Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 30  |  Issue : 2  |  Page : 393--399

The effect of peritoneal lavage with a mixture of lincomycin–gentamicin on postoperative infection in cases of colorectal cancer surgery


Alaa Abd A Elsisy, Mahmoud G Hagag, Marwan M Ewida 
 Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Correspondence Address:
Marwan M Ewida
El-behira, 22511
Egypt

Abstract

Objective The aim of this work was to evaluate the effect of the use of antibiotic solution formed of lincomycin and gentamycin in normal saline in decreasing the risk for postoperative infection in cases of colorectal cancer. Background Infection after colon cancer operations is still the most common and the most serious complication, with an incidence of more than 30%. Patients and methods This study was carried out on 40 randomly allocated patients with resectable colon and rectal cancer. Group 1 included patients who underwent intra-abdominal lavage with normal saline, followed by a second lavage with a gentamicin–lincomycin solution, and group 2 included those who underwent lavage with normal saline. Results There was a significant difference between groups as regards the presence of postoperative wound sepsis. Isolated organisms were mainly gram negative in both groups. In group 1, the isolated organism was Pseudomonas. In group 2, three cases were diagnosed with Escherichia coli and two cases for each of Pseudomonas, Klebsiella, and Enterobacter. Intraoperative abscess was diagnosed in three cases, two in group 2 and the remaining one in group 1. There was no significant difference between groups as regards the presence of intra-abdominal abscess. Conclusion Antibiotic lavage of the peritoneum is associated with a lower incidence of intra-abdominal abscesses and wound infection. A normal saline lavage did not significantly reduce the number of positive cultures, in contrast to an antibiotic one (gentamicin–lincoamycin), which resulted in negative cultures in 90% of the cases.



How to cite this article:
Elsisy AA, Hagag MG, Ewida MM. The effect of peritoneal lavage with a mixture of lincomycin–gentamicin on postoperative infection in cases of colorectal cancer surgery.Menoufia Med J 2017;30:393-399


How to cite this URL:
Elsisy AA, Hagag MG, Ewida MM. The effect of peritoneal lavage with a mixture of lincomycin–gentamicin on postoperative infection in cases of colorectal cancer surgery. Menoufia Med J [serial online] 2017 [cited 2019 Sep 21 ];30:393-399
Available from: http://www.mmj.eg.net/text.asp?2017/30/2/393/215454


Full Text

 Introduction



Cancer of the colon is considered as the fourth most common type of cancer in both sexes in Egypt [1].

Infections after colorectal resection are still by far the most common and troublesome complication for the surgeon, with an incidence ranging from ∼15% to more than 30% [2].

Wound infections after cancer surgery may result in severe consequences, significant psychological trauma, and delay in receiving adjuvant chemotherapy or radiotherapy [3].

Several authors observed an inverse relationship between infection/inflammation and local recurrence in patients with colorectal cancer [4] as well as in patients with other types of tumors [5].

Tumor development at inflammatory sites has been repeatedly observed in a variety of tissues, suggesting that a chronic wound microenvironment may stimulate cancer cell growth and recurrence [6].

To reduce the morbidity and mortality of intra- abdominal infections, surgeons aim to isolate and control the source of contamination. Lavage has been proposed to remove bacterial contamination and other materials that may promote bacterial proliferation (e.g., blood and proinflammatory cytokines) that may enhance local inflammation. Therefore, flushing the peritoneal cavity may reduce the bacterial load, inhibit bacterial proliferation, and possibly minimize peritoneal adhesions [7].

Antibiotics may be combined with the lavage to further reduce bacterial survival. Antibiotics used include metronidazole, gentamicin sulfate, and cephalothin. The aim of this study was to evaluate the effects of peritoneal lavage with normal saline or with antibiotic solution (linkomycin-gentamycin) on intra-abdominal abscesses and wound infection and to determine the microbiologic impact of both irrigations on peritoneal contamination.

 Patients and Methods



This prospective observational study was carried out on 40 randomly allocated patients with resectable colorectal cancer in hospitals of Menoufia Faculty of Medicine.

Inclusion criteria

Stage I, II, IIIa colorectal cancerSurgically fit patients.

Exclusion criteria

Recurrent colorectal cancerPreoperative diagnosis of chronic renal failureHistory of hypersensitivity to gentamycinHistory of hypersensitivity to lincomycin.

Methods

After explaining the procedure and the purpose of the study, informed consent was obtained from the patients.

Preoperative assessment was carried out for all patients for the diagnosis and staging of the tumor and for assessment of the fitness for surgery.

Preoperative consultation with medical oncologist was carried out for all cases, and locally advanced cases received neoadjuvant chemotherapy or radiotherapy according to their decisions.

Complete aseptic measures were ensured during all surgical steps.

