Characteristics of Surgical Site Infection Following Colorectal Surgery in a Tertiary Center: Extended-spectrum β-lactamase-producing Bacteria Culprits in Disease

Introduction. Surgical site infection (SSI) is a well-known complication of colorectal surgery associated with increased morbidity and hospital stay. Antimicrobial prophylaxis can reduce the risk of SSI by as much as 75%. Extended-spectrum β-lactamase (ESBL)-producing pathogens make the successful use of such prophylaxis a challenge and are a real threat to patient care following colorectal surgery. Objective. The aim of this study is to report the common characteristics of SSIs after colorectal surgery and to highlight the prevalence, risk factors, and clinical relevance of ESBL infections among these patients in a tertiary center. Materials and Methods. All patients who underwent bowel resection operation (ie, laparoscopy, laparotomy, or laparoscopic-assisted colectomy) for benign or malignant colorectal disease were identified retrospectively from the prospective database of the colorectal department in the authors’ tertiary center from March 2015 to March 2016. Results. There were 123 patients included in this study, of which 21% (n = 26) had a SSI. The microorganisms isolated in the surgical sites included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, Proteus mirabilis, Morganella morganii, and Enterobacter cloacae. Thirty-eight percent of the wound infections grew ESBL-producing pathogens in their wound cultures and 62% grew non-ESBL microbes. Conclusions. More than one-third of the wound infections were due to ESBL-producing pathogens, which were resistant to the antibiotic prophylaxis given. Inappropriate antibiotic usage can delay postoperative recovery. High-risk patients for ESBL colonization may benefit from preoperative screening based on an established protocol. The cost effectiveness of an ESBL screening program needs to be further studied.

Surgical site infection (SSI) is a common complication after colorectal surgery, with a reported incidence ranging from 3% to 30%^1-3 and up to 40% in the absence of antibiotics.⁴ It has been significantly and independently associated with increased length of inpatient stay, morbidity, and cost.⁵ In an era of enhanced recovery, early recognition and prompt treatment of SSIs should be at the forefront of medical care for patient safety and cost effectiveness of treatment.

Introduction of prophylactic antibiotics in 1940 marked an important cornerstone in the delivery of safer surgical care. Colorectal surgery is especially prone to surgical wound infections due to the nature of visceral handling intra-operatively and dissemination of microorganisms from bowel contents. Antibiotic prophylaxis refers to the use of antimicrobials before or during surgery to suppress the growth of contaminating microorganisms, thus reducing the risk of infection.^6,7

A meta-analysis including 182 trials and 50 different antibiotics published in the Cochrane Library of Systematic Reviews⁸ revealed up to a 75% reduction in the risk of surgical wound infection after colorectal surgery with prophylactic antibiotics when compared with no treatment/placebo. This assumes that the antibiotics used provide adequate cover of the expected pathogens and account for the local microbiologic epidemiology.^9,10

Since the introduction of preoperative prophylaxis 7 decades ago,¹¹ resistance to widely used antibiotics has become a sobering health burden to 21st century health care systems and providers. The emergence of extended-spectrum β-lactamases (ESBLs) appears to be a cardinal mechanism accountable for the resistance to widely used antibiotics.¹²

The ESBLs are enzymes produced by bacteria, found mainly among Enterobacteriacaea, which hydrolyse β-lactams (extended-spectrum penicillins, third-generation cephalosporins, and monobactams) conferring broad antibiotic resistance.^13,14 They often show cross-resistance to many other classes of antibiotics, further limiting treatment options. The enzymes are carried in plasmids capable of transferring to other strains and species of bacteria, allowing for resistance to spread rapidly.

It is of the utmost importance that an infection secondary to ESBL-producing organisms is prevented and well contained. The aim of this study is to report the common characteristics of SSIs after colorectal surgery and to highlight the prevalence, risk factors, and clinical relevance of ESBL infections among these patients in a tertiary center.

Study design and inclusion criteria

Patients were identified from a prospectively maintained database of the colorectal department in Chelsea and Westminster Hospital, London, United Kingdom. Consecutive patients undergoing bowel resection operation (ie, laparoscopy, laparotomy, or laparoscopic-assisted colectomy) for benign or malignant colorectal disease from March 2015 to March 2016 were included. All operations were performed by a specialist colorectal team on a case-by-case basis.

