D. W. Burdon

Comparison between systemic and oral antimicrobial prophylaxis in colorectal surgery.

In a prospective randomised trial in which 93 patients undergoing elective colorectal operations were given a short prophylactic course of metronidazole and kanamycin orally or systemically, postoperative sepsis occurred in only 3 (6.5%) of those given antimicrobials systemically, compared with 17 (36%) of those given oral prophylaxis (P less than 0.01). 15 of the 17 infections in patients who received antimicrobials orally were due to kanamycin-resistant bacteria present in the colon at operation. Bacterial overgrowth of Staphylococcus aureus was recorded in 6 of the patients who received oral therapy. Antibiotic-associated pseudomembranous colitis occurred in 7 patients, 6 of whom had received prophylaxis orally. These results indicate that oral administration of prophylactic antimicrobials in colon surgery should be avoided because of the risks of bacterial resistance, superinfection, and antibiotic-associated pseudomembranous colitis. Systemic per-operative antimicrobial prophylaxis is safer and more effective.

Antibiotic therapy for treatment in relapse of intestinal Crohn's disease

We have undertaken a prospective randomized trial of one months antimicrobial therapy for patients with symptomatic relapse of Crohns disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18=M, 16=C 21=C plus M, 17=P). After two weeks, improvement was reported as follows: M=67 percent, C=17 percent, C plus M=71 percent, P=35 percent. In the metronidazole group, two patients required surgery and one had trouble-some side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M=44 percent, C=62 percent, C plus M=57 percent, P=41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohns disease.

Oral neomycin and erythromycin compared with single-dose systemic metronidazole and ceftriaxone prophylaxis in elective colorectal surgery

A prospective randomized trial was performed to compare oral neomycin and erythromycin with single-dose intravenous metronidazole and ceftriaxone in elective colorectal surgery. The study was discontinued after 60 patients were entered. The overall rate of infection was 41 percent in the oral neomycin and erythromycin group (n = 29) compared with 9.6 percent in those who received intravenous metronidazole and ceftriaxone (n = 31) (p less than 0.01). Infections in the oral group were principally due to resistant Staphylococcus aureus, Bacteroides fragilis, and Escherichia coli. Preoperative administration of oral neomycin and erythromycin was associated with a significant reduction of Escherichia coli counts (1 X 10(7) to 3 X 10(5) organisms/ml, p less than 0.05) compared with the intravenous group, but there was no significant reduction in the counts of Bacteroides fragilis (2 X 10(8) to 1 X 10(7) organisms/ml) and there was an increase in the counts of Clostridia (2 X 10(4) to 1 X 10(6) organisms/ml). These results indicate that single-dose systemic prophylaxis with appropriate antibiotics is superior to oral neomycin and erythromycin.

DIARRHŒA AND PSEUDOMEMBRANOUS COLITIS AFTER GASTROINTESTINAL OPERATIONS: A Prospective Study

241 patients who had gastrointestinal operations were studied prospectively. Postoperative diarrhoea occurred in 58 patients (24%) and was significantly more common after exposure to antibiotics. 9 patients (4%) had high titres of a neutralisable faecal toxin characteristic of pseudomembranous colitis. Toxigenic Clostridium difficile strains were isolated from the stools of all patients with neutralisable faecal toxin. If pseudomembranous colitis is defined as the presence of neutralisable faecal toxin, then the diagnosis is often missed by sigmoidoscopy and rectal biopsy.

Failure of antimicrobial prophylaxis with cefoxitin, or metronidazole and gentamicin in colorectal surgery. Is mannitol to blame?

Abstract In a prospective randomized trial of 72 patients undergoing elective colorectal surgery for malignant disease the incidence of post-operative infection after cefoxitin prophylaxis was 27 per cent compared with 31 per cent after metronidazole and gentamicin prophylaxis. Sepsis from Bacteroides species occurred in five patients after cefoxitin (one septicaemia) compared with only one after metronidazole and gentamicin. Sepsis with aerobic bacteria was more common in patients who had received pre-operative oral mannitol for bowel preparation. Oral mannitol bowel preparation was associated with higher counts of Escherichia coli in the colon than other methods of bowel preparation. Five cases of antibiotic associated colitis occurred, all in patients receiving cefoxitin.