All patients received a single dose of intraoperative parenteral antibiotic (ceftriaxone.

Bowel clamps were used to avoid fecal contamination.

All anastomoses were performed using the hand sewing technique. Anastomosis was performed in two layers: the first was a continuous full-thickness layer and the second was an interrupted seromuscular layer. No staples were used in both groups.

The patients were randomized into two groups: those undergoing an intra-abdominal lavage with normal saline, followed by a second lavage with gentamycin–lincomycin solution (group 1, and those undergoing an intra-abdominal lavage with normal saline only) group 2.

After anastomosis was performed or after stoma fixation in some cases in which the decision was to create a stoma instead of primary anastomosis, lavage was performed immediately before abdominal wall closure.

In group 1, before lavage, a microbiological sample from the peritoneal surface (parietal and visceral was obtained with a swab (swab 1, followed by another swab (swab 2 obtained after lavage with 500 ml of normal saline.

A second lavage with an antibiotic solution including gentamycin (240 mg and lincomycin (600 mg dissolved in 500 ml of normal saline was performed. Thereafter, another swab was taken (swab 3 before abdominal wall closure. PDS or vicryl was used for closure of the rectus sheath, whereas silk and proline were used in skin closure. Interrupted sutures and subcuticular sutures were used in skin closure.

In group 2, irrigation of the entire abdominal cavity was performed with 500 ml of normal saline. The normal saline was left for 2–3 min, followed by aspiration of the liquid and abdominal wall closure. A swab was taken from the peritoneal cavity before closure of the abdomen. Proline was used for closure of the rectus sheath, whereas silk and proline were used in skin closure. Interrupted sutures and subcuticular sutures were used in skin closure.

All patients underwent close follow-up for 30 days postoperatively. This included in-hospital days and postdischarge days. The cases with suspected complications underwent ultrasound and computed tomography of the abdomen for confirmation.

Patients with intra-abdominal collection underwent ultrasound-guided aspiration and culture, and sensitivity tests were carried out to isolate affecting organisms and to start the appropriate antibiotic therapy.

In patients with wound infection, wound drainage was performed by inserting a small tube drain or by means of open drainage, as recommended by consultants, to drain the infected fluids and also specimens sent for culture and sensitivity tests.

Cases of burst abdomen were managed with urgent surgical intervention and abdominal wall repair using tension sutures.

Statistical analysis

All data were collected, tabulated, and statistically analyzed using SPSS 19.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for Windows (MedCalc Software bvba, Ostend, Belgium.

Quantitative data were expressed as the mean ± SD and median (range, and qualitative data were expressed as absolute frequencies 'number' and relative frequencies (percentage. Continuous data were checked for normality using the Shapiro–Wilk test. The Mann–Whitney U-test was used to compare two groups of non-normally distributed data. All tests were two-sided. P  value less than 0.05 was considered statistically significant (S, P  value less than 0.001 was considered highly statistically significant (HS, and P  value of 0.05 or more was considered nonstatistically significant NS).

 Results



The first group (group 1 consisted of 10 (50% male and 10 (50% female patients, with a median age of 56 years (range = 30–80 years, and the second group (group 2 consisted of nine (45% male and 11 (55% female patients, with a median age of 54.5 years (range = 18–80 years. According to residency, 16 patients (80% from group 1 were from rural areas, whereas only four (20% were from urban areas. In group 2, 17 patients (85% were from rural areas, and three patients were from urban areas. Differences between the two groups according to demographic data were statistically nonsignificant [Table 1].{Table 1}

The main clinical presentation in the two groups was colon obstruction, with seven cases (35% in group 1 and eight cases (40% in group 2. Another main complaint was bleeding per rectum, with four cases (20% in group 1 and five cases (25% in group 2. Accidental discovery during abdominal examination, either clinically or radiologically for nonspecific symptoms such as diarrhea or constipation or for investigating another medical problem (renal stone in two cases and chronic calcular cholecystitis in another two cases, was found in 11 cases: six (30% in group 1 and five cases (25% in group 2. Other cases presented with nonspecific symptoms such as colicky pain and anemia: three cases (15% in group 1 and two cases (10% in group 2.

According to the site of the affected part in the large intestine, 13 patients presented with right colon cancer, seven cases (35% in group 1 and six cases (30% in group 2. The left colon was the primary site of cancer in 11 patients, six (30% in group 1 and five (25% in group 2. The rectum was the site of the malignancy in 11 patients, five patients (25% in group 1 and six patients (30% in group 2. In only five cases the transverse colon was the primary site of affection, two cases in group 1 and three cases in group 2 [Table 2].{Table 2}

According to pathology, all cases in both groups had adenocarcinoma. According to the operative data of the cases, right hemicolectomy was performed in 18 cases. Of them, five cases underwent extended right hemicolectomy and the other 13 underwent formal right hemicolectomy, nine patients in each group of the study. Left hemicolectomy was performed in six patients (30% in group 1 and five patients (25% in group 2. Anterior resection was performed in four cases (20% in group 1 and in five cases (25% in group 2. Abdominoperineal resection was performed in two cases, one in each group.

