JAC Advance Access published online on July 15, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg331
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Antibiotic Research Unit,
Department of Medical Sciences, Clinical Bacteriology, Box 552,
Uppsala University,
S-751 22 Uppsala
* Corresponding author. E-mail: ingegerd.gustafsson{at}medsci.uu.se.
Received 7 February 2003
; revised 9 May 2003
; accepted 18 May 2003
Background: Antibiotic resistance
typically confers a biological fitness cost on bacteria that can
be manifested as a decreased growth rate in culture media and experimental
animals. However, there are limited experimental data on the relative
fitness of resistant and susceptible bacteria during growth in their
natural environment. Objective: We have developed a human competition
model to investigate the relative fitness of antibiotic-resistant
and -susceptible bacteria. Materials and methods: A non-epidemic Staphylococcus
epidermidis strain was isolated from skin, and a rifampicin-resistant
(RifR) clone was selected. The RifR marker was used to distinguish
the inoculated strains from the resident population of coagulase-negative
staphylococci. The RifR strains were further selected for resistance
to ciprofloxacin (CipR) and fusidic acid (FusR). A 1:1 mix of susceptible
and resistant bacteria was applied on the forearms of 12 volunteers.
Competition was monitored by sampling bacteria from skin and determining
their relative numbers. Results: Resistance to ciprofloxacin due to parC mutations did not decrease the growth rate in vitro, and the CipR/CipS ratio was close to
1 during day 1 and 3 in the in vivo competition
experiments. In contrast, fusidic acid resistance due to fusA mutations
resulted in a decrease in the growth rate in vitro and
a considerable loss of fitness in the competition. The FusR/FusS
ratio diminished from 1.3 to 0.023 in 3 days. Conclusions: These data show that human volunteers
can be used as a simple and relevant model to study the biological
cost of resistance.
Keywords: antibiotic resistance, biological fitness cost,
human in vivo model
Fitness of antibiotic resistant Staphylococcus
epidermidis assessed by competition on the skin of human volunteers
2 Antibiotic Research Unit,
Department of Medical Sciences, Clinical Bacteriology, Box 552,
Uppsala University,
S-751 22 Uppsala; Swedish
Institute for Infectious Disease Control, Solna, Sweden
3 Swedish
Institute for Infectious Disease Control, Solna, Sweden
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