Anastomotic leakage (AL) is a type of intra-abdominal infection (IAI) which requires appropriate antibiotics with proper intervention. This study aimed to improve the appropriateness of antibiotic treatment by assessing the patterns of antibiotic treatment and resistance of pathogen profiles in patients who had AL after colorectal cancer surgery.
From June 2006 through December 2017, the medical records of the patients who had AL after elective abdominal surgery for colorectal cancer in Kyung Hee University Hospital at Gangdong, Seoul, Korea were reviewed retrospectively. Baseline characteristics and consistence of antibiotics with culture study results were analyzed to evaluate the appropriateness of treatment.
Among 982 patients who underwent primary surgery for colorectal cancer, 41 (4.2%) had AL. Mean time of diagnosis of AL from surgery was 6.3 days. The most commonly used prophylactic antibiotics for the primary surgery was 2nd generation cephalosporin (66.6%). Mean duration of prophylactic antibiotics usage was 2.8 days. The most commonly used empirical antibiotics after AL occurred was piperacillin and tazobactam (32.6%). Mean duration of empirical antibiotics usage was 8.2 days. The most commonly identified pathogens were
Penetration of culture study for AL after colorectal cancer surgery appeared relatively low, although the profile of pathogens isolated from the AL patients can give important clues and evidence for appropriate antibiotics use. Surgeons should pay attention in performing culture studies for IAI including AL for proper patient treatment.
Intra-abdominal infection (IAI) represents a wide variety of pathological conditions that can involve lesions of all the intra-abdominal organs. It should be treated with appropriate antibiotic therapy with proper interventions for source control. Choice of appropriate antibiotic must be based on the results of the culture study; the strain that caused the infection, profile of bacteria, and resistance to antibiotics. However, because the results usually require a few days, empirical antibiotics should be administered first, and then, the extension of the administration or the replacement of antibiotics can be considered depending on the results of the test [
Antibiotic resistance disables several mechanisms of antibiotics against bacteria, subsequently increases medical expense, as well as affects effectiveness of antibiotics against infection [
Anastomotic leakage (AL) after colorectal cancer surgery remains the most feared and disastrous complication for both surgeon and patient, affecting long-term oncologic outcomes as well as frequent need for redo interventions, longer hospitalization, and high mortality rates [
From June 2006 through December 2017, consecutive patients who underwent elective abdominal surgery for colorectal cancer in our hospital were screened. The medical records of the patients were reviewed retrospectively after approval by the Institutional Review Board (IRB) of Kyung Hee University Hospital at Gangdong (IRB No. KHNMC 2018-08-017). Among the all screened patients, cases of surgery for recurrence or reoperation were excluded. Data of the patients who had AL after primary surgery were reviewed retrospectively.
Eligible patients’ sex, age, height, weight, location of tumor, type of surgery, type and duration of prophylactic antibiotics before surgery, date of AL diagnosed from the day of surgery, white blood cell count (WBC), C-reactive protein (CRP), type of procedure or operation for AL, and time from AL to procedure or surgery were recorded. In addition, results of culture study from the abdominal fluid or abscess after AL was diagnosed, antibiotic resistance, the type and duration of empirical or therapeutic antibiotics administered for the purpose of treatment for AL, hospital stay, and mortality were analyzed.
Location of tumor varied as right colon, left colon, and rectum, and transverse colon cancer was regarded as right side near the proximal part or left side near the distal part. As for data on WBC and CRP, the most recent data from the diagnosis of AL were recorded. Types of source control procedure were classified as follows; percutaneous drainage, surgical drainage, simple closure, surgical drainage and proximal diversion, resection and proximal diversion, resection, and re-anastomosis.
To evaluate the appropriateness of treatment, consistence of antibiotics with culture study results and recurrent infection including surgical site infection (SSI) occurring within 30 days after intervention were analyzed.
During the study period, a total of 982 patients underwent elective surgery for the treatment of primary colorectal cancer. Among them, 41 patients (4.2%) experienced AL (
Surgical drainage and proximal diversion was performed most for source control of AL (n=23, 56.1%), followed by simple closure (n=4), resection and proximal diversion (n=4), percutaneous drainage (n=3), surgical drainage (n=3), and resection and re-anastomosis (n=2).
Antibiotic use and the results of culture study for pathogens from intra-abdominal samples are listed in
Pathogens identified were described in
Prophylactic antibiotics administration was confined to the cephalosporins for 39 of 41 patients and combined with metronidazole in 11 patients (26.2%) (
The prescribed therapeutic empiric antibiotics patterns are listed in
Mean duration of empirical antibiotics use were 8.2 days (
Secondary peritonitis is a consequence of a mechanical breach of the gastrointestinal tract. The microbial species isolated reflect the patterns of colonization of the involved level of the gastrointestinal tract: perforation of the stomach or duodenum results in an inflammatory process that is primarily chemical, whereas perforations of the colon create polymicrobial infections including AL after colorectal cancer surgery [
The authors assessed the pathogens from the infected source from AL after colorectal cancer surgery and found a relatively low proportion of culture study performance (22/41, 53.7%) and appropriate antibiotics according to antibiotic resistance (12/22, 54.5%).
