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Title: Control of furunculosis by antimicrobial chemotherapy
Author: Barnes, Andrew C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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In vitro ativities of six fluoroquinolone antimicrobials, flumequine, sarafloxacin, PD127,391, PD117,596, enrofloxacin and Ro 09-1690, against Aeromonas salmonicida, isolated from outbreaks of furunculosis in farmed and wild Atlantic salmon (salmo salar), were evaluated in terms of minimum inhibitory concentration (MIC), bactericidal activity and the frequency at which mutation to resistance developed to the drugs compared to oxolinic acid, the 4-quinolone antibiotic currently licensed for furunculosis therapy in the UK. MICs were also determined for oxytetracycline and the β-lactam amoxycillin. In terms of MIC, the fluoroquinolones were more active than oxolinic acid with MICs reduced from 2- to 500-fold. Furthermore, the fluoroquinolones were bactericidal against both oxolinic acid-resistant and -susceptible isolates of A.salmonicida whereas oxolinic acid was not bactericidal against any bacteria tested. In addition to the increased antimicrobial activity, the frequency at which A.salmonicida mutated to resistance to the fluoroquinolones was lower than the frequency for resistance to oxolinic acid. Amoxycillin was active against all the A.salmonicida subsp. salmonicida isolates tested; however, the atypical A.salmonicida subsp. achromogenes isolates were resistant to amoxycillin with MICs in excess of 500mg/l. Ion effects were noted for the quinolones and oxytetracycline. For instance, the presence of 50mM MgCl_2 resulted in a 20- to 60- fold increase in the MICs of these drugs against the test strains. No ion effect was identified for amoxycillin. The quinolones were not affected by inoculum size but their efficacy, in terms of MIC, was reduced at the lower temperature of 10°C compared to 22°C. Mechanisms of resistance to the fluoroquinolones, oxytetracycline and amoxycillin were investigated. Low levels of resistance to the quinolones and oxytetracycline could be induced with either oxolinic acid or oxytetracycline, with each drug inducing cross resistance to the other. This phenomenon was discovered to result from alterations in outer membrane proteins, specifically the increase in expression of a 42kDa and a decrease in expression of a 37kDa protein.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available