Surgical Site Infections in Solid Organ Transplantation

Authors: Hugo JR Bonatti, M.D., Rajeev Sharma, M.D., Robert G Sawyer, M.D.

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Surgical site infections (SSI) have remained a common and major complication in solid organ transplant (solid organ transplant) recipients and are reported to occur in 5-40% of these patients (2,9,17,19,74). The frequency of surgical site infections after solid organ transplant is similar to other surgical procedures of comparable complexity. The incidences of surgical site infections are highest following intestinal (102) transplantation followed by liver (33,75) and pancreas (68,78) transplantation; after renal (52,66) and heart (77,82) transplantation low rates of surgical site infections can be expected. The risk factors for surgical site infections, the spectrum of organisms and clinical outcomes following solid organ transplant vary according to the organ transplanted. Microorganisms causing surgical site infections post solid organ transplant most commonly originate from the recipient’s skin, or an opened colonized organ such as the intestinal tract when creating a Roux-en-Y hepaticojejunostomy during liver transplantation or the bladder when creating the ureteral anastomosis in renal transplantation. In these sometimes critically ill patients, organisms may also seed the surgical site through hematogenous spread during the perioperative period. Another potential source that should always be considered is the graft itself (54). Despite the fact that donors usually are given antibiotics during their intensive care stay, there is always a possibility of an unknown infection. Occasionally, organ procurement is performed although the donors have documented infections that have undergone a variable duration of therapy (14). This includes donors with treated bacterial meningitis, donors with positive blood cultures and donors with pneumonia or urinary tract infections (15). Allografts from drowning victims should also be considered potentially contaminated as these individuals become almost universally bacteremic with aspirated pathogens (5). In addition, organs may become contaminated during the procurement, during back table handling at the procurement site, packing, unpacking and during back table work at the recipient center. These factors need to be considered when administering antimicrobial prophylaxis against surgical site infections and donor history may impact the choice of the applied antibiotics. In this article we will discuss surgical site infections in liver, kidney, pancreas, intestine, heart and lung transplants and following composite tissue allograft transplantation (Table 1).

DEFINITIONS

According to guidelines from the Centers for Disease Control and Prevention (39,40), surgical site infections (SSI) include deep and superficial incisional infections and organ and organ space infections that occur within 30 days of the surgical procedure or one year if a prosthetic implant is used. Superficial and deep wound infections do not differ between general surgical and transplant surgical patients; however, the spectrum of pathogens implicated in surgical site infections in solid organ transplant recipients is much more diverse due to various factors such as the underlying end stage organ failure and the applied immunosuppressive agents. Organ and organ space infections include any part of the body that is opened or manipulated during an operative procedure. In addition, at least one of the following must also be present: purulent drainage from a drain placed through a stab wound to the organ space (which plays no role in transplant surgery); organisms isolated from a culture of the fluid or tissue in the organ space; an abscess or other evidence of infection found on direct examination, during reoperation, or by histopathologic or radiologic examination; or clinical diagnosis of surgical site infection by a surgeon or attending physician. This definition has some shortcomings in transplant recipients as the graft itself may become a source of infection. One has to bear in mind that human allografts may be contaminated and once transplanted, infection may develop within the graft. It is not clear if early onset pneumonia post lung transplantation, pyelonephritis post renal transplantation, or cholangitis post liver transplantation should be considered surgical site infections; for practical reasons, in this article such infections are not considered, however we give some examples of scenarios that potentially meet standard criteria. It also should be noted that an implanted human organ does not meet the criteria of a foreign body as it will have blood supply and is of human composition. Therefore, a comparison with surgical site infections associated with implants such as mesh grafts for hernia repair or artificial joints is not appropriate. Whereas such implants usually require removal, this is not the case in organ transplantation even if deep wound infection develops. On the other hand, in severe cases of infection such as graft liver abscesses, infected pancreatitis, or lung grafts that develop bronchiolitis obliterans organizing pneumonia, removal of these organs or affected parts may be indicated. In many such cases a combination of infection, ischemia, rejection and other pathologies is present.

