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Effects of high antibiotic use on antibiotic resistance and mutation frequency among commensal bacteria


, : Effects of high antibiotic use on antibiotic resistance and mutation frequency among commensal bacteria. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 42: 329

Background: We have investigated how long-term antibiotic treatment affects the human normal flora with focus on resistance and mutation frequency. Four commensals were included; E. coli, enterococci spp. (ent), alpha-streptococci and coagulase-negative staphylococci (CoNS). Methods: Samples were collected from patients at the Center of cystic fibrosis (n=22), and the hematology ward (n=24) of University Hospital Uppsala, Sweden. The individually used amount of antibiotics for one year was recorded as defined daily dose (DDD). Primary health care patients (n =30), who had no antibiotic treatment for one year, were used as controls. Three isolates of each bacterium were isolated and verified. Antibiotic susceptibilities were determined by disk diffusion. Mutation frequency was measured on ten individual cultures of each isolate by plating on rifampicin plates. The resistant mutants were counted after 24 h at 35degreeC. Results: Isolates from the treated patients showed a shift towards more resistance. For example, ciprofloxacin (cip) resistance (R) for ent and CoNS were 63 and 67% respectively as compared to 0% in the controls. A wide variation of mutation frequency (MF) was noted between and within the species, especially in alpha-streptococci where the MF varied over a 100-fold range. There was no correlation between DDD and MF. However, patients with >150 DDD fluoroquinolone carried cipR strains of all four species. The MF did not correlate with resistance except in E. coli where a slight increase was noted in the cipR strains, MF 3X10-8, compared to the susceptible strains, MF 8X10-9. 1/21 of E. coli was defined as mutator with a MF of 3X10-6. Conclusions: Long-term antibiotic treatment selects for resistant strains but not for mutators among the four studied commensals. The role of mutators in the evolution of antibiotic resistance needs to be further elucidated.

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