSI rate in groin incision must be an objective for all surgeons performing femoropopliteal PTFE prosthetic bypass. Collagen implant with gentamicin sulphate reduces SSI in the groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. Days of hospitalization are also reduced by the topic use of collagen implant with gentamicin sulphate. Decreasing SSI rate and in-hospital days, this implant may also reduce health care costs. However, because this is a small pilot study, a multicentre RCT is necessary for validation of these results, and so that its use can be routinely advised. Ethics This work was ethically approved, and informed consent was obtained from patients. Funding No sources of funding.
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Author contribution CE Costa Almeida e study design, data collections and analysis, writing. L Reis e data collections and analysis, review. L Carvalho e data collections, review. CM Costa Almeida e study design, data collections, review. Conflicts of interest The authors declare no conflicts of interest. References [1] J. Turtiainen, E. Saimanen, T. Partio, J. Karkkainen, V. Kiviniemi, K. Makinen, Surgical wound infections after vascular surgery: prospective multicenter observational study, Scand. J. Surg. 99 (2010) 167e172. [2] S.T. Hussain, Local application of gentamicin-containing collagen implant in prophylaxis and treatment of surgical site infection following vascular surgery, Int. J. Surg. 10 (2012) S5eS9. [3] J. Turtianinen, E. Saimanen, T. Partio, J. Karkkainen, V. Kiviniemi, K. Makinen, et al., Surgical wound infection after vascular surgery: prospective multicentre observational study, Scand. J. Surg. 99 (2010) 167e172. [4] Shinji Hirai, Yoshiharu Hamanaka, Norimasa Mitsui, Masahiko Morifuji, Miwa Sutoh, Surgical treatment of methicillin-resistant staphylococcus aureus infection following infrainguinal arterial reconstruction, Ann. Thorac. Cardiovasc. Surg. 11 (2005) 139e141. [5] Andrew H. Stewart, Paul S. Eyers, Jonothan J. Earnshaw, Prevention of infection in peripheral arterial reconstruction: a systematic review and metaanalysis, J. Vasc. Surg. 46 (2007) 148e155. [6] Shervanthi Homer-Vanniasinkam, Surgical site and vascular infections: treatment and prophylaxis, Int. J. Infect. Dis. 11 (S1) (2007) S17eS22. [7] G. Salzmann, Perioperative infection prophylaxis in vascular surgery e a randomized prospective study, Thorac. Cardiovasc. Surg. 31 (4) (1983) 239e242. [8] Cagatay Engin, Hakan Posacioglu, Fatih Ayik, Anil Ziya Apaydin, Management of vascular infection in the groin, Tex. Heart Inst. J. 32 (2005) 529e534.
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