PREVENTION OF SURGICAL SITE INFECTIONS

The general principles of asepsis during transplant surgery must be followed. In some patients, however, infection is present at the time of transplantation and heavy microbial contamination cannot be avoided. Examples are intestinal transplantation and pancreatic transplantation when an enteric anastomosis needs to be created and in liver re-transplantation for biliary necrosis (81). On the other hand, cardiac transplantation should be considered a clean procedure. Table 2 summarizes antimicrobial prophylaxis for the different transplanted organs. These are examples of potential strategies and alternatives are suggested. As emphasized, a pre-transplant meticulous microbiological work up and adaptation of the prophylaxis and individualization is highly recommended particularly for complex cases. The applied antimicrobial skin preparation may have an impact on the incidence of surgical site infections (94); many different antibiotic prophylactic regimens are in use and the antibiotics used must be tailored according to the local resistance patterns and pre-transplant microbial findings in transplant recipients. Also, donor aspects must be considered in order to avoid transmission of pathogens. Studies on selective small bowel decontamination using non absorbable antibacterials and antifungals have not led to universal acceptance of this strategy (9,34). Factors that have been found to be associated with post transplant surgical site infections include long operation times, an unusually large intraoperative blood loss, hypoxemia, hypothermia, renal failure, diabetes mellitus and hemodynamic instability (25, 33, 51, 53, 66, 78, 83). Cytomegalovirus (CMV) infection and disease have also been linked to surgical site infections mainly due to the fact that this virus not only causes a typical spectrum of diseases but also exhibits indirect effects such as increased rejection rates and increased rates of other infections (56). Therefore, antiviral prophylaxis at least for high risk patients such as CMV negative recipients of CMV positive grafts and those receiving intensified immunosuppression is widely used (45,93). On the other hand one should be aware that ganciclovir may cause neutropenia and by that increase the risk for surgical site infections (45,93).

As standard, agents should cover skin pathogens and in case of potential spill of Gram negative rods (renal, pancreatic, liver, intestinal transplantation) these pathogens should also be covered (50,100). Antifungal prophylaxis is indicated in subsets of patients and extended spectrum prophylaxis is usually administered if multi drug resistant organisms are to be expected such as in the case of lung transplantation in patients with cystic fibrosis or liver retransplants in case of cholangiopathy with intrahepatic abscesses (2,32). Pre-transplant microbiological mapping and adaptation to the individual situation should be performed in these more complex cases.

Kidney

The overall incidence of surgical site infections after all solid-organ transplants, including kidney transplants, has decreased dramatically during the past 20 years. Menzes et al. (66) reported a 7.5 % overall rate of surgical site infections in their study of 1939 kidney transplant recipients, which is similar to other published reports (41,52,57). Lower rates have been reported in recent publications, probably reflecting better infection control practices and knowledge of risk factors (17,42,53). Menzes et al. (66) conducted a case-control study to describe the clinical and epidemiologic characteristics of surgical site infections in a large cohort of kidney transplant recipients and to systematically assess risk factors for surgical site infections associated with kidney transplantation. Of the 1,939 kidney transplant recipients, 120 developed a total of 145 episodes of surgical site infections, for an overall surgical site infections rate of 7.5%. One hundred six surgical site infections episodes (73.1%) were superficial incisional, (21) (14.4%) were organ/space, and 18 (12.5%) were deep incisional. The average time to diagnosis was 11 days for a superficial incisional surgical site infections, 11.5 days for a deep incisional surgical site infections, and 15.2 days for an organ/space surgical site infections. The overall rate of mortality due to surgical site infections was 0.8%. Fifty-five of 145 episodes (37.9%) were polymicrobial infections. Coagulase-negative staphylococci were the most frequently isolated microorganisms (42%) in the first surgical site infections episode, whereas gram negative bacteria were the most prevalent agents (58.8%) in the second surgical site infections episode. They found very high levels of antibiotic resistance: 77% of Staphylococcus aureus isolates and 53.5% of coagulase-negative staphylococci were methicillin resistant, 80% of Klebsiella pneumoniae isolates were extended spectrum β-lactamase producing, and 33.3% of Pseudomonas aeruginosa isolates were carbapenem resistant. Using a conditional logistic regression model, they found the following independent risk factors for surgical site infections: body mass index (44,59,60), pretransplant diabetes (53,60), pretransplant chronic glomerulonephritis, acute graft rejection (53), reoperation after transplant (42,60), and delayed graft function (60). The knowledge of risk factors for surgical site infections and directed interventions to improve these issues may result in shorter hospitalization periods and lower costs of medical care thereby improving the quality of life of kidney transplant recipients.

