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Biomedical subjects

Mark H Wilcox

Publications and source records attributed to Mark H Wilcox.

9 recordsLinked to original sources
PubMed2003

Effects of cefotaxime and desacetylcefotaxime upon Clostridium difficile proliferation and toxin production in a triple-stage chemostat model of the human gut.

Clostridium difficile is recognized as an important nosocomial pathogen. C. difficile infection (CDI) is thought to arise as a result of depletion of the normal gut flora by antimicrobial agents. Cefotaxime (CTX) is well-known for its propensity to cause CDI, but the reasons behind its particular predisposition to the disease remain unclear. Previous investigations have so far relied upon the hamster model of CDI or human volunteers. We have used a triple-stage chemostat model of the human gut to investigate the behaviour of C. difficile and components of the normal gut flora, in response to exposure to CTX alone, and in combination with its active metabolite desacetylcefotaxime (dCTX). C. difficile remained in a steady state during non-antibiotic exposed periods, with no detectable cytotoxin. During both antibiotic exposure regimens, proliferation of C. difficile and elevated cytotoxin levels were observed. Cessation of antibiotic instillation produced a reduction in cytotoxin levels and viable counts. Decreases in bacterial counts were observed in response to both antibiotic exposure regimens, notably for bifidobacteria and bacteroides. Numbers of bacteroides were profoundly affected by exposure to the CTX/dCTX combination, and this may indicate a possible role for bacteroides in colonization resistance. We believe that the gut model is a promising method for studying C. difficile pathogenesis in conditions analogous to the in vivo situation.

Bacterial Toxins↗
PubMed2003

Gastrointestinal disorders and the critically ill. Clostridium difficile infection and pseudomembranous colitis.

Clostridium difficile causes a spectrum of diseases ranging from diarrhoea to pseudomembranous colitis, primarily in the hospitalized elderly, although community-acquired infection is probably under-documented. Host factors are increasingly recognized as critical determinants of disease expression. Exposure to antibiotics, particularly those adversely affecting anaerobic gut flora, appears to create a niche which is exploited by C. difficile. Several retrospective and intervention studies have indicated that third-generation cephalosporins have a high propensity to induce C. difficile diarrhoea. Conversely, some broad-spectrum antibiotics, including ureidopenicillins (e.g. piperacillin-tazobactam) and ciprofloxacin, are less likely to induce C. difficile infection. Effective control of C. difficile in the hospital requires both antibiotic control and prevention of environmental seeding and bacterial spread. Epidemic C. difficile strains are widely distributed in the hospital environment, both as a cause and result of nosocomial diarrhoea. Current treatment options are antibiotic-based, which is less than ideal. Although many biotherapeutic approaches have been tried few have shown real benefit.

Clostridioides difficile↗
PubMed2003

Efficacy of linezolid versus comparator therapies in Gram-positive infections.

Treatment of Gram-positive bacterial infections is currently a therapeutic challenge because many of these pathogens are now resistant to standard antimicrobial agents. The emergence of multidrug-resistant, Gram-positive pathogens emphasizes the need for new antimicrobial therapy. Linezolid is an oxazolidinone antibiotic with a novel mechanism of action that works by inhibiting bacterial protein synthesis by blocking formation of the initiation complex. It is active against Gram-positive organisms resistant to other antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci (VRE). Results are encouraging from several large-scale, randomized, Phase III trials comparing the efficacy and safety of linezolid with standard comparator agents for the treatment of nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and infections due to MRSA and VRE. Intravenous/oral linezolid is a promising antimicrobial agent and provides the clinician with an additional treatment option, particularly among the limited therapies for resistant Gram-positive bacterial infections.

Acetamides↗
PubMed2003

Each lumen is a potential source of central venous catheter-related bloodstream infection.

OBJECTIVE: To determine the relative rates of microbial colonization of individual lumens in triple-lumen central venous catheters (CVCs) and calculate the chance of detecting catheter-related blood stream infection (CRBSI) if only one lumen is sampled. DESIGN: Prospective evaluation of CVCs from suspected and nonsuspected CRBSI cases. SETTING: University teaching hospital. PATIENTS: Triple-lumen CVCs from 50 cases of suspected CRBSI (a raised peripheral white blood cell count, temperature >37 degrees C, and/or local signs of infection at the catheter skin entry site) were evaluated. For comparison, 50 triple-lumen CVCs routinely removed at the end of use were evaluated. MEASUREMENTS: In both groups, peripheral blood cultures were taken before CVC removal. After CVC removal, each lumen was sampled in vitro using the endoluminal brush, and the tip was then cultured using the Maki roll technique. MAIN RESULTS: CVCs causing CRBSI had significant microbial colonization in one, two, or three lumens in ten (40%), ten (40%), or five (20%) cases, respectively. Overall, random sampling of only one lumen in CVCs causing CRBSI had a 60% chance of detecting significant colonization. CONCLUSIONS: If only one CVC lumen is sampled, a negative result does not reliably rule out infection. Each lumen of multiple-lumen CVCs should be considered as a potential source of CRBSI.

Aged↗
PubMed2003

Correlation between enterococcal biofilm formation in vitro and medical-device-related infection potential in vivo.