Although only 4.2% of AL was reported after overall colorectal cancer surgery, it scarcely occurred in right colon cancer surgery. When limited to left colon or rectal cancer surgery, 37 of 389 patients (9.5%) had AL after primary surgery.
We reviewed empirical antibiotics prescription pattern and infection severity with these patients. Only 22 patients (53.7%) had culture study from the intraperitoneal source (abscess or fluid) and the pathogens were identified from 21 patients. This low performance of culture study might be due to lack of interest by surgeons, rather than lack of time. Moreover, although most of the pathogens are expected to be gut flora (possibly one of the reasons culture studies were not performed), the authors found that proper antibiotics use rates were only 54.5% considering antibiotic resistance (
The pathogen distribution identified in this study was slightly different from previous reports. Data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) provide the best available evidence for the current status of complicated IAIs in Asia [
Rice [
AL belongs to the category of hospital acquired (HA)-IAI and the pathogen spectrum is different from those of community acquired-IAI. For this reason, treatment of AL patients should be administration of broad antibiotics, as in the treatment of HA-IAI patients, with an understanding of pathogen patterns in the region, and the selection of antibiotics to cover the resistant strains accordingly. Especially, it is recommended to consider prescribing agents covering MRSA when clinicians treat the secondary peritonitis caused by colon and rectum in this region due to higher rates of MRSA identification than other guidelines.
Regarding behavior of antibiotics prescription in accordance with published guidelines, it could be considered that 54.5% of 41 patients were prescribed appropriately with narrow-spectrum antibiotics. Broad-spectrum antibiotics such as piperacillin/tazobactam or carbapenem should have been prescribed for HA-IAI such as AL patients, and narrow-spectrum antibiotics, which can resist ESKAPE strains, should have been avoided [
There are several limitations in this study. Selection bias from the retrospective nature is inevitable. Moreover, culture study of pathogens, which is the most important procedure in this study, was performed only in about half of the patients with AL. Lastly, consistency of prophylactic and empirical antibiotic use lack regarding both kind and duration of antibiotics.
In conclusion, penetration of culture study for AL after colorectal cancer surgery appears relatively low, although the profile of pathogens isolated from AL patients can give important clues and evidence for appropriate antibiotics use. Surgeons should pay attention in performing culture studies for IAI including AL to treat patients with the proper method without wasting time and cost. Further studies are required to update the current status and problems of antibiotics use.
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government Ministry of Education (No. 017R1D1A1B03030948).
This work was presented as an oral presentation at the 51st Annual meeting of the Korean Society of Coloproctology, on March 30 to April 1, 2018, in Gwangju, Korea.
No potential conflict of interest relevant to this article was reported.
Patients characteristics
Variable | Value (n=41) |
---|---|
Age (yr) | 62.2±11.3 |
| |
Male sex | 31 (75.6) |
| |
Location of tumor | |
Right colon | 4 (9.8) |
Left colon | 8 (19.5) |
Rectum | 29 (70.7) |
| |
Duration between surgery and AL (day) | 6.3 (0–27) |
| |
Characteristics of index infection (AL) | |
WBC at diagnosis (/mm3) | 9,737±4,078 |
CRP at diagnosis (mg/dL) | 16.6±10.2 |
Culture study performed | 22 (53.7) |
Source control intervention | 39 (95.1) |
| |
Duration between AL and intervention | |
≤1 day | 19 (48.7) |
>1 day | 20 (51.3) |
| |
Intervention type | |
Percutaneous drainage | 3 (7.3) |
Surgical drainage | 3 (7.3) |
Simple closure | 4 (9.8) |
Surgical drainage and proximal diversion | 23 (56.1) |
Resection and proximal diversion | 4 (9.8) |
Resection and re-anastomosis | 2 (4.9) |
Conservative management | 2 (4.9) |
Values are presented as mean±standard deviation, number (%), or median (range).
AL, anastomotic leakage; WBC, white blood cell; CRP, C-reactive protein.