Pancreas

Postoperative infectious complications affect 7-50% of the patients undergoing a pancreas transplant, with some studies documenting an infection incidence of >75% (3,20,23,26,88). Surgical site infections (SSIs), abscesses and urinary tract infections (UTIs) are the most prevalent infections detected in these studies. Postoperative infections remain a significant source of morbidity and mortality in spite of available prophylactic and empirical antibiotic treatment regimens (74). Multi drug resistant bacteria and rare fungi should be expected in intraabdominal infections after pancreatic transplantation (11,89). According to previous studies, the incidence of surgical site infections after simultaneous pancreas and kidney transplantation (SPK) has ranged from 9.2% to 51% (4,6,49,55,72,97).

In a study conducted by Linhares et al. (55), a higher prevalence of bacterial infections (71%) was observed after transplantation, of which 44% were by Gram-negative rods and 27% by Gram-positive cocci. Additionally, this study reported that 16% of patients developed viral infections (12% were diagnosed with cytomegalovirus and 4% with herpes simplex) and 13% of patients developed fungal infections (8% were diagnosed with Candida spp. and 4% with other fungi). Michalak et al. also reported a higher prevalence of post-transplant bacterial infections (71.6%) and fungal infections (8%) (69). In a previous study by Steurer et al. 90, surgical site infections were most often caused by coagulase-negative staphylococci (CoNS), followed by Enterococcus spp., Streptococcus spp., Klebsiella spp. and Candida spp. Another study showed a high incidence of P. aeruginosa, Enterococcus spp., CoNS and C. albicans infections in pancreas-kidney transplant recipients (49). Perdiz et al. (78) in their study of 119 SPK recipients found that surgical site infections occurred in (55) (46.2%) patients. The mean time of detection of surgical site infections in their study was 17 days, and most infections (54.5%) were detected between the 15th and 30th days post transplant. They observed a high prevalence of bacterial infections, of which 69.4% were caused by Gram-negative rods and 27.8% by Gram-positive cocci. The most common microorganisms detected were K. pneumoniae, S. aureus and P. aeruginosa. This was in contrast to the study by Baktavatsalam et al. (3) that showed Gram-positive cocci as the most prevalent agents.

Also in their report, Perdiz et al. (78) found that significant risk factors for surgical site infections were acute tubular necrosis, post- transplant fistula and graft rejection. Acute graft rejection was also shown to be a significant risk factor for surgical site infections by multivariate analysis. Reoperation after the transplantation procedure, although significant in the univariate analysis, was not significant in the multivariate analysis. Acute graft rejection may predispose the patient to a higher risk of infection, because in these cases the patient must receive more aggressive immunosuppressive therapy, usually with high dose corticosteroids and antithymocyte globulin (62). The length of stay in ICU was also reported as a significant risk factor for the development of fungal infections after solid-organ transplantation by Pugliese et al. (80).

In a recent study, Verschuren et al. (97) demonstrated that the use of prophylactic cotrimoxazole in these patients is not a risk factor for urinary sepsis. This was one of the few studies that assessed antimicrobial prophylaxis as a risk factor for infection. However, the authors did not evaluate antimicrobial prophylaxis during the original surgical procedure. Infectious complications are the main cause of morbidity and mortality following SPK, especially after bladder drainage. The use of enteric drainage combined with the administration of a broad-spectrum prophylactic antibiotic is recommended by some authors (7,55). One study suggested that the use of a stapler device for enteric anastomosis caused a substantial reduction in the incidence of deep surgical site infections and the authors speculate that this may be due to a reduction in the intraoperative spillage of pathogens (91,92). Aggressive and early therapy against infections is mandatory.

Liver

Liver transplant recipients are particularly susceptible to infection (38). The surgical procedure itself is complex and can take many hours, even in the best of hands, and has the potential for contamination via the gastrointestinal tract (16,70,73,75). Immunosuppression not only increases susceptibility to infection but also mutes the inflammatory response, making early detection more challenging. In recent studies, infection rates after liver transplantation between 50% and 70% have been reported (18,48,65,98,99). Mortality attributable to infection, however, has declined from >50% before 1980 to <10% in the 1990s (38).

