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Original Investigation |

Discordance Between Perioperative Antibiotic Prophylaxis and Wound Infection Cultures in Patients Undergoing Pancreaticoduodenectomy

Zhi Ven Fong, MD1; Matthew T. McMillan, BS2; Giovanni Marchegiani, MD3; Klaus Sahora, MD1; Giuseppe Malleo, MD3; Matteo De Pastena, MD3; Andrew P. Loehrer, MD1; Grace C. Lee, MD1; Cristina R. Ferrone, MD1; David C. Chang, MPH, MBA, PhD1; Matthew M. Hutter, MD, MPH1; Jeffrey A. Drebin, MD2; Claudio Bassi, MD3; Keith D. Lillemoe, MD1; Charles M. Vollmer, MD2; Carlos Fernández-del Castillo, MD1
[+] Author Affiliations
1Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston
2Perelman School of Medicine, Hospital of Pennsylvania, Philadelphia
3Verona University Hospital Trust, Verona, Italy
JAMA Surg. 2016;151(5):432-439. doi:10.1001/jamasurg.2015.4510.
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Published online

Importance  Wound infections after pancreaticoduodenectomy (PD) are common. The standard antibiotic prophylaxis given to prevent the infections is often a cephalosporin. However, this decision is rarely guided by microbiology data pertinent to PD, particularly in patients with biliary stents.

Objective  To analyze the microbiology of post-PD wound infection cultures and the effectiveness of institution-based perioperative antibiotic protocols.

Design, Setting, and Participants  The pancreatic resection databases of 3 institutions (designated as institutions A, B, or C) were queried on patients undergoing PD from June 1, 2008, to June 1, 2013, and a total of 1623 patients were identified. Perioperative variables as well as microbiology data for intraoperative bile and postoperative wound cultures were analyzed from June 1, 2008, to June 1, 2013.

Interventions  Perioperative antibiotic administration.

Main Outcomes and Measures  Wound infection microbiology analysis and resistance patterns.

Results  Of the 1623 patients who underwent PD, 133 with wound infections (8.2%) were identified. The wound infection rate did not differ significantly across the 3 institutions. The predominant perioperative antibiotics used at institutions A, B, and C were cefoxitin sodium, cefazolin sodium with metronidazole, and ampicillin sodium–sulbactam sodium, respectively. Of the 133 wound infections, 89 (67.1%) were deep-tissue infection, occurring at a median of 8 (range, 1-57) days after PD. A total of 53 (40.0%) of the wound infections required home visiting nurse services on discharge, and 73 (29.1%) of all PD readmissions were attributed to wound infection. Preoperative biliary stenting was the strongest predictor of postoperative wound infection (odds ratio, 2.5; 95% CI, 1.58-3.88; P = .03). There was marked institutional variation in the type of microorganisms cultured from both the intraoperative bile and wound infection cultures (Streptococcus pneumoniae, 114 cultures [47.9%] in institution A vs 3 [4.5%] in institution B; P = .001) and wound infection cultures (predominant microorganism in institution A: Enterococcus faecalis, 18 cultures [51.4%]; institution B: Staphylococcus aureus, 8 [43.9%]; and institution C: Escherichia coli, 17 [36.2%], P = .001). Similarly, antibiotic resistance patterns varied (resistance pattern in institution A: cefoxitin, 29 cultures [53.1%]; institution B: ampicillin-sulbactam, 9 [69.2%]; and institution C: penicillin, 32 [72.7%], P < .001). Microorganisms isolated in intraoperative bile cultures were similar to those identified in wound cultures in patients with post-PD wound infections.

Conclusions and Relevance  The findings of this large-scale, multi-institutional study indicate that intraoperative bile cultures should be routinely obtained in patients who underwent preoperative endoscopic retrograde cholangiopancreatography since the isolated microorganisms closely correlate with those identified on postoperative wound cultures. Institution-specific internal reviews should amend current protocols for antibiotic prophylaxis to reduce the incidence of wound infections following PD.