According to the operative time, the median time of group 1 was 152 min (range = 120–250 min and 150 min (range = 110–250 min in group 2. Differences between the two groups as regards operative intervention and operative time were nonsignificant [Table 3].{Table 3}

In cases of group 1, three swabs were obtained during the operations and before abdominal wall closure. Twelve patients (60% were positive in the first swab, whereas 50% were positive in the second swab; only two cases (10% remained positive in the third swab. One of them was positive for Escherichia coli and the other was positive for pseudomonas. However, in group 2, only one swab only was obtained after abdominal lavage with saline and the results show that 45% of cases still had positive swab after normal saline lavage [Table 4].{Table 4}

All patients received intraoperative parental dose of third-generation cephalosporin. Postoperatively, six cases in group 1 (30% had fever and two cases (10% had ileus. In group 2, eight cases (40% had fever and ileus was present in nine cases (45%. There was a significant difference in the results as regards postoperative ileus between the two groups. Burst abdomen was present in three cases in group 2 but did not occur in group 1. Differences between the two groups were nonsignificant as regards postoperative fever and presence of burst abdomen postoperatively [Table 5].{Table 5}

According to the results of the two groups, there was a significant difference in the results between the two groups as regards the presence of postoperative wound sepsis. Ten cases of wound sepsis were diagnosed during the time of follow-up of the patients, one case (5% in group 1 and nine cases (45% in group 2. Wound sepsis was diagnosed during the regular follow-up of the patients mainly by means of clinical diagnosis and confirmed by means of ultrasound and culture and sensitivity tests. Isolated organisms were mainly gram negative in both groups. In group 1, the only isolated organism was Pseudomonas, one of the two cases with positive swab 2. In group 2, three cases were diagnosed with E. coli and two cases for each of Pseudomonas, Klebsiella, and Enterobacter. Intraoperative abscess was diagnosed in three cases, two of them in group 2 and the remaining one in group 1. It was diagnosed after clinical suspicion using ultrasound and abdominal computed tomography. There was no significant difference between the two groups as regards the presence of intra-abdominal abscess [Table 6].{Table 6}

In group 1, the median duration of hospital stay was 5.8 days (range = 5–24 days. In group 2, the median duration was 7 days (range = 5–24 days. There was a significant difference between the two groups as regards the hospital stay duration, as demonstrated in [Table 7].{Table 7}

 Discussion



The concept of lavaging a contaminated or infected peritoneal cavity makes good sense intuitively. However, because microbes adhere to mesothelial cells, it is very difficult to wash them off the peritoneal surface. During fecal contamination of the peritoneal cavity, it has been demonstrated that bacteria that adhered to the mesothelium were resistant to intraperitoneal lavage, resulting in only transitory reductions of bacterial populations [8].

This affirmation is supported in our study by our finding that there were significant differences in the cultures of the samples obtained before and after the irrigation with the antibiotic solution. This finding confirms that peritoneal irrigation with lincomycin–gentamycin solution is sufficient to decrease all fecal contaminations produced during the surgical act to the minimum. The results obtained after antibiotic lavage defend the hypothesis that the topical effect of the antibiotics could completely inhibit the growth of bacteria in the peritoneum, even when microorganisms have adhered to the mesothelial cells. Diverse antimicrobial drugs have been used in different studies, most of which were peritonitis cases. Some authors have presented similar mortality and intra-abdominal infection rates compared with normal saline irrigation [9].

Others have shown antibiotic lavage to protect against intra-abdominal infection and reduce the mortality rate by up to 65%. A meta-analysis clearly shows the superior value of antibiotics in lavage during experimental peritonitis compared with saline lavage. Although including antibiotics in lavage solutions optimizes survival in peritonitis, the use of simple saline irrigation is still better compared with no lavage, rejecting the classical affirmation that irrigation contributes to contamination spread throughout the peritoneal cavity [10].

In our study, we showed that an antibiotic lavage is very effective. We demonstrated that an antibiotic lavage impairs microbiologic growth and reduced the positive culture from 60% in sample 1 (before saline lavage to 10% in sample 3 (after antibiotic lavage. In group 2, the results showed positivity in 45% of cases after normal saline lavage. These data have clinical correlations because the surgical site infection rate was reduced from 45% in group 2 (only saline lavage to 10% in group 1 (saline lavage followed by antibiotic irrigation.

