Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. [Duration of the preventive use of antibiotics in colorectal surgery--single administration versus short-term prevention]. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Single-dose peroperative antibiotic prophylaxis in gastrointestinal surgery. A randomized prospective study to compare cefotetan with cefuroxime plus metronidazole as prophylaxis in elective colorectal surgery. Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics? Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Antibiotic treatment during surgery for diffuse peritonitis: a prospective randomized study comparing the effects of cefuroxime and of a cefuroxime and metronidazole combination.
A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium difficile-associated diarrhea (CDAD) was performed. Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. difficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11).Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P=0.059) appeared not to be cleared of C. difficile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed. Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group. A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic-associated colitis. Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in capsule form concurrently with antibiotics. Over 23 mo, 180 patients completed the study. Of the patients receiving placebo, 22% experienced diarrhea compared with 9.5% of patients receiving S. boulardii (p = 0.038). Risk factors found to be associated with AAD were multiple antibiotic combinations (containing clindamycin, cephalosporins, or trimethoprim-sulfamethoxazole) and tube feeding. Clostridium difficile, an anaerobe found in the stools of most patients with pseudomembranous colitis, was variably associated with AAD. We evaluated the role of C. difficile in AAD in the study population and found no significant association between the presence of C. difficile or cytotoxin with AAD. Approximately 33% of the patients without diarrhea harbored at least one C. difficile-positive stool and nearly 50% of these patients had detectable cytotoxin. Similar values were obtained in patients with diarrhea. Of C. difficile-positive patients, 31% (5/16) on placebo developed diarrhea compared with 9.4% (3/32) on S. boulardii; this difference was not statistically significant (p = 0.07). There were no discernable adverse effects of yeast administration. We conclude that S. boulardii reduces the incidence of antibiotic-associated diarrhea in hospitalized patients. The effect of a combination of 4 g mezlocillin and 0.5 g metronidazole for the prophylaxis against infections in a one-shot dose immediately preoperatively compared to a short-time dose of 2 days given to 90 patients with resection of colorectal carcinoma was investigated in a prospective and randomized study. 6 patients developed a wound infection in the early postoperative phase; 4 of these infections (3 were severe, 1 was mild) occurred in the one-shot group and 2 in the short-time prophylaxis group. After more than 20 days postoperatively 3 late infections were observed which had a mild course (2 cases in the one-shot group, 1 case in the short-time prophylaxis group). All infections were localized in the sacral wound region in patients with abdominoperineal resection. The abdominal wounds healed per primam in each case. Besides those, 26 infections of the urinary tract were observed, which occurred significantly more often after the one-shot dose (40.9%) than with the short-time prophylaxis (18.6%). Intraoperative smears of the lumen of the bowels showed a remaining bacterial settlement. Besides Bacteroides species, especially Escherichia coli were found among the isolates. Moreover in some cases Clostridium, Klebsiella, Proteus and Pseudomonas could be identified. Smears of the site of operation (sacral/peritoneal cavity) were contaminated in over 50%, above all by Bacteroides species; besides those, E. coli were found most often. The subcutaneous smears showed a growth of the germs only in a few cases. Aerobic bacteria in 93.8%, anaerobic bacteria except for thetaiotaomicron and B. asaccharolyticus in 85.1%.(ABSTRACT TRUNCATED AT 250 WORDS) High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three or four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial.
                The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assigned (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomycin orally four times daily for an average of 10 days.
                No significant differences in measurable responses to the two regimens were noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients.
                Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill. A single intravenous dose of tobramycin and lincomycin, given at the start of gastrointestinal operations, significantly reduced the incidence of postoperative wound infection from 34% to 5%. The occurrence of both anaerobic and aerobic bacteria was reduced. Therapeutic concentrations of the antibiotics were maintained throughout the operative period in most cases. No toxic effects of the antibiotics were detected, no anaesthetic complication occurred, and resistant strains of bacteria normally sensitive to the antibiotics were not isolated from wounds. This study compares the efficacy of cefotetan with the combination of cefuroxime plus metronidazole as antibiotic prophylaxis in elective colorectal surgery when given over the first 24 h postoperatively. There was no significant difference in wound infection rates between the two groups (14.7% for cefotetan and 13.9% for cefuroxime plus metronidazole), or the rates of other infective complications. Adverse reactions occurred with equal frequency in both treatment groups and no serious side effects occurred. Cefotetan is a safe and effective antibiotic for use as prophylaxis in elective colorectal surgery. Its advantages are that it is a single agent with a spectrum covering both aerobic Gram-negative rods and anaerobic organisms and, because of its long half-life, needs only to be given at 12-hourly intervals. The use of prophylactic antibiotics in addition to mechanical cleansing is the current standard of care prior to colonic surgery. The question of whether the antibiotics should be administered intravenously or orally, or by both routes, remains controversial. Our aim was to compare three methods of prophylactic antibiotic administration in elective colorectal surgery.