Culture result and antibiotics resistance
Patient | Primary surgery | Prophylactic antibiotics | Empiric antibiotics | Pathogens 1 | Pathogens 2 | Pathogens 3 | Sensitivity | ESKAPE |
---|---|---|---|---|---|---|---|---|
1 | uLAR | Ceftriaxone, metronidazole | Ceftezole, metronidazole | Sensitive | ||||
2 | AR | Ceftizoxime, metronidazole | Ceftizoxime, metronidazole | Resistant | MRSA | |||
3 | LAR | Cefotetan, metronidazole | Meropenem, metronidazole | Resistant | MRSA | |||
4 | LAR | Cefminox, metronidazole | Ceftriaxone, metronidazole | Resistant | IRAB | |||
5 | LAR | Cefminox, metronidazole | Cefminox, metronidazole | Resistant | ||||
6 | LAR | Cefminox, metronidazole | Cefminox, metronidazole | Sensitive | ||||
7 | LAR | Cefotetan | Meropenem | Sensitive | ||||
8 | LAR | Cefotetan | Ceftriaxone, metronidazole | Resistant | ||||
9 | LAR | Cefotetan | Piperacillin/tazobactam, levofloxacin | Sensitive | ||||
10 | RHC | Cefotetan | Piperacillin/tazobactam | Sensitive | ||||
11 | LAR | Cefotetan | Piperacillin/tazobactam, metronidazole | No growth | unknown | |||
12 | LAR | Cefotetan | Cefotetan | Resistant | ||||
13 | uLAR | Cefotetan | Cefotetan, metronidazole | Sensitive | ||||
14 | RHC | Cefotetan | Cefotetan | β-Hemolytic |
Sensitive | |||
15 | LAR | Cefotetan | Cefminox, metronidazole | Resistant | ||||
16 | LAR | Cefotetan | Piperacillin/tazobactam | Resistant | MRSA | |||
17 | LAR | No | No | Unknown | ESBL+ | |||
18 | LAR | Cefotetan | Moxifloxacin | Sensitive | ||||
19 | TC | Cefotetan | Piperacillin/tazobactam | Sensitive | ||||
20 | uLAR | Cefotetan | Piperacillin/tazobactam | Sensitive | ||||
21 | LAR | Cefotetan | Piperacillin/tazobactam | Sensitive | ||||
22 | ERHC | Cefotetan | Piperacillin/tazobactam, levofloxacin | Resistant |
LAR, low anterior resection; uLAR, ultra-low anterior resection; AR, anterior resection; RHC, right hemicolectomy; TC, total colectomy; ERHC, extended right hemicolectomy; MRSA, methicillin-resistant
Pathogens identified from intra-abdominal samples
Pathogens | No. (%) | Resistance (%) | |||
---|---|---|---|---|---|
Gram (+) | Aerobic | MSSA | NA | ||
MRSA | 3 (7.3) | 100 | |||
3 (7.3) | |||||
5 (12.2) | |||||
1 (2.4) | |||||
5 (12.2) | |||||
Anaerobic | NA | ||||
| |||||
Gram (−) | Aerobic | ESBL (−) | 10 (24.4) | ||
ESBL (+) | 1 (2.4) | 9.10 | |||
ESBL (−) | 4 (9.8) | ||||
ESBL (+) | NA | ||||
NA | |||||
ISPA | 5 (12.2) | ||||
IRPA | NA | ||||
ISAB | NA | ||||
IRAB | 1 (2.4) | 100 | |||
NA | |||||
1 (2.4) | |||||
2 (4.9) | |||||
Anaerobic | NA |
MSSA, methicillin-sensitive
Resistance for each ESKAPE pathogen.
Prophylactic antibiotics for colorectal cancer surgery
Antibiotics agent | No. (%) | |
---|---|---|
Cephalosporin | 1st G Cephalosporin+MTD | 1 (2.4) |
2nd G Cephalosporin only | 28 (68.3) | |
2nd G Cephalosporin+MTD | 4 (9.8) | |
3rd G Cephalosporin+MTD | 6 (14.6) | |
| ||
No antibiotics | 2 (4.9) |
G, generation; MTD, metronidazole.
Empiric therapeutic antibiotics
Antibiotics agent | No. (%) | |
---|---|---|
Penicillins/β-lactamase inhibitors | Piperacillin/tazobactam | 14 (32.6) |
| ||
Carbapenems | Meropenem | 1 (2.3) |
| ||
Fluoroquinolones | Levofloxacin |
2 (4.7) |
Moxifloxacin | 3 (7.0) | |
| ||
Cephalosporin | 1st G Cephalosporin+MTD | 1 (2.3) |
2nd G Cephalosporin only | 8 (18.6) | |
2nd G Cephalosporin+MTD | 5 (11.6) | |
3rd G Cephalosporin+MTD | 5 (11.6) | |
| ||
No antibiotics | 4 (9.3) |
G, generation; MTD, metronidazole.
Levofloxacin used for underlying pneumonia treatment.
Outcome measurement
Variable | Value |
---|---|
Primary outcome | |
Antibiotics use period (day) | 8.2±7.9 |
Mortality | 1 (2.4) |
Hospital stay (day) | 29.4±15.5 |
| |
Secondary outcome | |
Recurrent infection |
14 (34.1) |
Values are presented as mean±standard deviation or number (%).
Including surgical site infection.