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Biomedical subjects

M H Wilcox

Publications and source records attributed to M H Wilcox.

At least 19 recordsLinked to original sources

Implementation of sequential therapy programs--a microbiologist's view.

Sequential antimicrobial therapy is not new, but confusion about the timing and nature of the switch often negates perceived advantages. A common problem is the choice of oral antibiotic to follow empirical administration of an intravenous second or third generation cephalosporin. Where guidelines do not exist, particularly when data are lacking as the the best option, the Delphi technique of obtaining a consensus agreement by review of a series of case histories is recommended. Majority verdicts are used to determine what is acceptable practice, and as such the approach is also suitable for audit. Savings through reduced drug acquisition costs and shorter lengths of stay have been highlighted. However, other less obvious potential benefits of sequential antimicrobial therapy include reduced incidence of intravascular catheter infection because of shorter line dwell times and less endoluminal contamination. Sequential antimicrobial therapy may also be used as part of a policy to reduce the selective pressure, particularly due to cephalosporin use, for endemic hospital pathogens such as Clostridium difficile and extended spectrum producing gram-negative baccilli.

Administration, Oral

Recurrence of symptoms in Clostridium difficile infection--relapse or reinfection?

We have fingerprinted Clostridium difficile isolates from patients with symptomatic recurrences of infection, using random amplified polymorphic DNA (RAPD). The medical records of 55/79 patients were examined, from whom multiple C. difficile-positive faeces were received during hospitalization at least five days, but no more than two months, apart. In 20 of these cases symptoms either did not recur (i.e., absent for at least three days between episodes), or were explainable by other causes, such as laxative administration. Of the remaining 35 patients, 27 sets of C. difficile isolates (23 pairs and four triplicates) were available for RAPD fingerprinting. Differing C. difficile DNA fingerprints (at least three major bands difference) were obtained for 15/27 patients, and hence at least 56% of the clinical recurrences of infection were in fact due to re-infection as opposed to relapse. Since we found that an endemic C. difficile clone was present in 18 out of 27 patients (67%) and accounted for 53% (31/58) of all isolates, it is probable that the majority of symptomatic recurrences are in fact re-infections, with either a different or the same C. difficile strain. We conclude that more attention must be given to preventing the re-infection of C. difficile symptomatic patients. Isolation of symptomatic individuals is the preferred option for the protection of other patients, but measures must be taken to ensure that further strain acquisition by the index cases does not occur.

Adult

Incidence and impact of Clostridium difficile infection in the UK, 1993-1996.

Questionnaires were sent to 360 UK medical microbiologists to determine the incidence of Clostridium difficile infection in the UK between 1993-1996, and to establish the current laboratory testing protocols. Replies were received from 104 laboratories (29% response rate), 86, 7, 4 and 3% of which are in England, Scotland, Wales and Northern Ireland, respectively. The laboratories serve a total of approximately 90,000 hospital beds (median 750). C. difficile testing was performed by 83% of the laboratories, and 52, 45 and 31% used toxin A +/- B kits, cell cytotoxicity, and culture +/- isolate toxigenicity testing methods, respectively. Forty-seven percent of laboratories only performed testing when specifically requested, 19% if antibiotic use was stated, 15% tested all diarrhoeal specimens, and 14% examined all specimens except those from infants and community patients. The annual totals of positive C. difficile reports and cases increased from 3132 to 12,775, and from 1576 to 8211, respectively, between 1993-1996. In 1993 C. difficile infection caused ward closures in 5% of hospitals but 16% in 1996. Antibiotic policy changes, due to C. difficile infection, occurred in 21% of hospitals in 1996 compared with only 4% in 1993. C. difficile infection appears to be increasing markedly in the UK with major implications on hospital inpatient activity. Wide variations in laboratory selection and testing methods are likely to be masking the true epidemiology of C. difficile infection, and consensus is required on optimal protocols.

Aged

Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin-tazobactam.

BACKGROUND: Rates of Clostridium difficile diarrhoea have recently been rising, with the elderly being at highest risk. AIM: To compare the incidence of C. difficile colonization and diarrhoea in elderly patients treated for presumed infection with either empirical cefotaxime (CTX) or piperacillin-tazobactam (PT). METHODS: A prospective, ward-based, crossover study was carried out on two well-matched care of the elderly wards at a UK tertiary care hospital, in patients requiring empirical broad-spectrum antibiotic treatment. RESULTS: There was a highly significant increased incidence of C. difficile colonization (26/34 vs. 3/14, P=0.001) and diarrhoea (18/34 vs. 1/14, P=0.006) in patients who received CTX as opposed to PT. DNA fingerprinting suggested that most infections arose from strains acquired from the hospital environment. CONCLUSIONS: Elderly patients are significantly less likely to develop C. difficile diarrhoea after treatment with PT than after CTX. The source of C. difficile appears to be predominantly from the ward environment.

Aged

Treatment of Clostridium difficile infection.