Epidemiologic aspects of postsurgical infections have been described in the literature (38). The most frequently occurring infections are bacterial and fungal infections of the operative site, including the wound, abdomen, and organ space (9,48,67,75,99). Bacterial infections tend to occur earliest, most commonly during the first 4 to 6 weeks after transplantation (65). Fungal infections also appear early, within the first 8 weeks after transplantation (65). Several risk factors for posttransplantation infections have been identified in the literature. Patients with prolonged pretransplantation hospitalization (98), low pretransplantation hemoglobin levels (980, low serum albumin levels (16), high pretransplantation bilirubin levels (31,67,98), renal insufficiency (16), and those who had a previous transplant (1,48,99), are more likely to develop postsurgical infections. Surgical risk factors include leaks in the biliary anastomosis (65), duration of surgical procedure (48,67), and the amount of blood products transfused, particularly packed red blood cells (31,48,76). Posttransplantation risk factors include the use of OKT3 (51,99), and acute rejection (98), which are clearly related.

In their study of 777 first, single organ transplant recipients from the NIDDK Liver Transplantation Database, Hollenbeak et al. (38) found that transplant recipients who develop surgical site infections had a significantly higher rate of graft loss, accumulated more than 24 additional hospital days, and incurred approximately $131,000 in excess charges. The most common surgical site infections occurred in the biliary tract (32.1%) and were predominantly bacterial, with Enterococcus species identified as the most common infecting agent (26.1%). Peritoneal and wound infections were the next most common surgical site infections and accounted for approximately 45% of infections. The predominant organisms cultured at these sites were coagulase-negative staphylococci and S. aureus, respectively. Fifteen percent of infections occurred in the bowel. These infections were predominantly bacterial (82.2%) and intestinal infection had the highest proportion of fungal contributors (17.8%). Clostridium species were by far the dominant organism associated with intestinal infections (71%). Graft infections accounted for only 7.4% of surgical site infections and occurred at 10 weeks after transplantation. Similar to biliary infections, Enterococcus spp. were the most frequently cultured organisms in the setting of graft infections. Although surgical site infections were not associated with increased mortality, they were associated with increased 1-year graft loss (79.8% versus 86.5%), which led to increased hospital days and excess charges.

Asensio et al. (2) investigated surgical site infection (occurring within 30 days of transplant operation) in 1222 consecutive liver transplant recipients who underwent deceased-donor whole-liver procedures between August 2003 and September 2005 in eleven Spanish hospitals. Eighty-one patients (6.6%) developed surgical site infection, and the predominant sites of infection were the incision site (42%), peritonitis (39%), intra-abdominal abscess (16%), and hepatic abscess (10%). The timing of diagnosis after transplant of organ/space infection was slightly lengthened in comparison with incisional infections. The most common bacterial isolates were Escherichia coli (18.5%), S. aureus (15.3%), E. faecium (13.7%), Acinetobacter baumannii (12.9%), E. faecalis (11.3%), P. aeruginosa (6.4%), and Enterobacter spp. (4.0%). The risk of surgical site infection was related to choice of antibiotic prophylaxis, with the highest risk observed with use of cefazolin, but after a multivariate analysis, the only independent factors associated with surgical site infection were 1) choledochojejunal reconstruction, 2) previous solid organ transplant, and 3) red blood cell transfusion greater than four units.

Increased risk of infection associated with red blood cell transfusion has been observed in adult and pediatric liver transplantation (24,51). Allogeneic blood transfusion may cause immune down-regulation and dysfunction via the introduction of large amounts of foreign antigens into the host, a phenomenon not observed with autologous blood transfusion (36,95). The association of increased infection with choledochojejunostomy biliary anastomosis has been observed in the past (1,51). Positive intraoperative cultures at the time of liver transplantation from fascia, peritoneum, and bile have been associated with choledochojejunostomy (1). Significantly higher infectious complications involving enteric organisms secondary to liver biopsy have been reported in liver transplant recipients who had choledochojejunostomy versus choledochocholedochostomy (13). These observations are most likely explained by an invasion of gut organisms into the biliary tract through the biliary-enteric anastomosis and by spillage of bacteria at the time at which the anastomosis is created (50).

