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Antimicrobial resistance in haemophilus influenzae: epidemiology, mechanisms and therapeutic implications

Powell, Mair; (1990) Antimicrobial resistance in haemophilus influenzae: epidemiology, mechanisms and therapeutic implications. Doctoral thesis (M.D), UCL (University College London). Green open access

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Studies with 2,458 clinical isolates of Haemophilus influenzae collected from UK laboratories during 1986 are described. The prevalence and epidemiology of antimicrobial resistance was compared with that in eight European countries as determined by a multi-national survey. Resistance was analysed with reference to difficulties in identification of the species and determination of susceptibility. Mechanisms mediating resistance were investigated. Results from studies with this large collection of isolates often confirmed previously published observations. Beta-lactam susceptibility of 100 isolates possessing non-beta-lactamase-mediated resistance to ampicillin was variable in pattern and degree. Outer-membrane and penicillin-binding protein profiles of resistant wild-types and transformants showed variable agreement with other reports. Biochemical characterisation of chloramphenicol acetyltransferases (CATs) from 42 resistant isolates showed that they resembled Type II enterobacterial enzymes. New information was gathered on prevalence and mechanisms of antimicrobial resistance. Carbapenem activity was shown to be maintained against most ampicillin-resistant beta-lactamase negative isolates and transformants which were of reduced susceptibility to other beta-lactams. Exposure to increasing concentrations of ampicillin selected for mutants with non-beta-lactamase-mediated resistance. Type II CATs from H.influenzae and enterobacteria produced only monoacetylchloramphenicol while Types I and III enzymes produced diacetylated drug at pH 6.8 and pH 7.8 in contrast with previous reports. Polyacrylamide gel electrophoresis was used to separate biochemically characterized dihydrofolate reductases (DHFRs) from trimethoprim-resistant wild-types, mutants and transformants. Results indicated that overproduction of DHFR might be the mechanism of resistance. Data accumulated was used to make recommendations regarding optimal methods for identification of the species and determination of susceptibility in routine diagnostic laboratories. Temporal changes and geographical differences in the prevalence of antimicrobial resistance were considered in making suggestions for appropriate therapy of invasive and non-invasive H.influenzae infections. It was concluded that newly-developed agents must increasingly replace the more traditional antimicrobials as the prevalence of drug resistance in the species continues to rise.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Antimicrobial resistance in haemophilus influenzae: epidemiology, mechanisms and therapeutic implications
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10123348
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