Our study presents two main differences with the reported literature. First, our sample included patients undergoing elective colorectal surgery (contaminated surgery, but who did not present with peritonitis, as described in most reported studies. A limited number of outdated studies have analyzed the effect of prophylactic peritoneal lavage on postoperative infection. Such studies have shown a reduction in the number of aerobic and anaerobic bacteria in the peritoneal fluid after an intervention that included irrigation with a tetracycline solution, but they have not correlated these data with clinical variables [11]. The second main difference in our study is the combination of antibiotic drugs (gentamicin and lincomycin. These two drugs present a synergistic effect and provide protection against gram-negative and anaerobic microorganisms, which represent the main flora of the colon. Peritoneal lavage with a single antibiotic drug is probably sufficient to impair the growth of some, but not all, bacterial colonies. Previous studies have not specified which microorganisms survived after antibiotic lavage, possibly for this reason. Moreover, the culture that remained positive after the antibiotic lavage in our study grew microorganism that was resistant to both irrigated drugs. Logically, bacterial growth cannot be impaired by antibiotics to which the microbiota are resistant. Previous studies have referred to intra-abdominal infection, but little is known about the effect of peritoneal irrigation on wound infection. Tolhurst Cleaver et al. [12] reported that intraperitoneal antibiotic lavage accelerated wound healing and reduced the infection rate. Diverse factors contribute to the occurrence of wound infection, but infections arising from a contaminated peritoneal cavity are particularly common, indicating that wound infection rates are higher after a contaminated operation than after a clean one. In our study, we also observed a significant reduction in wound infections in the group undergoing an antibiotic lavage, compared with the group undergoing saline irrigation. These data show that, when the peritoneal cavity remains sterile, there is a lower risk for bacterium migration from the abdominal cavity through the fascia to the subcutaneous tissue. As in the patient with positive culture after antibiotic lavage, the same bacterium found in the culture was also responsible for the wound infection. Qadan et al. [10] noted that extrapolating results from animal models of peritonitis and antibiotic lavage to human disease is often disappointing, because in experimental peritonitis the interval between the onset of peritonitis and the start of the lavage treatment is usually only 1 or 2 h, which is not representative of the clinical situation (characterized by a longer time interval. In our study, the interval between peritoneal contamination and the lavage was shorter than 2 h. A long interval between the onset of peritonitis and treatment leads to exponential growth of the microorganisms. In this situation, an antibiotic lavage would not be sufficient to control such concentrations of microorganisms but may be sufficient for lower concentrations of bacteria.

Ruiz-Tovar and colleagues confirmed the decrease in the risk for wound infection from 14% in patients with peritoneal lavage with normal saline only to 4% in patients with the peritoneal lavage with antibiotic solution (clindamycin–gentamicin after normal saline. This result was obtained from studying 108 patients with ongoing surgery for curative purpose for colorectal surgery.

He found that microbiological specimens were negative in all patients after antibiotic solution irrigation except two cases, whereas positive in 59% of specimens after only normal saline irrigation and 68% in samples before any lavage [9].

His results were very satisfactory, but because of lack of injectable forms of clindamycin here in Egypt and because of a more local effect of lincomycin, we preferred the use of lincomycin with gentamycin.

Singh and colleagues used metronidazole in peritoneal lavage. That study was conducted in the Department of General Surgery, Moradabad, for the duration of 1 year. A total of 100 patients aged between 15 and 60 years were included in the study, of whom 75 were male and 25 were female. All these patients underwent laparotomy for the treatment of peritonitis. All these patients presented with clinical features of peritonitis. Blood tests, erect radiograph of the abdomen, and ultrasonography of the abdomen also showed positive results. These patients were randomly divided into two categories. Group S patients received intraoperative peritoneal lavage with 2 l of saline water. Group M patients received intraoperative peritoneal lavage using 2 l of saline mixed with 200 ml of metronidazole. The study showed that the incidence of infection (both wound infection and sepsis was statistically high in the group receiving saline peritoneal lavage. As regards other parameters such as the incidence of abscess and fistula formation, mortality rate, and duration of stay in hospital, no statistical difference was found [13].

In our study, an increase in the dose of gentamycin and addition of lincomycin changed the results. Our study showed results similar to that reported by Singh and colleagues with normal saline but different results in using a higher dose of gentamycin with lincomycin.

 Conclusion



Antibiotic lavage of the peritoneum before abdominal wall closure is associated with a lower incidence of intra-abdominal abscesses and wound infection. Microbiologic cultures of the peritoneal surface at the end of an elective colorectal operation were positive in 60% of the cases. A normal saline lavage did not significantly reduce the number of positive cultures, in contrast to an antibiotic one (gentamicin–lincoamycin, which resulted in negative cultures in 90% of the cases.

The postoperative surgical site infection and wound complication decreased with the use of antibiotic solution in peritoneal lavage.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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