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Title: An investigation of cefotaxime resistance in aerobic Gram-negative bacilli isolated from surveillance flora of patients undergoing a selective parenteral and enteral antisepsis regimen in the intensive therapy unit
Author: Hadley, Katherine M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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Disenchanted by the failure of conventional approaches to infection in a Dutch team developed a preventative approach stressing the importance of endogenously-derived infection and the protective role of the anaerobic flora in colonization resistance. They applied selective decontamination of the digestive tract (SDD) to the novel setting of the intensive therapy unit (ITU) with impressive results. SDD was part of a triple regimen which included systemic cefotaxime and intensive microbiological surveillance. Intrigued by the Dutch findings a Scottish team applied a similar selective parental and enteral antisepsis regimen (SPEAR) to patients in a local medical-surgical ITU with encouraging results. Such use of cefotaxime might result in 1) the selection in certain species of aerobic Gram-negative bacilli (AGNB) of stably derepressed mutants which hyperproduce AmpC b-lactamases or 2) the selection and dissemination of extended-spectrum b-lactamases. Both types of enzymes attack multiple b-lactam antibiotics. The objective was to investigate those AGNB from surveillance flora showing resistance to cefotaxime with reference to plasmid-mediation and b-lactamase characterization using molecular biology techniques. One hundred and seventy-five of 200 isolates collected over a period of two years and ten months fulfilled the criteria for the study. Plasmids were detected in 78 of 175 isolates by agarose gel electrophoresis with sizes ranging from 2 kb to 214 kb. Transconjugation experiments were carried out on all isolates. Both test and control systems were used. b-Lactamases were detected in 144 of 175 isolates by isoelectric focusing. All isolates were tested for susceptibility to a battery of b-lactam antibiotics chosen to facilitate the recognition of the resistance patterns associated with particular b-lactamase types. Disk diffusion and agar dilution methods were used. All isolates were tested for the production of extended-spectrum b-lactamases (ESBLs). Potential ESBLs were found in four isolates and their relevance is discussed. There was evidence of chromosomal b-lactamase derepression in 65 of the 175 isolates examined.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available