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Biomedical subjects

D W Burdon

Publications and source records attributed to D W Burdon.

At least 19 recordsLinked to original sources

Effects of chlorhexidine-coated intrauterine device on the bacteriology of the uterine cavity.

Twenty-nine women, aged 31-53 years, scheduled for an abdominal hysterectomy, participated in this study. The patients were divided into three groups. The first received a Multiload MLCu250 intrauterine device (IUD); the second group received a chlorhexidine acetate medicated Multiload MLCu250 IUD; the third group acted as a control group receiving no IUD. Bacteriological cultures of the vagina and ectocervix were taken prior to insertion of the IUD. At hysterectomy, some 18 hours later, specimens were taken from the cervical canal, uterine cavity, and the device itself, for culture of anaerobic and aerobic organisms using a standardized previously validated technique. In three of the nine control patients, organisms were cultured from the uterine cavity. There were no differences between the bacteriological results of the two groups with medicated and non-medicated devices, with regard to the cultures from the cervical canal, uterine cavity or the devices themselves. Nor was there any difference between the control and the IUD group.

Adult

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.

Aminoglycosides

Studies of a novel agent possessing resistance to moist heat and disinfectants: parallels with Creutzfeldt-Jakob agent.

The resistance to sterilization and disinfection of a novel replicating agent (IFDO) with similarities to Creutzfeldt-Jakob agent (CJA) was investigated. Moist heat at 121 degrees C for 30 min did not kill the agent. Increasing the temperature to 140 degrees C, and the length of the autoclave cycle to 120 min also failed to guarantee sterilization, although some samples were sterilized after these treatments. Dry heat at 160 degrees C for 1 h sterilized 24 of 25 samples. Overnight disinfection with 10% Stericol or 1.2% chlorhexidine left few detectable survivors. Samples pretreated with these disinfectants and then autoclaved at 134 degrees C for 20 min were sterilized. Disinfection with hypochlorite (500 ppm available chlorine) was very effective if organic matter derived from spent culture medium was removed. We have adopted overnight Stericol disinfection, followed by autoclaving at 134 degrees C for 1 h for sterilization of glassware contaminated by IFDO. The agent may provide a valid model for sterilization of items contaminated with CJA and, if so, our data suggest that current disinfection guidelines for CJA by autoclaving at 134 degrees C for 1 h are inadequate.

Creutzfeldt-Jakob Syndrome

The penetration of aztreonam, a monobactam antibiotic, into intra-abdominal abscesses.

We have studied the penetration of aztreonam into pus with a low mortality intra-abdominal abscess model in the Wistar rat. The mean peak serum concentration (standard error) of aztreonam was 74.6 +/- 9.88 mg/l at 30 min falling to 2.31 +/- 1.28 mg/l at 8 h. The mean concentration in pus was 17.04 +/- 2.01 mg/l at 2 h and was 14.47 +/- 2.23 mg/l at 8 h. These concentrations are in excess of the MICs of most Gram-negative aerobic bacilli commonly isolated from intra-abdominal abscesses.

Abdomen

A randomized trial to compare amoxycillin/clavulanate with metronidazole plus gentamicin in prophylaxis in elective colorectal surgery.

A randomized controlled trial was designed to compare antibiotic prophylaxis with a standard combination of agents, metronidazole and gentamicin, with a single preparation, amoxycillin/clavulanate in 400 patients undergoing elective colorectal surgery. There were 41 patients who were excluded or withdrawn (wrong dose, inappropriate operation, established sepsis or concurrent disease). Abdominal wound sepsis occurred in 14% of the assessable patients in the amoxycillin/clavulanate group and in 15% of the metronidazole plus gentamicin group. Perineal sepsis occurred in 27% of the amoxycillin/clavulanate group with a perineal wound compared with 18% in the metronidazole plus gentamicin group. Intra-abdominal abscess occurred in 8% of those who received amoxycillin/clavulanate compared with 6% of those given metronidazole plus gentamicin. Only two patients in each group developed septicaemia. Postoperative diarrhoea occurred in 11 patients receiving amoxycillin/clavulanate compared with four given metronidazole plus gentamicin. Clostridium difficile was not isolated from the stool cultures in any of these cases. Thirteen of the 164 abdominal or perineal wounds were infected by 15 strains of Bacteroides spp. in the group receiving amoxycillin/clavulanate compared with only three of the 165 wounds in those given metronidazole plus gentamicin. (P less than 0.01). There was no other significant difference in the pattern of isolates between the groups.