A prospective randomized trial to compare mezlocillin and metronidazole with cefuroxime and metronidazole as prophylaxis in elective colorectal operations

A prospective randomized trial has compared a broad spectrum ureidopenicillin with a broad spectrum cephalosporin for prophylaxis against the aerobic organisms encountered during elective colonic surgery. Even though only two doses of antibiotics were administered the incidence of severe sepsis was low. Severe wound infection occurred in three of the patients receiving mezlocillin and metronidazole (6 per cent) compared with six in the group receiving cefuroxime and metronidazole (13 per cent). Minor wound sepsis was recorded in 24 per cent of patients receiving mezlocillin and metronidazole compared with only 11 per cent after cefuroxime and metronidazole. There were two episodes of septicaemia, one in each group, and three abscesses, all of which occurred in patients receiving metronidazole and mezlocillin. The total number of surgically related infections was, however, significantly less with cefuroxime and metronidazole (N = 13) compared with mezlocillin and metronidazole (N = 23; P less than 0.03). Escherichia coli was the principal organism responsible for surgically-related postoperative sepsis: (22 isolates: 14 mezlocillin and eight cefuroxime) all of which sensitive to the agents used. Pseudomonas aeruginosa was recovered from 10 patients (three mezlocillin and seven cefuroxime), all of the isolates were resistant to both antibiotics and were associated with severe morbidity. There were 11 isolates of Staphylococcus spp. (nine mezlocillin and two cefuroxime: P less than 0.03). Postoperative diarrhoea occurred in six patients, all were in the group receiving cefuroxime and metronidazole. (Clostridium difficile was recovered from the stool in three of which one was associated with Cl. difficile cytotoxin.)

Prophylactic saline peritoneal lavage in elective colorectal operations.

The influence of a single peroperative five-liter saline peritoneal lavage has been assessed in 21 consecutive patients undergoing elective operation for colorectal cancer. The aim of the study was to investigate whether reduction in bacterial counts by saline lavage would reduce the incidence of infection and thereby avoid the need for prophylactic antimicrobials. Saline lavage was shown to reduce significantly counts in peritoneal fluid of aerobic bacteria from 2×104 to 5×101 (P less than 0.001) and to reduce the counts of anaerobes in peritoneal fluid from 8×104 to 1×102 (P less than 0.001). Despite the profound reduction in peritoneal bacterial counts the rate of postoperative sepsis was extremely high; wound infection 47 per cent, intra-abdominal abscess 26 per cent and septicemia 13 per cent. These results indicate that saline peritoneal lavage alone is no substitute for short-term antimicrobial prophylaxis.

Comparison of short-term antibiotic cover with a third-generation cephalosporin against conventional five-day therapy using metronidazole with an aminoglycoside in emergency and complicated colorectal surgery

In a prospective, randomized control trial, 152 consecutive patients requiring emergency or complicated colorectal surgery were allocated either to two doses of cefotetan or to five-day cover with gentamicin, and a single dose of metronidazole. Twenty-one patients received 6 gm of cefotetan before prolongation of prothrombin time dictated a change in the dose regimen such that all remaining patients (N=55) received only 4 gm of cefotetan. The groups were well matched for diagnosis and surgical procedure. Rates of postoperative infection did not differ significantly between the groups, with wound infection rates occurring in 17 of 75 patients receiving gentamicin and metronidazole (22.7 percent) compared with ten of 75 receiving cefotetan (13 percent). Although wound infection rates were lower in the cefotetan group, the incidence of intra-abdominal abscess was similar in both groups. Eight patients receiving cefotetan developed intra-abdominal abscesses (11 percent), compared with seven receiving gentamicin and metronidazole (9 percent). Prolongation of prothrombin time in excess of 13 seconds occurred in six patients receiving cefotetan compared with no patients receiving gentamicin and metronidazole. None of these patients developed clinical bleeding, however.

Sources of staphylococcal wound sepsis in surgical patients

Abstract Sources of Staphylococcus aureus have been studied in 124 surgical patients of whom 20 (16%) developed wound sepsis. Staph. aureus was isolated from the gastro-intestinal tract only once, but 26 of 113 (23%) patients were found to be nasal carriers. Twenty-seven per cent of carriers developed infections whereas only 10% of non-carriers became infected. Phage typing of strains causing wound infections showed that they originated from multiple and mostly unidentified sources. Three of seven infections in nasal carriers were with organisms of the same phage type as those found in the nose. These results indicate that staphylococci of nasal origin are not the major source of infected surgical wounds.

Short-term chemoprophylaxis with ceftizoxime vs. Five-day aminoglycoside with metronidazole in ‘contaminated’ lower gastrointestinal surgery

In a prospective, open, randomized controlled trial, 173 patients requiring surgery for potentially “contaminated” lower gastrointestinal surgery were allocated to receive either two doses of ceftizoxime (2 gm) with one dose of metronidazole (1.5 gm) or gentamicin 3 mg/kg/day for five days with one dose of metronidazole (1.5 gm). Eighty-nine patients received ceftizoxime and 84 patients received gentamicin. The groups were comparable with respect to diagnosis, procedure, type of anastomosis, and wound closure. The incidence of withdrawal due to failure to respond to the study drug (11.5 percent) was equivalent in the two groups. There was no difference in the overall incidence of postsurgical infection between the ceftizoxime and metronidazole group (22.2 percent) and the gentamicin and metronidazole group (25.7 percent). The incidence of wound infection (ceftizoxime and metronidazole, 6.9 percent; gentamicin and metronidazole, 10 percent) and deep sepsis (ceftizoxime and metronidazole, 15.3 percent; gentamicin and metronidazole, 15.7 percent) was similar.