Figures in this Article


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Figure 1.
Microorganisms Grown From Intraoperative Bile Cultures in Institutions A and C

aStatistically significant at P < .05 compared with institution C.

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Figure 2.
Microorganisms Grown From Wound Cultures in Patients With Postoperative Wound Infection in All 3 Institutions

aStatistically significant at P < .05 compared with the other 2 institutions.

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Figure 3.
Institution-Specific Comparison of Microorganisms Grown in Intraoperative Bile Cultures and Wound Cultures
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Surgical Site Infection Post Pancreaticoduodenectomy: Rising Cognizance to Abridge Morbidity
Posted on August 3, 2016
Kumar Jayant, Tomokazu Kusano, Madhava Pai
Dept of HPB, Imperial College London
Conflict of Interest: None Declared
Corresponding Author:
Mr. Madhava Pai
Department of hepato-pancreato-biliary surgery (HPB),
Hammersmith Hospital,
Imperial College, London, UK
Email address: madhava.pai04@imperial.ac.uk

To The Editor,
All of us wish to thank Fong et al., for their efficient handling of the project on microbiological analysis intraoperative bile and surgical site wound infection with the effectiveness of perioperative antibiotic protocol in patients undergoing Pancreaticoduodenectomy (PD). Although advancement in surgical techniques and perioperative care have been able to decrease the mortality risk following PD to less than 3–5% in defiance of this morbidity rates are still very high. The wound infections play a significant contribution to the patient’s morbidity and are associated with a prolonged hospital stay and also impose a significant economic burden (1)

Although there is a lack of any meta-analysis or systemic review on this topic couple of studies exists in literature which evaluates the current pieces of evidence for the importance and application of intraoperative bile culture (IBC) during PD. To better understand the role of IBC and extrapolating it results to select proper prophylactic antibiotic, we have analysed and summarized existing literature while highlighting key issues as postoperative wound infection rate, wound culture & resistance pattern, intraoperative biliary culture, type of antibiotic prophylaxis and preoperative biliary stenting (PBS). The reported incidence of wound infection following PD in various studies exists between 8.2% to 29% (2).
The bacteriobilia is an important determining factor behind the increased postoperative wound infection. It is frequently encountered following preoperative endoscopic stent placement, which is a widely performed despite evidence based limitations in indications (3–5). Sourrouille et al., have done a prospective study over 175 patients and have reported positive bile culture in 81% cases (6). Similarly, a study by Gavazzi et al., have reported bacteriobilia in 58.9% patients following preoperative biliary drainage (PBD) before PD. The reported incidence of SSI in PBD group was 20.8% (7).
The study by Fong et al., further reinforces the difficulties faced by clinicians in the perioperative period following PD and presents some interesting findings, some of which have already been described by others. They have reported wound infection in 8.2% cases of which 67.1% were a deep-tissue infection; bacteriobilia has seen 98.8% patients with preoperative stenting. The bacteriobilia was associated with higher rate of postoperative wound infection (12.4% vs. 5.3%) than in patients without it (8). Realizing the importance of these factors we totally agree with the report that the increase incidence of surgical site infection is secondary to bacteriobilia which are predisposed by preoperative biliary stenting in patient undergoing PD. Furthermore, as the bacteria grown in wound culture resemble that of bacteriobilia. A practice to routinely obtain bile culture during PD would be a nice approach to tailor antibiotics in the presence of pending wound culture report. As this is the protocol we are following in our practice after our study by Limongelli et al., 2007 over 220 patients. In this report, we have reported 29% incidence of wound infection of which 69% were noticed in cases with active IBC after preoperative biliary drainage (9).
There is no doubt that this prospective study by Fong et al., has further added to our understanding regarding management of patients following PD, and thus we are grateful to them for their efforts, however, few points deserve mention (8).
First, is that the inclusion of data from institution B is non-descript as they had not performed any IBC. They have only reported the results of wound culture which show St. aureus (43.9%) and K. pneumoniae. It is important to know the stand of various studies done to assess the prevalence of microorganisms in bile in cases of obstructive jaundice. In a separate study by Neve et al., and Michael et al., have reported prevalence of St. aureus as 8.3% and 0.03% respectively (10,11). This, in turn, frames some bias in the study by Fong et al., which should be cleared.