Hospital-acquired infections caused by enterococci have increased dramatically since the 1970s. Many nosocomial enterococcal bloodstream infections are associated with medical devices such as central venous catheters. The ability to form biofilm on medical devices is a potential virulence trait that may allow enterococci to cause infections in the expanding population of patients managed with such devices. In this study, the hypothesis that increased ability to form biofilm in vitro is associated with medical-device-related infection in vivo was tested. A microplate assay was employed to assess biofilm-forming characteristics of enterococci in 0.9 % (w/v) sodium chloride, an oligotrophic environment, and BHI, a nutrient-rich environment. Results were compared in isolates from different sources of infection. One hundred and nine enterococcal bloodstream isolates were assayed. Biofilm formation on microplates was demonstrated by all Enterococcus faecalis isolates and 16/38 (42 %) Enterococcus faecium isolates. E. faecalis isolates produced significantly more biofilm than E. faecium isolates in both media (P < 0.0001, Mann-Whitney U test). E. faecalis isolates from intravascular-catheter-related bloodstream infections (CRBSIs) produced significantly more biofilm than non-CRBSI isolates (P < 0.0001), or isolates of uncertain clinical significance (P < 0.0001). Biofilm formed by E. faecium isolates was not significantly affected by culture medium and did not differ between isolates from the different clinical categories. In conclusion, there was significantly more biofilm formed by E. faecalis isolates causing CRBSI compared with isolates from other types of infection or from isolates of uncertain clinical significance. The ability of E. faecalis isolates to form biofilm in vitro appears to be a marker of a virulence trait that enhances the ability of isolates to cause CRBSI.

Bacteremia↗
PubMed2002

Enterococcal intravascular catheter-related bloodstream infection: management and outcome of 61 consecutive cases.

Enterococci are an increasingly important cause of intravascular catheter-related bloodstream infection (CRBSI), but the evidence base for treating such cases is limited. Successful antimicrobial treatment of CRBSI while leaving the central venous catheter (CVC) in situ has been reported for some bacteria, such as coagulase-negative staphylococci, but the effectiveness of this approach for treating enterococcal CRBSI is unknown. We aimed to determine the effectiveness of treatment options for enterococcal CRBSI and whether CVC removal is mandatory. Treatment and outcome was determined in a 3 year cohort of patients with enterococcal CRBSI from a university teaching hospital. All episodes of enterococcal bacteraemia during the study (n = 268) were examined to identify the cohort of 61 CRBSIs. Outcomes were determined for various antimicrobial regimens with or without CVC removal. Forty-eight episodes were managed with CVC removal and 13 were managed with the CVC in situ. Forty of 48 (83%) and five of 13 (38%) episodes were cured with the CVC removed or left in situ, respectively. All five episodes cured with the CVC in situ were treated with a cell wall-acting antimicrobial plus an aminoglycoside. This antimicrobial combination was significantly more effective than either ampicillin or vancomycin monotherapy (P < 0.05), or antimicrobials to which isolates were not susceptible (P < 0.01) when the CVC remained in situ. We conclude that enterococcal CRBSI can be treated successfully without CVC removal. The combination of a cell wall-acting antimicrobial with an aminoglycoside was the most effective regimen when the CVC remained in situ in this small group of patients. Although CVC removal was associated with a high cure rate, it did not guarantee treatment success.

Adolescent↗
PubMed2002

Clostridium difficile.

Clostridium difficile is the most commonly identified infective cause of antibiotic associated diarrhoea. Broad spectrum antibiotics, are most frequently incriminated, although short (<3 day) antibiotic courses cause fewer episodes. Gold standard cell-culture based cytotoxin assays have been compared to rapid immunoassays, which are less effective, especially since toxin A negative, toxin B positive strains have been shown to be truly virulent. Details of colonization and adherence mechanisms have been revealed, and clonal spread has been demonstrated. The mainstay of treatment of C. difficile infection remains metronidazole. Justified fears over resistance are leading to development of alternative therapeutic strategies. These include a toxin binding polymer and ongoing biotherapy research. An antibody rise to toxin A during an episode of C. difficile diarrhoea protects against recurrence, and trials are in progress to investigate immunization: a toxoid vaccine which is immunogenic and safe in healthy volunteers shows promise for the future.

Bacterial Toxins↗
PubMedDate not supplied

The use of a rapid in situ test in the detection of central venous catheter-related bloodstream infection: a prospective study.

BACKGROUND: Acridine orange leukocyte cytospin (AOLC) is a highly sensitive and specific test for the detection of catheter-related bloodstream infection (CRBSI). We evaluated the role of the AOLC test in early detection or exclusion of CRBSI and compared the cost of managing patients with suspected CRBSI. METHODS: On the day of clinical suspicion of CRBSI, blood samples were obtained from the catheters for the AOLC test, and peripheral blood samples were obtained for quantitative blood cultures. Catheters with positive AOLC results were immediately removed for culture and replaced if necessary. Catheters with negative AOLC tests were left in situ. We compared the catheter lifespan in patients with suspected CRBSI who had positive and negative AOLC tests and calculated the cost of using the AOLC test to prevent indiscriminate catheter removal. RESULTS: Fifty patients with suspected CRBSI were tested and prospectively followed up. Catheters were removed in 10 patients (20%) with a positive AOLC test, and CRBSI was confirmed in each case subsequently. Selective removal of catheters based on AOLC tests significantly extended the lifespan of catheters compared with an indiscriminate removal of catheters based on clinical suspicion of CRBSI (median, 24 versus 11 days; p < .0001). The cost of an AOLC test and selective catheter replacement strategy was significantly lower than the cost of routine removal and replacement of catheters (median, pounds sterling 9.53 versus pounds sterling 64.20; p < .0001). CONCLUSION: The AOLC test enables a rapid detection of CRBSI, avoids unnecessary removal of catheters, and provides a cost-efficient management approach in patients with suspected CRBSI.

Acridine Orange↗