Kawecki et al. (46) evaluated the frequency of microbial isolates and their susceptibility profiles from cultures at the surgical site of 83 liver recipients in the early posttransplantation period. In the first week after OLT, (80) (96.4%) patients had at least 1 or more surgical site samples investigated microbiologically yielding 105 microbial strains. Among them, 88 were Gram- positive (83.8%) and 17 were Gram-negative (16.2%). The most common bacterial strains isolated in the first week after OLT were Gram-positive cocci with a predominance of coagulase-negative staphylococci (53%) and enterococci (15%). Antibiotic susceptibility of tested bacterial strains of Staphylococcus spp. showed MRSA (50%) with a dominance of MRCNS (87.2%) strains. The Gram-negative bacteria (n=17) included the Enterobacteriaceae family (41%) but no strains of ESBL. MDR Gram-negative non-fermenting rods included 3 strains of A. baumannii and 1 strain of Stenotrophomonas maltophilia. From the second to the end of the fourth week 65 (78%) recipients had at least 1 or more surgical site samples investigated microbiologically yielding 177 bacterial and 2 fungal (Candida dubliniensis) strains; 133 strains of Gram positive bacteria (75.1%) and 44 (24.9%) of Gram negative microorganisms. The most common bacterial strains isolated from surgical site samples were Gram-positive cocci with dominance of coagulase-negative staphylococci (48%) and enterococci (36%). Antibiotic susceptibility of Staphylococcus spp. showed a predominance of MRSA (100%) and MRCNS (80%) strains. The susceptibility of Gram-negative bacteria showed the presence of four ESBL strains from the Enterobacteriaceae family, and MDR Gram-negative non fermenting rods included seven strains of A. baumannii and two strains of S. maltophilia.

Hellinger et al. 33 in their study of 370 liver transplant recipients, identified surgical site infections in 66 (18%) of 370 patients undergoing their first liver transplantation. Of these 66 infections, 43 were classified as organ or space, 18 as superficial, and five as deep. Thirty-four of the 43 organ or space infections were non localized peritonitis with or without biliary disruption; five were intraabdominal abscesses unrelated to the hepatic allograft or to the biliary system; three were abscesses resulting from a biliary leak; and one was an abscess of the hepatic allograft resulting from hepatic artery ischemia. More than one bacterial or fungal pathogen was recovered in 22 (33%) infections. Coagulase negative staphylococci were recovered in 23 (35%) infections, enterococci in 22 (33%), methicillin-resistant S. aureus in 16 (24%), methicillin-susceptible S. aureus in eight (12%), gram-negative bacilli not including P. aeruginosa in six (9%), Candida species in five (8%), vancomycin-resistant enterococci in three (5%), anaerobes in three (5%), and P. aeruginosa in two (3%). The surgical site infections were associated with the occurrence of the composite endpoint of death or graft loss within one year of transplantation. Overall, surgical site infection was found to be associated with an increased risk of graft loss and death when considered as separate endpoints and, although not statistically significant, with an increased risk of death without prior graft loss. Organ or space surgical site infections, which were responsible for approximately two-thirds of all surgical site infections, were significantly associated with all three of these separate endpoints.

Recent studies of cadaveric-donor and living-donor liver transplantation by Hollenbeak et al. (38) and Iinuma et al. (43), respectively, identified rates of surgical site infections of 37% to 38%, both of which are lower than that reported by Hellinger et al. (33). This appears to be due to differences in case definition and particularly due to differences in time of onset of infection. Whereas the criteria for the anatomical site of infection in this investigation were identical to those used by Hollenbeak et al. (38) and Iinuma et al. (43), their studies included infections occurring up to 1 year after liver transplantation, while infections occurring more than 30 days after liver transplantation were excluded in the study by Hellinger et al. (33).