Adolescent

A novel replicating agent isolated from the human intestinal tract having characteristics shared with Creutzfeldt-Jakob and related agents.

A novel replicating agent (IFDO) was isolated from ileal fluid. Growth occurred in vitro under aerobic and anaerobic conditions, and was faster at 37 degrees C than at room temperature. The doubling time was 15.8 min. Colonies were dark brown in colour and occurred beneath the surface of agar after conventional surface inoculation. Provisional data indicate that the agent may be a normal intestinal commensal. The agent was remarkably resistant to inactivation by steam at 134 degrees C, formaldehyde and glutaraldehyde; it was relatively resistant to ionising radiation, and it was filterable through membranes with a nominal pore diameter of 10 nm. Such properties, with the exception of growth in cell-free medium, are shared by "unconventional agents" such as those of Creutzfeldt-Jakob disease and scrapie. Further comparison of the properties of the intestinal agent and of slow viruses revealed additional shared characteristics, including resistance to proteinase K and trypsin, and inactivation by guanidine thiocyanate, diethyl pyrocarbonate, phenol and sodium hydroxide. The agent differs from that of scrapie in being inactivated by ethidium bromide, zinc nitrate, EDTA, hydroxylamine in the presence Sarkosyl, and, under certain circumstances, by ribonuclease. Broth cultures of the agent contained particles possessing considerable size heterogeneity. The smaller filterable particles were generally more susceptible to inactivation, did not survive autoclaving, and were inactivated by papaya protease and lipase. It is possible that the replicating agent may be formed by crystallisation from constituents of the medium, and not by a biological process. This does not exclude the postulated relationship to slow viruses.

Anti-Bacterial Agents

A comparison of the penetration of two quinolones into intra-abdominal abscess.

A low-mortality model of an intra-abdominal abscess in the rat has been used to study the penetration of two quinolone agents into pus. Maximum concentrations in pus after intravenous injections were achieved at four hours (ciprofloxacin: 12.7 +/- 3.69 mg/L, fleroxacin: 2.25 +/- 1.82 mg/L), whereas fleroxacin given orally reached the maximum level at two hours (13.39 +/- 3.13 mg/L). Higher concentrations of fleroxacin were recorded in pus than in serum at each time point up to eight hours after administration, but pus levels of ciprofloxacin only exceeded serum levels after 1.5 hours. These antibiotics appear to have a unique property of high penetration into established abscesses and may have an important therapeutic role in the treatment of patients with multiple interloop abscesses.

Abdomen

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.

Cefotetan

Single dose, oral antibiotic cover for transurethral prostatectomy.

A double-blind, randomised, placebo-controlled study was carried out to determine the incidence and significance of bacteriuria in 110 patients undergoing transurethral resection of the prostate (TURP) and to assess the effect of a single pre-operative dose of Ciprofloxacin, a 4-quinolone antibiotic. Fifteen (68%) of the 22 patients in the placebo group with a positive post-operative urine culture subsequently developed a clinically apparent urinary tract infection (UTI) or received antibiotics in view of a positive urine culture. Adequate prostatic concentrations of Ciprofloxacin were achieved in all who received the drug. A significant reduction in the number of positive post-operative urine cultures and urinary tract infections requiring antibiotic therapy was achieved in this group. Six patients (5.5%) developed clinical evidence of septicaemia, 5 of whom were in the placebo group. No organisms resistant to Ciprofloxacin were encountered. Prior to surgery, 19% of all patients were found to have previously unsuspected bacteriuria. Ciprofloxacin tended to reduce the chances of this group developing a UTI or requiring antibiotics. Further, there was a highly significant reduction in post-operative infective complications in those with sterile urine at the time of resection who had received the drug. This study suggests that antibiotic cover for TURP is of clinical benefit. Ciprofloxacin may prove suited to this purpose, although further experience with the drug is still required.

Administration, Oral

The effects of Clostridium difficile crude toxins and purified toxin A on stripped rabbit ileal mucosa in Ussing chambers.

Clostridium difficile crude toxins and purified toxin A had similar effects on stripped rabbit ileal mucosa in Ussing chambers. Both toxin preparations caused secretion of sodium and chloride ions by increasing serosa to mucosa (s----m) fluxes. Transmural potential difference and resistance decreased after toxin treatment. Onset of changes in electrical measurements and ion fluxes coincided with onset of histological changes. The response to theophylline was greatly reduced in toxin-treated tissue compared with control tissue.

Animals

Biological mode of action of Clostridium difficile toxin A: a novel enterotoxin.