The second point in the panel of this commentary is the data produced by institution ‘C’. They have reported similar pattern of predominant organism in intraoperative bile and wound culture as E.faecalis (44.8%), K. pneumoniae (23.9%), E.coli (19.4%) and E.faecalis (36.2%), E.coli (36.2%) respectively. As the most prevalent organisms are of enterobacteriaceae group in almost all other studies too. We put forward a thought to check resistance pattern against 3rd generation cephalosporin as ceftriaxone or cefoperazone while IBC as they could be an antibiotic of consideration in cases of bacteriobilia. Over and above that the resistance pattern in this group had shown the high incidence for Methicilin Resistance St. aureus (MRSA) that should be taken care off (8).
The third salient point to mention is the comment of Fong et al., referencing the study by Donald et al., over 140 PD where they have first analyzed wound cultures in 34 patients only, which showed cefoxitin-resistant E. faecalis and E. cloacae. Based ¬¬¬¬on the resistance pattern they tailored prophylaxis to piperacillin-tazobactam in the next group of 106 patients, which manifested in the form of reduction of wound infection rates from 32.4% to 6.6%. However, apart from the bacterial resistance, the reported serum albumin level was significantly lower in higher disease group (12). Here we like to quote a prospective study by Harvard Medical School in Boston involving 550 pancreatic resections. Where they have reported that 14% patients had postoperative wound infection of these 20% arose from preoperative biliary drainage. They have also outlined the negative impact of lower serum albumin on wound infection following PD (13).
Considering this fact that the Surgical Care Improvement Project (SCIP) was initiated to reduce the preventable surgical complications as SSI. Unfortunately, they haven’t laid any guidelines regarding the use of prophylactic antibiotics against biliary pathogens for PD (14). We do advocate the need of development of prophylactic antibiotic protocol based on intraoperative bile culture and institutional resistance pattern at the same time we do emphasize the role of other factors in the development of these complications. In a retrospective study by Suguira et al., involving 408 patients a total of 51 % patients developed SSI following PD. Here they have delineated various risk factors associated with SSI following PD. The strongest risk factor is pancreatic fistula whereas operative time, main pancreatic duct diameter =<3mm, abdominal wall fat thickness >10mm were other notable ones (5).
Ceppa et al., had developed a questionnaire based on various risk factors as surgical technique, wound protection, antibiotics, drain management, glycaemic control, temperature control, blood transfusion, bowel management, oxygenation. They have reported a significant decrease in the SSI incidence from 24.5% to 17.1% (15).
We should not underestimate these points which give us more insight for the better management of post PD patients. An another important factor is the duration of prophylactic antibiotic coverage; this was well dealt in a study by Fathi et al. They have evaluated the effect of tailored prophylactic broad spectrum antibiotic coverage for 72 hrs has significantly decreased the infectious complications of PD. Moreover, they have reported no significant increase in the incidence of Clostridium difficile colitis against routine coverage of 24 hrs (16).
Some might argue that this is stretching a point, but we like to make a heavyweight appeal to consider all the factors laid in various studies as we think that controlling these factor provides helpful ballast in minimizing SSI post PD. In view of high risk of infectious complication, we contemplate a judicious use of biliary stenting could be a probable answer for prevention of these SSI (17). We do believe in the strength of the recommendation given by Fong et al. and others, but there should be a note of caution as going up in the ladder of newer antibiotics, will make the postoperative crisis worse, not better. Having said that, we are more concerned about a return to the scene of complete resistance like MRSA where they have almost won the knockout stage against many antibiotics. As going up on the ladder of higher antibiotics, the scale will be a self-inflicted risk that is out of our control that we just don’t know how hard it will hit on the future patient’s recovery.

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17. Bonin EA, Baron TH. Preoperative biliary stents in pancreatic cancer. J Hepatobiliary Pancreat Sci. 2011;18(5):621–9.

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