The literature lacks randomized trials for bacterial prophylaxis in transplant recipients, and therefore one can examine only what has been recommended in surgery prophylaxis (50). In 2003, guidelines were established regarding antimicrobial prophylaxis for surgery by the National Surgical Infection Prevention Project, but the document did not specifically address biliary surgery (12). The general purpose of surgical prophylaxis is to prevent wound infection and be active against bacteria assumed to be present in the type of surgery offered. An adequate dose should be given on the basis of body weight, and if the operation lasts more than 2 half- lives of the antibiotic, a dose should be repeated. The first dose should be given within 60 minutes of incision and usually should not continue more than 24 hours after surgery. Usually the bile is sterile, but it tends to be colonized with bacteria in pathological conditions, such as obstruction or occurrence of previous biliary surgery. Organisms involved in biliary infection are usually facultatively anaerobic enteric bacteria and sometimes S. aureus and anaerobes; therefore, a cephalosporin with anaerobic coverage may be the first choice for biliary surgery. Liver transplantation is a long (approximately 6-hour) operation and involves creation of an anastomosis with the biliary tree and often bowel. Therefore, most liver transplant operations are, at best, clean-contaminated procedures, and perhaps even dirty if one is operating on an actively infected liver (based on the old surgical wound classification) and bacterial prophylaxis is therefore recommended in liver transplantation in order to decrease surgical site infections.

These studies provide useful insight into the risk, cost and outcomes of surgical site infections following OLT, which is important in making crucial decisions regarding patient selection, transplantation procedure and infection control. Since the most important risk factors are related to surgical technique or are endogenous to patients, it is unlikely that standard infection control measures will be effective; instead efforts may be better directed at preemptive treatment strategies targeted at high-risk patients (37).

Intestinal

As mentioned above, this type of transplant has a very high incidence of surgical site infections. This can be explained by several factors including pretransplant severe malnutrition, extensive intraabdominal dissection, adhesions after previous abdominal surgery, potential intraoperative spillage, the necessity of an intestinal anastomosis and intensified immunosuppression. In a large series from Miami, more than 90% of patients developed bacterial infections and intraabdominal infection (IAI) was one of the most frequent sites (58). In addition, IAI was a predictor of mortality. This very high infection rate was also observed by Guaraldi et al. who reported on 19 patients from the Modena series (29). This high infection incidence has been reported in adult as well as pediatric recipients of intestinal grafts and is equally high after isolated small bowel and multivisceral transplantation (100). Closure of the abdominal wall can be very difficult, in particular if patients had undergone multiple previous laparotomies and if at time of transplantation intraabdominal infections or enterocutaneous fistulas are present. Zanfi et al. reported that in their series of 39 intestinal transplants, they experienced difficulties with abdominal wall closure in 40% of cases (102). To overcome these problems they performed two graft reductions, five skin-only closures, one two-step abdominal wall closure, four prosthetic mesh closures, and three abdominal wall transplants. Transplantation of the abdominal wall has been suggested by several centers; however, this technique is in general only used in cases when intraabdominal organs are transplanted. A group from Argentina recently published a series of 16 cases including 14 intestinal transplants, in which they used the abdominal rectus fascia instead of a vascularized graft (28). They experienced seven cases of wound infection. Superficial wound infections are usually not a major problem as long as the causative pathogens are not multi drug resistant and no cellulitis develops. Deep wound infections manifest as intraabdominal abscesses, which are not always accessible to percutaneous drainage and may require relaparotomy, which can be technically very challenging. Organ space infection is poorly defined in this type of surgery and would imply infection of the wall of the small bowel graft or the mesentery. If the small bowel is transplanted together with the liver, both implant sites may develop surgical site infections. In the case of a multivisceral transplant, which includes liver, pancreas and intestinal organs, the risk for surgical site infections is further increased. In these cases additionally one must consider graft pancreatitis with superinfection, which is associated with a high mortality rate.

Cardiac

Cardiac transplantation has an overall relatively low incidence of surgical site infections ranging from 1% to 15%. Whereas superficial surgical site infections are of minor clinical significance, deep surgical site infection is a life threatening disease. Organ space infection is extremely rare and would include bacterial or fungal myocarditis and possibly early onset endocarditis. As mentioned above, there are significant problems in defining organ space infection; Coll et al. reported on one patient with fatal MRSA myocarditis (15). In this case they found clear evidence that the infection was transmitted with the graft. Whereas this infection may fit the definitions of organ space infection, a case of endocarditis with an Aspergillus species, which could be clearly traced to the donor, seems to be different and the reactivation or transmission of Chagas’ disease with myocarditis in the transplanted heart certainly represents a very different and unique entity (27,47).