The treatment options for Clostridium difficile infection remain limited, although promising agents are currently being assessed. Metronidazole is the first-line drug of choice for those patients requiring specific anti-C. difficile treatment. Much of the interest in alternative therapies has centred on the difficult management issues posed by patients with multiple symptomatic recurrences of C. difficile infection. However, it is now clear that the majority of these episodes are due to reinfections with new C. difficile strains and not relapses caused by the original bacterium. Hence, the true efficacy of the alternative regimens remains unclear. Individuals susceptible to C. difficile reinfections need to be protected from exposure to C. difficile until their bowel flora recovers. While several biotherapeutic approaches to the treatment and prevention of C. difficile infection have been described, few controlled data are available. Preliminary studies with anti-C. difficile bovine immunoglobulin concentrates for treatment and prevention have produced promising results. Vaccination to prevent C. difficile infection, particularly in high-risk elderly patients managed within institutions where C. difficile is endemic, is a worthwhile therapeutic goal.

Animals

Evaluation of a novel endoluminal brush method for in situ diagnosis of catheter related sepsis.

AIMS: To determine the accuracy of a novel endoluminal brush method for the diagnosis of catheter related sepsis (CRS), which is performed in situ and hence does not require line sacrifice. METHODS: 230 central venous catheters in 216 patients were examined prospectively for evidence of CRS or colonisation using an endoluminal brush method in conjunction with peripheral blood cultures. The results were compared with those obtained using methods that require line sacrifice: extraluminal sampling (Maki roll) or endoluminal sampling (modified Cleri flush) of microorganisms. RESULTS: Only 16% of 128 patients suspected clinically of having line associated infection were confirmed as having CRS. In addition, 2 of 102 patients not suspected of having line associated infection had CRS. Line colonisation was apparent in approximately twice as many catheters using the Maki roll criteria (92%) compared with either the endoluminal brush (43%) or Cleri flush (43%). Furthermore, colonised catheters sampled using the Maki roll technique yielded mixed growth twice as often as when examined by endoluminal methods (17 and 8 cases, respectively). It was rare to detect either only endoluminal (4 of 22 episodes) or extraluminal (1 of 22 episodes) microorganisms in cases of CRS. In contrast, catheters defined as being colonised most frequently (59% of episodes) yielded only significant extraluminal growth. Only one case of CRS (5%) would have been "missed" if lines yielding a negative result from endoluminal brush sampling had been left in situ. Conversely, four episodes of CRS (18%) would not have been diagnosed by relying on extraluminal sampling alone. CONCLUSIONS: Diagnosis of CRS by the endoluminal brush method can be achieved without line sacrifice and is more sensitive (95%) and specific (84%) than extraluminal sampling of the catheter tip by the Maki roll technique (82% and 66%, respectively).

Adolescent

Subdural empyema due to Enterococcus faecalis.

Central nervous system infections due to Enterococcus species are uncommon. We report the first case of subdural empyema due to Enterococcus faecalis. Following partial treatment of a middle ear infection due to Enterococcus species and mixed coliforms, the patient developed signs of meningeal involvement. A lumbar puncture showed a raised polymorph cell count, but was sterile on culture; broad-spectrum antimicrobial therapy with cefotaxime, flucloxacillin and metronidazole was commenced. Following development of focal neurological signs, a CT scan revealed a subdural collection. Drainage and culture of the pus yielded a pure growth of Enterococcus faecalis. This case demonstrates the need to remain aware of the ability of the Enterococcus to cause serious infections and to direct specific antimicrobial therapy accordingly.

Adolescent

Financial burden of hospital-acquired Clostridium difficile infection.

Clostridium difficile infection has become endemic in many hospitals and yet few data on the associated costs of such cases are available. We prospectively followed 50 consecutive cases of C. difficile infection and 92 control patients, who were admitted to the same geriatric wards within 72 h of the cases. Cases and controls had similar age, sex and major diagnosis distributions. Cases stayed significantly longer (mean 21.3 days, median 20.5 days; P < 0.001) in hospital than controls, including an average 14 days in a side room. Diarrhoea developed in cases on average 10.8 days after admission, which, when compared with a mean duration of stay for controls of 25.2 days, implies that C. difficile infection caused an increased duration of stay, as opposed to infection occurring because of longer residence. There was a significantly higher death rate in cases compared with controls (P < 0.01). Antibiotic treatment of C. difficile infection cost an average of Pounds 47 per case. The average number of laboratory investigations per day was similar for cases and controls, but the increased length of stay meant an extra cost for tests of approximately Pounds 210 per case. Assuming hotel costs of Pounds 150 (Pounds 200) per day stay (in a side room), 94% of the additional costs associated with C. difficile infection were due to increased duration of stay (Pounds 3850). The total identifiable increased cost of C. difficile infection was, therefore, in excess of Pounds 4000 per case. Such high costs can be used to justify expenditure on personnel and/or other control measures to reduce the incidence of this hospital-acquired infection.

Aged