Definitions

A SSI was defined in agreement with the standard set of clinical criteria for infection, outlined by the US Centers for Disease Control and Prevention (CDC)¹⁵ as infection involving the skin or subcutaneous tissue (superficial SSI) or fascial and muscle layers (deep SSI) of the surgical incision sites. It should occur within 30 days of the operation and demonstrate at least 1 of the following:

• Purulent discharge;
• Organisms isolated in aseptically obtained wound cultures;
• At least 1 of the 4 cardinal signs of infection: erythema, heat, pain, and swelling of incision deliberately opened by surgeon;
• Development of an abscess; or
• Diagnosis of a SSI by attending surgeon.

Sample

The data on the total number of operations that met the inclusion criteria (n = 123) and the number of operations that were complicated by SSI (n = 26) were derived from the monthly Mortality and Morbidity data for colorectal surgery.

Data sources

Patient demographics, mode of admission to hospital (elective or emergency), operation details, length of stay, microbiology results, and antibiotic regime were determined by accessing case notes including the operation note, discharge summaries, and electronic patient records. Key individuals contacted included the Tissue Viability Clinical Specialist Nurse (TVN), Microbiology Department, Lead Antimicrobial Pharmacist, and Theatre Coordinator. The data collection proforma used is shown in Table 1.

A total of 123 patients admitted both electively (n = 92) and due to emergency (n = 31) were included in this study. Twenty-nine percent (n = 9) of the emergency admissions and 19% (n = 17) of the elective admissions developed a SSI, averaging to a total of 21% (n = 26) overall for the time period between March 2015 and March 2016 (Figures 1,2,3).

From the sample of the 26 patients who developed a SSI, the median age was 65 and 65% (n = 17) of the group were white British and 54% (n = 14) were female. Patients with an American Society of Anesthesiologists score between I–II and III-IV were 46% (n = 12) and 54% (n = 14,), respectively. Thirty five percent (n = 8) had hypercholesterolemia, 48% (n = 11) hypertension, and 17% (n = 4) asthma or chronic obstructive pulmonary disease (COPD). No patient was noted to have diabetes mellitus. The average length of stay was 19 days (Table 2). 

One hundred percent of the SSIs had a wound culture taken at the time infection was suspected. Thirty-eight percent (n = 10) of the wound infections grew ESBL-producing pathogens and 62% (n = 16) grew non-ESBL microbes (Figure 4). The microorganisms isolated included Enterobacter cloacae, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Morganella morgana, and Proteus mirabilis. The ESBL- producing isolates were identified in 100% (n = 3) of the E cloacae, 25% (n = 1) of the K pneumonia, and 60% (n = 6) of the E coli (Figure 5). The most common ESBL-producing pathogen was E coli.

On the preoperative MRSA screen, 92% (n = 24) tested negative, 4% (n = 1) positive, and 4% (n = 1) did not receive screening. Seventy-three percent (n = 19) received preoperative screening for resistant gram-negative bacteria, and all had a negative result (Figure 6). 

The TVN reviewed 81% (n = 21) post infection, and 54% received negative pressure wound therapy (NPWT) using dedicated dressing as a means of treatment. Negative pressure wound therapy with PICO (Smith & Nephew, London, UK) was applied to 1 patient in the operating room, and the patient still got an infection. Forty-six percent (n = 12) did not receive NPWT.

Surgical site infections are of particular concern in large bowel surgery due to the inherent likelihood of antimicrobial contamination at the operative site. The 2014-2015 report on Surveillance of Surgical Site Infections in NHS Hospitals in England,¹⁶ published by Public Health England, reported colorectal surgery as the type of surgery with the highest risk of SSIs, with cumulative incidence risk in the last 5 years at 10.4%. In 1981, Baum et al⁴ reported that SSIs occurred in 40% of patients undergoing large bowel surgery in the absence of antibiotic prophylaxis.

Wound infection is a sobering burden on health care outcomes as it increases the risk of morbidity and mortality, likelihood of admission to intensive care, length of hospital stay, and the economic implications of prolonged medical care.^17-21 In 2004, Nespoli et al²² reported the survival rates in patients who underwent surgery for removal of colon cancer were reduced in the presence of a surgical wound infection.

The national clinical guidelines produced by the Scottish Intercollegiate Guidelines Network (SIGN), updated in 2014,¹⁰ report that the numbers needed to treat (NNT) with antibiotic prophylaxis to prevent SSI or an intra-abdominal abscess in colorectal surgery is 4. When compared with other surgeries, such as hepatobiliary where the NNT is 11, it is made clear that prophylaxis is highly applicable and beneficial to colorectal surgery.⁸ Further supportive evidence is found in a Cochrane meta-analysis, which demonstrates up to a 75% reduction in postoperative wound infections with prophylaxis.⁸ A national study assessing real-world use of prophylactic antibiotics in open colectomies showed up to a 44% decrease in SSIs depending on the choice of antibiotic.²³ The aforementioned statistics show the appropriate choice of antimicrobial prophylaxis can prevent postoperative wound infections and hence contribute to better patient outcomes and safer care in colorectal surgery.