Anterior mediastinitis and/or sternal osteomyelitis are both difficult to treat infections and usually require temporary open therapy. In some series very low incidence of sternal infections has been reported, such as in a recent article from the Mayo clinic: the authors observed only three such cases in a series of more than 300 cardiac transplants (96). Mattner et al. reported on the series from Hannover and observed surgical site infections in 10% patients after cardiac transplantation but 35% patients after combined heart-lung transplantation (64). They also reported that 11% of their lung recipients had surgical site infections. In their series, Enterococci and coagulase negative staphylococci were by far the most commonly isolated pathogens. Of 27 patients with surgical site infections, 21 fulfilled the criteria of deep surgical site infection. Vaccuum assisted wound closure devices (VAC) are commonly used as they allow stabilization of the chest and subsequent easy approximation of the sternum for secondary repair after the acute infection has been controlled (87). Routledge et al. reported six patients with deep surgical site infection after thoracic transplants and in all cases the infection was well controlled using the VAC device (85). Also Fleck et al. reported on successful use of this technique in five cardiac transplant recipients (22). This system also allows mobilization of these patients, which is a particular advantage over the traditional packing approach.

Lung

Similar to cardiac transplantation, surgical site infection is rare after lung transplantation and superficial surgical site infection is in most cases of minor clinical significance (84). Deep surgical site infection includes both chest wall infections and pleural empyema. Pleural empyema is a well known complication in lung recipients and may be caused by rather atypical microorganisms. Although S. aureus and various Gram negative rods are the predominant pathogens, fungi and other rare bacteria may also be found (11,30,101). For example, Fairhurst et al. treated a lung recipient with Mycobacterium abscessus empyema (21). In a series of almost 400 lung transplants from Pittsburgh, fourteen patients (3.6%) developed pleural empyema and they also found a very broad spectrum of pathogens (71). Such empyemas require surgical drainage or placement of a chest drain. Herridge et al. found pleural empyemas predominantely in double lung recipients and Burkholderia cepacia was a particularly common problem in patients with cystic fibrosis (35). An alternative to surgery is CT-guided or ultrasound guided percutaneous drainage. Marom et al. performed CT guided pleural drainage in 31 lung recipients and in more than 50% of patients, the pleural space was infected (61). However, such infections may result in significant scarring and require decortication of the pleural space in order to allow the graft to adequately expand (8). In a series of more than 500 lung transplants from the Cleveland clinic, 24 patients underwent decortication and the vast majority of cases were due to empyema or loculated effusions.

Composite Tissue Allografts

This new treatment concept, also referred to as reconstructive transplantation, is a rapidly evolving option for replacement of lost limbs or other body parts (79). The most common transplanted body part is the hand and more than 30 such cases have now been performed worldwide. Other composite tissue allografts include arms, face, knees, penis and larynx and this list will continue to grow. Abdominal wall transplantation is almost exclusively performed in conjunction with intestinal transplantation and therefore, discussed in this section. Surprisingly, thus far only a single case of significant surgical site infection has been reported. Additional cases that involved infections were knee transplants that were lost due to degeneration, ischemia and rejection and became superinfected before being removed. As this field is further developing and will include other body sites, infection prophylaxis will become a more important issue, in particular if larger body parts are replaced or the surgical field includes potentially contaminated areas such as the perineum or oral cavity. One reason why these patients may not be at such high risk for surgical site infection is the fact that they do not suffer from end stage organ failure prior to these rather complex surgical procedures. On the other hand, opportunistic infections such as CMV disease or rare fungal infections seem to be common and difficult to treat complications in this patient population (10,86).