                Three hundred consecutive elective colorectal resections were studied. All patients had preoperative mechanical colon cleansing with oral sodium phosphate and intravenous antibiotic prophylaxis with cefoxitin (one dose before skin incision and two postoperative doses). Patients were randomised to one of the following three groups: group A: three doses of oral antibiotic (neomycin and metronidazole) at the time of mechanical colon cleansing; group B: one dose of oral antibiotic; group C: no oral antibiotics. All patients were followed during their hospital stay and at 7, 14 and 30 days post-surgery.
                Vomiting occurred in 31%, 11% and 9% of the studied patients (groups A, B and C, respectively) (p<0.001). Nausea was present in 44%, 18% and 13% of patients (p<0.001). Abdominal pain was recorded in 13%, 10% and 4% of patients (p: 0.077). Wound infection was present in 7%, 8% and 6% and suture dehiscence occurred in 2%, 2% and 3% of the patients in the three groups (no differences among them). Neither were differences found among the three groups in terms of urinary infections, pneumonia, postoperative ileus or intra-abdominal abscess.
                The addition of three doses of oral antibiotics to intravenous antibiotic prophylaxis is associated with lower patient tolerance in terms of increased nausea, vomiting and abdominal pain, and has shown no advantages in the prevention of postoperative septic complications. Therefore, we recommend that oral antibiotics should not be used prior to colorectal surgery. 101 patients with Clostridium-difficile-associated diarrhoea or colitis were prospectively randomised to 10-day oral courses of metronidazole, 250 mg four times a day, or vancomycin, 500 mg four times a day. 7 did not complete the protocol and were dropped from analysis. Pseudomembranous colitis (PMC) was diagnosed after endoscopy in 33 patients. Of the remaining patients without PMC, 38 had both C difficile culture and cytotoxin and 23 had only culture evidence of C difficile. 52 evaluable patients received vancomycin and 42 received metronidazole. There were two treatment failures with metronidazole and none with vancomycin (p = 0.20); and two relapses with metronidazole versus six with vancomycin (p = 0.17). Treatment in 1 patient in each group was discontinued because of drug intolerance. Response and relapse rates of the 33 patients with PMC were no different from those of the remaining patients. Pharmacy cost for the dosage used was $387.48 to $520.00 for vancomycin and $11.84 for metronidazole. Metronidazole and vancomycin have equivalent efficacy and relapse rates and are tolerated to a similar extent by patients with C-difficile-related diarrhoea and colitis, but metronidazole is considerably more economical. In a prospective randomized open study of patients operated upon for diffuse peritonitis, the effects of two different antibiotic regimens were evaluated. Cefuroxime given as a single drug (Group I; n = 59) was compared with a combination of cefuroxime and metronidazole (Group II; n = 63). Bacteriological cultures, both aerobic and anaerobic, were obtained peroperatively and in the event of any complication. The antibiotic sensitivities of isolated bacteria, and the serum and tissue concentrations of cefuroxime were determined. Postoperative infectious complications occurred in 22 per cent of Group I patients (cefuroxime), and in 17.5 per cent of Group II (cefuroxime plus metronidazole). The mortality rates were 5 per cent for Group I and 8 per cent for Group II. Tissue concentrations of cefuroxime were well above the MIC (minimal inhibiting concentration) values for most of the bacteria isolated. From a few patients in Group I, however, cultures were obtained with isolates sensitive to metronidazole but resistant to cefuroxime. Our findings suggest that, in the antibiotic treatment of patients operated for diffuse peritonitis, an agent which is primarily effective against aerobic bacteria (but not entirely without effect on anaerobes) is as effective as combination therapy covering both aerobic and anaerobic bacteria.
Antibiotics covering aerobic and aerobic bacteria should be delivered orally and intravenously prior to colorectal surgery.  Antibiotics delivered within this framework will reduce the risk of postoperative SWI by at least 75%.  Further research is required to establish the optimal timing and duration of dosing, and frequency of longer-term adverse effects such as Clostridium difficile pseudomembranous colitis.