Maple, Peter Alan Christopher; (1991) Multiple antibiotic resistance in methicillin-aminoglycoside resistant Staphylococcus aureus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Antibiotic susceptibility profiles of 100 strains of methicillin and gentamicin resistant Staphylococcus aureus (MGRSA) from 32 centres in 23 countries were determined. This is the first survey to document the international problem of multiple antibiotic resistance in MGRSA. Many differing susceptibility profiles were found, some strains being sensitive to a range of currently available antistaphylococcal agents; others were resistant to many of these agents. More than 50% of MGRSA studied were non-typable with the "International Set" of phages. Those strains which typed, mostly reacted with phage 85 alone, or with other Group III phages as well. Typing with supplementary phages revealed many of the non-typable strains to possess Group Ill-related patterns. The variety of phage-typing and antibiotic resistance patterns seen suggests that the worldwide occurrence of MGRSA is probably not due to widespread dissemination of a single clone. The aminoglycoside modifying enzyme APH (2")/AAC (6') was found in 44% of strains, while 56% produced APH (2")/AAC (6') and APH (3')-IV. Gene probing experiments showed the same gene for APH (2")/AAC (6') in MGRSA worldwide. Options for treating MGRSA infections are limited, currently few agents can reliably be used in place of vancomycin. Fosfomycin and pristinamycin appear to be promising. For treating MGRSA carriage, azelaic acid and nitrofurazone may be useful alternatives to mupirocin. Few, if any, agents currently under development appear to be promising alternatives to vancomycin. Widespread resistance was found to the fluoroquinolones (eg. ciprofloxacin) in MGRSA. Experimental studies showed fluoroquinolone resistance to readily occur. Analysis of resistant clinical isolates showed the high incidence of ciprofloxacin resistance in the MGRSA studied resulted from independent evolution and not cross-infection. Strains were least able to develop resistance to ofloxacin, and newer fluoroquinolones (eg. sparfloxacin) have improved activity against MGRSA. Multiple antibiotic resistance in MGRSA is a major problem which could become significantly worse should vancomycin resistance develop.

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