This study was mainly fueled by the sincere concerns of the authors’ colorectal team who found that, despite great advancements in surgical care progressing colorectal surgery towards enhanced recovery, SSIs remained an obstacle to optimal patient care. The data revealed that 21% of the colectomies completed in this tertiary center were complicated by a SSI, which is higher than the national average. Insight into the factors accountable for this is crucial to overcome existing challenges and guide better practice in the management of surgical wound infections.

The main findings of this study showed that 38% of wound infections after colorectal surgery in the tertiary center were due to ESBL-producing pathogens. This finding revealed that more than one-third of the infections were resistant to the empirical antibiotic prophylaxis (ie, amoxicillin-clavulonic acid), which defeats the purpose and benefits of preemptive antimicrobial administration. This indicates that inadequate empirical antibiotic prophylaxis is a potential contributor to the high incidence of SSIs.

The ESBL production undermines the effectiveness of prophylactic antimicrobials, which have so far been a failsafe mechanism against SSIs. It is an important risk factor for increased mortality in infections and a major determinant of resistance against β-lactams.²⁴ Considering that β-lactams account for more than 50% of all global antibiotics in use, the ESBL phenomenon is threatening to jeopardize an era of relatively safe colorectal surgery by complicating previously easily treatable infections.^25-27 Empirical antibiotic treatment needs to account for the emerging challenges of multidrug resistance, and ESBL-producing pathogens need to be addressed more aggressively.

The current study has limitations, therefore conclusions should be interpreted with caution. First, this is an observational study with a relatively small number of patients and events. It was performed at a single center, including patients operated on by a single colorectal team. Lastly, a cost analysis of SSIs would have been desirable but was beyond the aim of this research study.

However, data were prospectively collected with a rigorous method and the definition of SSI was in agreement with the CDC.¹⁵ The team included a TVN, who further enhanced the relevance of the study.

Albeit a small-scale observational study, the substantial burden of SSI after colorectal surgery secondary to ESBL pathogens in the treating tertiary center raises concern that action must be taken. Enterobacteriaceae are the most common pathogen responsible for SSIs in colorectal surgery¹⁶ and ESBL prevalence is rapidly growing amongst them.²⁰ It is imperative that clinicians improve the current practice and actions, such as adding an ESBL screening program for patients having colorectal surgery, to help address part of the problem. Despite asymptomatic colonization being a risk factor for infection, the literature remains torn regarding the cost effectiveness of routine ESBL screening. Current practice advocates screening for high-risk populations only, such as critically ill/intensive care unit patients, patients from high-risk countries, those experiencing prolonged hospitalization, and those for whom medical devices are present.²⁸ Extending routine ESBL screening to include patients undergoing colorectal surgery as an additional high-risk population may be integral to the prevention of SSI in colorectal surgery. Positive screening and colonization per se might not be indications for active treatment but can provide more accurate guidance on the limited choices for antimicrobial prophylaxis.

As outlined in the guidelines for antimicrobial prescribing, it is crucial that criteria in the choice of correct antibiotic prophylaxis are respected, on the basis of the microorganisms expected in the operative site and with consideration to local and disease-specific antimicrobial sensitivities.^10,29 Inability to cover for the likely pathogens in the operative site results in failure to recognize and appropriately treat a postoperative complication and the associated implications in morbidity and economic cost.

Extended-spectrum β-lactamase- producing pathogens were accountable for a substantial burden of disease on SSIs after colorectal surgery. The high prevalence of ESBL in the authors’ hospital cannot be ignored and is of great clinical concern. The authors recommend routine screening of ESBL in patients undergoing colorectal surgery and optimization of antibiotic prophylaxis based on an established protocol. The cost effectiveness of a dedicated screening program requires further study.

Affiliations: Department of Colorectal Surgery, Chelsea and Westminster Hospital, London, UK; and The Royal Marsden NHS Foundation Trust, London, UK

Correspondence: Christos Kontovounisios, MD, FRCS, FACS, Locum Consultant Colorectal and General Surgeon - Honorary Clinical Senior Lecturer, Department of Surgery and Cancer, Chelsea and Westminster Hospital, Imperial College London NHS Trust, 369 Fulham Road, London, SW10 9NH, UK; c.kontovounisios@imperial.ac.uk

Disclosure: The authors disclose no financial or other conflicts of interest.