SUMMARY AND CONCLUSIONS

Surgical site infection will continue to be a common complication after solid organ transplantation. Due to the current allocation system for liver and lung transplantation, an increase in the proportion of patients with advanced disease and/or comorbid conditions, who are at high risk for surgical site infection, has been observed. Recently, an alarming increase of surgical site infection caused by multi drug resistant (MDR) organisms has been observed. Important MDR pathogens involved in transplant infections include MRSA, VRE, MDR Pseudomonas aeruginosa, Acinetobacter baumanii and ESBL and carbapenemase producing Gram negative rods (63,64). Also non-albicans Candida has emerged as common fungus in these patients (11). Overall the spectrum of pathogens causing surgical site infection in solid organ transplant is extremely broad and this should be considered in the management of these patients (2,89). Reid et al. recently emphasized that pre-LT administration of antibiotics was associated with a significant risk for subsequent intraabdominal infections caused by MDR organisms (83). It also should be recognized that transplant recipients may become primary source of significant nosocomial outbreaks as they have a reduced capacity to clear MDR organisms. With the increasing utilization of grafts from extended criteria donors, transmission of infection with the grafts has become a major concern. Without further data, the prevention of surgical site infection among transplant recipients is the same as that for other surgical patients. Management of surgical site infection post transplant follows the principles of source control with drainage and antimicrobial chemotherapy according to susceptibility testing. Contact isolation of solid organ transplant recipients with ongoing infections due to MDR organisms should be standard. The definition of organ space infection following solid organ transplant remains controversial.

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Table 1. Epidemiologic Characteristics of Post-transplant Surgical Site Infections

Type of Transplant	Estimated Frequency	Time to Onset	Predominant Pathogen	Additional Pathogen	Typical Superficial SSI	Deep SSI	Organ Space Infections
Renal	7.5%	11-15 days	Coagulase negative staphylococci, Gram-negative bacteria	Candida albicans	Abdominal wall	Intra abdominal	(Peri)nephritis of allograft
Pancreas	7-50%	15-30 days	Gram-negative rods, Gram-positive cocci	Candida spp., VRE	Abdominal wall	Intra abdominal	(Peri)pancreatitis
Liver	6.6->25%	First 4-6 weeks	Enterococcus species, Coagulase-negative staphylococci, SA, Gram negative bacteria	Acinetobacter baumannii, P. aeruginosa, Enterobacter spp. VRE, Candida spp.	Abdominal wall	Retroperitoneal	(Peri) hepatitis
Heart	10.0%	First month	Staphylococci, streptococci	MRSA	Presternal	(Sub) sternal	Pericarditis, myocarditis
Lung	11.0%	First month	S.aureus, Gram negative bacteria	MRSA, Candida spp.	Chest wall	Intercostal space	Pleural empyema
Small bowel	100.0%	9-17 days	Enteric pathogens	VRE, MRSA, Candida	Abdominal wall	sSbfascial	Peritonitis
Composite tissue	10.0%	Not reported	S.aureus, Coagulase negative staphylococci, streptococci	MRSA	Subcutaneous abscess	Osteomyelitis, myositis	Not defined

Table 2. Antimicrobial Prophylaxis Options for the Prevention of SSI in Solid Organ Recipients

Type of transplant	Antibacterial agent	Alternative antibacterial agent 1	Alternative antibacterial agent 2	Duration	Special Considerations
Renal	Cefazolin	Aminopenicillin/ beta-lactamase inhibitor	Fluoroquinolone	Single dose	Consider urinary tract colonization with MDR Gram negative rods or VRE: accordingly alter prophylaxis
Pancreas	Cefuroxim, Cefoxtin	Aminopenicillin/ beta-lactamase inhibitor	Fluoroquinolone	24-48 hours	For bladder drainage 2nd generation cephalosporin, for enteric drainage anaerobic coverage recommended, consider combination prophylaxis (Beta-lactam+ Fluoroquinolone)
Liver	Cefoxtin	Piperacillin/ Tazobactam	Carbapenem	24-72 hours	For straight forward cases 2nd/3rd generation cephalosporin; for complex cases high end agents including (lipo) glycopeptides and antifungals
Heart	Cefazolin, Cefuroxim	Ceftriaxone	Clindamycin	24-72 hours	In case of assist device, add glycopeptides
Lung	Cefepime, Aztreonam/ Vancomycin	Carbapenem	Fluoroquinolone	48-96 hours	Tailor prophylaxis according to pre transplant cultures including results from donor
Small bowel	Piperacillin/ Tazobactam	Carbapenem	Fluoroquinolone	48-96 hours	Pretransplant continuous monitoring of colonizing/infecting pathogens crucial: accordingly alter prophylaxis