抗生素英文课件精品Lisa Drummond University of .pptVIP

Lisa DrummondUniversity of Edinburgh Antibiotics and Clostridium difficile Introduction Gram positive spore- former obligately anaerobic first described in asymptomatic neonates increased use of antibiotics led to an increase in C. difficile disease Introduction cont. infection ranges from asymptomatic, mild diarrhoea, colitis to pseudomembranous colitis risk factors - antibiotics, age, environment and virulence of infecting strain third generation cephalosporins, clindamycin and amoxycillin associated with the greatest risk disease occurs after depletion of patient’s normal protective flora Disease process Incidence of C .difficile in the population Pathogenicity Locus (PaLoc) 19.6kb element replaced by 115bp in non-toxigenic strains tcdD alternative sigma factor tcdC putative negative regulator toxins transcribed on entry to stationary phase PaLoc cont. toxin production affected by glucose, sub-inhibitory concs. of antibiotics, amino acids, temperature, oxidative stress, biotin insufficiency, biocarbonate concentration... AIMS to analyse MIC data, patient antibiotic regimes, S-types, resistance to look at effects of sub-MICs on growth and toxin production investigate toxin transcripts using RT-PCR investigate total cell protein between controls and sub-MIC antibiotics using 2D gel electrophoresis and MALDI-TOF MICs 186 strains and 6 antibiotics (NCCLS) the two treatment agents - vancomycin and metronidazole 4 precipitating agents - amoxycillin, clindamycin, cefoxitin and ceftriaxone database utilised for any connections Clindamycin resistance 12 isolates tested had clindamycin MIC of ?128?g/ml all contained ermB gene 2 different sizes noted smaller band lack leader peptide (Farrow et al., 2002) Recurrences and reinfections some patients produced up to 12 samples over the 18 months allowed comparisons of their isolates over that time some patients had changing S-types over this time some patients also had different isolates in the same faecal sample MIC