Antibody neutralisation and toxin A elution experiments showed that toxin A uptake from rabbit intestinal lumen was a continuous process. The kinetics of the ileal and colonic responses were significantly different; a much longer incubation (4 h) with toxin was required for colon, compared with 45 min for the ileum, to induce fluid accumulation at 12 h. Fluid secretion was induced only when toxin had gained access to deeper tissues, probably achieved by several toxin uptake-tissue damage cycles. Toxin A induced haemorrhage in both ileal and colonic tissues. In ileum, the villus architecture was severely damaged and this gave rise to protein-rich bloody luminal fluid. In the colon, although colonocytes were removed, the basement membrane remained intact; this resulted in a tissue-localised haemorrhage and a protein-low watery ultrafiltered luminal fluid. Toxin A is thus a novel type of histotoxic enterotoxin.

Animals

The effects of Clostridium difficile crude toxins and toxin A on ileal and colonic loops in immune and non-immune rabbits.

Rabbits were solidly immunised by parenteral injection of purified Clostridium difficile toxin A such that they resisted an intravenous challenge with a normally lethal dose of toxin A. Ileal and colonic loops constructed in non-immune and immune animals received challenge injections of crude culture filtrate or purified toxin A of C. difficile. Protection of ileum was manifest after sufficient initial mucosal damage resulted in release of high levels of antitoxin A into the loop lumen of immune animals. There was less fluid accumulation in ligated ileal loops of immune than of non-immune rabbits. Less protection was observed when loops were challenged with crude culture filtrate containing toxins A and B than when challenged with purified toxin A. In-vitro studies with Ussing chambers yielded no evidence for tissue-localised immunity as judged by electrical responses and histology of toxin-treated tissue from non-immune and immune animals. No differences were found in the degree of epithelial damage, or volume or composition of fluid accumulating in colonic loops of non-immune and immune rabbits challenged with toxin A or crude culture filtrate. However, in colonic loops of immune rabbits there was no overt tissue-localised haemorrhage, whereas in those of non-immune rabbits tissue-localised haemorrhage was marked. In contrast to our findings with ileal loops, fluid accumulating in colonic loops was watery and contained substantially less total protein and (in immune animals) antitoxin A.

Animals

Analysis of latex agglutination test for Clostridium difficile toxin A (D-1) and differentiation between C difficile toxins A and B and latex reactive protein.

Virulent toxigenic and avirulent non-toxigenic strains of Clostridium difficile gave a positive result in the latex agglutination test (LAT) for C difficile toxin A (D-1). Similar concentrations of latex agglutinating antigen were produced by these strains in vivo. Positive reactions were also given by C sporogenes, proteolytic C botulinum Types A, B, and A/F, and Bacteroides assaccharolyticus. The latex agglutinating antigen was denatured by boiling for 10 minutes, but not by heating at 56 degrees C for 30 minutes. The reaction was abolished by incubation of test material with crude C difficile antitoxin but not with other clostridial antitoxins or specific antitoxin to C difficile toxin A. The latex agglutinating antigen present in C difficile eluted between 0.39% and 0.47% M sodium chloride, and that produced by the other clostridia, between 0.35% and 0.43% M sodium chloride by fast protein liquid chromatography. The latex agglutinating antigen of C difficile was neither cytotoxic nor mouse lethal and was distinct from toxin A and toxin B. In the analysis of faecal specimens from patients with diarrhoea the latex agglutination test correlated better with the presence of C difficile than with toxin B and detected both toxigenic and non-toxigenic strains. The latex agglutination test should only be used in the laboratory as an alternative to culture for C difficile and not as a method for the detection of C difficile toxins.

Animals

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.

Administration, Oral

Bacteraemia in diabetics.

During a period of 22 months one or more episodes of bacteraemia were detected in 168 patients in hospital. Of these, 29% also had diabetes compared with 10% of the total number of patients admitted to hospital during this time (P less than 0.001). The diabetics with bacteraemia were elderly and diabetes had usually been present for many years. Most of them were not receiving insulin at the time bacteraemia was diagnosed. Escherichia coli was the commonest pathogen (33%) in the diabetics, the main source of infection being the urinary tract. This finding may be due to diabetic autonomic neuropathy, which leads to a poorly emptying, chronically infected bladder. Urinary tract infections with bacteraemia in elderly diabetics are often accompanied by vague non-specific symptoms and poor diabetic control. Fever is infrequent. Prompt antibiotic therapy and insulin injections to control the diabetes usually cure these serious infections.

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